Microbial Transformations of Steroids. A Handbook

MICROBIAL TRANSFORMATIONS

OF STEROIDS

ACADEMIC PRESS New York and London

A Handbook

William Charney Manager, Industrial Microbiology, Schering Corporation, Union, New Jersey

and

Hershel L. Herzog Director of Chemical Development, Schering Corporation, Bloomfield, New Jersey

1967

<3

COPYRIGHT © 1967, BY ACADEMIC PRESS INC.

ALL RIGHTS RESERVED

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TEN PERMISSION FROM THE PUBLISHERS.

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United Kingdom Edition published by ACADEMIC PRESS INC. (LONDON) LTD. Berkeley Square House, London W.l

LIBRARY OF CONGRESS CATALOG CARD N U M B E R : 68-18661

PRINTED IN THE UNITED STATES OF AMERICA

To Mita and Levonna

PREFACE

The principal purpose of this volume is to provide those who wish to use micro-bial transformations of steroids with a single source book for the period from 1937 to the present. This handbook should answer the following questions: Has a particular compound been prepared with the aid of microorganisms? If so, how efficient are these methods, and which among them is likely to be the best? Has a particular microbial genus (or species) been used with a particular substrate (or substrates), and what was the observed result? Where can the required culture be obtained? Is there a United States Patent or a published scientific article (through December 31, 1963, with selected entries thereafter) which discloses the product of the organism in question in a detailed example ?

The literature of this field has been spread widely in chemical and biological journals throughout the world. To the extent that we have been able, we have combed this literature and tabulated selected data which we believe may be useful. We have continued our scrutiny to the present, and all important developments subsequent to December, 1963, are discussed, with references appropriately noted in the Biblio-graphical Appendix. The Tables contain essentially no reference to this later work.

A secondary purpose of ours has been to survey the historical development and present status of the field. We have been closely associated with the commercial production of steroids for 15 years and have participated in some of the events which influenced the evolution of microbial transformations. It has been our intention to interpret the many developments in the theory and practice of the field from our largely applied viewpoint.

To the extent that we have considered theory, we have concentrated on the pro-cesses occurring within the steroid and have given little attention to the nature of the enzymes responsible for the observed changes or to the chemical changes which they might experience.

We extend our special thanks to the management of the Schering Corporation and to our colleague and guide, Dr. E. B. Hershberg, for their aid and understanding during the lengthy preparation of this volume. We also thank Miss Lisette Harris, Mrs. Marie Marshall, and Mrs. Elizabeth Wesson for their cheerful completion of the arduous task of typing the manuscript, and Miss Dorothy Mizoguchi for the trans-lation of articles published in Japanese.

We are grateful to Dr. C. H. Robinson and Dr. A. L. Nussbaum for reading and criticizing the historical and chemical transformation sections.

William Charney Hershel L. Herzog

October, 1967

vii

CHAPTER I

Introduction

Microbial transformations of organic compounds have been known in an empiri-cal way from the dawn of history. In almost every civilization, primitive or advanced, man has practiced the fermentation of fruit, grain, or milk to obtain intoxicating and nourishing dietary factors. Evidence of wine production from as early as approxi-mately 3000 B . C . has been found in excavations at Lachish and other sites. *

The rational application of these early techniques could come only after the scientific practice of organic chemistry and microbiology was begun. A sufficient understanding had developed by 1857 to provide the necessary background for the work of Louis Pasteur on the fermentation of sugar to lactic acid and ethanol. Herein was elucidated for the first time the concept that individual microbial species were re-sponsible for discrete chemical alterations of selected substrates.2"5 These experi-ments and their publication have been called "the birth of microbiology."5

EARLIEST WORK - NONSTEROID

After Pasteur and until the end of the 19th century, few studies of the application of microorganisms to organic chemistry were carried out. None of these were of an intensive, systematic nature, which might have emphasized the broader possibilities of a fusion of the two sciences,6?7 although Brown recognized that such possibilities did exist. He gave individual examples of the oxidation of secondary alcohols to ke-tones and of primary alcohols to aldehydes and carboxylic acids.

Beginning in 1896, Bertrand carried out extensive studies of the simple, oxida-tive process resulting from the action of Acetohacter xylinum on a series of polyhydric alcohols, and thereby established the generality of the illustrated scheme.8"10

1Wooley, L . , "The Beginnings of Civilization," Vol. I, Part II, p. 234. The New American Library, New York, 1965.

2Pasteur , L . , Compt. Rend. 45, 913 (1857). 3Pasteur , L . , Ann. Chim. Phys. [1] 58, 323 (1860). 4Pasteur , L. , Ann. Sei. Nat. 16, 5 (1861). 5Vallery-Radot, L. P . , "Pasteur Fermentation Centennial," p. 4. Chas. Pfizer and Co.,

Inc. , New York, 1957. 6Boutroux, L . , Compt. Rend. 86, 605 (1878). 7Brown, A. J . , J . Chem. Soc.,pp. 172 and 432 (1886). 8Bertrand, G., Compt. Rend. 122, 900 (1896); 126, 984 (1898). 9Bertrand, G., Ann. Chim. Phys. [7] £, 3 (1904).

10Bertrand, G., Bull. Soc. Chim. France 15, 627 (1896); 19, 502 (1898).

1

2 I. INTRODUCTION

CH?-OH CH20H I 2 I 2

H-Ç-OH Axylinum^ Ç=0 (H-Ç-OH)^ * " ( Η - 0 - Ο Η ) Λ

CH2OH CH20H

As "Bertrand's rule" was finally elaborated, it was shown that a pair of adjacent, eis, secondary hydroxyl groups, next to a primary hydroxyl group, suffice to establish conditions favorable for the oxidation.11 The reaction eventually became important for the conversion of sorbitol to Z-sorbose,12 an intermediate in the manufacture of vita-min C. Dihydroxyacetone, which has been used extensively in recent times to tan human skin in vivo (for cosmetic reasons), can also be made on a commercial scale in the same way.13 A favored organism for these reactions is Acetobacter suboxydans.

Following the work of Bertrand, the next major development in the field arose from the finding of Lintner and von Liebig14 that a fermenting yeast reduced furfur-aldehyde to the alcohol. Neuberg and his school explored the application of yeasts to a wide variety of substrates. Their studies are summarized in extenso by Fischer (F-245) and Stodola.15

EARLIEST WORK - STEROID

Steroidal substrates were used first, in 1937, by Mamoli and Vercellone (M-550, M-551), who began by extending the findings of the Neuberg school. They showed that fermenting yeast may be used to reduce 17-ketosteroids to 17ß-hydroxysteroids. This method had some passing importance in the manufacture of the male hormone,

fermenting yeast

testosterone (M-543), and later of the female hormone, estradiol (W-1085), but was superseded by more convenient and efficient nonenzymatic procedures.

Through the use of impure yeast cultures, Mamoli and Vercellone (M-538, M-540, M-542, M-552) discovered a useful class of sequential oxidation-isomeriza-tion reactions which they later attributed correctly to the action of the bacterial con-taminants (M-553). A representative transformation of this type (including a hydroly-sis step, as well) is the conversion of 3)3,21 -dihydroxy-5-pregnen-20-one 21-acetate to deoxycorticosterone by Corynebacterium mediolanum (Corynebacterium helvolum) (M-541, M-546). Schering (USA) employed a similar process to manufacture Reich-stein's Compound S (17α, 21-dihydroxy-4-pregnene-3, 20-dione) for a time. It is now clear that nonenzymatic methods are more efficient for the synthesis of Compound S.

11 Some later modifications of the rule are summarized by Sowden, J . S. , in "The Carbohydrates" (W. Pigman, ed.) , Po 132. Academic Press , New York, 1957.

12Wells, P. A., Stubbs, J . J . , Lockwood, L. B . , and Roe, E. T . , Ind. Eng. Chem. 29, 1385 (1937).

13Underkofler, L. A. , and Fulmer, E. I . , J . Am. Chem. Soc. 59, 301 (1937). 14 Lintner, C. J. , and von Liebig, H. J . , Z. Physiol. Chem. 72, 449 (1911). 15Stodola, F. H. , "Chemical Transformations by Microorganisms," Chapter 2. Wiley,

New York, 1958.

* •h

EARLIEST WORK - STEROIDS 3

c=o

CHLOH I 2

c=o

Mamoli and his colleagues also recognized a class of bacterial reductions, which they attributed to an anaerobic bacterial species identified as Bacillus putrificus. Al-

B. putrificus

though this culture has since been lost, the same (5/3) and related (5a) reductions have been demonstrated with a variety of aerobic and anaerobic microbial species and have some academic interest since they parallel normal modes of mammalian metabolism of 3-keto-Δ4-steroids.

Considered in the historical context, the timing of Mamoli's pioneering application of microbial methods to the organic chemistry of steroids was logical. Just a few years earlier the correct structure of the steroid nucleus had been established. In 1935 testosterone was isolated from steer testis by Laqueur and was shown to be a powerful male hormone in a variety of animal tests . The structure was established by Butenandt and Ruzicka during the same year. The possibility of important medical

Testosterone

application was on the horizon. We appreciate the element of inevitability in the de-velopment of microbiological transformations in the steroid field, arising as it did from the knowledge of the chemistry of yeasts developed by Neuberg and from the availability of 17-ketosteroid intermediates.

The period from 1940-1949, following the early efforts of the Mamoli school, was rather quiet with respect to the further evolution of microbial transformations. Eco-nomic incentive for further study was absent because adequate nonenzymatic method-ology had been devised for the synthesis of testosterone and related male hormone products, and estradiol. Also, the war disrupted scientific activity in Italy and Germany, where all the work had been done. Nevertheless, key observations which foreshadowed the subsequent explosive growth of the field were made.

Horvath and Kramli (H-406) in 1947 reported the 7-dehydrogenation of cholesterol with Azotobacter sp. and in 1948 (K-474, K-475) they reported the 7-hydroxylation of cholesterol with Proactinomyces sp. These reactions, both novel at this time, were the first examples of what later proved to be the most important contributions of

4 I. INTRODUCTION

microbiology to steroid chemistry. There was no basis, at the time these observa-tions were made, to appreciate their future import.

Turfitt (T-1029, T-1030, T-1031, T-1032, T-1034) studied the use of steroids, as a sole source of carbon for microbial growth, and the steroid transformation pro-ducts produced thereby. The key observations he made, which lay fallow until greater understanding of the field developed [cf. the work of Whitmarsh (W-l l l l ) and parti-cularly of Sih and his collaborators (Ap-79, Ap-83, Ap-95) ] were that cholestenone and 3-keto-4-cholenic acid were transformed by Proactinomyces erythropolis, albeit to a very minor degree, into 3-keto-4-androstene-17/3-carboxylic acid. The idea which this illustrated was that cholesterol conceivably might be transformed by a microbiological degradative method into useful steroid entities of substantially lower molecular weight.16

SIGNIFICANCE OF DISCOVERY OF ANTIINFLAMMATORY ACTION OF CORTISONE

The most important chapter in the history of microbial transformations of steroids has had to do with the synthesis of the hormones of the adrenal gland and of their more powerful and therapeutic ally selective synthetic analogs. Studies of the composition of steroids in bovine and other mammalian adrenal glands by Kendall, Reichstein, and Wintersteiner, and their respective collaborators, begun in the early 1930's, led eventually to the isolation, characterization, and structural proof of cortisone (1938).

CH20H I 2

c=o

Cortisone

Understanding of the therapeutic possibilities of this agent did not begin to develop until 1949, when Hench and associates17 announced the successful use of cortisone 21-acetate as a palliative in rheumatoid arthrit is . For their contributions to this discovery Hench, Kendall, and Reichstein shared the Nobel Prize.

Since rheumatoid arthritis was (and is) a grave and crippling disease, with a high incidence, there was a tremendous incentive to provide cortisone by an efficient syn-thetic technique. Sarett, among others, had been working on the partial synthesis of adrenocorticoid hormones, and in 1946 he achieved the first synthesis of cortisone. The cortisone for the Hench-Kendall clinical experiment was prepared at Merck based on synthetic methods devised by Sarett and by Kendall and his co-workers. The starting material was deoxycholic acid, which was readily available from bovine

16 At this time cholesterol was still the major starting material for steroid hormone synthesis. It was transformed by oxidation with chromic acid into dehydroepiandrosterone in about 10% yield. In the late 1940 Ts cholesterol was supplanted by diosgenin as the pre -ferred starting material.

17 Hench, P. S., Kendall, E. C. , Slocumb, C. H. , and Polley, H. F . , A. M. A. Arch. Internal Med. 85, 545 (1950).

ANTIINFLAMMATORY ACTION OF CORTISONE 5

bile. The introduction of the 11-oxygen atom, an essential element of structure, was a major task.18

While Merck, beginning in 1949, and Schering, in 1951, manufactured cortisone from deoxycholic acid, Peterson and Murray, biochemist and microbiologist, respec-tively, with the Upjohn Company, chose to attack the problem of the introduction of 11-oxygen by the potentially more direct, microbiological method. They have said (P-723) that they were stimulated to enter this field by the successes of the Mamoli school. They were also encouraged, early in their work, by the report of Hechter and collaborators19 that perfusion of deoxycorticosterone through isolated adrenal glands resulted in the formation of corticosterone by enzymatic 11/3-hydroxylation.

FIRST HYDROXYLATIONS

In 1950 Peterson and Murray observed the first microbial 11-hydroxylation, namely, the lla-hydroxylation of progesterone with the fungus, Rhizopus arrhizus. "The culture was isolated from the air when an agar plate was exposed on a window sill" (P-721). Shortly thereafter, Rhizopus nigricans was found to lla-hydroxylate progesterone in high yield. The first publication of this work in extenso was in a U. S.

c=o

patent which was issued in July 1952 (M-601) and described, with a wealth of detail, the hydroxylations at 60 and 11a of a variety of substrates by fungi of the order Mucorales. Selected examples of 7ξ- and 14 ξ-hydroxylations were also given.20

Emphasis was placed on lla-hydroxylation, since it was apparent that herein lay the great economic value of this invention.

The importance of the Murray-Peterson discovery was manyfold. It led to a new technology for the manufacture of adrenocortical hormones and, eventually, of their synthetic analogs. It introduced the use of fungi, heretofore unexplored as a source of enzymes for microbiological transformations. And perhaps most important of all, it caused a surge of interest in the field. Much new, basic information for science was developed subsequently from the study of microbiological transformation of steroids.

Colingsworth, Brunner, and Haines (C-134), also of the Upjohn Company, dis-covered the llß-hydroxylation of Compound S with the actinomycete, Streptomyces fradiae shortly after the original Murray-Peterson findings were made. This was to

18 Flow chart 26 from "Steroids" (L. F. Fieser and M. Fieser, p. 644, compounds I to DC. Reinhold, New York, 1959), is an accurate representation of the complexity of this process, as it was actually practiced on an industrial scale. More generally, the background for all important early developments in steroid chemistry is given in detail by the Fiesers.

19Hechter, O., Jacobsen, R. P . , Jeanloz, R., andSchenker, V., J. Am. Chem. Soc. 71, 3261 (1949).

20 Hydroxylation at the 8-position was also described, revised to 9OJ, and in some cases Iß.

Levy, H., Marshall, C. W., Pincus, G.

These assignments were later

Rhizopus nigricans

6 I. INTRODUCTION

be the prototype for a second class of hydroxylation of considerable commercial significance.

CH-0H

Compound S Hydrocortisone

The same investigators also found that Cunninghamella blakesleeana was consid-erably more efficient at promoting this same reaction (H-339).

The motives which induced Murray, Peterson, and their Upjohn colleagues to enter this field were equally impelling for Perlman, Titus, and Fried of Squibb. In-dependently,21 they discovered the 16a-hydroxylation of progesterone with an actino-mycete later shown to be Streptomyces argenteclus. In 1956, when the antiinflamma-tory activity of triamcinolone was reported by Bernstein (B-60), the considerable value of this hydroxylation was first appreciated (T-1002). Fried and his colleagues

Triamcinolone

also discovered the useful lla-hydroxylation of progesterone by Aspergillus niger early in their studies.

FIRST DEHYDROGENATIONS

An immediate and major result from all of these early findings was the improve-ment of the methodology of steroid chemistry and the opening of a new avenue for r e -search. Microbiological transformation studies were begun in the laboratories of most of the pharmaceutical houses with interests in steroid chemistry (Lederle, Merck, Pfizer, Schering, and Syntex, among others). Since Schering was producing cortisone acetate at this time and was attempting to develop a useful synthesis for hydrocortisone (cortisol), we were prompted to extend the investigations of the early workers into new lines which might improve our production techniques. In this connection we began, in 1953, the study of the enzymatic hydrolysis of hydrocortisone 11, 21-diacetate. The diacetate had been prepared 22 in the hope that a chemical hydrolysis might afford

21 The first Squibb patent application in this field was filed in July 1951. 2201iveto, E. P . , Gerold, C. , and Hershberg, E. B . , Arch. Biochem. Biophys. 43, 234

(1953).

FIRST DEHYDROGENATIONS 7

hydrocortisone. The 11-ester was then found to be exceptionally difficult to hydrolyze, and we turned to the use of microorganisms.

One of the early experiments, which was run by Nobile in our laboratories, was the treatment of the diacetate with Corynebacterium simplex. The rationale was that an apparently related and then unavailable culture, Corynebacterium mediolanum, had been shown by Mamoli to have a good esterase (M-541, M-546). As it turned out, C. simplex afforded an interesting new reaction product in high yield, but that product was not hydrocortisone. More detailed investigation with other substrates, particu-larly Compound S, showed that the major transformation was 1-dehydrogenation (H-389, N-671).

II 0CCH,

The microbial 1-dehydrogenation reaction was not new, having been described at a Gordon Conference in the summer of 1953 by Fried2 3 and published in November of the same year (F-284). Vischer and Wettstein had also observed 1-dehydrogenation (V-1056). In none of the cases described by Fried, Thoma, and KLingsberg or Vischer

ChLOH I 2

C=0

23 Josef Fried, not to be confused with his brother, John Fried, also a steroid chemist. All the early work in microbial transformations reported by J . Fried was done by Josef Fried.

8 I. INTRODUCTION

CH, i 3

and Wettstein, several of which are illustrated here, did a steroid with a pregnane skeleton pass through the dehydrogenation process to an identified product with side-chain intact. In all instances wherein a 1-dehydro product was characterized, either 1, 4-androstadiene-3, 17-dione, 17/3-hydroxy-l, 4-androstadien-3-one, or 1-dehydro-testololactone was formed, the side chain having been altered in the illustrated way.24

Since we had shown that C. simplex dehydrogenated without concomitant side-chain degradation, we were able to use this transformation to prepare the previously unknown 1-dehydro analogs of cortisone and hydrocortisone, later named prednisone and prednisolone, respectively. These were tested in animals by Tolksdorf, Perlman,

ÇHLOH CHLOH I 2 I 2

C=0 C=0

Prednisone Prednisolone

and their collaborators at Schering25 and found to be three to five times more potent than the parent 1, 2-dihydro compounds by a variety of criteria (H-387, H-389). In July 1954, prednisolone was given to M. M. Pechet, then at the National Institutes of Health, who with J . J . Bunim and A. Bollett tested the compound in an arthritic hu-man. This first test and the many subsequent tests with both prednisone and prednis-olone in corticoid-responsive diseases confirmed the enhanced potency predicted from the animal experiments. In addition, and even more important, they showed that there was essentially no drug-induced salt retention at therapeutic dose levels. Since salt retention had been a significant complication resulting from the use of cortisone and hydrocortisone, the improved therapeutic index of prednisone and prednisolone en-couraged a much wider use of adrenocorticoids in the treatment of dermatologie, allergic, and collagen diseases.

Using fermentation techniques, the Schering Corporation made prednisone and prednisolone broadly available early in 1955. These agents quickly supplanted corti-sone and hydrocortisone for most indications requiring systemic (as opposed to topical) treatment. These 1-dehydro compounds continue to be used widely (1966) in spite of the many additional synthetic corticoids which have been produced. In the

24 Vischer and Wettstein mentioned Chromatographie evidence for the formation of pro-ducts, from Compound S and cortisone, which had suffered no degradation.

25 Tolksdorf, S. , Battin, M. L. , Cassidy, J. W., McLeod, R. M., Warren, F. H. , and Perlman, P. L. , Proc. Soc. Exptl. Biol. Med. 92, 207 (1956).

F sol ani F. caucaslcum

FERST DEHYDROGENATIONS 9

subsequent development of the corticoid field, 1-dehydrogenation played a vital role. All synthetic corticoids for systemic use contain this structural unit.

The other contributions from microbiology toward the realization of new struc-tures have been in providing improved technology for manufacture. Triamcinolone, whose preparation and properties were announced by Bernstein and his collaborators

CH2OH

C=0

Triamcinolone

of Lederle in 1956 (B-60), was the first useful antiinflammatory agent to embody the potency-enhancing effort of the 9a-fluorine atom, discovered by Fried and Sabo in 1954. To counteract the concomitant, increased, s alt-retention component, also con-tributed by the halogen, the insertion of Δ1 -unsaturation was insufficient. Bernstein found that the presence of a 16a-hydroxyl group effectively blocked salt retention in 9a-fluorosteroids, at the expense of the potency enhancement normally found in 9a-fluorocorticoids. Triamcinolone has essentially the same milligram potency as pred-nisone and prednisolone, but has been found to be somewhat more active in the treat-ment of certain, rather common dermatologie conditions, particularly psoriasis. This property has led to its widespread use. The considerably poorer therapeutic index of triamcinolone (as measured in dogs) does not seem to have become a problem in human medicine, although the pattern of side effects varies somewhat from that usually observed with other synthetic corticoids.

Bernstein and his associates achieved the introduction of the lto-hydroxyl group by chemical means in their first synthesis, and hence microbiology cannot be said to have contributed significantly to this aspect of the discovery. In the ultimate commer-cial exploitation, however, advantage was taken of the findings of Perlman, Titus, and Fried (P-718), and subsequent improvements by Thoma and Fried (T-1002), to intro-duce the 16a-hydroxyl group microbiologically. Lederle eventually cross-licensed with Squibb, exchanging triamcinolone rights for rights to use the 9a-fluoro discovery of Fried and Sabo and the 16a-hydroxylation technology.

Many synthetic corticoids were introduced following the discovery of triamcino-lone. These include triamcinolone 16,17-acetonide, 6a-methylprednisolone, 16a-methyl-9a-fluoroprednisolone(dexamethasone), 16/3-methyl-9a-fluoroprednisolone (betamethasone), 6a-fluoro-16a-methylprednisolone (paramethasone), 16-methylene-prednisolone, and 6a, 9a-difluoro-16a-hydroxyprednisolone 16,17-acetonide (fluocino-lone acetonide). Microbiology played no essential role in their discovery, although in some cases microbiological technology has been employed to advantage in their manu-facture.

MANUFACTURE OF NATURAL AND SYNTHETIC CORTICOSTEROIDS

As far as we are able to determine, the present status of manufacture of the important bulk corticoids is illustrated in the flow diagrams which follow. Since manu-facturing details are rarely available for public inspection, there is an element of guesswork in some of these charts. Paramethasone and üuocinolone acetonide are thought to require microbial 11/3-hydroxylation steps in their manufacture.

10 I. INTRODUCTION

Hydrocortisone and Cortisone

Upjohn

Hydrocortisone

CH,OH

Cortisone

Schering A.G. and Pfizer

CHOH I 2

c=o

*- Cortisone

Compound S Hydrocortisone

Dexamethasone and betamethasone have been made principally from deoxycholic acid and hecogenin, respectively, by nonmicrobiological routes.

Microbiology has had a passing role in the discovery of the anabolic agent, 1-dehydromethyltestosterone. First prepared by Nobile in our laboratories by the ac-tion of Cornybacterium simplex on methyltestosterone (N-667a), and independently

Progesterone

MANUFACTURE OF CORTICOSTEROIDS 11

Upjohn

Prednisolone and Prednisone

Prednisolone

CH-OH

Schering A.G. Prednisone

CH,OH

> - Prednisone

Prednisolone

by Vischer, Meystre, and Wettstein (V-1052), its application to medicine was pioneered by Ciba. It is questionable whether the microbiological route to this compound has any current commercial importance.

I - Dehydromethyltestosterone

NEW TRENDS IN RESEARCH

The most interesting new prospect for the commercial application of microbio-logical transformations comes from the work of Sih and his collaborators. In the

12 I. INTRODUCTION

course of his studies on the microbiological degradation of steroids, Sih observed that estrone and estradiol were very resistant to attack by Nocardia restrictus, which he showed degraded nonaromatic steroids readily (e.g. , androstenedione) (Ap-83).26

Since N. restrictus was also capable of using cholesterol as a sole carbon source, Sih conceived that a suitable cholesterol-like substrate might be devised which would suffer side-chain degradation to a 17-ketosteroid, followed by A-ring aromatization, to afford estrone. From earlier studies by Dodson and Muir (D-170, S-849) of the aromatiza-tion of 19-hydroxy-4-androstene-3,17-dione, taken together with these new observa-tions, he concluded that 19-hydroxy-4-cholesten-3-one would be a suitable substrate for conversion to estrone. In the first tests reported, Sih and Wang (Ap-83) obtained

Estrone

N. restrictus Estrone

an 8% yield of estrone from the action of N. restrictus. Later improvements both in choice of substrate (19-hydroxycholesterol 3-acetate) and culture (CSD-10, an uniden-tified organism isolated from soil) have given estrone in 72% yield (Ap-81).

AcO'

Pb(0Ac)„

H0H2C

Estrone suitable

microorganism AcO'

Zn

AcO'

26 The work of Sih depended in great part on the earlier findings of Dodson and Muir (D-169, D-170, D-171, D-172), who established the fundamentals of microbial A-ring aromatization and B-ring cleavage of androstenedione and related structures.

NEW TRENDS IN RESEARCH 13

Since 19-hydroxycholesterol 3-acetate is readily available from cholesterol by the il-lustrated synthesis, it is possible to predict that this method or one closely allied to it will supplant presently used technology for estrone manufacture to some degree. Estrone, in addition to its uses as a female hormone is a key intermediate for the commercial synthesis of many widely used contraceptive agents. It has been selling for a price in the range of $0.50-$1.00/gram (1965).

In a broader sense, Sih and others have shown that a number of microbial genera, e .g. , Pseudomonas, Mycobacteriurn, Corynebacterium, Proactinomyces, etc., are also able to use cholesterol as a sole carbon source. It is reasonable to assume that re-presentative species of all these genera will be useful for estrone production in the same way thai No cardia restrictus has been (Ap-95). Sih has also shown that sub-strates related in structure to cholesterol, like ß-sitosterol, can act as sole carbon sources for Nocardia. By analogy with the cholesterol case, 19-hydroxy-4-stigmasten-3-one has been used to prepare estrone (Ap-83). The importance of this finding is that ß-sitosterol is a somewhat cheaper and more readily available raw material than cho-lesterol. It occurs widely in plants and has been accumulated for many years by the Upjohn Company as a by-product of stigmasterol purification. Upjohn has been purch-asing soybean sterols (from General Mills), from which they separate stigmasterol for use as a starting material in progesterone manufacture. The combined ß-sitosterol-campesterol by-product, which is produced in considerably larger amounts than the de-sired stigmasterol, has been cast in large blocks and buried in the ground for want of a better application. This sterol mine, which up to now has had essentially no value, may become the major source for estrone in the future.

'CVH-C;:C H- HP Ha H c:xtfCV?^<C

H2 C H^C H, H,

/3-Sistosterol Campesterol

This brief history has emphasized those discoveries which have had the greatest impact on commerce, because these findings were also pivotal in stimulating the sub-sequent studies of mechanism, and thereby had also the greatest impact on science. A more highly developed appreciation for the mechanistic basis of microbiological trans-formations was developed by Hayano, Talalay, Bloom, and Shull and their respective collaborators, and most recently by Ringold and Sih, all following the breakthrough dis-coveries and applications of the 1949-1954 period. Although this appreciation has until now had no decisive effect on the development of the field, which was shaped principally by the earlier, empirical findings, we may see in the work of Sih and his students the first instance of the successful synthesis of theory and practice.

In summary, microbiology applied to steroid chemistry has resulted in major contributions to technology, medicine, and science. Murray and Peterson, and Perlman and Fried laid the basis for the efficient application of microbiology to the synthesis of antiinflammatory steroids. The renewed interest in the field which they provoked led then to the one finding which was directly implicated in an improvement of therapy, namely, the application of microbial 1-dehydrogenation to the preparation of synthetic adrenocorticoid substances in our laboratory. Studies of mechanism which followed have clarified certain aspects of the stereochemistry and mechanism of microbial transformations and have established relationships with the larger corpus of knowledge of enzymatic chemistry.

CHAPTER II

CHEMICAL CLASSIFICATION OF MICROBIAL TRANSFORMATIONS OF STEROIDS

THE ROLE OF ENZYMES IN MICROBIAL TRANSFORMATIONS

Practical Implications Microbial transformations of steroids are part of the larger class of organic

chemical reactions which are catalyzed by enzymes. The microorganism functions as a convenient source of the required enzymes and, in some cases, provides iden-tifiable reagent species (cofactors) which act on the steroid in the presence of the enzyme or contribute to the regeneration of the active site on the enzyme. That the reactions are indeed enzymatic has been proved in several cases by the isolation of the crystalline enzyme from the microbial species and by the subsequent transforma-tion of the steroid in vitro, using the crystalline enzyme and an added reagent. The resulting transformation was identical with that obtained employing the intact micro-bial system with the same substrate.

Hiibener and collaborators have isolated a crystalline "20/3-hydroxy steroid de-hydrogenase" (H-410) from Streptomyces hydrogenans, which on incubation with a wide variety of 20-ketosteroids (S-803) afforded the corresponding 20/3-hydroxy com-pounds in high yields, but at rates which varied with the functional groups elsewhere in the molecule. The enzyme also catalyzed the oxidation of 2 Oß-hydroxy steroids back to 20-ketosteroids in the appropriate medium (H-410). NADH or another hydrogen source, e .g . , NADPH, is required for the reduction (H-408), the stoichiometry of which is illustrated. In the microbial culture the NADH (or NAD+) is regenerated by an appropriate reducing (or oxidizing) system already functioning to supply the other needs of the organism for the same coenzyme.

CH3 I 3

c=o

^ 3

HO-C-H

enzyme NADH 4- H 4- NAD

Another crystalline enzyme which has been studied is the isomerase of Kawahara, Wang, and Talalay (K-437, K-438), an induced enzyme isolated from Pseudomonas testosteroni. In this case, Malhotra and Ringold (Ap-44) have proved that the reaction

is entirely intramolecular and that no reagent or cof actor is required, of this reaction is discussed in the section on isomerization.

The mechanism

14

ROLE OF ENZYMES IN MICROBIAL TRANSFORMATIONS 15

An interesting example of an endogenous reagent class was described by Gale, and associates (G-291), who have shown that vitamin K2(35) can be isolated from Bacillus sphaericus. These investigators concluded on the basis of rate and inactiva-tion-reactivation studies with a cellfree Δ1 -dehydrogenating system derived from B. sphaericus that vitamin K ^ ^ is the natural cofactor for this reaction. Talalay27

prefers to view the role of vitamin K2(35) as that of a secondary hydrogen acceptor with a flavin acting as the primary oxidizing agent.

The regeneration of the oxidized forms of coenzymes or reagents of the NAD, flavin, or vitamin K types depends in the final analysis on oxygen from the air . For efficient transformation to take place, oxygen must be placed in intimate contact with the cellular material so that diffusion into the cells can occur. The solubility of oxy-gen in aqueous media is limited, which means that efficient aeration and agitation may be required to maintain an oxygen-saturated medium. Shake-flask agitation may be inadequate, which sometimes explains the observed superiority of the aerated, inter-nally agitated fer mentor in achieving the desired transformation.

As a practical matter, the microorganism of choice provides the necessary enzymes and cofactors for the desired transformation. It has never been necessary to do more than provide the organism with a medium which is both suitable for growth and known to provide adequate levels of enzymes and cofactors by direct test with the steroid substrate in question. The knowledge of the enzymatic nature of these reac-tions, however, does serve to instruct the user to seek optimum pH and temperature conditions, known to be important factors in controlling enzymatic reaction ra tes . These optima are not necessarily the same as the optima for enzyme production, and so, the phasing of steroid transformations as a function of the microbial growth cycle can be quite important. An illustration of this idea is the separation of the growth of the organism from the transformation of the steroid. This is accomplished by filtra-tion of the mycelium (S-871) [or spores (V-1048)] after growth under optimum condi-tions, followed by washing, and resuspension of the cellular material in a medium selected as optimum for transformation (often one in which there is no further micro-bial growth).

In some instances it has been proved that microorganisms produce enzymes for the transformation of steroids in response to a steroidal enzyme inducer contained in, or added to, the medium. Septomyxa affinis has been shown by Murray and Sebek (M-647) and Koepsell (K-456) to produce its 1-dehydrogenase best in the presence of 3-ketobisnor-4-cholen-22-al. This inducer did not, however, induce the enzyme(s) responsible for the Baey er -Villiger type reaction which S. affinis is also known to cause.

On the other hand, in the many cases in which microbial cultures are grown in steroidfree media, filtered to separate the mycelium [e.g. , Curvularia lunata (S-871)] or spores [e .g . , Aspergillus ochraceus (V-1048)], and the resulting, cellular material resuspended in water to which steroid is then added, no enzyme induction is likely to be involved. The transformation with these resting cells most probably results from

27Talalay, P . , Ann. Rev. Biochem34, 347 (1965).

16 II. CHEMICAL CLASSIFICATIONS

the action of enzyme synthesized during an earlier growth stage when exogenous ste-roid was absent.

To achieve optimum results with a given culture on a commercial level it is ob-viously desirable to know whether the required enzymes are induced or constitutive. In the laboratory it is judicious to avoid conclusions concerning a failure to transform until it is clear that this failure does not arise from inadequate conditions for enzyme induction.

Many organisms produce an overabundance of steroid-transforming enzymes, which lead, in turn, to multiple transformations, (e.g. , Rhizopus arrhizus hydroxyl-ates progesterone at both the 6/3- and 11a-positions). It is sometimes desirable to sup-press selectively the formation of the enzyme which leads to by-product formation or to inhibit the competing reactions after the enzymes have been formed. This has been accomplished in a few instances, but expectation for success in a previously untried case is modest at best. Dulaney, Stapley, and Hlavac (D-193) showed that the 6ß-hydroxylating enzyme of Aspergillus ochraceus requires zinc ion for its formation. Growth of cultures in zinc-deficient media effectively abolished the 6ß-hydroxylating ability of the culture without damaging its lla-hydroxylating power. Sih and Weisen-born (S-897) have described the partial inhibition with cyanide ion of the 1-dehydrogen-ation of progesterone by Nocardia restrictus. In this case the major steroidal pro-duct became 9a-hydroxyprogesterone. Sih attributed the diminished rate of 1-dehydro-genation to inhibition of a coenzymatic oxidation-reduction system by the cyanide (S-885).

As far as we know, transformations of steroids, carried out with intact micro-bial cells, occur within the cell and not in the medium surrounding the cell.28 To enter the cell the steroid being transformed must dissolve to some extent in the medium so that it can diffuse through the cell wall and into the enzyme-rich interior. The practical implication of this requirement is that solubility and rate of diffusion may become the rate-limiting factors for transformation. Most steroid substrates ordinarily employed have modest, though measurable, solubilities in water and in the aqueous media used for microbial culture. To ensure saturation of the medium and to minimize this rate-limiting effect, steroids are often introduced into reactions in micronized form or, more conveniently, in solution in a water-miscible solvent from which precipitation in very fine particles occurs upon dilution with the aqueous medium containing the microorganism.

The experimental findings summarized in this treatise may be interpreted rea-sonably to show that microbial enzymes are not highly substrate specific.29 The alter-nate explanation for the diversity of substrates which a given species can transform is that the organism has a different enzyme for each new substrate. The latter explana-tion is much less satisfying, and no evidence has been adduced in its support.

THE CLASSES OF CHEMICAL REACTIONS It is probably true that any class of enzyme-catalyzed reaction presently known,

or to be discovered, will eventually find an illustration in the microbial transformation of steroids. At the present time examples of all of the listed categories are known.

28An apparent exception is the report of Krider, Cordon, and Wall (K-478) that cultures of Aspergilli and Penicillia produce an induced, extracellular saponase in response to the pres-ence of saponins.

29Very recent transformations of steroids of 9j3,10a-configurâtion ("retrosteroids") illus-trate that there is no requirement for anything approaching a "natural" steroid structure. Cf. French Patents 1,372,850, 1,372,851, and 1,372,852 issued to N. V. Philips Co. of The Netherlands (see also Ap-16, Ap-92, Ap-93).

CLASSES OF CHEMICAL REACTIONS 17

1. Oxidation a. Hydroxylation b. Dehydrogenation c. Epoxidation d. Oxidation of alcohols to ketones or aldehydes e. Oxidation of ketones to esters or lactones f. Oxidation of sulfides to sulfoxides g. Oxidation of amines to ketones h. Oxidative degradation - a composite

2. Reduction a. Reduction of ketones, aldehydes, and acids to alcohols b . Reduction of double bonds c. Reduction of bromide

3. Esterification, amide formation, and hydrolysis a. Hydrolysis of esters to give steroid alcohols b . Esterification of steroid alcohols to esters c. Hydrolysis of oxides to alcohols d. Hydrolysis of acetals to steroid alcohols e. iV-Acylation of amines

4. Isomerization 5. Miscellaneous addition, rearrangement, and elimination processes 6. Resolution of d,l -mixtures In the application of these reactions to problems in organic chemistry, one must

recognize that each reaction class is likely to have substrate limitations. Superim-posed on these limitations are the normal difficulties associated with reproducing ex-perimental conditions in, and results derived from, biological systems. In the likely event of the absence of precisely applicable earlier findings, it is desirable to select an organism for the transformation being sought, which prior work has shown to be suitably nonspecific in substrate requirement. To help with these choices the tabular material presented in the later chapters has been provided.

The discussion of reaction classes with illustrations is offered here to give a concise overall view of the historical basis of the field, and its present condition, with particular reference to applications in organic chemistry and technology.

Oxidation The most important single category of microbiological transformations is oxida-

tion. The impetus for the recent, explosive development of the entire field came from the discovery of the fungal hydroxylation process by Murray and Peterson. At present, the only steroid transformations with continuing technological significance are hydroxy-lation and dehydrogenation, because of the ways in which they are used as parts of the syntheses of adrenocortical hormones and analogs. A promising new application, which remains to be proved on a commercial scale, is the oxidative degradation of sterols to estrone. This transformation may have great significance for the manu-facture of estrogens, progestins, and related contraceptive drugs. The many other transformations which are described here have special interest for the insights they provide into the biochemistry of microbial systems and for their applications to diffi-cult synthetic problems.

18 Π. CHEMICAL CLASSIFICATIONS

Hydro xylation

It is known that enzymatic hydroxylation processes for steroids observe these rules. (a)The entering oxygen atom is provided by gaseous oxygen (usually from the air), and not by water or any other oxygen-containing compound present in the medium prior to the initiation of the aeration process, (b) The stereochemistry of the carbon atom which is hydroxylated is always preserved. The newly formed hydroxyl group has the same configuration as had the hydrogen atom which occupied the same site prior to reaction. Thus, 1 la-hydrogen is transformed into 11a?-hydroxyl, 11/3-hydrogen into 1 Iß-hydroxyl, etc.

The evidence for the first rule comes from the work of Hayano, Dorfman, and associates. In the earliest studies they showed that beef adrenal homogenates could be used to llß-hydroxylate a variety of steroids which were saturated at C- l l (H-372). When labeled oxygen and ordinary water were used in the incubation system, the label was incorporated in the resulting 11-oxygenated steroid. When oxygen-labeled water and ordinary oxygen were used, no label was introduced in the resulting 11-oxygenated product. It was also proved that Δ9 ( 1 1 ) -steroids are not precursors of llß-hydroxy-lated steroids produced using beef adrenal homogenates as the enzyme source.30

Hayano, Dorfman, and collaborators showed later that the conclusions about the source of incorporated oxygen were equally true for microbial hydroxylations at 6/3, 11a, l lß , 12β, 15α, 17α, and 21 (Η-374, Κ-485).

Hayano, Peterson, and collaborators (H-371) and Corey, Gregoriou, and Peter-son (C-137) demonstrated that stereochemistry is preserved at the carbon atom which undergoes substitution. The former carried out the 11a-hydroxylation of pregnane-3,20-dione-lla,12a-H3 with Rhizopus nigricans and showed that tritium was lost at the 11- but not at the 12-position. Complementary experiments by Corey, using l l ß -deuterated pregnane-3,20-dione and Rhizopus nigricans afforded lla-hydroxypregnane-3,20-dione-llß-H2 (label retained). This proved that deuterium on carbon which be-comes substituted will survive the oxygénation process if the deuterium configuration is not the same as that taken by the entering oxygen. Taken together, the cited studies provide the basis for rules (a) and (b), and no contradictory evidence has, as yet, been found.

Ringold31 has put forward the interesting proposition that hydroxylation at 2ß9 6ß, 10ß, and 17α, in systems capable of being enolized toward these positions, in-volves the enol as an activated species. Ringold then suggests that both the enoliza-tion process and oxygen introduction involve enzyme participation, the OH+ attacking

3 0Hayano, M. , and Dorfman, R. I. , J. Biol. Chem. 211, 227 (1954).

3 1 Hayano, M. , in "Oxygenases" (O. Hayaishi, e d . ) , pp. 225-229. Academic P r e s s , New York, 1962.


reagent being generated by the action of enzyme on oxygen. It seems to us that it may only be necessary to assume that enzyme is responsible for generating the enol. At this point undissociated oxygen can react with the enol, as has already been shown by Barton32 for the nonenzymatic 17a-oxygénation of 20-ketopregnanes in the presence of strong base (ί-butoxide ion) and oxygen. If our proposal were indeed true, the first product of this type of microbial oxygénation would be hydroperoxide, as observed by Barton in the chemical process, and not the hydroxy compound. Completion of the reaction would then require the enzyme-mediated reduction of hydroperoxide to hy-droxyl (e.g. , by NADPH). Stable compounds bearing hydroperoxide at the 10/3- and 17o?-positions have been described by Shapiro, Legatt, and Oliveto33 and Barton,32

respectively. These intermediates might be used to establish whether hydroperoxides can be reduced by a hydroxylating culture.

The rather surprising paucity of microbially induced 2a-, to-, l t a - , and 17/3-hydroxylations is consistent with the thesis that the enzymes which lead to 2/3 -, 6β -, 10/3 -, and 17ûf-hydroxylations are concerned principally with the enolization process and that the oxygénation stage is controlled by purely chemical factors. It is well established, for example, that electrophilic chemical attack at the 6-position, under kinetic control, is directly entirely to 6/3, even though the thermodynamically more stable species is the to-substituted product.

We believe it might be instructive to attempt the independent confirmation of the enolization hypothesis according to either one of the following schemes.

If a 17a-20-ketopregnane (e.g. , 17a-deoxycorticosterone) is subjected to the ac-tion of a 17a-hydroxylating organism (e.g. , Trichothecium roseum) the isolation of either a 1 la-hydroxy-20-ketopregnene (e.g. , Compound S) or a 17ß-20*-ketopregnane (e.g., deoxycorticosterone) would give important evidence for the enolization hypothe-s is . Since the formation of the former would be an apparent violation of the rule for

Bailey, E. J. , Elks, J . , and Barton, D. H. R. , Proc. Chem. Soc , p. 214 (1960). 3Shapiro, E. L . , Legatt, T . , and Oliveto, E. P . , Tetrahedron Letters, p. 663 (1964).


CH20H

C=0 C - 0 "

reketonization CH,0H I C=0

Botrytis peoniae

reketonization

reketonization

preservation of configuration in the hydroxylation process, it would be best explained by the prior enolization of the starting material, thereby destroying configuration at the 17-position. If the oxygénation process were incomplete, it might still be possible to detect deoxycorticosterone formed by the reketonization of the enol to the normal, more stable 17ß-form.

The second scheme involves the use of a 10a-3-keto-A4-estrene as the substrate for what is normally a 10/3-hydroxylation process. The reasoning follows the same line developed for the first scheme.

At those sites which cannot be activated by enolization, a mechanism for hydrox-ylation other than that proposed for 2/3, 6)3, 10/3, and 17a must be operating. Hayano has enumerated the sequence of steps as follows: (a) oxygen activation, (b) substrate activation, if any, and oxygen transfer, and (c) regeneration of coenzymes. She sug-gested that the Jrydroxylation enzyme acts by providing the species OH+ from oxygen, NADPH, and a proton. The resulting ion then displaces the hydrogen atom by OH, with retention of configuration, at the site in the steroid under attack.

While this hypothesis is interesting, it is not compelling. Since it is already well recognized that molecular oxygen can react with electron-rich centers or radicals without the intervention of an agent (e.g. , enzyme) whose purpose might be to activate oxygen, one may argue that the oxygénation process at a saturated carbon atom seems


to require activation of the C - H link only. One might therefore postulate that the function of the oxygénation enzyme is to confer upon the C-H link either radical or ionic character.

C-H ^ C _ \ _ _ _ H

*- C* H+ (C+ H")

The dashed line symbolizes the bond which is incompletely broken, but polarized, as a result of enzyme action. Given one of these premises, one may then depict the oxygénation process in the illustrated terms below. The first product of such a reac-tion will be a hydroperoxide which then requires reduction with NADH or an equivalent

[e n z y m e

H i 0

i \ Vu

fil n z y m e 1

) Electron pair migration )

H / v 0 l <> l l

Single electron migration

reducing system.34 This scheme embodies the 1 : 1 molar relationship of oxygen to NADH which Cooper, Estabrook, and Rosenthal35 find exists for steroid hydroxyla-tions.

H I

R-C-0-O-H I

R'

+ NADH + H R-C-OH + I R'

NAD +

One merit of the hydroperoxide proposal is that it might be subject to experi-mental test. As has already been pointed out, reasonably stable 10j3- and 17a-hydro-peroxides have been prepared. One might prepare 17a-hydroperoxyprogesterone as a reference and carr ier substance to identify the hydroperoxy intermediate, if indeed one be formed, from the 17ai-hydroxylation of C14-labeled progesterone with a suitable microorganism [ e . g . , Cephalothecium roseum (H-374)]. Incubation of a

So Kaufman [in "Oxygénases" (O. Hayaishi, ed.) , p. 170. Academic Press , New York, 1962] has summarized four proposals for a general mechanism of oxygénation, of which one is the formation and reduction of an intermediate hydroperoxide depicted here. B. Imelik [Compt. Rend. 226, 2082 (1948)] reported that Pseudomonas aeruginosa caused the transient formation of cyclohexane hydroperoxide when cyclohexane was the substrate.

35Cooper, D. Y. , Estabrook, R. E . , and Rosenthal, O. , J . Biol. Chem. 238, 1320 (1963).


17a-hydroperoxy substrate with a 17o;-hydroxylating culture would help to decide whether 17a-hydroperoxyl can indeed be reduced to 17a-hydroxyl under these condi-tions .

Sites of Reaction, la-Hydroxylation. Dodson, Goldkamp, and Muir (D-162, D-163) observed ΐα-hydroxylation with[Pénicillium sp. on 4-androstene-3,17-dione, 5a-androstane-3,17-dione, and 3ß-hydroxy-5-androsten-17-one (dehydroepiandro-sterone). The organism also oxidizes the 3-hydroxyl and isomerizes the double bond,

but hydroxylation precedes these reactions. Few instances of la-hydroxylation are known. Some recent, interesting examples were given by Sax and associates (Ap-68). These are discussed in greater detail under 2a-hydroxylation.

1/3-Hydroxylation. Greenspan and Schaffner, in association with our laboratory, reported Iß-hydroxylation of Compound S with Rhizoctonia ferrugena (G-315). The configuration of the entering group was established by Nussbaum (N-688, N-689)

through comparison with the same product synthesized from ruscogenin (lß-hydroxy-diosgenin), a sapogenin from Ruscus aculeatus. The same transformation has been seen in the androstane series with Haplosporella and Xylaria sp. (D-165). Nozaki has demonstrated Iß-hydroxylation of digitoxigenin (N-679) and 3)3,140, 21-trihydroxy-5ß-pregnan-20-one (Ap-59) using Absidia orchidis. In these latter instances, the site of hydroxylation seems to be influenced by the configuration or nature of the substituent (s) at the 5- and/or 14-position, since Absidia hydroxylates principally at the 11a- and 1 Iß-positions in the 4-pregnene series (H-334, N-682, S-841).

2a-Hydroxylation. This transformation was recently seen for the first time by Sax and co-workers (Ap-68) and Modelli (Ap-51). The former reported that Nocardia corallina afforded simultaneous la- and 2a-hydroxylation of ethisterone (I), 9a-fluoro-llß,17ß-dihydroxy-17a-methyl-4-androsten-3-one (II) (together with oxidation at the 11-position), andllß,16a,17a,21-tetrahydroxy-4-pregnene-3,20-dione 16,17-acetonide. No monohydroxylated products were isolated. Since N. corallina is normally (and in these cases, also) a Δ1 -dehydrogenating organism, Sax has proposed that the Δ1 -compounds are intermediates in these hydroxylation processes. This was proved with the Δ1-containing compound (III), which was dihydroxylated under the same fermenta-tion condition as (II). A different mechanism from those normally operating in hydrox-ylations must be involved. Sax has suggested for consideration a number of pathways from the A1'4-dien-3-one to the la,2a-dihydroxy product. To his suggestions might also be added direct eis hydroxylation of the Δ1 double bond in the way that chemical


CEECH

(I)

(II) (III) agents like permanganate do in related unsaturated systems. This question remains to be settled.

Modelli (Ap-51) has described the 2o?-hydroxylation of 19-nortestosterone (17j3-hydroxy-4-estren-3-one) and 19-nor-4-androstene-3,17-dione with Nocardia italica. These are the only examples of 2a-hydroxylation which arise from a "normal" mechanism of hydroxylation at a saturated carbon (as distinct from the Sax results).

..OH

• OH

Satisfactory, conventional chemical methods for introducing the 2a-hydroxyl group are available.

2/3-Hydroxylation. Simultaneous reports from our laboratories (G-315, H-383) and by Dodson, Goldkamp, and Muir (D-162, D-163) contained the first descriptions of 2ß-hydroxylation. We found that Streptomyces sp. and Rhizoctonia ferrugena trans-formed Compound S. The Searle workers used 4-androstene-3,17-dione as the

CH20H

:0H

j Streptomyces sp.

Rhizoctonia ferrugena


substrate with Pénicillium sp. In actuality, 2ß-hydroxylation of progesterone (to-gether with 16a-hydroxylation) was among the first hydroxylations which were carried out (P-716, P-718), though no assignment was made until recently (Ap-42).

3-Hydroxylation. No hydroxylation at the 3-position had been described until very recently, when Cherry, Jones, and Meakins (Ap-12) reported the 3ß,12ß-dihy-droxylation of 5-androsten-7-one by Calonectria decora. Since all naturally occur-ring steroidal raw materials are oxygenated at the 3-position, the problem has had only academic implications.

4-Hydroxylation. No hydroxylation at the 4-position has been reported.36 The usual substrates for microbial transformations are A4-3-ketosteroids. The double bond at the 4-position interferes with normal modes of hydroxylation, accounting for the bulk of the experience to date. Saturated substrates might reasonably be hydrox-ylated at the 4-position with appropriate microorganisms. Substrates of the 3-keto-5ß-pregnane series might be preferred since their normal mode of enolization is to-ward the 4-position, thereby offering the possibility of more than one mechanism of hydroxylation.

5o?-Hydroxylation. One organism has been reported to cause 5a-hydroxylation. Pan and co-workers (P-706a) described the 5a-hydroxylation of A-nor-5a-pregnane-2,20-dione by Cokeromyces recurvatus. The paucity of observed 5a-hydroxylations is probably a function of the infrequent use of 5a-steroids as substrates.

5ß-Hydroxylation. Hydroxylation at the 5ß-position is limited to the 5ß-hydrox-ylation of cardiac aglycones (e.g., digitoxigenin) with Absidia orchidis, and was dis-covered by Nozaki (N-679).

others

36Cherry, Jones, and Meakins (Ap-12) have recently made a tentative assignment of 4ß,12ß-dihydroxylation to one of the products from the action of Calonectria decora on 5-andro-sten-7-one.

others


6û!-Hydroxylation. No microorganism is known to cause enzymatic 6a-hydrox-ylation.37 Mallett, Fukuda, and Guynes (Ap-45; see also M-536, M-537) described the transformation of 3/3-hydroxy-5-androsten-17-one into 6a(and 6ß-)-hydroxy-l,4-androstadiene-3,17-dione with Actinoplanes mis sour iensis. These transformations depend on the nonenzymatic oxygénation of 5-androstene-3,17-dione, a reaction inter-mediate. Actinoplanes missouriensis seems to be deficient in Δ5-isomerase, which is an uncommon situation.

o o

Bridgeman and associates have mentioned the transformation of 5Œ-androstan-17-one into the 1β, 6α -diol by an unnamed organism in connection with structural studies of the product thus formed (Ap-6).


6ß -Hydroxylation. One of the most common transformations is 6ß-hydr oxy la -tion. It is often, though not always, associated with 11a?-hydr oxy lation, 14a:-hydrox-ylation, or 17 a-hydr oxy lation. Peterson, Murray, and their collaborators discovered that Rhizopus arrhizus transforms progesterone into 6/3,11 a -dihydr oxy progesterone (M-601, M-616, P-729), 17a-hydroxyprogesterone into 6/3,17a-dihydroxyprogesterone (M-580), and Compound S into 60,17a,21-trihydroxy-4-pregnene-3,2O-dione (M-601, M-615, P-725). They reported the action of many other genera of the order

CH, I 3

c=o

Rhizopus arrhizus

Mucorales on a variety of steroidal substrates, observing 6/3-hydr oxy lation as a fre-quent occurrence (M-601). From our own experience, corticosteroids and their ana-logs (e.g. , prednisone) are 6/3-hydroxylated efficiently by Chaetomium sp. (C-108).

7 or-Hydr oxy lation. This transformation was first seen by Meystre, Vischer, and Wettstein with Peziza sp. on deoxycorticosterone (M-585) and by Fried and asso-ciates with Phycomyces blakesleeanus on progesterone (F-285, F-286).

The questions of assignment of configuration at the 7-position have been reviewed thoroughly by Tweit, Goldkamp, and Dodson (T-1037). From their analysis of rota-tional data, together with appropriate chemical information, unambiguous assign-ments can be made.

7 ff-Hydr oxy lation. The first microbial hydr oxy lation, reported by Kramli and Horvath (K-474), was that at the 7 ξ-position by Proactinomyces sp. on cholesterol. Although this may have been 7/3, no unambigious assignment can be made. Kahnt and collaborators (K-433) reported the unequivocal 7/3-hydr oxy lation of 21-hydroxy-5a-pregnane-3,20-dione by Rhizopus sp. Some confusion, which crept into the later assignments of 7a- and 7/3-hydroxy-3-keto-Δ* -steroids, was resolved by Tweit, Goldkamp, and Dodson (T-1037).


HCT v : v ^ -OH 8a-Hydroxylation. There is no 8a?-hydrogen in the normal steroid structure.

Considerations of mechanism therefore rule out 8a-hydroxylation as a reasonable event. With steroids of abnormal skeleton, bearing an Sa-hydrogen atom, there is no a priori reason for excluding the possibility of 8a-hydroxylation. Such a reaction remains to be discovered.

8ff-Hydroxylation. Kondo and his collaborators have observed the only 8/3-hydroxylation described thus far (K-472, T-1014), from the action of Cercospora melonis on Compound S. Earlier transformations, for which 8/3-hydroxylation was

proposed as one of several alternatives [ e . g . , Helicostylum piriforme on Compound S (M-601)], have since been shown to be 9a-hydroxylations.

9o-Hydroxylation. This transformation was observed first by Peterson and Murray (E-204, M-601) with Helicostylum piriforme on Compound S, although the choice of assignment between 8/3 and 9a was not made. Schubert and associates (S-815) developed chemical methodology from which a more precise assignment could be made and deduced thereby the 9a-hydroxylation or progesterone by Circinella sp.

Dodson and Muir provided the first completely unambiguous evidence for both position and configuration (D-172) in the 9a-hydroxylation of progesterone by Nocardia sp. The formation of the illustrated 3,9-oxide can only occur if the hydroxyl at the 9-position is a.


The 9û!-hydroxylation has considerable theoretical and practical significance. Dodson and Muir (D-169 - D-171) recognized it as a key s tage in a major path of microbial degradation of the steroid nucleus. The cleavage of ring B results from a

spontaneous reverse aldol reaction, following 1-dehydrogenation and 9a-hydroxylation. Bacterial 1-dehydrogenating genera have, by and large, been shown to act also as 9a-hydroxylators. Examples include No car dia (D-172), Pseudomonas (D-171), Arthro-bacter, or Cor ynebac ter turn sp. (C-138, D-171), and others. As a consequence, an inherent hazard in the use of these cultures as 1-dehydrogenators for the preparation of synthetic adrenocorticoids and other hormonal agents has been the loss of product through 9o!-hydroxylation and degradation. This phenomenon has been attributed generically to a"destructase" (F-230), and techniques for suppression of the secondary reactions have been suggested. The quinonoid species used for this purpose probably act by suppressing 9a-hydroxylation (or the formation of the required enzyme).

It is probably also true that the many bacteria, which can use cholesterol (or steroids generally) as a sole carbon source, break down the steroid nucleus by approx-imately the same sequence of reactions. This will be taken up in greater detail in a later section devoted to degradation.

9/3-Hydroxylation. On mechanical grounds, steroids with conventional skeletons should not give this transformation. "Retro" steroids38 of the 9/3,10a?-configuration, however, could lead to 9/3-hydroxy products. Microbiological transformation studies with representative structures of this type have been made at the Phillips-Duphar Laboratories.39 In the light of the interesting hormonal activities found within this class (e.g., dydrogesterone-progestational agent) further developments may reasonably be anticipated. CH

I 3

Dydrogesterone

lQg-Hydroxylation. Some 19-nor steroids with the 10a-configuration have been prepared.40 These have yet to be oxygenated microbiologically.

38Westerhof, P . , and Reerink, E. H. , Rec. Trav. Chim. 7^, 771 (1960). 39French Patent 1,372,851 (Sept. 18, 1964); see also Ap-16. 40Wenger, R. , Dutler, H. , Wehrli, H. , Schaffner, K., and Jeger, O. , Helv. Chim.

Acta45, 2420 (1962).


1 Off-Hydroxylation. Peterson, Murray, and their collaborators (M-642, P-708) described the 1Off -hydr oxy lation of 19-nortestosterone by Rhizopus nigricans. The major product, however, was lla,17ff-dihydroxy-4-estren-3-one. More recently,

DeFlines and co-workers (D-150) reported the efficient use of Botrytis paeoniae and other organisms for uncomplicated 1 Off-hydr oxy lation of the same substrate.

llq-Hydroxylation. One of the first hydroxylations described and also one of the most important for industry is lla-hydroxylation. Peterson and Murray discovered 11 a-hydr oxy lation by Rhizopus sp. and other members of the Mucorales order, using a wide variety of substrates (e.g., progesterone, 17a-hydroxyprogesterone,

Compound S), as part of a rational program to improve the synthesis of cortisone (M-601). This goal was realized through their work and that of the Levin and Hogg chemical groups at Upjohn. The hydrocortisone synthesis via the 11 a-hydr oxy lation of progesterone remains the cornerstone of the most efficient method for the prepara-tion of a variety of natural and synthetic adrenal hormones. The price of natural glucocorticoids has fallen from in excess of $200/gram (1949) to about $0.45/gram (1965) as a result of the perfection of both the chemical and microbiological stages of the hydrocortisone synthesis.

Subsequently, it was shown that lla-hydroxylation is one of the most common transformations. The better cultures may be identified in Table I, "Transformation by Products," by the high yields recorded for the illustrated conversions (e.g. , 11a-hydroxylated products in the C21H30O3, C21H30O4, and C21H30O5 series).

1 Iff-Hydr oxy lation. Although many claims for llff-hydroxylation are made in the literature, very few organisms afford a clean reaction in high yield. The first recorded llff-hydroxylation, by Colingsworth, Brunner, and Haines (C-134), was the transformation of Compound S into hydrocortisone with Streptomyces fradiae. The yield with this organism was very low. The first practical llff-hydroxylation pro-cesses were those of Shull, Kita, and Davisson (S-871, S-875) using Curvularia lunata and those of Hanson, Mann, and co-workers (H-339; M-556) using Cunninghamella blakesleeana. The former has continued to be important for the commercial produc-tion of hydrocortisone from Compound S, as practiced by Charles Pfizer, Inc. and its licensees (particularly Schering A. G. ). In contrast with the liai-hydr oxy lation of progesterone by Rhizopus nigricans, which affords yields in excess of 90%, llff-hydroxylation of Compound S by Curvularia lunata has rarely been reported to be better than 60-65%. Further improvement of this yield or a related llff-hydroxylation would have significant consequences for industry.


12ohHydroxylatioa This rare transformation has been seen in our laboratories^ also by Fried and Thoma and by Kondo and Tori in rather special cases. We observed that testosterone was transformed into 12a,17/3-dihydroxy-4,14-androstadien-3-one in very low yield by Wojnowicia graminis (H-381). The presumed precursor of the 12a?-hydrox-ylated product is the 12a,14o!-diol (in view of the formation of 14a-hydroxy-4-andro-stene-3,17-dione in the fermentation). The required elimination of the 14a-hydroxy

+ others products

group to give the Δ14-unsaturation is logically, though not necessarily, an artifact from the processing of the fermentation. Fried and Thoma (F-277) observed that fermentation of 9(ll)-dehydroprogesterone with Colletotrichum phomoides, Tham-nidium elegans, or Aspergillus nidulans gave 6/3,12a-dihydroxy-4,9(ll)-pregnadiene-3,20-dione as a major product. This product was transformed in part into the corre-sponding 9/3,llj3-oxide, presumably through the action of an 11/3-hydr oxylating enzyme. Kondo and Tori (K-473) reported the 12a-hydr oxylation of 9a-hydroxy-4-androstene-3,17-dione by Cercospora melonis. The same culture also transformed 4-androstene-3,17-dione to the same 9a,12a-dihydroxy product.

+ others products

12/3 -Hydr oxylation. First reported by A. Schubert, Siebert, and collaborators by the action of Calonectria decora on progesterone and 15a-hydroxyprogesterone (S-814; see also S-810, S-816, S-817), this transformation remains infrequent with conven-tional 3-keto-A4-steroidal substrates (D-152, T-1036). The reaction is somewhat

ÇH3

c=o

C. decora

ΌΗ ΌΗ


more common with cardiac aglycone substrates. The earliest examples of the latter were described by Gubler and Tamm (G-320, T-977, T-979) and include the 12/3-hydroxylation of digitoxigenin to digoxigenin by Fusarium lint.

Hydroxylation at the 15a-position often co-occurs with that at the 12/3-position.

13-Hydroxylation. No studies with 13-demethylsteroids have been reported. 14o?-Hydroxylation. The earliest example of 14a?-hydroxylation was reported

by Murray and Peterson (M-601) with Helico s tylum piriforme on Compound S. This transformation is quite common with progesterone, deoxycorticosterone and Com-pound S. Mucor sp. are among the more effective 14oi-hydroxylators (E-204, M-614, M-635, T-980).

CH2OH

C=0

CH?0H I 2

C=0

-f others

14/3-Hydroxylation. No reports of transformations with steroids bearing a 14/3-H (C-D eis ring fusion) have been recorded. Cardiac aglycones customarily contain a 14ß-hydroxyl group. Microbiological conversion studies with 14β,17αι-progesterone or a related substrate might conceivably lead into the former ser ies .

15 a -Hydroxylation. This hydroxylation was discovered by Fried and colleagues with Colletotrichum antirrhini on progesterone (F-285, F-287, F-288) and by Meystre, Vischer, and Wettstein with Gibberella baccata on deoxycorticosterone (M-585, U-1043, W-1087). It can be accomplished efficiently with a variety of substrates (B-58, C-139, D-158, G-319, T-980).


15/3-Hydroxylation. The first reports of 15/3-hydroxylation were from Fried and associates with Phycomyces blakesleeanus on progesterone (F-285 - F-288) and from Meystre, Vischer, and Wettstein with Lenzites abietina on deoxycorticosterone (M-585, W-1087). The 15/3-hydroxylation of Compound S goes especially well with Bacillus megaterium (H-382).

CH90H I c=o

CH?OH I c=o

16a -Hydroxylation. One of the earliest examples of microbial hydroxylation, reported by Perlman, Titus, and Fried (P-718) in 1952, was the 16a-hydroxylation of progesterone by an actinomycete later shown to be Streptomyces argenteolus. This

5. argenteolus^

CH, I 3

C=0

ΌΗ others

class of hydroxylation has been studied carefully subsequent to the discovery of triam-cinolone, a widely used antiinflammatory steroid. (The manufacture of triamcinolone incorporates more microbiological manipulation than that of any other steroid presently in commerce.) Many streptomycetes (e.g. , S. roseochromogenus) are not very sub-strate specific, 16a-hydroxylating a wide range of steroids from testosterone (F-288) and 1-dehydrotestololactone (P-706, T-1000), on the one hand, to 9a-fluorohydrocor-tisone (G-297, S-912, T-1002), on the other, with good efficiency in many instances.

5. roseochromogenus^


CHo0H

C=0

CHLOH

S. roseochromogenus

16ff-Hydroxylation. This transformation has been seen infrequently. It was reported from our laboratory using Wojnowicia graminis with testosterone (H-381). Dodson and Mizuba (D-166) have described the 16/3-hydroxylation of androstenedione

(minor) (major)

with Corticium centrifugum. In their discussion they make the point that introduction of the 160-hydroxyl group in their (and our) case cannot be ascribed unambiguously to a 160-hydroxylation reaction. They suggest the illustrated, alternative path, which proceeds via 16a-hydroxylation, rearrangement, and reduction. Evidence for this

C centrifugum^

proposal is that the 16-keto-17/3-hydroxy intermediate (I) was isolated from the fer-mentation by Dodson and Mizuba. In our case, all the intermediates between testos-terone and 16/3-hydroxytestosterone required by the Dodson-Mizuba proposal were isolated from the reaction mixture.

Nawa and co-workers (N-651) have described the 16/3-hydroxylation of digitoxi-genin to gitoxigenin by Helicostylum piriforme. Identification was by paper chroma-tography. This example cannot be accommodated within the Dodson-Mizuba proposal.

(I)

others

34 IL CHEMICAL CLASSIFICATIONS

17o?-Hydroxylation. This transformation was considered at one time to have potential importance as a stage in the preparation of adrenocorticoids bearing the dihydroxyacetone side chain. Meystre, Vischer, and Wettstein (M-584) described the 17a-hydroxylation of deoxycorticosterone by Trichothecium roseum. A strain of the same culture with similar properties (Cephalothecium roseum) was reported at

CHo0H

about the same time by Meister and co-workers (M-581). The Meister culture was distinguished from the Meystre culture by its ability to lla-hydroxylate also.

In practice, chemical methods of 17a-hydroxylation have turned out to be supe-rior to microbiological methods. This fact, combined with the relative rarity of 17a-hydroxylating species, has led to neglect of serious study of this reaction, and it is not employed for other than research applications today.

17/3-Hydroxylation. Substrates with which this reaction might be observed have not been studied. There has been little incentive to look for this reaction since good chemical methods are available for the synthesis of 17/3-hydroxy-17a-pregnanes and 17/3-hydroxyandrostanes.

18-Hydroxylation. For a time some interest was attached to the search for an 18-hydroxylator. After Reichstein and co-workers4 1 showed that aldosterone, one of the adrenal hormones regulating salt metabolism in the human, was substituted at the

CI-LOH OH I

Aldosterone

18-position, a convenient synthetic route to this compound was sought. Several bril-liant and versatile chemical solutions to the problem were found, which have resulted

4 1 Simpson, S. A. , Tait, J . F . , Wettstein, A. , Neher, R. , von Euw, J. and Reichstein, T . , Helv. Chim. Acta 37^ 1200 (1954).

Schindler, O. ,


in greatly diminished interest in this potential application for microbiological t rans-formations. Kondo and Tori (K-473) reported the first 18-hydroxylation with Cerco-spora {Corynespora) melonis on androstenedione and 9a-hydroxyandrostendione.

+ others

Kondo, Mitsugi, and Tori (Ap-38) extended this finding to develop a synthesis of aldosterone, using Corynespora cassiicola.

(I)

CHo0H

C=0

(II) Aldosterone

The conversion of 18-hydroxycorticosterone (I) into the 11,18-oxide (II) was accomplished by chemical means. This step, taken together with the two microbio-logical stages, completes a novel partial synthesis of aldosterone from corticosterone.

19-Hydroxylation. Hasegawa and Takahashi (H-347) first described the 19-hydroxylation of Compound S with Corticium sasakii. The structure was established by Hagiwara (H-326). This hydroxylation remains quite r a re .

The 19-hydroxylation process has become an object of renewed interest in the light of the findings of Sih concerning the efficient microbial conversion of 19-hydroxy-cholesterol 3-acetate to estrone. Excellent chemical methods, however, which were developed during the search for techniques of 18-oxygénation, exist for the introduc-tion of the 19-hydroxyl group. It is unlikely that microbiology will make an important contribution to this aspect of the new estrone technology.


CHL0H I 2

Hydroxylation at the 20- and 22-positions and beyond. The 20-position is usually occupied by a carbonyl group in the commonly employed pregnane substrates and is thereby not available for reaction; C-22 and beyond are absent. With the work of Sih, interest has revived in C^ and higher sterol substrates.

Working with two Nocardia sp . , Sih has shown that cholesterol is degraded by fission between C-24 and C-25, C-22 and C-23, and C-17 and C-20.410

One may speculate that hydroxylations at C-26 and perhaps at C-24 and C-22 are involved in the degradative sequence, although Sih has not chosen to reach these conclusions as yet, nor is there any evidence in their support. His evidence and pro-posals are discussed in greater detail in the section on degradation.

Mammalian hydroxylations of cholesterol at C-20 and C-22 have been demon-strated .41& It would not be surprising to find microorganisms with the same capaci-t ies.

21-Hydroxylation. Just as 17a-hydroxylation is of interest for corticoid syn-thesis, so too is 21-hydroxylation. Here again, excellent chemical methods were available for oxygénation which inhibited any continuing, deep study of this problem. The microbial process was first shown by Meystre, Vischer, and Wettstein (M-584) using Ophiobolus herpotrichus on progesterone and 17a-hydroxyprogesterone, among

others. This hydroxylation was later applied to the total synthesis of aldosterone, as an ingenious method of simultaneously introducing the required 21-oxygen function and resolving the d,l -mixture (W-1102). Only the natural form of the starting material was transformed.

0. herpotrichus , L- starting material

4 1 0 Sih, C. J . , Wang, K. C. , and Tai, H. H. , J . Am. Chem. Soc. 89, 1956 (1967); Sih, C. J . , Tai, H. H. , and Tsong, Y. Y. , ibid., p. 1957.

4lb Chaudhuri, A. C. , Harada, Y. , Shimizu, K., Gut, M. , and Dorfman, R. I . , J . Biol. Chem. 237, 703 (1962).


Dehydrogenation

Following the discovery of 1-dehydrogenation by Fried, Thoma, and Klingsberg (F-284) and Vischer and Wettstein (V-1056), alternative formulations of the path for this reaction were presented (V-1053, W-1087). Levy and Talalay, from studies with

the dehydrogenating enzyme mixture isolated from Pseudomonas testosteroni, con-cluded that direct dehydrogenation (no intermediate hydroxylation) is the most probable path with this organism (L-509). The evidence was that the in vitro dehydrogenation reaction did not require oxygen, whereas the enzymatic hydroxylation process with steroids has been shown to require oxygen. They also demonstrated that phenazine methosulfate is an efficient oxidizing agent for A4-3-ketosteroids, when acting in concert with an enzyme preparation from Pseudomonas testosteroni under anaerobic

conditions.42 These results, together with the observations of Levy and Talalay that suitable l a - and lß-hydroxylated substrates (e.g. , la-hydroxy-4-androstene-3,17-dione) were not converted to 1-dehydro species with the same enzyme mixture in the presence of phenazine methosulfate, can be taken to affirm the dehydrogenation mech-anism and to exclude the hydroxylation-dehydration mechanism.

The dehydrogenation mechanism is also supported by the work of Gale and asso-ciates (G-291). They showed that Bacillus sphaericus contained a quinone, character-ized by them as vitamin K2(35), which was essential for the dehydrogenation of hydro-cortisone to prednisolone. In a cellfree preparation derived from B. sphaericus, photoinactivation of vitamin K2(35) destroyed the dehydrogenation power of the system. The system was reactivated fully by the addition of vitamin K2(35) or related quinoid structures (e.g. , menadione or hexahydrocoenzyme Q). Gale and collaborators con-cluded that vitamin K2(35) is the cofactor for dehydrogenation with B. sphaericus.

Other oxidizing agents which were ineffective in this system were NAD, NADP, ribo-flavin monophosphate, FAD, ferricyanide ion, and cytochrome c. The inference should not be made that in vivo transformation with Ps . testosteroni can be run anaerobically with any degree of efficiency. Since the necessary oxidizing reagent species are rarely present in stoichiometric quantities, oxygen is required to regenerate the natural equivalent(s) of phenazine methosulfate.


cellfree preparation of B. sphaericus

^ Ö > t +

Rm

OH

OH

^ R

^ R

From his studies with Ps. testosteroni, Talalay43 favors the views that flavins are required intermediates in the oxidation-reduction chain and that they are truly coenzymatic, whereas quinones are, more likely, secondary oxidizing agents, playing their role later in the oxidation-reduction cycle. For the present, at least, there is no evidence for a unity of mechanism in the diverse microbialdehydrogenation processes.

Most recently, Iida and colleagues (Ap-31) have prepared a cellfree enzyme sys-tem with reversible A^hydrogenase-dehydrogenase activity. The enzyme mixture was isolated from cultures of Bacterium cyclo-oxydans, and the production of enzyme was promoted by the addition of steroidal inducers (e.g. , l,4-androstadiene-3,17-dione).44

The dehydrogenation reaction was stimulated by a quinone (menadione) and hydrogéna-tion by NADH. The activities could not be separated by enzyme fractionation techni-ques. Further detailed studies with B. cyclo-oxydans might throw more light on dehy-drogenation mechanisms.

The stereochemistry of the microbial dehydrogenation process at the 1- and 2-positions has been studied with one microorganism, Bacillus sphaericus, by Ringold, Hayano, Stefanovic, and co-workers (H-373, R-769). The relevant indirect evidence is that substrates with Iß- or 2a-substituents are dehydrogenated successfully by B. sphaericus, whereas those with l a - or 2/3-substituents are not. From these findings

R = OH or CH

it was inferred that the l a - and 2/3-hydrogen atoms are required for the microbial dehydrogenation to take place (H-373).

This conclusion was supported by the observation (R-769) that 1/3-deuterium largely survives the dehydrogenation process, whereas la-deuterium is lost.

B. sphaericus cellfree enzyme preparation

43 Talalay, P . , Ann. Rev. Biochem. 34, 347 (1965). 44 The ability of B. cyclo-oxydans to produce both hydrogenase and dehydrogenase activity

was first recognized by Goodman, May, and Smith (G-296).

CLASSES OF CHEMICAL CLASSIFICATIONS 39

Ringold, Hayano, and Stefanovic then proposed that the dehydrogenation process takes place via the illustrated reaction sequence, the first step of which is the enzyme-mediated enolization of the 3-ketone toward the 2-position. This is followed by hydride transfer of the α-hydrogen at the 1-position to the coenzyme, with subsequent collapse

+ Enz + Coenz H

of the enzyme-substrate complex. That enolization occurs readily in the fermentation medium was established by isotope exchange studies. This evidence was then used to support the contention that enolization is a necessary stage in the dehydrogenation pro-cess. The failure of the attempted dehydrogenation of 5/3-androstane-3, 17-dione by B. sphaericus, in contrast to the successful dehydrogenation of 5a-androstane-3,17-dione, was explained in terms of the normal modes of enolization of the two substrates. The former enolizes toward the 4-position and thereby fails to provide the necessary intermediate for elimination of the hydrogen at the lo:-position. The latter enolizes toward the 2-position, leading to the completion of the anticipated reaction.

A subsequent refinement of this proposal has been made by Jerussi and Ringold (Ap-33). The crux of the refinement is that the enzyme which promotes enolization is also implicated in the oxidation-reduction process, in that it has bound to it a flavin or some other redox system, which acts to abstract hydride ion from \a as the second stage of the process. Jerussi and Ringold illustrated the reaction system as follows:

c·

Enz

V.

-H

• H · ^ A - H

( A = proton donor, B= proton acceptor, C= hydride acceptor )

The conclusions were derived from the study of deuterium isotope effects on reaction rates at the la- and 2/3-positions.

These proposals are very satisfying in many ways. An obstacle, however, to the extension of the proposed mechanism to all microbiological dehydrogenation of 3-ketosteroids at the 1-position is the work of Fonken and Murray (F-253). They showed that the 20-ketal of 5ß-pregnane-3,ll,20-trione is dehydrogenated at the 1-position by Septomyxa affinis. Either the illustrated 3-keto-5/3-pregnane (I) enolizes abnormally


(I) AO

(toward 2- instead of toward 4-), or the Ringold-Hayano-Stefanovic proposal does not extend to S. affinis and organisms which behave like it. This qualification applies only to the enolization part of the hypothesis for the time being. It might be desirable to establish the direction of enolization of the 3-ketone in (I) . A more ambitious under-taking, which could be justified if enolization is indeed toward the 4-position, would be to show the stereochemistry of hydrogen abstraction in the Fonken-Murray case by appropriate labeling techniques.

Sites of Reaction. Dehydrogenation has been reported at the 1-, 4-(5a- and 5ß-), 7-, 9(11), 14-, and 16-positions. The dehydrogenation reaction was described first by Horvath and Kramli in 1947 (H-406, H-407) for the conversion of cholesterol into 7-dehydrocholesterol with Azotobacter sp. No other examples of this reaction have been

reported, and this method is of significance only as a milestone in the evolution of microbial transformations.

In 1953, after the resurgence of interest in the field, Fried, Thoma, and Klings-berg (F-284) and Vischer and Wettstein (V-1056) discovered the 1-dehydrogenation reaction. The former, using Cylindrocarpon radicicola with progesterone, testos-terone, and Compound S showed that in all instances 1-denydrotestololactone was

o o II , II

R = 0H(R '=H) , R = C-CH_ (R' = H ) , R = C-CH 0H(R' = 0H)

formed in about 50% yield. Streptomyces lavendulae, with progesterone, on the other hand, gave a mixture of 1,4-androstadiene and 17/3-hydroxy-l,4-androstadien-3-one.


Vischer and Wettstein reported the use of Fusarium solani and Fusarium cau-casicum to dehydrogenate 4-androstene-3,17-dione and related C19 species to 1,4-

androstadiene-3,17-dione. Progesterone and deoxycorticosterone were also dehydro-genated and degraded to the same product. Saturated substrates and 3/3-hydroxy-A5-

steroids were transformed to l,4-androstadiene-3,17-dione, as well, but in poorer yield. Wix and Albrecht (W-1116, W-1118) investigated the use of F. caucasicum as a practical tool for the preparation of l,4-androstadiene-3,17-dione, which has been an important precursor in the manufacture of estrone.

After the discovery of prednisone and prednisolone through the use of Coryne-bacterium simplex (N-671) with cortisone and hydrocortisone, respectively, many 1-dehydrogenating cultures were described. Among the most significant of these were Bacillus sphaericus (S-942), Bacterium cyclo-oxydans (K-480),and Septomyxa affinis (M-573), all of which have been or are being used for the manufacture of antiinflam-matory steroids.

In general, preferred substrates for 1-dehydrogenation are A4-3-ketosteroids. Saturated 3-ketosteroids have also been used, but chemical methods of dehydrogena-tion are usually superior to microbial methods for these substrates.


The 1-dehydrogenation reaction is also a very convenient way to aromatize a 19-nor steroid (C-128, H-386). Ordinarily, the reverse sequence has been the

o-^K o<^K> economically significant one, insofar as phenols have been the precursors of 19-nor-steroids. The total synthesis of 19-norsteroids, however, by Velluz and his collabo-rators at Roussel45 has made these compounds available by a route independent of aromatic antecedents. Hence the microbial synthesis of steroidal phenols can become more than academic.

Dehydrogenation at the 4-position was first described by Vischer and Wettstein (V-1056) with the conversion of 5o?-androstane-3,17-dione and related species into l,4-androstadiene-3,17-dione by Fusarium solani. This class of transformation has

also been reported in the pregnane series by Stoudt and associates (S-943) with No cardia blackwellii and by Coronelli, Kluepfel, and Sens i (C-138, K-451) with Corynehacterium simplex, and in the bile acid series by Hayakawa and collaborators (H-359, H-365, T-975) with Streptomyces and Corynehacterium sp. The work of Coronelli, Kluepfel, and Sensi raises an interesting problem. In each of the illus-trated cases the A-ring saturated substrate is transformed into a 1,4-diene46 as the

CHoOH

45Chem. Eng. News 42 ,̂ 42 (1964). 46 With concomitant 9a, lla-epoxidation of the Δ 9 ' 1 1 substrate.


major product. With 16/3-methyl-17o!,21-dihydroxy-5a!-pregnane-3,ll,20-trione, the minor product is the monounsaturated Δ1-compound, which is implicated as an inter-mediate in the formation of the 1,4-diene (K-451). From 16/3-methyl-17o!,21-dihy-droxy-A9(11)-5a-pregnene-3,20-dione 21-acetate, the products of dehydrogenation are the Δ1?4- and the Δ4-species. The Δ4-species might be formed either as a pri-mary product of reaction from the A-ring saturated substrate or as a product of re -duction of the ΔΜ-diene (G-296). If the former were true, it would present yet another dilemma with which the enolization hypothesis of the microbial dehydrogena-tion process must contend.

Dehydrogenation at the 9(11)-position has been reported from the action of Glomerella fusaroides on estrone (L-494). Glomerella is orginarily a good hydrox-ylating species, with no hint of dehydrogenating activity. The course of this dehydro-genation, which is also accompanied by a bizarre inversion at the 14-position, r e -mains to be clarified.

We observed dehydrogenation at the 14-position with Wojnowicia graminis on testosterone (H-381), together with 12ce-hydroxylation. It is our view that this is not a true dehydrogenation, but is an artifact arising from prior formation of the 12o!,Ha'-diol,47 followed by elimination (not necessarily enzymatic) of the labile 14 a?-hydroxyl. The driving force for the postulated elimination may come from the 1,3-diaxial inter-action of the hydroxyl groups at 12a and 14a.

Dehydrogenation at the 16-position by Trichothecium roseum on digitoxigenin has been reported (T-1013). Since this organism is normally a 17ai-hydroxylator, the question remains whether the 17o?-hydroxy derivative of digitoxigenin is the precursor of the observed product.

Epoxidation

Bloom and Shull deduced the generalization that microorganisms which can cause axial hydroxylation at a given carbon atom can also cause epoxidation of a double bond attached to the same carbon atom (B-66). The epoxide oxygen will have the same configuration as the hydroxyl group which is normally introduced at the saturated carbon atom. Their explanation of this thesis was that the pi electrons of the double

bond assume an orientation similar to that of the electrons of the axial C,H bond and that the hydroxylating enzyme does not differentiate between the two situations. The initial stage of reaction, namely attack by oxygen (originating in the gas phase), is the same for hydroxylation and epoxidation. The natures of the transition state and any reaction intermediates remain to be elucidated.

Sites of Reaction. Bloom and Shull (B-66) showed that Curvularia lunata epox-idized 17a,21-dihydroxy-4,9(ll)-pregnadiene-3,20-dione to the 9/3,11/3-epoxide and

14a-Hydroxy-4-androstene-3,17-dione is also a product of the same fermentation.

XX


17a,21-dihydroxy-4,14-pregnadiene-3,20-dione to the 14a,15a-epoxide. They also indicated that other known axial hydroxylators at the 11-position (Cunninghamella blakesleeana) and at the 14-position (Helicostylum piriforme, Mucor griseocyanus, etc. ) also formed epoxides with the appropriate substrates.

Prochazka and colleagues (P-741) have reported the formation of a 5,6-oxide of unspecified configuration from the action of Rhizopus nigricans on 3/3-hydroxy-B-nor-5-androsten-17-one. Based on the known ability of Rhizopus sp. to 6/3-hydroxylate, we think the oxide must be 5/3,6/3. This is consistent with the observed formation, in

other products

the same transformation, of a5a,6/3-dihydroxy product, which probably arises from the diaxial opening of the oxide with water (possibly enzymatic; cf. C-87).

From the action of Nocardia sp. on Δ 9 ( 1 1 ) compounds, 9a, liai -epoxides have been formed (S-886). This is attributable to the 9a-hydroxylating ability of Nocardia.

Corynebacterium simplex behaves in a similar fashion (C-138). Kurosawa, Hayano, and Bloom (K-484) reported the 11/3,12/3-epoxidation of 4,ll-pregnadiene-3,20-dione with Curvularia lunata.


C. lunata

CH, I 3

C=0

In general, chemical methods of epoxidation are superior to the microbiological. The principal significance of the latter has been to provide a better understanding of the chemical mechanism of the microbial oxygénation process. Oxidation of Alcohols to Ketones or Aldehydes

The oxidation-reduction process for the conversion of hydroxysteroids to keto-steroids (and the reverse reaction) has been studied in detail by Talalay and his col-laborators48 with induced enzymes isolated from Pseudornonas testosteroni. They purified one enzyme system which oxidized the 3a-hydroxyl group and another which oxidized both 3/3- and 17/3-hydroxyl groups. Talalay has characterized the oxidation-reduction reaction with these enzymes as NAD-linked and illustrated the general r e -action as:

-OH NAD enzyme \

-T. " C = 0 + NADH -I- H

There is little substrate specificity among microorganisms producing hydroxy-steroid dehydrogenases. The only limitation which is usually found is that the formal stereochemistry and position of the hydroxyl group to be oxidized should be the same as that in the model from which the proposed transformation is derived. For example, 3a-hydroxysteroid dehydrogenase studied by Talalay is effective irrespective of whether the 3a-hydroxyl group is axial or equatorial. The same is also true for the 3/3-hydroxysteroid hydrogenase.

There is some evidence from the work of Ringold and collaborators with Pseudo-rnonas testosteroni that the presence of electron-withdrawing groups at the 6-position in 3-keto-A4-substrates shifts the direction of net change (and hence the equilibrium) from oxidation to reduction. From these results it may be inferred that electron density at the carbonyl group can be decisive in determining equilibrium. This is also consistent with the formulation of the oxidation-reduction process as hydride ion transfer between diphosphopyridine nucleotide and substrate.49 These findings are discussed in greater detail in the section on reduction of carbonyl groups.

48 Talalay has reviewed his work in extenso, in "The Enzymes" (P. D. Boyer, H. Lardy, and K. Myrbäck, eds.) 2nd ed. , Vol. 7, p. 177. Academic P ress , New York, 1963.

4 9 H. R. Levy, P. Talalay, and B. Vennesland [Progr. Stereochem. 3̂ , 299 (1962)], have reviewed the evidence for the chemical change in NAD+ which accompanies the oxidation of an alcohol to a ketone or aldehyde.

XH„

R

II C-NH,

H J .C—NH,


Useful oxidation of alcohols to ketones has been known since the work of Bertrand in 1896.8"10 The application of this reaction to steroid chemistry was first made by Mamoli and his collaborators (S-808, V-1047), who showed that 5-androstene-3/3,17/3-diol could be oxidized to 4-androstene-3,17-dione with bacteria isolated from contam-inated yeast. The same crude culture also oxidized 5-pregnen-3/3-ol-20-one to

progesterone (M-540). Various pure strains identified as Micrococcus dehydrogenans (E-215), Corynebacterium mediolanum (A-l, M-546), and Flavobacterium dehydro-genans (N-688, N-689) have been very useful in the laboratory for the oxidation of the 3/3-hydroxyl group, often together with deacetylation at the 3-position (and elsewhere) and isomerization of a double bond at the 5- to 4-position. This technique remains the method of choice for combined deacetylation-oxidation-isomerization (3/3-acetoxy-Δ5— 3-keto-A4) in the presence of oxidation-sensitive or pH-labile groups elsewhere in the molecule.

Oxidations of hydroxyl groups have also been observed at the 3a*- (S-799, S-800, S-818, S-943), 6/3- (B-32), 7a«- (S-799, S-800), 11/3- (H-344, M-556), 12a-(S-799, S-800, S-810), 15/3- (T-1036), 16a?- and/or 16/3- (S-793a), 18 (Ap-38), and 20/3-positions (C-128, N-665). In general, chemical methods of oxidation have been preferred for reaction at these sites.

The many instances of apparent direct introduction of carbonyl groups at unsub-stituted sites are almost certainly hydroxylation followed by oxidation. There are as yet no grounds for believing that a mechanism exists for the direct transformation of the méthylène group into carbonyl by microorganisms. Oxidation of Ketones to Esters and Lactones

The microbiological counterpart of the Baeyer-Villiger oxidation of ketones to esters or lactones was discovered by Fried, Thoma, and Klingsberg (F-284) and Peterson, Murray, and co-workers (P-726). Fried and his co-workers appreciated the parallel with the Baeyer-Villiger reaction and suggested correctly the sequential nature of the degradation of progesterone into testololactone by Pénicillium chryso-genum. Using Streptomyces lavendulae with progesterone, Fried was able to isolate

? H,

C=0 I 0

OH

P. chrysogenum · ■■

also other Penicillia and Aspergilli (P-726)

(I) (2)

(3)


17/3-hydroxy-l,4-androstadien-3-one (equivalent to stage 2) and 1,4-androstadiene-3,17-dione (equivalent to stage 3). He also observed that the presence of the 17a-hydroxyl group in a 20-ketopregnane did not prevent the reaction (e.g., Cylindrocarpon radicicola with Compound S).

ChLOH 1 2

Ά c=o irOH

1 C. radicicola

j -V

\

_ J

CH, Ί 1 3

c~o ! i 1

^

0

J

/°γ°

Fonken, Murray, and Reineke (F-254) isolated testosterone acetate (stage 1) from the degradation of progesterone with Cladosporium resinae, thereby substanti-ating further the thesis of Fried, Thoma, and KLingsberg. They proved unequivocally, with appropriately labeled progesterone, that the 21-carbon atom of progesterone is the precursor of the methyl carbon atom of acetate in testosterone acetate.

Prairie and Talalay (P-737) showed that the ether oxygen of testololactone (as distinct from carbonyl oxygen) is provided by oxygen from air in the transformation of testosterone into testololactone by P. lilacinum (P-726).

If one makes a judicious choice of organism and fermentation conditions, any of the intermediates between progesterone and testololactone (or 1-dehydrotestololactone) may become a major product. The potential value of this degradative technique was appreciated in the early, independent report of Vischer and Wettstein (V-1056) con-cerning the degradation of progesterone into l,4-androstadiene-3,17-dione by Fusarium sp. They proposed that a more efficient synthesis of estrone than the one employing dehydroepiandrosterone as starting material might incorporate the proges-terone degradation as a key stage. This possibility was investigated in some detail by Wixand Albrecht (W-111Ç W-1117,W-1118) using Fusarium solani In the final analysis, the purely chemical routes to androstadienedione and estrone have been more econom-ical, although the question has been reopened again recently by the findings of Sih con-cerning the microbial degradation of 19-hydroxycholesterol. Oxidation of Sulfides to Sulfoxides

This reaction has been reported by Holmlund and co-workers (H-405) and Dod-son and Soliman (D-174, D-176). Holmlund converted 17/3-hydroxy-7o?-thiomethyl-4-androsten-3-one 17-acetate into the corresponding deacetylated 7a-sulfoxidomethyl compound by the action of Calonectria decora. Dodson and Soliman described the


transformation of 17a-thiomethyl-4-androsten-3-one into two sulfoxides (and an 11a-hydroxylated sulfoxide) whose configurations differed at sulfur. Nothing is known about the mechanism of this reaction, but it is reasonable to suppose that the entering oxygen is provided by air .

CH, I 3

Oxidation of Amines to Ketones

Only one example of this interesting and possible useful transformation has been reported. DeFlines and co-workers (D-148) described the conversion of conessine to A4-conenin-3-one by Gloeosporium cyclaminis and Hypomyces haematococcus. Rich sources of 3-aminosteroids have been found in the Funtumia sp. of African plants.50

HX.

H.O 3 " ^

— C H ,

While no evidence has been adduced in support of a mechanism for this reaction, one may speculate that a complex chain of events is involved. We think that enzymatic iV-demethylation is a likely, early stage,51 followed by some form of transamination process. Oxidative Degradation — a Composite

Many microbiol genera can degrade a variety of steroidal substrates to carbon dioxide and water (T-965 and references cited therein). This degradative ability is particularly prominent among the genera which dehydrogenate A4-3-keto-steroids into the corresponding Δ1 compounds, such as Corynebacterium, Mycobac-terium, Pseudomonas, and Nocardia. As a consequence, the production of the

50

51

R. F . ,

Goutarel, R. , "Les alcaloids steroidiques des apocynacées." Hermann, Par is , 1964. Cf. Williams, R. T . , Proc. European Soc. Study Drug Toxicity 4, 9 (1964); McMahon,

J. Pharm. Sei. 55, 457 (1966).


antiinflammatory 1-dehydrocorticoids by this route requires careful control to prevent loss. The paths whereby degradation occurs have been elucidated through the combined efforts of Dodson and Muir (D-171, D-172), Schubert, Böhme, and Hör hold (S-818-S-821), and Sin,. Wang, and their collaborators (Ap-79, Ap-81, Ap-83), and these paths are illustrated in the charts which follow. The first of these had to do with the degradation of the steroid nucleus.

Reduction products

Mixed products of reduction of carboxyl and carbonyl

CH3CH2-C-CH-C-C-OH

H (9)

Ap-25 0 0 II II

* - C H C H C + CH C - C - O H

Note: Stereochemistry remains the same at all centers in the degradation products as in the parent.

Dodson and Muir were the first to show that degradation followed the paths 1 - 3 - 5 or 1 - 2 - 5 , depending on the organism used. For selected Nocardia sp.


it is obligatory that 9a-hydroxylation precede 1-dehydrogenation (D-172). For certain Pseudomonas sp . , on the other hand, 1-dehydrogenation must precede 9a?-hydroxyla-tion (D-171). In both instances the 9,10-seco species 5 results from the spontaneous, presumably nonenzymatic, reverse aldol reaction of postulated intermediate 4. These conclusions were confirmed later by Schubert and Sih using other organisms.

A later stage of degradation, namely, the opening of ring A, was first appreci-ated by Schubert, Böhme, and Hör hold (S-819), who isolated the degradation product having partial structure 8 from the action of Mycobacterium sp. on progesterone. This pathway was later confirmed by Sih and Wang (S-895), who used Nocardia re-strictus with androstenedione.

Sih, Wang, and their collaborators elucidated the pathway whereby 5 is trans-formed into 8 via 6 and 7. A key reaction is the 4-hydroxylation of the phenolic inter-mediate 5. Sih has recently shown that the same process is also implicated in the microbial degradation of estrone by a particular Nocardia sp. (Ap-13), which is illus-trated here. Intermediate B corresponds to 6 and C to 7. The probable structure of

Nocardia sp.

(A) (B)

HO-

HO-C

(F)

C (and 7) was deduced by the formation of the heterosteroid F (or its equivalent from 7) by reaction with ammonia. The processes which lead from C to D and from 7 to 8 have been rationalized by Sih in identical chemical terms. Compound E is pre-sumed to arise from D by further degradation. Sih and Wang and their collaborators also showed that 8 is further fragmented into 9 and thence to propionaldehyde and pyruvic acid.

(E) (D) (C)

I


A second problem of great current interest has to do with the microbial degrada-tion of the side chains of cholesterol and related sterols. In 1948, Turfitt (T-1034) observed that Proactinomyces erthropolis degraded cholestenone and bile acids to a very minor degree to the corresponding etio acids. No further transformations of

C00H

C ^ H ^ C ^ ^COOH

H2

this class were disclosed until 1964, when Whitmarsh (W-1111) reported that choles-terol was degraded in poor yield by Nocardia sp. into 3-ketobisnor-4-cholenic acid, 3-ketobisnor-l,4-choladienic acid, 4-androstene-3,17-dione, and 1,4-androstadiene-3,17-dione! "

CH-COOH H C 3 ^CH-COOH

In apparently unrelated investigations, which were to assume importance later on, Dodson and Muir (D-171) showed that 19-hydroxy-4-androstene-3,17-dione was converted into estrone readily and in good yield by Pseudomonas sp. Sih and Rahim (S-894) showed that this was also true for Nocardia restrictus. Sih recognized that


HOHX

estrone thus produced was singularly stable to further microbial attack, in contrast with 3-keto-A4-androstenes or 3-keto-A4-pregnenes. He reasoned that it might be possible to ferment an appropriate substrate in such a way that side-chain degrada-tion to a 17-ketone and A-ring aromatization would occur. If attack on the steroid nucleus could then be directed toward aromatization via retro-aldol loss of the angu-lar substituent at the 19-position rather than by 9a-hydroxylation and 9,10-secosteroid formation, estrone would result.

For this purpose he chose 19-hydroxy-4-cholesten-3-one, which might yield 19-hydroxy-4-androstene-3,17-dione as the sought-after intermediate of degradation. When he incubated the former with Nocardia restrictus, estrone was indeed formed in 8% yield. A culture (CSD-10), isolated from soil using cholesterol as the sole

Η·ι Πο

C*H X 2

source of carbon, gave estrone in 30% yield from the same 19-oxygenated substrate, the greatest part of the remainder being unreacted starting material. In the same way, 19-hydroxy-/3-sitost-4-en-3-one was also converted into estrone in 10% yield, thereby illustrating a desirable lack of side-chain specificity in CSD-10. In a later

H·» H?

H ,

study, Sih, Wang, and their collaborators (Ap-81) made further refinements of their method consisting principally of the replacement of 19-hydroxy-4-cholesten-3-one by 3/3,19-dihydroxy-5-cholestene 3-acetate (5) as substrate for CSD-10. Thereby estrone was produced in 72% yield. The proposed process for estrone manufacture from cho-lesterol is illustrated on the next page. Stages 1 ~5 employ methodology worked out to a high degree of perfection by a Ciba group.52 Sih has told us that the entire pro-cess, 1 ^estrone, has been carried out in his laboratory in an overall yield of 50%. Because of the brevity and efficiency of this process, one may anticipate that it or a variant will become a commercially significant method of estrone manufacture.

52Kalvoda, J . , Heusler, K., Ueberwasser, H. , Anner, G., and Wettstein, A., Helv. Chim. Acta46, 1361 (1963).


π-ι Ho Ho

^ C ^ ^C"^ C

(I)

Ho H

H» Ho H2 H j

^ C ^ ^ C ^ ^ C ^ H? H^C

H,

(3) (4) (5)

CSD-lol

Estrone

In later investigations, Sih and his collaborators52a proved that cholesterol is degraded to a 17-ketosteroid by Nocardia, Mycobacterium, Corynebacterium and Arthrobacter via a sequence which involves a cholanic acid and a bisnorcholanic acid as intermediates. They also established unequivocally, using labeled substrates, the nature of the fragments to which the side chain is degraded. The pathway and label locations are illustrated.

H3 H2 H2 x

H, H^CH,

CH3CH2COOH +

C J A /COOH

C ^ / C ^ C O O H

H2 COOH

C.H -COOH

+ CH^H^COOH

5 2 aSih, C. J . , Wang, K. C. , and Tai, H. H. , J . Am. Chem. Soc. 89, 1956 (1967); Sih, C. J . , Tai, H. H. and Tsong, Y. Y., ibid., p. 1957.


COOH

CH3CH2COOH

From these findings Sih has inferred the details of the mode of microbial degra-dation of the bisnorcholanic acid in the following manner. He reports that this latter sequence does not require oxygen, on which basis he presumably excludes hydroxyla-tion of the bisnorcholanic acid as an alternative path.520

COOH

-2H

C—COOH

+ H?0 tf ■COOH

aldol

He has not reached similar conclusions about the degradation of the cholanic acid to the bisnor acid. The location of the labels in the propionic acid derived from the degradation of the cholestane to the cholanic acid require that oxidative attack occur at C-26. This need not necessarily be the initiating stage of the entire degrada-tion, but if it is, the repetitive dehydrogenation52C-hydration-reverse aldol mechanism could be the means of degrading C27 to C19 steroids with the indicated microbial species. Hypotheses involving hydroxylation stages at C-24 and C-22 can be con-structed which are the equivalent of the dehydrogenation-hydration sequence, but there is no evidence for such hydroxylations.

The efficient microbial degradation of the spiroketal side chain in diosgenin and tigogenin to give l,4-androstadiene-3,16-dione (I), 16a-hydroxy-l,4-androstadien-3-one (II), and 16/3-hydroxy-l,4-androstadien-3-one (III) has been described by Ko ndo

.OH

(I) (II)

52^ A proof of his proposal is possible using H2018as the medium, thereby leading to a 17-ketosteroid labeled at the 17-carbony 1 oxygen.

52c The organisms reported here to degrade cholesterol are known to be active 1-dehydro-genation species for 3-ketosteroids.


and Mitsugi (Ap-37). This degradation is effected with the representative 1-dehydro-genating species, Fusarium solani and Corynehacterium simplex. In these instances there are both parallels with and differences from the degradation of the cholesterol side chain. The pathway proposed by Kondo and Mitsugi is illustrated as follows.

y

H3C 3 I HC—

(1)

oxidation _̂_

y

H_C 3 I HC

(3)

H 3 C

1 HC

hydrolysis

J ώ

l x C / 0 H2

0 II HO-

^ 0 H2

-OH

^

- c > -

-H<

H2

-CH3

-CH3

hydrolysis

Baeyer-

Villiger

reverse nlHnl

y

H,C 3I

HC-

(2)

\

/

H,C

HC^

Λ (4)

\ y ^

II H0CH2 — C ^ c C > H - C H

OH H2 H2

0 .0>JI Η0ΗΧ.

J

f° J (5) (6)

Evidence for the intermediate stages is that the listed substrates are also transformed to (I): stage 3, kryptogenin (F. solani)) stage 5, 3/3-acetoxy-20o!-hydroxy-5-pregnen-16-one (F. solani). The parallel with the cholesterol degradation lies in the apparent requirement for an aldolase in both sequences. The structures of the end-products of degradation in the two cases appear to require different chemistry at C-20 and C-22 to rationalize their formation.

Reduction

Reduction of Carbonyl Compounds to Alcohols

Reduction of carbonyl to hydroxyl is part of the equilibrium process described in the section on oxidation of alcohols to ketones. The same mechanistic principles apply. Evidence for the correctness of the stoichiometry of the illustrated represen-tation of this reaction has been provided, using crystalline enzyme, by Hübener, Schmidt-Thome, and co-workers (H-410, N-657, S-803).

; C = 0 + NADH + H — enzyme^

H-C-OH + NAD

If it is assumed that hydride ion transfer from NADH to carbonyl is the rate-controlling step for the forward reaction, it would be expected that decreasing the electron density at the carbonyl group should increase the rate of the reduction pro-cess. Ringold and associates (R-767) have shown that cellfree extracts of Pseudo-monas testosteroni, which do not reduce the 3-carbonyl of testosterone, 2a-methyl-testosterone, or 6/3-methyltestosterone to any significant degree, do reduce testos-terones bearing fluorine at the 2a-, 4-, 6a-, or 6/3-positions, or chlorine at the 4-position to a mixture of the corresponding 3a- and 3/3-ols. Robinson, Bruce, and


Oliveto (R-774) have shown that Flavobacterium dehydrogenans, which does not reduce a 17-ketosteroid unsubstituted at the 16-position, does indeed reduce 16,16-difluorode-hydroepiandrosterone and 16,16-difluoroestrone methyl ether to 17a-hydroxysteroids.

HO*

Since the presence of these highly electronegative species at positions where they may, by induction, withdraw electrons from carbonyl does have the anticipated effect, we infer support for the interpretation that hydride ion transfer is rate-controlling in this oxidation-reduction mechanism.

Sites of Reaction. Reduction of the carbonyl groups at the 3- and 17-positions by yeasts (mainly Sac char omy ces cerevisiae) were among the first microbial transforma-tions recognized by Mamoli and Vercellone (M-549, M-551, V-1046). Estradiol was synthesized conveniently from estrone (W-1085) and testosterone from androstene-dione using this method (M-543). Following the early work, many additional examples of reduction at the 3- and 17-positions have been reported, and also instances of reduc-tion at the 7-, 9-, 16-, 19-, 20-, 21-, and 22-positions.

In general, and where applicable, the use of yeast is the preferred mode of microbial reduction of carbonyl compounds, since it is unlikely to cause other trans-formations simultaneously. This specificity is equally true of protozoa, but the latter are much less convenient to use. The bacteria, fungi, and actinomycetes, in addition to their many other abilities, will often oxidize or reduce at the same site with greater facility. The direction of the change is a function of the substrate and the medium, as well as the organism.

Ordinarily the conjugated 3-carbonyl resists reduction by yeast at both the car-bonyl and unsaturated sites. An apparent exception is the case reported by Butenandt, Dannenberg, and Suranyi (B-80) of the reduction of 5a-l-androstene-3,17-dione to


5a-androstane-3/3,170-diol. An instructive group of reductions at the 3-position by Saccharomyces cerevisiae was reported by Camerino, Alberti, and Vercellone (C-83).

S. cerevisiae,

HO*

ÇH3

C=0

CH, I 3

C=0

(3)

Although a major stereochemical change at the 5-position (5a in 1 vs. 5ß in 2), which alters the geometry of the A- and B-rings profoundly, does not interfere with the r e -duction at the 3-position or alter the formal stereochemistry of the resulting carbinol, the apparently minor change at the 11-position in compound 3 ( l l a -o l in 3 vs. 11-C = O in 1) leads to a carbonyl of opposite stereochemistry at the 3-position.

A more predictable approach to reduction, developed by Schubert, involves the anaerobic application of Clostridium paraputrificum to A4-3-ketosteroids (Ap-71, S-823). In all instances (testosterone, progesterone, corticosterone, cortisone) the product is the corresponding 3a-hydroxy-5ß-steroid. From A1>4-3-ketosteroids the corresponding A^a-hydroxy-öß-s te ro id is formed in good yield, with a lesser amount of fully saturated hexahydrosteroid as a by-product. From A1,4,6-3-keto-steroids or A4>6-3-ketosteroids the end-product of hydrogénation is the A6-3a-hy-droxy -5/3- steroid.

Reduction of 7-ketone to 7a-hydroxyl has been reported with Streptomyces gelaticus (H-363) and Corynebacterium sp. (T-975) among others. Reductions of this type are commonly seen with substrates in the bile acid ser ies .

In the 9,10-&Ê£Q series, 9-ketones of the type of Compound 5 (p. 49) are con-verted into 9a- and 9/3-hydroxy products by the action of Nocardia restrictus (W-1063) or Mycobacterium sp. (S-818, S-820).


Several examples of simultaneous 16a- and 16/3-hydroxylation, accompanied by formation of the corresponding 16-ketone, have been reported. We described the ac-tion of Wojnowicia graminis on testosterone (H-381) leading to the aforementioned three species, and Sax and co-workers (S-793a) reported the same processes from the action of Bacillus megaterium on 4-estren-3-one. Dodson and Mizuba (D-166)

OH OH

Ύ .OH

.OH

presented an ingenious argument to the effect that 16/3-hydroxy products need not arise from 16j3-hydroxylation, but could be formed equally well from an initial 16a-hydrox-ylation of a 17-ketosteroid followed by Marker-Laws on rearrangement and reduction at the 16-position in the illustrated way. This argument cannot account for the

OH

results of Sax, since no possibility for Marker-Lawson rearrangement exists. It is not possible, however, to exclude an alternative formulation involving one oxidation and


.OH

reduction stage, following 16a-hydroxylation. In any event, evidence for reduction at the 16-position remains hypothetical.

Reduction of the 17-ketone to 170-hydroxyl has been demonstrated with a wide variety of substrates and organisms. Saccharomyces cerevisiae is a very convenient and reliable reducing culture for this reaction. Reduction to 17a-hydroxyl has been reported only once in the special case of 16,16-difluoro-17-ketosteroids (R-774), dis-cussed in the mechanism section.

Reduction of 19-carbonyl to hydroxyl has been described by Sih and co-workers (S-892) from the action of Pénicillium thomii on 14/3-hydroxy-3,19-dioxo-4;20(22)-cardadienolide. This reaction was described as reversible, with the equilibrium favoring the alcohol.

Reduction of the 20-carbonyl in pregnanes of widely varied structure has been reported by many investigators. The reduction to 20/3-ol was first described by Fried, Thoma, and Klingsberg with Streptomyces lavendulae (F-284). The product of reduc-tion accumulated in the mycelium, whereas the products of oxidation remained in the

CH3 I 3

C=0

CH, I 3

HO-C-H

broth. For synthetic purposes, the preferred organisms for this reduction are Streptomyces hydrogenans (L-522) and other Streptomyces sp. (C-110), which afford the desired process, uncomplicated by major competing reactions. Hiibener and col-laborators (H-410, N-657, S-803) isolated an inducible, crystalline 200-hydrogenase from S. hydrogenans, which they demonstrated could be used to catalyze reduction or oxidation at the 20-position with a wide variety of substrates.


Reduction of 20-ketopregnanes to 20a-hydroxyl compounds, by a microbial pro-cess free from unrelated coincident reactions, was first reported in our laboratory with the use of Rhodotorula longissima (C-110). The application of this organism to a

broader selection of 20-ketopregnanes was described subsequently by Idler and co-workers (C-122, I-413a). No examples of this reduction have been reported with fungi, actinomycetes, or bacteria. Thus far, yeasts (C-88), algae (L-527), alfalfa seedlings (L-526), and many mammalian species have been shown to give reduction products with this stereochemistry.

Reduction of 22-aldehydes to the respective carbinols was first described by Murray, Peterson, and their collaborators (M-578) with Rhizopus nigricans and Rhizopus arrhizus, concomitant with hydroxylation at the 11a- and 6/3-positions. Pénicillium lilacinum (E-202) and Gliocladium catenulatum (W-1068) have been re -ported to give reduction at the 22-position, free of major side reaction. Ambiguity in the descriptions of the starting materials in these reactions make it uncertain as to whether the reductions occur principally with'retention of configuration at the 20-position or with inversion. It is clear, however, thatG. catenulatum leads to an equilibration of the starting material at the 20-position, at least in part.

Reduction of Carbon-Carbon Double Bonds

This type of reaction may be divided into two categories: (1) reduction of iso-lated double bonds and (2) reduction of conjugated double bonds. There are very few examples of the former in the steroid field, all involving the use of unidentified fecal anaerobes to reduce Δ5-compounds to the 5/3-series (C-133, S-914), and there is no adequate basis for the presentation of arguments about mechanism.53

The reduction of double bonds conjugated with keto groups may be viewed as part of the illustrated equilibrium process, the reverse of which is the dehydrogena-tion of ketosteroids. The nature of the reagent X, be it protein-bound flavin, quinone,

XH,

or another oxidizing agent, has been discussed in the section on dehydrogenation. If this view is accepted, then the stereochemical restrictions developed for dehydrogena-tion should apply.530 These restrictions are that the leaving (or entering) hydrogens at the 1- and 2-positions are axial and trans (ley,2/3). The evidence for the equilibrium

53 The conversion of cholic acid into 7-deoxy bile acids by mixed intestinal microorganisms is considered to proceed via elimination of the 7a-hydroxyl group followed by reduction. These reductions have not been demonstrated with pure cultures. Bergstrom, S. , Danielsson, H. , and Samuelson, B. , in MLipid Metabolism" (K. Bloch, ed.) , p. 316. Wiley, New York, 1960.

530 Whether these may be generalized from the studies with one organism, B. sphaericus, remains to be established.


nature of the reaction comes from Goodman, May, and Smith (G-296) who showed that C. simplex and B. cyclo-oxydans interconvert triamcinolone and 1,2-dihydrotriam-cinolone.

C. simplex or B. cyclo-oxydans

Sites of Reaction. Reduction of conjugated double bonds was first observed by (M-548) with a crude culture of putrefactive bacteria. The pure

reduced 3-keto-A4-androstenes to 3-keto-This culture is no longer

Mamoli and Schramm culture, described as Bacillus putrificus, 5ß-androstanes and 3a-hydroxy-5/3-androstanes (M-545). available (E-202), but a modern equivalent is Clostridium paraputrificum, described by Schubert (Ap-71, S-823). The properties of the latter are described in greater detail in the section on reduction of carbonyl groups.

Butenandt, Dannenberg, and Suranyi (B-80) reported the reduction of A ^ - k e t o -5a-steroids to 3/3-hydroxysteroids with yeast.

S. cerevisiae

HO Λ ^ ,

Reductions of 3-keto-Δ4-substrates with fungi or actinomycetes may lead to either 4,5a- or 4,5/3-dihydro products, but these reactions are usually incidental to hydroxylation elsewhere in the substrates (E-201, P-718, P-725, P-729). Selective reduction of A1?4-3-ketosteroids to Δλ-5β-steroids with Streptomyces sp. has also been described (G-314).

Sfreplomyces sp.

There is indirect evidence for the reduction of 12a-hydroxy-3-keto-4,6-chol-adienic acid at Δ6. Hayakawa and collaborators (H-358, H-367, T-974) have shown that cholic acid is transformed into the illustrated products (1-5) by Corynebacterium simplex and other Corynebacterium sp.

If one places the products in the sequence shown here, the elimination of the 7a-hydroxyl group in 2 need not necessarily be enzyme-catalyzed. Conversion of 3 into 4 follows logically and requires enzyme mediation. Other routes to the formation of the same products are not excluded.

The reduction of 16-dehydroprogesterone, accompanied by 11 «-hydroxylation, from the action of Rhizopus nigricans (M-579, M-601, M-605) or Aspergillus niger


HO*

COOH Corynebacterium sp.

COOH

(2) (3)

COOH

(4) (5)

(M-603) affords lla-hydroxy-17û!-4-pregnene-3,20-dione. The thermodynamically more stable configuration of the side chain in pregnenolone and 3/3-hydroxy-5a-pregnan-20-one is the /3-form.54 If one makes the reasonable assumption that this

0 '

is also true for lla-hydroxyprogesterone vs. its 17o?-epimer, it becomes possible to develop a speculative argument about the stereochemistry of the attachment of the steroid to the enzyme. If one chooses to argue that reaction is complete at the enzyme surface by 1,2-addition in the illustrated sense, then the hydrogen at the 17-position must have been delivered from the /3-side, and the product thus produced must be free to alter the angle of attachment at the 17-position from the initial plana-rity of the starting material to the quasi-axial of the product without steric inter-ference from the enzyme. This may be accommodated if the steroid is attached to the enzyme by its ß-face.

Butenandt, A. , and Fleischer, G., Ber. 70, 96 (1937); Butenandt, A. , and Mamoli, L. , ibid., £3, 1847 (1935). —


CH3

I c=o

An alternative treatment of the problem is to assume the reversal of the Ringold mechanism for dehydrogenation (as developed for A-ring transformations) to account for the observed reaction. In specific terms this involves enzyme-mediated attack by hydride ion on the 16-position as the initiating stage. The mechanism requires the formation of the illustrated enol as the intermediate. The enol must then be protonated

CH, I 3

c=o

[H]"

enzyme

CH3

C -0~

H +

CH3

C=0

and go back to the ketone before it leaves the enzyme surface in order to attain the thermodynamically less favorable 17o?-stereochemistry. This treatment again implies attachment of the substrate and the transition state derived from it to the enzyme by the /3-face. The Ringold mechanism has the apparent merit of requiring no change in geometry at the 17-position during the enzyme-mediated, hydride ion transfer stage. Protonation of the enol would be spontaneous, and it would be necessary to invoke only a steric but not a catalytic role for the enzyme during this part of the process.

Reduction of Steroidal Bromide

Laskin and Diassi (L-492) have reported the only example of reduction of a ste-roidal bromide. Cylindrocarpon radicicola transformed 9a-bromo-ll-ketoprogester-one into 1-dehydro-ll-ketotestololactone. Reductive removal of halide from an a-halo -ketone is well known in organic chemistry and can be done very efficiently with a vari-ety of reducing systems.

Esterification and Hydrolysis

Hydrolysis of Esters to Give Steroid Alcohols

The mechanism of catalysis for hydrolysis of steroid esters to steroid alcohols has not been elucidated in particular. In view of the nonspecific nature of esterases, however, it might be possible to carry over mechanistic conclusions from the studies with simpler esters . A favored formulation of this process by Bender and Kezdy55 is

'Bender, M. L. , and Kezdy, F. J. , Ann. Rev. Biochem. 34, 49 (1965).


shown here. The enzyme provides the required imidazole and hydroxyl groups. Water may participate in the cleavage of the steroid ester and is involved in the regeneration of the enzyme hydroxyl site.

enzyme

H NI l \ C—OR

N1

enzyme

f*l ° Ν χ

ΊΗ ^R

0

enzyme

enzyme

R = steroid

1 1 , -l\L 0 ^ .OR

Ή CC I R 0

H

JO ί \ i J

Hydrolysis of steroidal 21-acetates was among the earliest transformations recognized. Mamoli (M-541) found that Cor ynebac ter turn mediolanum could be used to transform 21-acetoxypregnenolone into deoxycorticosterone. Since then it has been shown that nonspecific esterases are common among bacteria, fungi, and actino-mycetes.

Acetylation is employed widely as a protective device for hydroxyl groups during the chemical manipulation of steroids. Successful use in this way implies the ability to remove the protective group following completion of the synthetic pro-gram. We have found that Flavobacterium dehydrogenans (A-16) contains what we believe to be a "universal" system of deacetylase(s). The acetates which we have hydrolyzed with its aid include Iß- (N-689), 30- (N-689),56 11a- (unpublished), 11/3-(C-129), 15a- (unpublished), 16a- (S-839), 16/3- (S-839), 17a- (N-690), 17/3- (G-304), 20/3- (unpublished), and 21- (C-129).56 The yields are usually very high, and major coincident reactions, namely, oxidation of 3-hydroxyl to ketone and isomerization of Δ5 to Δ4, are often useful.

While microbial hydrolysis of esters other than acetates might be expected to be equally common, relatively little reliable documentation of these reactions exists in the steroid field. The reason for this is clearly that acetates are the preferred esters

See also South African Patent 3462 (1955).


for most synthetic purposes, and consequently other esters have been subjected only rarely to study in microbial transformations. Among the few examples are the hydrolyses of tes tololac tone to testolic acid by Pénicillium lilacinum (P-737), other Pénicillium sp. (H-398), Cephalosporium acremonium (H-398), and Aspergillus flavipes (H-398).

A convenient source of esterase for "in vitro" laboratory use is malt enzyme (diastase, J . P . ) the application of which was described by Noguchi (N-672, N-673). Noguchi reported the successful hydrolysis of acetates at the 16a-, 170-, 20a-, 20/3-, and 21-positions (N-672). He also extended this method to 21-esters of other straight-chain aliphatic carboxylic acids (formate, butyrate, and caprylate), dibasic aliphatic hemiesters (hemisuccinate and hemitartrate) and AT-substituted amino acid esters (dimethylaminoacetate and diethylaminoacetate) (N-673). 17/3-Formate was hydro-lyzed, but 17ß-propionate was not.

Esterification of Steroid Alcohols

Only two reports of examples of this reaction class have been made. McGuire, Maxwell, and Tomkins (M-572) described the action of Saccharomyces fragilis on androstenedione, which afforded testerone acetate. The product arose from sequential

reduction followed by acetylation. Holmlund and collaborators (H-404) observed the acetylation of the 16,17-acetonide of 9a-fluoro-16ai-hydroxyhydrocortisone by

ChLOH

Trichoderma glauca. These examples are principally of academic interest as further evidence of the reversibility of enzymatic reactions. The mechanism which operates here is possibly the reverse of that illustrated for hydrolysis.

N-Acetate Formation from Amines

The only example of this reaction class was described by Smith and co-workers (S-911) from the action of Streptomyces roseochromogenus on 21-amino-9a-fluoro-ll/3, 17a-dihydroxy-l,4-pregnadiene-3,20-dione to give the 21-N-acetate.

ΗΟ^

I 2 2

C=0

WoH S. roseochromogenus

-CH,


The mechanism of acylation may be related to that of esterification of hydroxyl groups.

Hydrolysis of Oxides to Alcohols

The simple hydrolysis of oxides with Saccharomyces cerevisiae, first described by Camerino and Sciaky (C-87), leads to glycols with diaxial opening. This reaction is then the mechanistic equivalent of a normal, acid-catalyzed opening of an oxide,

C H , I 3

C=0

CH, I 3

c=o

c=o

with water acting as the nucleophile. One may speculate that the enzyme is acting as a reversible proton donor-proton acceptor species, perhaps involving an imidazole as the combined proton source-proton sink. The stereochemical problems attendant to the formation of a cyclic 9-member ring transition state might be mitigated by con-sidering that the participating water need not be a single molecule, but may be a hy-drogen-bonded agglomerate.

H ^

0 I 0 - H H

H

enzyme enzyme

A special case of oxide opening involving Wagner-Meerwein rearrangement was described by Camerino and Vercellone (C-88). This is analogous to a nonenzymatic, acid-catalyzed process studied by Heusler and Wettstein57 and in our laboratory.58

57Heusler, K., and Wettstein, A. , Ber. 87, 1301 (1954). 58Shapiro, E. S., Steinberg, M. , Gould, D. , Gentles, M. J. , Herzog, H. L. , Gilmore,

M., Charney, W. , Hershberg, E. B . , and Mandell, L . , J . Am. Chem. Soc. 81, 6483 (1959) (and preceding papers in the series).


C-CH3 •••OH

;H3?V

The initiating stage here appears to be identical with the normal oxide opening. Molecular geometry then favors intramolecular methyl migration (13 -17) over nucleo-philic, intermolecular hydration at the 17-position. The reaction is completed by proton loss from the 14-position.

Hydrolysis of Glycosides

Cleavage of glucose from selected steroidal glycosides by fungi was recognized and studied by Stoll, Renz, and Brack (S-936a). Ability to perform this transforma-tion is especially prominent among Aspergillus and Pénicillium sp. It is not clear from the available evidence whether the reaction in question is hydrolysis or a t rans-glycosylation. The generic form of the reaction, which embodies this uncertainty, can be given as follows:

R-O-R1 4- R-0H -R ' -O -R" + R-OH

R = steroid portion of glycoside R'= sugar portion of glycoside R"= sugar moiety or hydrogen

The substantial literature on transglycosylation has been reviewed by Stodola.59

The Stoll group observed the selective cleavage of glucose from several cardio-active glycosides. In each case (scilliroside, digilanide A, and deacetyldigilanide A) glucose was an end group, the cleavage leading thereby to a partially degraded glyco-side. Such a result is difficult to obtain by other than enzymatic techniques. Later work by Krider, Cordon, and Wall (K-478), using the same fungal genera, showed that this technique could be applied to steroidal saponins to give sapogenins.

Isomerization of Double Bonds Isomerization of the double bond from Δ5 to Δ4 was among the reactions first

recognized by Mamoli. With Corynebacterium mediolanum he converted 3/3,21-dihy-droxy-5-pregnen-20-one 21-acetate into deoxycorticosterone (M-541). From our

experience Flavobacterium dehydrogenans can be used very efficiently in the same way (N-688, N-689). In general, enzymes which promote the isomerization reaction are

Stodola, F. , "Chemical Transformations by Microorganisms," p. 65. Wiley, New York, 1958.


widely distributed among oxidizing microorganisms. We know of only one oxidizing organism, Actinoplanes mis s our tens is (Ap-45), which does not also sequentially iso-merize Δ5 to Δ4.60

The mechanism of the enzyme-catalyzed isomerization has been studied in de-tail by Talalay and Ringold. Talalay, Wang, and Kawahara isolated and crystallized the induced isomerase from Pseudomonas testosteroni (K-437, T-972)61 and showed that its use required no cofactor. From study of the isomerization in deuterium oxide, they demonstrated no deuterium incorporation into the steroid and inferred that the isomerization involved a transfer of hydrogen from C-4 to C-6. Malhotra and Ringold proved that hydrogen is transferred from the 4/3- to the 6/3-position by using appropriate, deuterium-labeled substrates (Ap-44). They also established that the transfer is intramolecular. The present view of the mechanism which repre-sents a synthesis of the Talalay and Ringold findings is illustrated here.62 This for-mulation requires 8-member ring (1) and 10-membered ring (2) transition states

which Talalay has asserted are shown to be accommodated easily, in appropriate scale models.62 Talalay has inferred the histidine catalysis from enzyme inactiva-tion studies with méthylène blue. Some evidence for probable reversibility comes from the work of Ward and Engel63 with sheep adrenal enzymes. They showed that 4-androstene-3,17-dione could be transformed into dehydroepiandosterone. The first

stage of this reaction is presumed to be the deconjugation of Δ4 to Δ 5 . It has also been reported that Bacillus pulvifaciens converts 6/3-hydroxy-4-androstene-3,17-dione into 5a-androstane-3,6,17-trione (1-420), which may be accounted for by the action of an isomerase.

6 While Flavobacterium dehydrogenans isomerizes the double bond smoothly in a 3/3 -hydroxy^ 5 -subst ra te , presumably after oxidation at the 3-position, it does not isomerize the double bond in a 3 - k e t o ^ 1 , s -substrate (N-690).

61 Kawahara, F. S., Wang, S. F. , and Talalay, P. , J . Biol. Chem. 237, 1500 (1962); Wang, S. F . , Kawahara, F . S., and Talalay, P. ibid., 23§, 567 (1963).

62Talalay, P . , Ann. Rev. Biochem. 34, 352 (1965). 63Ward, M. G. , and Engel, L. L. , J. Biol. Chem. 239, PC3604 (1964).


The isomerase from Ps. testosteronih&s also transformed A5(10)-3-ketosteroids into their Δ4-counterparts in vitro (T-972). The appropriate substrates have not been investigated with intact cultures, but there is no reason to doubt than an equivalent r e -action would take place in vivo.

Miscellaneous Addition, Rearrangement, and Elimination Processes The following reaction classes have been identified in the presence of microbial

systems. The necessity for enzymatic catalysis is not proved in many of these cases and is specifically excluded in two.

a. Wagner-Meerwein rearrangement b. Decarboxylation c. Aldol and reverse aldol reactions d. Michael addition e. D- Ho mo annulatio n f. Enolization of carbonyl compounds g. Dehydration h. Amination

Wagner-Meerwein Rearrangement

Saccharomyces cerevisiae was used by Camerino and Vercellone (C-88) to trans-form 16o?,17û!-oxido-20-ketopregnanes. The products thus produced are those which have also resulted from acid-catalyzed, hydrolytic attack on the oxide64 followed by

reduction at the 20-position. The Wagner-Meerwein rearrangement of the angular methyl group from the 13- to the 17-position is presumably not under enzymatic con-trol per se, but follows as a consequence of the enzyme-catalyzed opening of the oxide, a reaction which has been demonstrated in other cases (cf. p. 66) with yeasts.

Decarboxylation

Decarboxylation of a 0-ketolactone has been shown by Urech, Vischer, and Wett-stein (U-1044) in the illustrated case. The reaction also proceeded in the medium alone, in the absence of Fusarium solani or enzymes from it, when the appropriate 17-keto-(18 — 11) lactone was used as substrate.

Heusler, K. , and Wettstein, A. , Ber. 87, 1301 (1954).


Reverse Aldol Reaction

Dodson and Muir showed that the reverse aldol reaction is a key step in the degra-dation of the B-ring (D-171, D-172). In the illustration, 9a-hydroxylation of a Δ1?4-3-ketosteroid with Pseudomonas sp. affords an intermediate which then experiences clea-vage between the 9- and 10-positions. The same investigators also reported another

variant of the same reaction, in which formaldehyde is lost from 19-hydroxy-l,4-andro-stadiene-3,17-dione, which was produced in situ by the A^dehydrogenation of 19-hy-droxy-4-androstene-3,17-dione. The latter sequence represents a key transition in the conversion of cholesterol into estrone as described by Sih.

Pseudomonas s p. HOHX

There is no evidence that an enzyme is required for the reverse aldol stage of either of the illustrated reactions. It is likely that an aldolase is required for the reverse aldol reactions described in the section on degradation of the cholesterol and diosgenin side chains (Ap-37; Sih and collaborators52a).

Michael Addition

Intramolecular Michael addition of an 11/3-hydroxyl group to a 3-keto-Δ1-system has been reported by Gnoj and associates (G-292). There is no reason to believe that an enzyme is required for the addition, which follows enzymatic deacetylation at the 11-position.

CI-LOH I 2


D- Horn oannulation

D-Homoannulation was among the first transformations described by Fried and his collaborators (F-283) using Aspergillus niger with 17a-hydroxyprogesterone.

Later work by Goodman and Smith (G-297) with triamcinolone and related 16ai-hy-droxycorticoids established that, for the examples studied, D-ho mo annulation is non-enzymatic, the reaction being promoted by ferrous or ferric ion in the presence of

Λ

CHoOH I C-O X-OH

•OH ^

CHoOH

• OH 0

OH

calcium carbonate and inhibited by phosphate ion. Whether this mechanism also applies to the reaction of ΙΊα-hydroxyprogesterone is open to some question, since 17a-hydroxy-20-ketosteroids D-homoannulate much less readily than do 16a-hydroxy-corticoids.

Enolization of Carbonyl Compounds — Inversion at the a-Carbon

From deuterium exchange experiments with 3-ketosteroids, it has been inferred that enolization is a common, microbially induced process. The same conclusion is also supported by the observed isomerization at 20- of 22-aldehydes. Wechter (W-1068) has described the inversion of 3-ketobisnor-4-cholen-22-al to the 20-iso compound by Gliocladium catenulatum, for which a reasonable mechanism is the illustrated enoliza-tion.

Dehydrative elimination of hydroxyl groups is well known from the enzymatic conversion of saturated to mo nouns aturated fatty acids.65 Incubation of cholic acid with rat feces under anaerobic conditions gives a mixture of 7-deoxy products, which were presumed to have arisen through dehydration of the la -hydroxyl group, followed

1962. 65Hayano, M. , in MOxygenasesM (O. Hayaishi, ed.), p. 229. Academic Press, New York,

Dehydration


by reduction of the resulting Δ6 double bond.66 A related process has been seen by Hayakawa and his collaborators from the action of Corynebacterium simplex (H-358, H-367, T-974) and Streptomyces rubescens (H-362) on cholic acid. One may infer

CH2

CH2 I 2

C-0H 0 £ simplex^

0' ^ ^ 0 "

(2) (3)

that the antecedent of the three illustrated products is 7 a, 12a-dihydroxy-3-keto-4-cholenic acid [actually isolated from the reaction (H-365, H-367)], which then suffers dehydrative elimination to give the Δ4>6 -diene (1), followed by reduction to the 3-keto-Δ4 (2), and finally dehydrogenation to the Δ1*4 -diene (3).

Whether the elimination at the 7-position is enzyme-catalyzed or merely a purely chemical reverse Michael reaction has not been established.

Dehydration of the 50-hydroxyl group in cardiac aglycones has been reported by Nozaki (N-679) with Absidia orchidis and by Sih and associates (S-891) with Chaeto-mium globosum. In each case elimination presumably followed oxidation of the 3/3-hydroxyl to ketone and may be nonenzymatic.

Amination The only example of amination in the steroid field has been reported by Smith

and collaborators (S-911). Streptomyces roseochromogenus on 9a-fluoroprednisolone afforded the 21-deoxy-21-acetylamino product. This reaction may be following the illustrated path.

S. roseochromogenus

••OH

0 II C-H | c=o | > ^ 0 H

CH2—NH2

C=0

|ΑθΗ

1 1

R 1

CH=N-C-C00H C=0 H 1

K

\y

> \ 0 H

' '

Γ ? Ί CH2—N=C—COOH

ç=o

K

r"

^Λ-ΟΗ

1 66Bergstrom, S., Danielsson, H. , and Samuelsson, B . , in "Lipide Metabolism" (K.

Bloch, ed.) , p. 305. Wiley, New York, 1960.


Resolution of Steroids from Total Synthesis Total synthesis has become an important factor in the commercial production

of steroids. Velluz and collaborators at Roussel have devised a practical method for the manufacture of 19-nor steroids and estrogens.67 Implicit in any total synthesis is the requirement for either a resolution or a stage of asymmetric reaction. Both methods have been used successfully to provide steroids of natural configuration. Of the two techniques the latter is to be preferred, since it is capable of converting all the substrate into useful product, whereas the former can only provide half of the pro-duct in natural configuration.

Gibian and collaborators (Ap-24) succeeded in devising an efficient asymmetric microbiological stage as part of a synthesis of estradiol methyl ether. The optically

CH,0

Saccharornyces sp.

CH.0

(I) (2)

inactive diketone 1 was reduced to the optically active, natural series (d) ketol 2 with the aid of Saccharornyces pastorianus, S. carlsbergensis, or, best of all, S. uvarum. Bacillus thuringiensis, on the other hand, afforded exclusively the epimer at the 13-position.

The first successful use of a microbial stage to separate a racemic mixture was described by Vischer, Schmidlin, and Wettstein (V-1055) who prepared natural {d)~ aldosterone by 21-hydroxylation of a <i,Z-precursor with Ophiobolus herpotrichus.

d,L-

CHoOH HO I

I C=0

/ - starting material

The natural series of steroids is not necessarily the preferred substrate for all microorganisms. Greenspan and collaborators (Ap-28) have described oxidation of 17/3-hydroxysteroids with Flavobacterium dehydrogenans and A1-dehydrogenations with Corynebacterium hoagii, which resulted in the transformation of both d and I substrates.

Chem. Eng. News 42, 42 (1964).

CHAPTER I I I

THE CONSTRUCTION AND USE OF TABLE I

ORDER OF THE TABLE

The entries in Table I are all products of microbial transformation. With few exceptions, compounds are recorded in this table only when a detailed procedure has been given in the cited reference. Specifically excluded are the lists of transforma-tion products, given without experimental detail, which occur often in the patent liter-ature. As a general rule, one is better advised to use the scientific literature, as distinct from the patent literature, as the prime guide.

The table entries are recorded in an order determined by the following rules, which are applied sequentially :

(a) According to increasing carbon content (b) According to increasing hydrogen content (c) According to increasing oxygen content (d) According to the alphabetic placement of hetero atoms, e .g. , Br, Cl,

F, I, N, S; for compounds of identical C, H, and O content; BrCl (as in C21H2803BrCl) precedes Br2 (as in C21H2803Br2 ); FS precedes N (e.g., C21H2803FS precedes C21H2803N)

Products of known empirical formula, but unknown structure, are shown at the end of each group of entries having common empirical formulas. Systematic organic chemical nomenclature has been used, except for sapogenins and steroidal alkaloids. Common names of the principal hormones are given parenthetically.

Where an isotope (other than the most common) of a given element is present, the empirical formula is constructed without special reference to the label (e.g., C21H29H303 is given under C21H30O3 ). The label is indicated by the use of a suffix symbol in the product name (e.g., 21-hydroxy-4-pregnene-3,20-dione 21-018).

NOMENCLATURE

The following systematic stem names were used for the indicated structures.

C21 I

Estrane Androstane Pregnane

74

NOMENCLATURE 75

I2' /C=0 r ç/ 23

C H > 0 22

Cardanolide Bufanolide

C I X^ X^ /C

23 ^ C 2 7

C ho la nie acid Cholestane

Stigmastane

The problem of the nomenclature of the few sapogenin and steroidal alkaloid entries was evaded by the use of common stem names. These are defined elsewhere.68

Configuration of any substituent attached to a ring carbon of the steroid nucleus is defined as ß when that substituent projects above the plane of the steroid nucleus and as a when the substituent projects below the plane. Substituents which have the 0-configuration are shown attached to the nucleus by solid lines, and those which have the «-configuration, by dotted lines. Configuration of hydrogen at the 5-position is always defined by 5a- or 5/3- preceding the stem. Configurations at the 8-, 10-, 13-, and 17-positions are*understood to be ß unless otherwise indicated, and configurations at the 9- and 14-positions are understood to be CÜ. Configuration at the 20-position is specified as a or ß following the Fieser convention.68

No more than one class of suffix designation for substituents is affixed to any stem. All remaining substituents are expressed in prefixes, arranged alphabetically. The alphabetical arrangement of prefixes depends only on the root term for the pre-fix and is independent of the number of substituents of the particular type. For ex-ample, fluoro precedes hydroxy, fluoro precedes dihydroxy, hydroxy precedes methyl, and trihydroxy precedes methyl.

68 Fieser, L. F . , and Fieser, M., "Steroids." Reinhold, New York, 1959.

76 III. CONSTRUCTION AND USE OF TABLE I

The prefix nor defines a steroid with cne less carbon atom than the stem indi-cates (bisnor - two carbon atoms less, etc. ). Where no number or letter precedes nor, the carbon which has been dropped is the highest-numbered stem member. In other instances, the carbon atom which is missing is shown by the number or letter preceding nor (e.g., 19-nor-4-pregnene-3,20-dione or A-nor-3-androstene-2-one). Where the letter designation is used, ring contraction of the indicated ring is present, and the highest numbered carbon atom in that ring is absent.

The prefix homo defines a steroid with one more atom than the stem indicates. The rules for definition of the locus of the change follow those for norsteroids. The homo atom, which is usually a ring member in the compounds treated here, is given a number designation of the highest-numbered atom of the given ring, followed by the letter a.

I7a

D [ D- homo- i7a-oxa 16

15

Oxa, aza, and thia designate the replacement of an actual or hypothetical carbon by oxygen, nitrogen, and sulfur, respectively.

Seco defines a bond normally present in the steroid skeleton, which is broken in the case in question.

9,10-seco-

Retro defines a steroid with the 9/3,10a-configuration (in place of the normal 9a, 10/3).

Entries of the same empirical formula are placed in alphabetical sequence ac-cording to the name defined by the stem plus the suffix: androstadiene, androstane, androstene, pregnadiene, pregnane, and pregnene.

For compounds with identical stem names, ranking is determined by the alpha-betical position of the prefix: bromo, ethyl, fluoro, hydroxy, methyl, etc. Where there is more than one prefix, that which begins with the letter closest to a deter-mines the rank of the compound. Designations such as di and t r i are ignored for this purpose, e .g. , dihydroxy is an h prefix, not a d prefix. For compounds with identical prefixes and stem names, the order is determined by the position of the lowest-num-bered substitutent, e .g . , l a -hydroxy- 4-pregnene- 3,20-dio ne precedes 6/3-hydroxy-4-pregnene-3,20-dione. For identically positioned substituents ot always precedes ß.

DESCRIPTION OF THE TRANSFORMATION LEADING TO THE PRODUCT

A shorthand notation is used to show the transformation(s) which led to the illus-trated product. Symbols are defined as follows.

DESCRIPTION OF THE TRANSFORMATION LEADING TO THE PRODUCT 77

,x>y

,x(y)

Δ (y-a)

x-OH

x-OH- x - C = 0

x -C=0 ^ x - O H

ΔΧ - y ß - H

enol. o r enoliz .

ketoniz.

degradat ion [X,Y] (substra te)

Me

Inser t ion of a double bond between the numbered carbon (x=l, 2, 3, e tc . ) and that of next higher number

Inser t ion of two double bonds, x defining the un-sa tura t ion of the lower number and y the unsa tu r -ation of the higher number (according to the p r e -ceding rule)

Inser t ion of a double bond between the indicated, nonconsecutively numbered carbon a toms

Inser t ion of a double bond into a p r e c u r s o r with hydrogen or another subst i tuent in the i l lus t ra ted configuration, e . g . , Δ4(5/3-Η) means double bond introduction into a 5/3-steroid at Δ4

Hydroxylation at the indicated s i te

The i l lus t ra ted functional group is t r ans fo rmed in the indicated way

The indicated hydroxyl group is oxidized to ketone

The indicated ketone is reduced to hydroxyl

The indicated double bond is reduced and hydrogen en te r s in the noted configuration, e . g . , Δ4 ·-5/3-H means that the Δ4 double bond has been r e -duced, with the hydrogen at the 5-posit ion entering ß -Enolization of a carbonyl group Revers ion of an enol to the corresponding ketone

The degradat ion of the indicated r ings [X,Y] of the i l lus t ra ted subs t r a t e has o c c u r r e d . The chem-ical changes he re a r e so numerous and, in some c a s e s , incompletely unders tood that individual s t eps a r e not shown

CH,

Fo

O II

H - C -

Ac

O

CH3C-

O

P r

Bu

i-Bu

CH 3 -CH 2 -C-O II

CH3-CH2-CH2-C-O

(CH 3 ) 2 -CH-C-

78 ΙΠ. CONSTRUCTION AND USE OF TABLE I

rev. aldol or reverse aldol

o l i

HCH

YIELD

Where a yield is reported by the investigators, it is recorded in the table. The term (cr. ) following yield means that the figure applies to a product which in our judgment is significantly less pure than the analytical sample of the indicated com-pound. Where no yield has been reported, the yield column shows a dash (-). Where the yield is less than 1%, it has sometimes been given as " trace" (tr. ).

ORGANISM

The organism is described in the language of the particular reference, with few exceptions {Corynebacterium is used in preference to Arthrobacter, and Streptomyces in place of Actinomyces). When an organism has been unidentified in early work, but characterized in later reports, the final assignment is used. For a more exact des-cription of the organism (source or culture number), it is necessary to consult Table III "Transformation by Genus. " Where the author has catalogued a list of identical transformations, using different species from the same genus, we have sometimes abbreviated his report as a single entry with a generic description (e.g. , Aspergillus sp. for a list of Aspergilli which all 1 la-hydroxylate Compound S ). These cultures are listed individually in Table III "Transformation by Genus" and are marked with an asterisk in that table.

Transformations with mixed cultures have been omitted from this table except in a few cases of historical interest.

In general, reactions with cellfree enzymes and enzyme systems, which have not also been reported for the intact culture, have not been included in this table.

CONSTANTS

Melting points are given to the nearest degree (centigrade), excepting those values which have been reported by the investigators to the half degree (e.g., 244. 5-246). Rotations are rounded off to the nearest degree, with the same exception. The rotation solvent is given in brackets after the reading: a, acetone; c, chloroform; d, dioxane; e, ethanol; m, methanol; and p, pyridine.

In several instances a rotatory dispersion curve has been reported by the in-vestigator with no sodium D line read-out. An asterisk has been entered in the rota-tion column in these cases. No temperatures have been recorded for rotations on account of the lack of space in the table and the relative insensitivity of rotations to minor temperature changes. Almost all rotations were reported at 25 ± 5°C.

REFERENCES 79

REFERENCES

The reference for each entry is given by coded citation in the reference column. These citations are arranged alphabetically in the Bibliography. None of these refer-ences are listed in the Bibliographical Appendix. The references are drawn from the scientific literature and the United States Patent literature through January 1964, with a few subsequent inclusions.

Many later references to the scientific literature (not patent literature) through December 1966 are in the Bibliographical Appendix. These are annotated briefly in most cases and have been used, where pertinent, in the discussion sections but not in the tabular sections of this book.

80

TABLE I

T r a n s f o r m a t i o n s by Product

EMPIRICAL FORMULA

C 1 3 H 1 8 ° 3

C 1 3 H 1 8 0 4

^13^20^3

C 15 H 22°4

C 1 5 H 2 4 ° 3

C1 8H1 903Br

C 1 8 H 1 9 ° 3 F

^1 8^20^2

^18"20^3

C1 8H2 102F

^18"22θ2

NAME OF REACTION PRODUCT

3 a a - H - 4 a - [ 3 ' -propionic ac id]-5a -hydroxy - 7a/3 - methyl -hexahydro -1 -indanone lactone

3aa-H-4a-[3* -propionic acid]-5/3-hydr oxy -7a/3- methyl -hexahydro-1 -indanone lactone

3aa-H-4a- [3 f -propionic acid]-7a/3 -methylhexahydro - 1 , 5 -indanedione

3aa-H-4a- [3 f -n -propanol ] -7a/3 - methy lhexahydr o - 1 , 5 -indanedione

l /3-acetyl-3aa-H-4a-[3» -propionic acid]-7a/3-methyl-hexahydr o - 5 - indanone

l /3-acetyl -3aa-H-4a-[3 f -n-pr opanol] - 7aß - methy lhexa -hydro - 5 - indanone

9 a - b r o m o - 3 - h y d r o x y - 1 , 3 , 5 ( l O ) - e s t r a t r i e n e - l l , 17-dione

6a - f luo r0 -3 -hydroxy-1 ,3 ,5 ( l O ) - e s t r a t r i e n e - l l , 17-dione

3 - h y d r o x y - l , 3 , 5 ( 1 0 ) , 6 -es t r a te t r aene -17 -one

3-hydroxy-1 ,3 ,5(10) , 7 - e s t r a -te t raene-17-one (equilin)

3-hydroxy-14/3-l ,3,5(10),9 ( l l ) - e s t r a t e t r a e n e - 1 7 - o n e

3 -hyd roxy -9ß , l l / 3 -ox ido - l , 3 , 5(10)-es t ra t r ien-17-one

6 a - f l u o r o - 3 - h y d r o x y - l , 3 , 5 (10) -es t ra t r ien-17-one

3 -hydroxy- l , 3 ,5 (10 ) -es t r a t r i en -16-one

TRANSFORMATION

degradation [A,B] ( tes tos terone) ; 17ß-O H - > C = 0

degradation [A, B] ( tes tosterone) ; 17/3-O H - » C = 0

degradation [A,B] (4 -androstene - 3 , 1 7 -dione)

degradation [A,B] ( tes tosterone) ; 17/3-O H — C = 0

degradation [A,B] (progesterone)



1

Δ ; enol.

1

Δ ; enol.

1

Δ ; enol.

1

Δ ; enol.

9 ( 1 1 ) Δ ; 14α-Η-+14/3-Η

1

Δ ; enol.

1

Δ ; enol.

1

Δ ; enol.

Δ ; enol. ; 16α-OH— 1 6 - C = 0

Δ ; enol. ; 16/3-OH->16-C=0

YIELD %

2

12

13

—

2-10

—

—

—

-

> 6 0

-

< i

—

-

67

ORGANISM

Nocardia r e s t r i c t u s




Mycobacter ium smegmat i s

Mycobacterium smegmat i s


Corynebacter ium s implex

Septomyxa affinis

Corynebacter ium simplex


Septomyxa affinis


Glomerel la fusaroides


Septomyxa affinis

Nocardia coral l ina



CONSTANTS m.p.° [α]Ό

124-127

128.5-130.5

110-111.5

109-110

110-114

90-93

112-116

—

—

-

237-240

-

250-252

-

-

244.5-246

+ 24[c]

"

+121[c]

—

—

+ 79[c]

+ 86[c]

—

—

-

+29 5 [c]

-

+299[e]

-

-

-

R E F .

W-1063

W-1063

S-895

W-1063

S-821

S-819

S-821

R-762

P-709

Z-1127

Z-1126; Z-1127

B-72

B-72

L-494

R-762

P-709

S-793a

S-793a

S-793a

81

TABLE I


EMPIRICAL FORMULA

C18H2202

1 ^18"22^3

NAME O F REACTION PRODUCT

3 -hyd roxy - l , 3 , 5 (10 ) -e s t r a t r i en -17 -one (estrone)

18 -no r -13a -H- l l j 3 -hyd roxy-1 ,4 -and ro -stadiene -3 ,17-d ione

TRANSFORMATION

3-OAc-^3-OH

3 - O P r ^ 3 - O H

3-OBu^3-OH

17/3-OH—17-C=0

d,I-17/3-OH— d - 1 7 - C = 0 + 1-17/3-OH

1

Δ ; enol. ; 17/3-OH^17-C=0

4 ,

Δ (5α); enol.

1

Δ ; r e v e r s e aldol (formaldehyde t ); enol.

17/3-Ac->17-C=0; 13/3-COOH^13a-H;

Δ1

YIELD %

17

17

18

32

-

50

t r .

95

-

-

—

60

22

-

67

55

-

-

-

—

20

ORGANISM

Saccharomyces ce rev i s i ae



Bac te r ium s te ro id ic las ium

Corynebacter ium sp.

Micrococcus dehydrogenans

P roac t inomyces e ry thropol i s

S t reptomyces albus

St reptomyces d ias ta t icus

St reptomyces r i m o s u s

St reptomyces albus

Baci l lus sphaer icus


Nocardia cora l l ina

Pseudomonas t e s tos t e ron i

Septomyxa affinis


Ar throbac te r s implex


Pseudomonas cruciviae

Pseudomonas dacunhae

Pseudomonas sp.

F u s a r i u m solani

CONSTANTS m.p.° [a]D

-

-

-

254-255

-

254

-

-

-

-

257-259

262-264

258-262

-

253-256

-

-

260-262

260-262

260-262

260-262

260-262

248-251

-

-

-

-

-

—

-

-

-

-

+161

+162[d]

-

-

+154[d]

-

-

-

-

—

*

R E F .

M-539

M-539

M-539

A-23

Z-1133

M-546

T-1034

W-1082

S-835; V-1048

S-835; U-1048

W-1102

G-317

K-487

H-399

L-507; L-508

M-573; W-1072

L-508

M-597

M-597

M-597

M-597

D-169; D-171; M-597

U-1044

82

TABLE I


EMPIRICAL FORMULA

C18H2203


18-£Or-13j3-H-llj3-hydroxy-1,4 -andr ostadiene - 3 , 1 7 -dione

3 , 7 ö - d i h y d r o x y - l , 3 , 5 ( 1 0 ) -e s t r a t r ien -17 -one

3 ,15a -d ihydroxy- l , 3 ,5 (10 ) -e s t r a t r i en -17-one

3 ,16a -d ihydroxy- l , 3 ,5 (10 ) -e s t r a t r ien -17 - one

TRANSFORMATION

17j3-Ac-^17-C=0; 13/3-COOH^13/3-H;

Δ 1

7a -OH

7a-OH; 17/3-OH^17-C=0

15a-OH

15a-OH; 17/3-OH->17-C=0

16a -OH

16a -OH; 17 /3-OH-17-C=0

YIELD %

6

2

15

2 1 0

3

-

-

-

-

32

-

5

5

-

-

-

-

-

-

-

ORGANISM

Fusa r ium solani

Aspergi l lus ca rneus

Glomerel la cingulata



Glomerel la glycines






F u s a r i u m moniliforme







Glomere l la fusaroides

St reptomyces cal ifornicus

St reptomyces hals te dii

S t reptomyces mediocidicus

St reptomyces halstedi i


CONSTANTS m.p.° [α]Ώ

199-202

-

260-262

258-260

258-260

—

-

-

-

232-233

-

228-230

228-230

-

228-230

-

-

214-216

-

-

*

-

+ l l l [ e +117[d

-

-

-

-

-

-

+212[e]

-

+197[e]

+202[e;

-

-

-

-

+175[m]

-

-

R E F .

U-1044

L-497

L-494

L-497

L-494

L-497

L-494

L-497

L-497

L-497

L-497

C-139

L-494

L-497

L-494

L-494

L-497

L-497

L-497

L-491

K-448

K-448

K-448

K-448

83

TABLE I


EMPIRICAL FORMULA

Cx 8H2203

C l 8H2402


3-hydroxy-D-homo-17a-oxa-1,3,5(10)-estratrien-17-one

1,3, 5(10)-estratriene-3,17/3-diol (estradiol)

l-5a-estrene-3,17-dione

4-estrene-3,16-dione

TRANSFORMATION

17/3-Ac—* 17a-oxa-17-C=0; Δ1; enol. 1

Δ ; enol.

1 Δ ; enol.; 17j3-Ac->17/3-OH

17-C=0—170-OH

d,l-17-C=0-+ d-17/3-OH + 1-17-C=0

17-C=0-»17ß-OH; 3-OAc—3-OH

17-C=0^17ß-OH; 3-OPr—3-OH

17-C=0-*17/3-OH; 3-OBu-*3-OH

3-OPr-3-OH

A1; 17/3 -OH -^ 17-C=0

16-C=0; (via 16a-OH and 16j3-OH)

YIELD %

3

-

52

75

-

12

-

-

60-75

70

-

77

—

68

-

-

71

33

33

ORGANISM

Streptomyces lavendulae

Actinoplanes missouriensis

Corynebacterium simplex


Pseudomonas testosteroni

Septomyxa affinis

Septomyxa affinis


Rhizobium sp.

Sac char omy ces cerevisiae

Saccharomyces cerevisiae

Trichomonas gallinae






Pseudomonas testosteroni

Bacillus megaterium

Cephalospor ium acremonium


338-339

-

174-180

171-173

-

-

-

-

-

177-179.5

174

-

177-178

173-174

-

-

173-174

188-189

139.5-149.

~~

-

-

-

-

-

-

-

-

+ 83[e]

-

-

+ 82[e]

-

-

-

-

+221 [c]

5 -

REF.

G-317

M-536

K-487

C-128

L-508

M-573

W-1072

G-317

C-114

W-1085

S-806

S-830; S-829

W-1094; V-1055

M-539

M-539

M-539

M-539

L-508

S-793a

S-793a

84

TABLE I

T r a n s f o r m a t i o n s by Produc t

EMPIRICAL FORMULA

C 1 8 H2 4 0 2

C 1 8 H2 4 0 3


4 -es t r ene -3 ,16 -d ione

4 -e s t r ene -3 ,17 -d ione

9a-hydroxy-A-nor -3-andros tene-2 ,17-d ione

D-homo-17a -oxa -A-no r -3 -andros tene-2 ,17-d ione

6ξ -hyd roxy -B-no r -4 -andros tene-3 ,17-d ione

1 l a -hydroxy-B-nor-4 -andros tene-3 ,17-d ione

10/3,17/3-dihydroxy-l,4-es t rad ien-3-one

1,3, 5(10) - e s t r a t r i e n e -3,6ß,17j3-triol

TRANSFORMATION

1 6 - C = 0 (via 16a-OH and 16j3-OH)

1 6 a - O H ^ 1 6 - C = 0

16/3-OH^16-C=0

17/3-OH—17-C=0

1 7 / 3 - A c ^ l 7 - C = 0

9a-OH; 17/3-OH->17-C=0

17/3-OH— 17/3-oxa-17-C=Q

6ξ-ΟΗ

l i a - O H

1

Δ

6/3-OH

6/3-OH; 17-C=0—17|3-OH

YIELD %

-

-

-

-

-

-

-

2

-

-

-

-

-

76

71

-

36

34

4

32

-

—

ORGANISM

Streptomyces roseochromogenus

Bacil lus mega te r ium

Cephalosporium acremonium







Tr ichomonas gallinae

St reptomyces lavendulae

Bac te r ium eye looxy dans


Mycobacter ium rhodocrous



Pseudomonas t es tos te ron i

Pénic i l l ium c i t r inum

Absidia orchid is

Absidia orchid is


Mor t ie re l la alpina



-

-

-

-

-

-

162-166

170-173

-

163-166

-

-

—

279-280

281-283

-

229-230

210-213

115-180

230-234

-

—

—

-

-

-

-

-

-

-

-

-

-

-

-

-

+ 46[e]

+ 76[c]

-

- 91[c]

+57.5[c]

+ 23[c]

- 28[m]

-

-

R E F .

S-793a

S-793a

S-793a

S-793a

S-793a

S-793a

S-793a

G-317

K-487

S-829

G-317

S-885

S-885

S-*885

S-885

W-1080

| I S-885

L-500; L-502

P-741

P-741

D-150

L - 4 9 3 ; L-497

L-493

85

TABLE I


EMPIRICAL FORMULA

^18"24^3

C18 H24°4


1,3 , 5 (10) -es t ra t r i ene-3 , 7 a , 1 7 ß - t r i o l

l , 3 , 5 ( 1 0 ) - e s t r a t r i e n e -3,15a,17j3-tr iol

1,3,5(10) - e s t r a t r i ene -3,16a,17/3-tr iol

17ß -hyd roxy -4 -e s t r ene -3 ,16 -dione

1 la -hydroxy -4 - e s t r ene -3,17-dione

12ß-hydroxy-4 -es t r ene -3,17-dione

15a-hydroxy-4-es t rene -3,17-dione

16a-hydroxy-A-nor-D-homo-17a-oxa-3 -andros tene -2,17-dione

TRANSFORMATION

7a-OH

7a-OH; 17-C=0-»17ß-OH

15a-OH

15a-OH; 17-C=0— 17j3-OH

16a-OH

16a-OH; 1 7 - C = 0 ^ 1 7 ß - O H

1 6 - C = 0 (via 16/3-OH)

l l a - O H

l l a - O H ; 17ß-OH-*17-C=0

12j3-OH; 17ß-OH->17-C=0

15a-OH; 17ß-OH->17-C=0

16a-OH

YIELD %

3

-

-

-

-

1

21(cr.)

-

-

1-2

1-2; 4

-

-

-

-

-

1

69

9

4

8

10

75

ORGANISM



Glomere l la glycines





F u s a r i u m moniliforme





Glomere l la glycines

St reptomyces hals tedi i


St reptomyces sp.

S t reptomyces halstedi i

Steptomyces mediocidicus

Mycosphaerel la l a t ebrosa

Aspergi l lus ochraceus


Col le totr ichum d e r r i d i s

Fusa r ium o r thoce ra s

Pénic i l l ium sp.

S t reptomyces roseochromogenus


225-257

-

-

-

-

250-251

-

-

248-250

248-250

281-283

281-283

-

-

-

120-130

-

212-214

185-187

200-201

200-201

202-203

-

-

-

-

-

+150[e]

-

-

-

-

+ 56[d]

+ 56[d]

-

-

-

- 90[c]

-

+ 5[c]

+121[c]

+162[c]

+162[c]

-114[c]

R E F .

L-497

L-497

L-497

L-497

L-497

L-497

L-497

C-139

L-497

L-497

L-497

L-494; L-497

L-494; L-497

K-448

K-448

S-788

K-488

K-488

D-149

D-150

D-150

D-152

D-151

D-151

L-503

86

TABLE I

T r a n s f o r m a t i o n s by P r o d u c t

EMPIRICAL FORMULA

C 1 8 H 2 6 0 2

^ 1 8 " 2 6 ^ 3


16a-hydroxy-4-es t ren-3-one

16/3 -hydr oxy -4 - e s t r e n - 3 -one

1/3,17/3-dihydroxy-A-nor-3-andros ten-2-one

3/3-hydroxy-5,6-oxido-B-nor-andr ostan -17 -one

3/3, l l q - d i h y d r o x y - B - n o r - 5 -andros ten-17-one

3/3,X-dihydroxy-B-nor-5-androsten -17-one

17/3-hydroxy-5a-es t rane-3 ,6-dione

6/3,17/3-dihydroxy-4-estren-3-one

10ß, 17/3-dihydroxy-4-estren-3-one

TRANSFORMATION

16a-OH

16/3-OH

16-C=0->16/3-OH

16a-OH-*16/3-OH (via 16-C = 0)

1/3-OH

5 Δ -+5ξ ,6ξ -oxide

11α-OH

X-OH

6/3-OH; Δ 4 ^ Α 5 ; ketoniz0

6β-ΟΗ

10/3-OH

YIELD %

7

-

13

2

-

-

-

-

-

-

-

-

-

17

17

1

-

29

18

16

-

46

19

t r .

1

ORGANISM


Cephalosporium ac remonium











Gnomonia f ragar iae

Rhizopus n igr icans



Rhizopus reflexus

Helminthosporium kusanoi



Rhizopus re lexus

Botryt is paeoniae

Curvular ia lunata

Helminthospor ium buchloes



163-164

-

163-163.5

149-150.5

-

-

-

-

-

-

-

-

-

192-200

110-150

268-270

-

209-213

217-219

-

-

205-210

205-210

209-211

199-205

+ 21[m]

-

+20[m]

+23[m]

-

-

-

-

-

-

-

-

-

+11.5[c]

- 85[c]

- 10[e]

-

- 53[c]

- 63 [m]

-

-

+ 70[c]

+ 70[c]

-

+ 76 [m]

R E F .

S-793a

S-793a

S-793a

S-793a

S-793a

S-793a

S-793a

S-793a

S-793a

S-793a

S-793a

S-793a

L-496

P-741

P-741

P-741

M-623

D-153

P-708

M-642

M-618

D-150

D-150

D-153

P-708; M-642

87

TABLE I


EMPIRICAL FORMULA

C 1 8 H 2 6 0 3

C 18 H 26°4

C18 H28°4

C19 H20°4

C 1 9 H 2 1 ° 3 F

1 ^19"22^"'2

C19H2202C12


11a, 17ß-d ihydroxy-4-es t ren-3 -one

l l ß , 17ß-d ihydroxy-4-es t ren-3-one

12/3,17ß-dihydroxy-4-est ren-3-one

14α, 17ß-d ihydroxy-4-es t ren-3-one

15a, 17ß-d ihydroxy-4-es t ren-3-one

15ξ , 17j3-dihydroxy-4-estren-s ' o n e

16a, 17/3-dihydroxy-4-estr en-s ' o n e

16/3,17ß-dihydroxy-4-esi ren-3-one

3/3, l l a - d i h y d r o x y - 5 | , 6ξ -oxi do - B - nor- andr o stan -17 -one

10/3, l l ß , 17ß- t r ihydroxy-4-e s t r en -3 -one

3 ß , 5 a , 6 ß - t r i h y d r o x y - B - n o r -andros tan-17-one

l l ß - h y d r o x y - 3 , 1 7 - d i k e t o -l , 4 - and ros t ad i en -18 -o i c acid (18-*l l ) - lac tone

6a -fluoro -1 ,4 -andr ostadiene -3 ,11 ,17- t r ione

9a-fluor o -17/3-hydroxy-1,4,6 -andr os ta t r i ene - 3 , 1 1 -dione

1,4 ,7 -andr os ta t r i ene - 3 , 1 7 -dione

9 a , l l ß - d i c h l o r o - l , 4 - a n d r o -stadiene -3 ,17 -dione

TRANSFORMATION

11a-OH

11/3-OH

12ß-OH

14a-OH

15a-OH

1 5 | -OH

16a-OH

16ß-OH

l i a - O H ; Δ5-^5ξ , 6 | -oxide

10/3-OH; l l ß - O H

Δ5->5ξ ,6£ -oxide-> 5a,6ß-diol

1 7 ß - A c - 1 7 - C = 0

Δ1; 1 7 ß - A c ^ l 7 - C = 0

Δ1

1 7 - C = 0 ^ 1 7 ß - O H

Δ1

Δ1

YIELD %

34

4

-

3

19

2

15

-

2

9

-

35

32

2

ca. 1

12

35

-

—

-

ORGANISM

Asper gillus ochraceus


Rhizopus ref lexus

Curvular ia lunata

Col le totr ichum d e r r i d i s

Curvular ia lunata

Helminthosporium buchloes

Mucor gr i seocyanus

Fusa r ium o r thoce ra s

F u s a r i u m o r thoce ra s


Pénic i l l ium ur t icae

Hypomyces auran t ius

Mycosphaerel la l a tebrosa


Curvular ia lunata




Septomyxa affinis

Sac char omy ces ce rev i s i ae

4

Septomyxa affinis

Corynebac ter ium s implex

CONSTANTS m . p . ° [α]Ό

165-166

167-168; 185-187[p]

-

214-219

163-165

-

192-194

-

136-139

136-139

-

185-186

153-154

235-240

-

170-173

320-322d.

-

-

-

- 43[c]

- 46 [c]

-

+ 92[c]

+ 92[c]

-

+ 84[c]

-

+ 95[c]

+ 95[c]

-

+ 30[c]

+ 51[c]

- 18[e]

-

+ 61

-

-

-

R E F .

D-150

P-708

M-618

D-150

D-152

D-150

D-153

M-610

D-151

M-599

D-151

M-639

D-149

D-149; S-950

P-741

D-150

P-741

U-1044

U-1044

P-709

G-305

B-72

G-308

88

TABLE I


EMPIRICAL FORMULA

^19"22^ - ' 3

C 1 9H 2 2 , 0 4

C 1 9 H 2 3 0 3 C 1

^ 1 9 ^ 2 3 ^ 3 **

C 1 9 H 2 3 0 4 F

C 1 9 H 2 4 0 2


1,4 -androstadiene - 3 , 1 1 , 1 7 -t r ione

1 ,4 -and ros t ad i ene -3 ,11 ,17 -t r ione-4C1 4

17/3 -hydroxy - 1 , 4 , 6 - and ro -s t a t r i ene -3 ,11 -dione

14a -hydroxy-1 ,4 -andro -stadiene - 3 , 11 ,17- t r ione

l l /3,17/3-dihydroxy-3-keto-1,4 -andr ostadien-18 -oic acid (18—>11) lactone

9a-chlor o-11/3-hydroxy-1,4-andros tad iene-3 ,17-d ione

6 a - f l u o r o - l l ß - h y d r o x y - l , 4 -androstadiene -3 ,17 -dione

6 /3-f luoro- l l /3-hydroxy- l ,4-andros tad iene-3 ,17-d ione

6a -fluoro -17/3 -hydroxy - 1 , 4 -androstadiene -3 ,11 -dione

12a - f luo ro - l l / 3 -hydroxy- l ,4 -andr ostadiene -3 ,17 -dione

9 a - f l u o r o - l l ß , 17/3-dihydroxy-1,4,6 - andros ta t r i en -3 -one

9a -fluor o - 16a -hydroxy -4 -andr ostene -3 ,11 ,17 - t r ione

1,4 -androstadiene -3 ,17 -dione

TRANSFORMATION

17a-OH-17j3-(20-C= 0 - 2 1 - O H ) - 1 7 - C = 0 ;

Δ1

1 7 / 3 - A c ^ l 7 - C = 0 : Δ1

Δ 1 ; 17a-OH-17j3-(20-C = 0 - 2 1 - O A c ) ^ 1 7 - C = 0

17-C=0—17/3-OH

Δ1

1 1 - C = 0 (probably via 11/3-OH): 14a-OH

l l / 3 - 0 H - * l l - C = 0 ; 14a-OH

Δ 1 ; 17/3-Ac^l7/3-OH

17/3-Ac-^ 17/3-OH

17ß-(20-C=O-21-OH) ^ 1 7 - C = 0 ;

Δ1

Δ1

Δ1

Δ1

A 1 ; 17/3-OH->17-C=0

17-C=0^17/3-OH

16a-OH

Δ1

YIELD %

40

-

96

-

-

-

3

-

-

-

-

-

-

-

47

-

8

-

-

ORGANISM

Septomyxa affinis

Septomyxa affinis

Bacil lus sphaer icus



Pe l l i cu la r i a f i lamentosa

Pe l l icu lor ia f i lamentosa

Fusa r ium solani

Fusa r ium solani

Septomyxa affinis

Septomyxa affinis

Septomyxa affinis

Septomyxa affinis



St reptomyces roseochromDgenus

Actinoplanes mi s sou r i ens i s

Ar throbac te r s implex

Arthrobacter sp .

Bacil lus lentus

Bacil lus pulvifaciens



186-190

-

-

-

300-305do

308-310d. (

305-307

310-314

-

-

-

-

-

-

-

132-135

-

141-143

143-144.5

-

-

-

-

-

+212 : - m , l : l )

-

-

-

-

-

-

-

-

-

-

-

+115[c]

-

R E F .

S-901

W-1072

C-120

G-305

T-955

T-955

T-955

U-1044

U-1044

H-399

P-709

P-709

P-709

R-772

G-305

T-1008

M-536; M-537

M-597

D-171 ; D-170

R-750

1-420

S-942; H-399; H-373

89

TABLE I


EMPIRICAL FORMULA

C 19 H 24 0 2


l , 4 - and ros t ad i ene -3 ,17 -d ione

TRANSFORMATION

Δ1

Δ1

(from laf l 3 , 2/3-H)

Δ4

(from 5a-H)

Δ 1 ' 4

(from 5 Q - H )

17/3-OH-*17-C=0

A 1 ; 17 /3-OH^17-C=0

YIELD %

-

-

-

4

42-44

-

-

-

-

-

-

-

-

-

-

-

-8

-

-

ORGANISM

F u s a r i u m caucas icum

Fusa r ium solani

Mycobacter ium flavum


Pseudomonas sp.

Pseudomonas t e s tos te ron i

Pycnodothis sp .

Septomyxa affinis



Calonectr ia decora

Fusa r ium caucas icum


P ro taminobac te r alboflavum

Pro taminobac te r r u b r u m


Cyl indrocarpon rad ic ico la


Actinoplanes sp .




Corynebac te r ium s implex



-

-

142-143.5

142-143.5

140.5-141 +123[c]

-

-

-

-

145-146 +110[c]

-

-

-

- -

-

-

: :

-

-

-

-

R E F .

V-1056; W-1117; C-97; H-399; W-1116; W-1118

V-1056

C-100

M-597

D-171

L-507; L-508

K-450

W-1072; H-399

B-75a; G-323

L-507; L-508

W-1096

W-1116; V-1056

V-1056

S-866

S-866

L-507; L-508

P-733

P-733

M-537

1-420

H-373

N-665

C-128

W-1118; C-97

90

TABLE I


EMPIRICAL FORMULA

C19H2402


1,4 -andr ostadiene -3 ,17 -dione

TRANSFORMATION

Δ 1 ; 1 7 ß - O H ^ 1 7 - C = 0

Δ 1 ; 17j3-OFo — 1 7 - C = 0

Δ 1 ; 17ß-OAc->17-C=0

Δ 1 ; 1 7 j 3 - O P r - 1 7 - C = 0

3o-OH->3-C = 0 ; Δ1 ' 4 (from 5a-H)

A 1 , 4 ( f rom 5/3-H); 3a -OH-^3-C=0

17 j3 -OH->17-C=0; Δ1,4 (from 5/3-H)

Δ 1 ; 3j3-OH->3-C=0; Δ 5 - Δ 4

YIELD %

-

-

-

-

'-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

45

ORGANISM

Fusa r ium la te r i t ium

Fusa r ium solani

Mycobacter ium f la vu m


Pseudomonas ch lororaphis


Septomyxa affinis





F u s a r i u m la te r i t ium




Fusa r ium solani

Mycobacter ium fortuitum


Mycobacter ium tubercu los i s





4ct inoplanes mi s sou r i ens i s

Bacil lus lentus



- -

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

140-142 + l l l [ c ]

139.5-140

R E F .

C-97

C-97

C-100

H-399

N-648

L-507

S-835; W-1072

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

S-818

S-818

S-818

S-818

S-818

S-818

L-507

M-537; M-536

R-750

T-1027; 1-420

91

TABLE I


EMPIRICAL FORMULA

^19"24^2



TRANSFORMATION

3ß-OH-*3-C = 0 ; Δ5->Δ4

1 Δ ; 3j3-OAc-^3ß-OH;

3jS-OH-*3-C=0; Δ —*Δ

A 1 ; 3/3-OH-^3-C = 0 ; 17 /3-OH^17-C=0; Δ 5 - Δ 4

1 Δ ;

17j3-Ac-*17-C=0

YIELD %

-

-

—

-

-

17

-

-

-

80

-

-

-

-

-

27-37

39

7

ORGANISM






Bacil lus lentus

Baci l lus pulvifaciens

Corynebacter ium Simplex

Calonectr ia decora

Cylindrocarpon rad ic ico la



Fusa r ium la t e r i t ium


Fusa r ium solani




Pycnodothis sp .

Septomyxa affinis

Septomyxa affinis


S t rep tomyces lavendulae


-

-

- -

- -

140-142 +112[c]

139-140 +110[c]

-

145-146 +110

-

145-146 +110[c] +112[a]

140-141

-

-

-

139-140 +119[c]

143-144.5 +115[c]

-

138-139.5 +115[c]

REF .

W-1118

V-1056

S-818

S-818

S-818

R-750

1-420

N-665 ; C-128

V-1053

P-733

V-1056

W-1116; W-1117; W-1118; C-97

C-97

W-1095; V-1056

N-663

S-949; C-97

C-100

S-820

K-450

W-1072

S-901

F-284; F-271

P - 7 3 3 ; P-719

92

TABLE I


EMPIRICAL FORMULA

C19H2402



TRANSFORMATION

A1; A 1 6 - 1 7 - A c ^ l 7 - C = 0

1

A : 16α, 17α -oxido-17/3-Ac—17-C=0

1

A ; 1 la -OH -17/3 -Ac— 1 7 - C = 0

A1; 17j3(-20-C=O-21-OH) ->17-C=0

Δ 1 ; 17ß(-20-C=O-21-F) - 1 7 - C = 0

Δ 1 ; 17a-OH-17j3(-20-C=0-21-OH) — 1 7 - C = 0

A 1 ; 17ß-(20/3-OH-21-H)

- 1 7 - C = 0

« 4 Δ ' ;

Δ — Δ 4 ; 17/3-Ac— 1 7 - C = 0 ; 3 ß - O H - 3 - C = 0

Δ 5 - Δ 4 ; Δ1; Δ 1 6 - 1 7 - Α ο - 1 7 - Ο = 0 ; 3/3-ΟΗ—3-C=0

Δ ^ ' - ί δ α - Η ) ; 17ß-Ac-*17-C=0

Δ1 , 4-(5α-Η); Δ 1 6 -17-Αο-*17-Ο=0

Δ ' ^ - ί δ α - Η ) ; 3j3-OH—3-C=0; 17ß-Ac->17-C=0

Δ ^ ^ ί δ α - Η ) ; 3 /3 -OAc-3-C=0 · 17|3-Ac-»17-C=0

YIELD %

-

-

—

42

-

-

-

40

46

10-15

—

_

-

-

-

-

ORGANISM


Pycnodothis sp.


Septomyxa affinis


Fusa r ium solani


Pycnodothis sp.

Septomyxa affinis

Septomyxa affinis

Septomyxa affinis

Septomyxa affinis



Fusa r ium solani



Fusa r ium solani




Fusa r ium solani

CONSTANTS m . p . ° [ÛÎ]D

-

-

"

"

~

- -

-

-

-

- -

~ -

-

-

-

-

—

R E F .

W-1118

K-450

W-1118

S-901

W-1118; V-1056

V-1056

C-100

K-450

W-1072

S-901

S-901

S-901

C-100

W-1118; V-1056

V-1056; W-1095

W-1118

W-1116; W-1118; V-1056

V-1056; W-1095

W-1118

W-1118

V-1056

V-1056 1

93

TABLE I


EMPIRICAL FORMULA

C19H2402

1 ^19^24^2 *2

C19H2402N2

C 19 H 24°3


l , 4 - a n d r o s t a d i e n e - 3 , 1 7 - d i o n e

1,4 -andr ostadiene - 3 , 1 7 -dione-1-H3

1 7 ß - h y d r o x y - l , 4 , 9 ( l l ) -andros t a t r i en -3 -one

3-hydroxy-2-methy l -1,3,5(10) - e s t r a t r i e n - 17-one

3-hydroxy-4-methyl -1,3,5(10) - e s t r a t r i en -17 -one

16 ,16 -d i f l uo ro - l , 3 ,5 (10 ) -e s t r a t r i e n e - 3 , 1 7 a - d i o l - 3 -methyl e ther

16 -d i azo -4 -and ros t ene -3 ,17 -dione

17ß-hydroxy-1 ,4 -andro -stadiene -3 ,11 -dione

2 -hyd roxy -1 ,4 - and ro -s tad iene-3 ,17-d ione

6 o -h y d ro xy -1 ,4 - and ro -stadiene -3 ,17 -dione

6ß -hyd roxy -1 ,4 -and ro -stadiene -3 ,17 -dione

1 l a - h y d r o x y - 1 , 4 - a n d r o -stadiene - 3 , 1 7 - dione

TRANSFORMATION

17ß-(2' -isooctyl) - 1 7 - C = 0 ; 3ß-OH-> 3-C = 0 ; Δ*—Δ«; Δ ' Δ1

17-C=0-^17ß-OH

A1(2a-CH3); enol . ; 1 7 ß - O H - 1 7 - C = 0

Δ1; enol.; 17ß-OH->17-C=0

1 7 - C = 0 - ^ 1 7 ö - 0 H

3ß-OH—3-C=0; Δ 5 ->Δ 4

A 1 ; 17ß-Ac->17ß-OH

A 1 ; 17α-ΟΗ-17β(-20-C = 0 - 2 1 - O H ) - ^ 17β-ΟΗ

Δ 1 , 4 - ( 5 α - Η ) ; 1 7 ß - A c ^ l 7 ß - O H

Δχ-(2α-ΟΗ); 17ß-OH->17-C=0

Δ 1 -(2α-ΟΗ); 2o-OAc-»2a-OH; 17ß-OAc->17-C=0

Δ 1 -(2β-ΟΗ); 2ß-OAc->2ß-OH; 17ß-OAc-*17-C=0

3ß-OH->3-C = 0 ; Δ 5 - Δ 4 ; Δ 1 ; 6α-ΟΗ

3β-ΟΗ—3-C=0; A W ; Δ 1 ; 6β-ΟΗ

11α-ΟΗ

1 7 ß - A c ^ l 7 - C = 0

Δ1 ; Π α - Ο Η ; 1 7 ß - A c ^ l 7 - C = 0

YIELD %

-

—

55

17

13

35(cr„)

-

—

9

29

-

13

-

-

"

"

37

~

14

ORGANISM

No card ia sp.



Septomyxa affinis

Septomyxa affinis

F lavobac ter ium dehydrogenans

Flavobacter iu m dehydrogenans

Septomyxa affinis

Septomyxa affinis

Hypomyces haematococcus

Septomyxa affinis








Sporot r ichum bombycinum

Fusa r ium javanicum

Septomyxa affinis

F u s a r i u m javanicum


-

—

145-148

243-244

244-247

111-113

217-218

—

208-210d.

233.5-2340

-

148-150

-

~

255-259

200-204

212-214

190-192

-

-

- 28[dl

+167[cl

+147[c]

+ 48[d]

-112[dl

-

5 +169

-

+ 67[c]

-

-

—

"

-

+86. 5[c]

+ 79[c]

R E F .

W - l l l l

B-75a

R-775

P-731

P-731

R-774

R-763

W-1072

S-901

M-574

M-574

G-318; H-373

H-399

H-399

H-399

H-399

M-536; M-537

M-536; M-537

M-582

F-276

W-1072

F - 2 7 8 ; F-274

94

TABLE I


EMPIRICAL FORMULA

C19H2403


1 l a - h y d r o x y - 1 , 4 - a n d r o -stadiene -3 ,17 -dione

l l / 3 - h y d r o x y - l , 4 - a n d r o -s tadiene-3 ,17-dione

1 4 a - h y d r o x y - l , 4 - a n d r o -stadiene -3 ,17 -dione

D - h o m o - 1 7 a - o x a - l , 4 - a n d r o -stadiene -3 ,17 -dione

TRANSFORMATION

170-OH->17-C=O

Δ1

A 1 ; 17/3-Ac-^17-C=0

A 1 ; 17/3-(20-C=O-21-O H ) - 1 7 - C = 0

17α-ΟΗ-17β-(20-C = 0-21-OH)-> 1 7 - C = 0

1

17α-ΟΗ-17β-(20-C=0-21-OH)-> 1 7 - C = 0

Δ1

1

Δ 5 - ^ Δ 4 ; Δ ;

3 /3 -OH^3-C=0 ; 14α-OH

Δ1

17-C=0->17a-oxa-1 7 - C = 0

17/3-OH-*17a-oxa-1 7 - C = 0

A 1 ; 17 -C=0-»17a -oxa -1 7 - C = 0

A 1 ; 17j3-OH-*17a-oxa-1 7 - C = 0

YIELD %

-

70-80 ( c r . )

-

55

—

-

-

60

-

-

-

-

-

-

-

-

-

-

ORGANISM



Septomyxa affinis

Septomyxa affinis

Pseudomonas chlororaphis




Bacil lus lentus

Cylindrocarpon radic icola





Fusa r ium solani

Septomyxa affinis





Hypomyces solani

Septomyxa affinis


-

176-179

-

185-186

—

-

284-287d„

207.5-208

219-220

-

-

-

-

216-218

-

-

-

-

-

-

—

-

—

-

-

+ 69[ai

- 45

-4901

-

-

-

-

- 46[c]

-

-

-

-

-

R E F .

M-536

C-128 ; N-666 ; N-667

W-1072

S-901

N-648

N-648

1-420

S-792; 1-420

R-750

P-733

W-1095

P-733

C-97

C-97

C-97

W-1072

F - 2 6 9 ; F - 2 7 4 ; F-284

C-97

C-97

C-97

L-525

W-1072

95

TABLE I


EMPIRICAL FORMULA

^ 1 9 " 2 4 ^ 3


D - h o m o - 1 7 a - o x a - l , 4 - a n d r o -s tad iene-3 ,17-d ione

TRANSFORMATION

1 7 ß - O F o ^ 17a -oxa -17 -C=0

1 Δ ;

17/3-OAc— 17a -oxa -17 -C=0

1

Δ ; 17 /3 -OPr^ 17a -oxa -17 -C=0

17ß-Ac-> 1 7 a - o x a - 1 7 - C = 0

A 1 ; 17a-OH-17/3-Ac^ 1 7 a - o x a - 1 7 - C = 0

Δ 1 ; 17/3-(20-C=O-21-O H H 1 7 a - o x a - 1 7 -

c=o A 1 ;

17/3-(-20-C=O-21-F) -+17a-oxa -17-C=0

A 1 ; 17α-ΟΗ-17β-(20-C = 0 - 2 1 - O H H 17a-oxa=17=C=0

YIELD %

-

-

-

-

-

-31-50

-

33

-

75

-

21

-19

60

20

35

ORGANISM









Fusa r ium solani





Fusa r ium solani


Septomyxa affinis

Septomyxa affinis

Septomyxa affinis

Fusa r ium solani

Fusa r ium solani

Septomyxa affinis



-

-

-

-

-

-218-219

~~

220-222

-

213-215

-

-

221-223

~

-

~

-

-

-

-

-

-- 44[c]

-

- 47[cl

-

- 44[c]

-

-

-

-

-

-

REF.

C-97

C-97

C-97

C-97

C-97

C -97

C-97

C-97

C-97

F - 2 6 9 ; F - 2 7 4 ; F - 2 8 4 ; P-733

E-202 ; C-97 ; W-1116

F - 2 7 4 ; F-278

C-97

K-462; N-663

S-949; C-97

S-901

W-1072

S-901

K-462

S-901

S-901

F - 2 6 9 ; F - 2 7 5 ; F-284

96

TABLE I


j EMPIRICAL FORMULA

C 19 H24°3


D-homo-17a -oxa -1 ,4 - and ro -s tadiene-3 ,17-dione

1 Iß , 17ß-dihydroxy- l , 4 ,6 -andros ta t r i en-3-one

9 ,10 - seco-3 -hydroxy-1,3, 5(10)-andros ta t r iene-9,17-dione

1 -5a -andros t ene -3 ,11 ,17 -t r ione

TRANSFORMATION

17α-ΟΗ-17β-(20-C=0-21-OH)-> .17a-oxa-17-C=0

1

Δ 5 - Δ 4 ; ' 3ß-OH->3-C = 0 ; 17j3-(20-C=O-21-O A c ) - 4 7 a - o x a - 1 7 -c=o Δ 1 , 4 - ( 5 α - Η ) ; 17ß-Ac-+17a-oxa-1 7 - C = 0

17-C=0->17ß-OH

1 Δ ; reVc a ldol ; enoL

9a-OH; Δ 1 ; r ev . a ldol ; enol.

9a-OH; Δ1; r ev . aldol; e n o l ; 17/3-O H - 1 7 - C = 0

9α-ΟΗ;Δ*; rev0 aldol; enol. ; 17β-A c ^ l 7 - C = 0

9α-ΟΗ;Δχ; Δ 5 -+Δ 4 ; 3ß-OH-> 3-C = 0 ; reve aldol; enol0

9a-OH; 3 a - O H ^ 3 - C = 0 ; Δ 1 , 4 - ( 5 α - Η ) ; reVo aldol; enol„

9a-OH; 3 a - O H - > C = 0 ; Δ 1 Μ - ( 5 β - Η ) ; r ev . aldol; enol.

1 7 ß - A c - > 1 7 - C = 0 ; Δ1

YIELD %

-

46

10

ca0 20

-1

26

1

<1

—

ORGANISM

Pseudomonas ch lora raphis

Fusa r ium solani



Ar throbac te r sp .


Ar throbac ter sp .




Pseudomonas sp.



Mycobacter ium sp .

Mycobacter ium spc

Mycobacter ium sp .

Septomyxa affinis


~

-

123-129

122-129

120-126

145.5-147

124-129

122-124

123.5-125

122-124

—

—

—

-

+ 96[cl

-

-

--

+100.5[c

—

-

~

"

R E F .

N-648

K-462

W-1116

G-305

D-170;

D-172

K-473 D - 1 7 1 ; M-597

D-172; M-597

M-597

S-895;

D-169; D - 1 7 1 ; M-597

W-1063

S-820

S-818

S-818

S-818

W-1072

TABLE I


97

EMPIRICAL FORMULA

C19 H24°3

C19 H24 04


l - 5 a - a n d r o s t e n e - 3 , 1 1 , 1 7 -t r ione

1 - 5j3 -andr ostene - 3 , 1 1 , 1 7 -t r ione

9û, 1 l a -oxido -4 -andr ostene -3,17-dione

4 -andr os tene - 3 , 6 , 1 7 - t r ione

4 -andr ostene - 3 , 6 , 1 7 - t r ione -7-H3

4 -andr ostene - 3 , 1 1 , 1 7 - t r ione

unknown

1 l a -hydr oxy-D-_homo -17a-oxa -1 ,4 -andr ostadiene -3,17-dione

15a -hydr oxy -D-homo -17a -oxa -1 ,4 -and r ostadiene -3,17-dione

16a -hydr oxy -D-homo-17a-oxa -1 ,4 -andr ostadiene -3,17-dione

3 ,18 -d ihyd roxy -9 ,10 - seco -1,3,5(10)-andr o s t a t r i e n e -9,17-dione

14a-hydroxy-4-andros tene -3 ,11 ,17 - t r ione

TRANSFORMATION

17/3-Ac-*17-C=0

17ß-Ac->17-C=0; Δ1

1 Δ ;

1 7 ß - A c - 1 7 - C = 0

Δ —>9α,11α-oxido

6 - C = 0

6 - C = 0 (via 6j3-OH)

llj3-OH— 11-C = 0

17/3-OH^17~C=0

1 7 j 3 - A c ^ l 7 - C = 0

17α-ΟΗ-17β-( 2 0 - C = O - 2 1 - O H ) ^ 17-C = 0

17a-OH-17/3-( 2 0 - C = O - 2 1 - O A c H 1 7 - C = 0

unknown

17/3 -Ac -> 1 7 a - o x a - 1 7 - C = 0 ; 11a-OH

15a-OH

16a-OH

A 1 ; r ev . aldoL enolQ

14a-OH

YIELD %

28-45

-

5-10

53

-

2

-

-

-

-

-

-

-

0 .3 -5

< 1

42

45

~

ORGANISM

Septomyxa affinis

Septomyxa affinis

Septomyxa affinis

Nocardia sp.

Euglena g rac i l i s

Rhizopus a r r h i z u s

Gibberel la saubinett i


Aspergi l lus o ryzae

Gliocladium catenulatum

Pénic i l l ium expansum


Pénic i l l ium l i lacinum










2440 5-246.5

-

174.5-177.5

273-275

-

205-208

-

-

-

-

-

-

-

284-287

251-253

260-262

196-198; 213-214

148-150

"

+188[c]

-

+205[c]

+180[c]

-

-

-

-

-

-

-

-

-

-

- 58[c]

- 55[c]

- 68[c]

+ 91[c]

"

REF.

E -207 ; M-573

W-1072

E-207 ; M-573

S-886

G-322

B-32

U-1043

S-829

C-102

M-633

M-637

M-633

M-637

M-633

M-637

T-1027

F - 2 7 4 ; F-278

D-158; P-706

T-1000; P-706

K-473

K-473

98

TABLE I


EMPIRICAL FORMULA

C 19 H 24 0 4

C19H2502F

C 1 9 H 2 5 ° 3 F

C19H2504F

C 19 H26°2


14a-hydroxy-4-androstene -3 ,11 ,17- t r ione

15a-hydroxy-4-androstene -3 ,11 ,17- t r ione

6a - fluor o - 17a -methyl -1,3, 5(10) - e s t r a t r i ene -3,17j3-diol

9a-fluoro-ll j3,17/3-dihydroxy-1,4 -andr ostadien - 3 -one

12a-fluoro-l l /3,17/3-d ihydroxy-1 ,4 -andro -Stadien-3-one

9a -fluoro -1 1/3 -hydroxy -4 -andros tene-3 ,17-d ione

9a- f luoro- l l /3 ,16a-d ihydroxy-4 -andr ostene -3 ,17 -dione

1 7 ß - h y d r o x y - l , 4 - a n d r o -s tadien-3-one

TRANSFORMATION

14a-OH; l l / 3 - O H ^ l l - C = 0

n-c=o

Δ ; enoL

17-C=0^17/3-OH

Δ1

17 j3 -Ac-17-C=0

16a-OH

Δ1

17-C=0-*17/3-OH

A 1 ; 1 7 - C = 0 - 1 7 ß - O H

YIELD % -

~

-

-

-

58(cr0)

57(cr . )

21

-

-

---

--

---

84

82

-

-

-

ORGANISM

Pel l i cu la r ia f i lamentosa

Pe l l i cu la r ia fi lamentosa

Septomyxa affinis




St reptomyces roseochromogenus






Fusa r ium solani




Ramula r i a robus ta

Septomyxa affinis

Volutella ci l iata

Saccharomyces ce rev i s iae





CONSTANTS m . p . ° [û?]D

301-304do

199-201

-

_

—

260-262

280-282

262-270

159-165

165-167

-

---

--

---

168

163-167

-

-

-

+263 | c ; m - l : l ]

-

-

-

—

+ 177[c'|

+173[c|

+ 157[m]

-

~

-

---

--

----

-

—

-

-

R E F .

T-955

T-955

C-93

# - 6 6 6

R-772

T-996

T-1008

B-62

N-665

C-128

C-97

C-97

C-97

S-873

H-399

L-507

L-525

W-1072

L-525

D-143

C-128

S-829

C-97

C-97

99

TABLE I


EMPIRICAL FORMULA

| C19H2602


17/3 -hy dr oxy -1 ,4 - and ro -s tadien-3-one

TRANSFORMATION

Δ 1 ; 17-C = 0 - 1 7 / 3 - O H

4

Δ ; 17-C=0->17ß-OH

Δ 1 , 4 - (5β-Η)

Δ 1 , 4 - ( 5 α - Η ) ; 1 7 - C = 0 - 1 7 / 3 - O H

1 5 4

Δ ; Δ —Δ ; 3/3-OH-3-C = 0

ι Δ ; 17/3-AC-17/3-OH

1

Δ ; 17j3-(20j3-OH-21-H) ^17/3-OH

Δ ; 17a-OH-17/3-Ac^ 17/3-OH

ι Δ ; 17/3-(20-C=O-21-

ΟΗ)-17/3-OH

1

Δ ; 17/3-(20-C=O-21-F) ->17β-ΟΗ

1

Δ ; 17a-OH-17/3-(20-C= 0-21-OH)->17ß-OH

YIELD %

Γ -

-

-

-

-

7

-

-

-

-

--

8

18

12

~

50

14

20

11

<ι

ORGANISM

Fusa r ium solani


Pseudomonas tes tos te roni

Septomyxa affinis


Pseudomonas tes tos te ron i






Fusa r ium solani

Fusa r ium solani


Septomyxa affinis

Septomyxa affinis



Septomyxa affinis

Septomyxa affinis


Septomyxa affinis

Septomyxa affinis

Septomyxa affinis

Septomyxa affinis


_

-

~

-

-

-

164-166 4-25|c |

-

-

-

-

167-168

-

172-173 + 23

-

167-168 +21[c ]

~ ~~

-

— -

- _

REF.

C-97

C-100

L-508

W-1072

L-508

L-508

L-508

N-665 ; C-128

P-733

C-97

C-97

C-97

N-663

C-100

W-1072

S-901

F - 2 8 4 : F -271 : P-733

C-100

W-1072

S-901

C-100-

W-1072

S-901

S-901

S-901

100

TABLE I


EMPIRICAL FORMULA

C19 H26 0 2


1-5« -andr ostene -3 ,17 -dione

1 -5/3 -andr ostene -3 ,17 -dione

4 -andros tene-3 ,17-d ione

TRANSFORMATION

1 Δ

Δ1 - ( la-H2)

ΔΧ-(1α-Η3)

1

* ; 17/3-OH-17-C=0

Δ 4 - 5 β - Η

1 7 ß - O H - 1 7 - C = 0

3j3-OH— 3 - C = 0 ; Δ 5 - Δ 4

YIELD %

-

-

-

-

80

6

-

-

-

—

-

-

-

-

47

-

-

-

1

-

18

-

47

-

87

ORGANISM





Clos t r id ium paraputr i f icum

Aspergi l lus oryzae


Cladosporium r e s inae




Fusa r ium solani



Proac t inomyces ery thropol i s

Pseudomonas chlor or aphis



Wojnowicia graminis

Acetobacter pas teur ianu m


Corynebacter ium helvolum


Flavo bac te r ium androstenedionicum



-

-

-

-

168-169

167-169

-

-

-

-

-

-

-

-

171

-

-

-

160-167

173

169-170

-

167-169

-

168-169

-

-

-

-

+222[el

-

-

-

-

-

-

-

-

-

-

-

-

-

-

_ +198[c]

+216[c]

-

-

-

-

R E F .

H-373

R - 7 6 8 ; R-769

G-323 ; B-75a

H-373

S-824

K-482

1-420

F-254

C-128

C-97

C-97

C-97

H-399

P-737

T-1032

N-648

L-508

S-829

H-381

K-457

T-1027 ; 1-420

M-546

N - 6 6 5 ; C-128

E-219

E-214

101

TABLE I


EMPIRICAL FORMULA

C19H2602


4-andros tene -3 ,17-d ione

TRANSFORMATION

3 /3 -OH^3-C=0 ; Δ —»Δ

3/3-OAc->3-C=0; Δ5->Δ4

3 ß - O H - 3 - C = 0 ; Δ 5 - Δ 4 ; 17/3-OH-*17-C=0

3a -OH->3-C=0 ; Δ4-(5α-Η)

3 a - O H ^ 3 - C = 0 ; Δ4-(5β-Η)

17ß-OH->17-C = O j Δ4-(50-Η)

1 7 / 3 - A c ^ l 7 - C = 0

YIELD %

70

-

-

96

84

-

40

18

4

6

76

-

-

-

-

-

-

-

-

—

ORGANISM

"Milan y e a s t "



Mycobacter ium tuberculos is

P roac t inomyces ery thropol is

St reptomyces globisporus

Streptomyces v i r idochromogenes


Corynebacter ium sp0

Fla vo bac te r ium androstenedionicum

Fla vo bac te r ium carboni l icum

Micrococcus denydrogenans


S t reptomyces globisporus

St reptomyces v i r idochromogenes



My cobacter ium tubercu los i s





Aspergi l lus cheval ie r i

CONSTANTS m.p.° [ a ] p |

168-169

_

-

169

171-172 +192[cl

- -

165-169

170-171

167-168

170

- -

~ —

- -

- -

— —

-

-

-

-

"

R E F .

M-552

S-818

S-818

S-818

T-1032

H-335

H-335

C-128

Z-1133

E-220 ; E-219

M-592

E-217

T-1032

H-337

H-337

S-818

S-818

S-818

S-818

S-818

S-818

L-508

C-102

102

TABLE I


EMPIRICAL FORMULA

C19H2602


4-andros tene-3 ,17-d ione

TRANSFORMATION

17j3-Ac—17-C=0

17/3-Pr->17-C=0

17a-OH-17j3-Ac-17-C = 0

17j3-(20-C=O-21-O H ) - 1 7 - C = 0

YIELD %

-

-

-

-

-

-

-

-

-

-

4

-

-

-

-

16

~

-

-

-

-

-

ORGANISM

Aspergi l lus f la vus



Cephalosporium subver t ic i l la tum

Cladosporium re s inae

C ylindr o cephalu m aureum



Fusa r ium solani



Nocardia sp.

Pénic i l l ium brevicompactum

Pénic i l l ium chrysogenum


Pénic i l l ium frequentans



Pénici l l ium stecki i


Pycnodothis sp.




Cylindrocephalum aureum

CONSTANTS |m.p.° H D

-

-

-

-

-

-

-

-

-

174-176 +194[c]

169-171

170-172

-

- -

-

175-176.5 +194[cl

_

-

-

-

— —

-

1

R E F .

P-726

C-102

H-398

B-67

F-254

S-880

C-97 ; W-1116

C-97

C - 9 7 ; S-949

P-726

M-633

D-172

M-637

C-102

C-102

M-637

M-637

P - 7 2 6 ; S-832

C-102

C-102

K-450

M-633

C-102

M-637

S-880

103

TABLE I


EMPIRICAL FORMULA

^ 1 9 " 2 6 ^ 2

C^HjjgOjjFa

1 C19H2603


4 -andr ostene -3 ,17 -dione

16,16-di f luoro-17a-hydroxy-4-andros ten-3-one

11α, 1 Iß -dihydroxy - 1 , 4 -androstadien -3 -one

l l ß ,17 j3 -d ihyd roxy- l , 4 -andr os tadien-3-one

TRANSFORMATION

17/3-(20-C=O-21-OH) - 1 7 - C = 0

17/3-(20-C=O-21-OAc)-->17-C = 0

17ß-(20-C=O-21-OPr ) -*17 -C=0

17a-OH-17j3-(20-C=0-21-OH)-> 1 7 - C = 0

1 7 0 - A c - 1 7 - C = O ; Δ4-(5ο-Η)

17ß-(2' -isooctyl) - 1 7 - C = 0 ; 3 /3 -OH-3 - C = 0 ; Δσ->Δ4 17-C=0->17a-OH; 3 / 3 - O H - 3 - C = 0 ; Δ 5 - Δ 4

l i a - O H

l l a - O H ; 17/3-(20-C=O-21-OH) —17/3-OH

1

Δ ; 17j3-Ac->17/3-OH

1

Δ ; 17j3-Ac->17/3-OH; l l a - O H

1

Δ ; 17/3-Ac->17/3-OH

YIELD %

-

-

-

-

-

-

-

-

-

—

-

-

-

-

-

46

59

44

~

—

ORGANISM


Pénic i l l ium nigr icans

Gliocladium del iquescens

Gliocladium luteolum

Gliocladium r o s e u m

Pénici l l ium canescens

Pénic i l l ium char les i i

Pénic i l l ium lividum


Didymella lycopers ic i



Pénic i l l ium li lacinum



Nocardia sp.

Flavo bac te r ium dehydrogenans

Sporotr ichum sulfurescens

Spror t r i chum epigaeum


Septomyxa affinis


Septomyxa affinis


-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

190-193

174-175

—

183-185

183-185

-

-

-

-

-

-

-

-

-

-

-

-

-

-

- ■

+ 64[d]

- 7[cl

-

- 15[cl

"

REF.

M-633

M-637

M-633

M-633

M-633

M-637

M-637

M-637

S-880

V-1048

M-633

V-1048

M-637

N-648

W-1116

W - l l l l

R-774

M-582

M-582

W-1072

W-1072

F - 2 7 4 ; F-278

W-1072

104

TABLE I


EMPIRICAL FORMULA

C 19 H26°3


11/3,17j3-dihydroxy-1,4-androstadien-3 -one

12a, 17/3-dihydroxy-4,14-andros tadien-3-one

5a-andr o s t a n e - 3 , 6 , 1 7 - t r i o n e

5ß -andros t ane -3 ,6 ,17 - t r ione

5a -andr ostane -3 ,11 ,17 - t r ione

5/3-andr o s t ane -3 ,12 ,17 - t r i one

3 ,17/3-dihydroxy-9,10-seco-1,3, 5 (10) -andros ta t r ien-9-one

3 ,9a -d ihydroxy-9 ,10 - seco -1 ,3 ,5(10)-andros ta t r ien-17-one

3 ? 9/3-dihydroxy-9.10-seco-1,3, 5(10) -andros ta t r ien -17-one

3 9 9ξ -dihydr oxy -9 ,10 - seco -1,3, 5(10)-andros ta t r ien-17-one

TRANSFORMATION

17/3-(20-C=O-21-OH) -17j3-OH

14

12a-OH 4 5

Δ ->Δ ; ketoniz0

6-C = 0 ; 3/3-OH-3-C = 0 ; Δ 5 ->5α-Η

6 - C = 0 ; Δ4~>5α-Η

1 7 ß - A c - 1 7 - C = 0

17/3-Ac->17-C=0

17 |3 -Ac-17 -C=0

9a-OH; Δ 1 ; r ev . aldol. ; enol. ; 1 7 - C = 0 - 1 7 ß - O H

9α-OH; Δ 1 ; rev„ aldoL ; enolc ; 9 - C = 0 — 9 a - O H ; 17j3-OH-*17-C=0

9a-OH; Δ 1 ; r ev . aldol. ; enoL ; 9-C=0->9ß-OH; 17 /3 -OH-17-C = 0 3/3-OH—3-C=0; Δ 5 - > Δ 4 ; Δ 1 ; 9α-OH; rev„ aldol0; enoliz. ; 9 -C=0—9ξ -OH

3a -OH->3-C=0; Δχ»*-(5α-Η); 9a-OH; r ev . a ldo l . ; enoliz. ; 9 - C = 0 - 9 £ - O H

3a -OH—3-C=0 ; Δ1?4-(5/3-Η); 9α-ΟΗ; r ev . aldol. ; enoliz.; 9 - C = 0 - 9 £ - O H

YIELD %

13

< 1

-

7-9

-

-

-

-

-

-

< 1

< 1

7(cr„)

-

-

-

-

-

ORGANISM

Septomyxa affinis

Wojnowicia graminis





Pénic i l l ium novae zeelandiae




Pseudomonas sp.


No cardia r e s t r i c t u s







My cobacter ium fortuitum



156

166-168

-

196-196.5

195-196

-

-

-

-

-

133-134

195-197

155-157

-

-

-

—

-

-

+136[c]

-

+79.5[c]

-

-

-

-

-

-

+ 16[c]

+ 48[e]

+ 90[el

-

-

-

-

-

R E F .

S-901

H-381

1-420

T-1027; 1-420

M-604

M-633

M-637

M-633

M-637

M-637

D - 1 7 1 ; M-597

W-1063

W-1063

S-818

S-818

S-818

S-818

S-818

S-818

S-818

S-818

105

TABLE I


EMPIRICAL FORMULA

^19"26^3


3 , 9 | - d i h y d r o x y - 9 , 1 0 - s e c o -1,3, 5(10) -andros ta t r ien -17-one

17ß-hydroxy-4-andros tene -3,11 -dione

17/3 -hydroxy -4 -androstene -3,16-dione

lö -hydroxy-4-andros tene -3,17-dione

1/3 -hydroxy -4 -androstene -3 ,17-dione

2a-hydroxy-4-andros tene -3,17-dione

2/3 -hydroxy -4 -andros tene -3,17-dione

6/3 -hydroxy -4 -andros tene -3,17-dione

TRANSFORMATION

3a -OH->3-C=0 ; Δι>4(5/3-Η); 9α-ΟΗ; rev . aldol. ; enoliz.; 9 - C = 0 ^ 9 £ - O H

17/3-Ac— 1 7 - C = 0 ; Δ 1 ; 9a -OH; r ev . aldol. ; enoliz.; 9 -C=0->9£-OH

1 7 - C = 0 ^ 1 7 ß - O H

1 7 ß - A c ^ l 7 ß - O H

1 6 - C = 0

1 6 - C = 0 ; 1 7 - C = 0 - 1 7 ß - O H

la -OH

la -OH 3j3-OH-*3-C=0; Δ 5 - Δ 4

Iß-OH

2a-OAc-*2a-OH; 1 7 ß - O A c - 1 7 - C = 0

2ß-OH

2 ß - O A c ^ 2 ß - O H ; 1 7 ß - O A c ^ l 7 - C = 0

6ß-OH

YIELD

% i

< 1

62

-

94

12

-

51

3

12

7

3

10(cr.)

25

1

-

-

-

-

-

ORGANISM




Tr ichomonas foetus


Asperg i l lus oryzae

Neocosmospora vas infecta

Pénic i l l ium notatum

Wojnowicia g ramin i s

Cor t ic ium centrifugum

Pénic i l l ium sp0


Haplosporel la sp .

Xylar ia sp0







Septomyxa affinis

Aspergi l lus niger



CONSTANTS m . p . ° [ e ] p |

177-180

-

-

-

-

182-184

153-155

161-162.5

21505-218

216-218

155-156.5

_

143-145

-

-

-

194-195

-

+182[a]

-

-

-

-

+200[c] +183.5ja]

- 54[c]

- 66[c]

+184[c]

+127.5[c]

+126 [c]

_

- 37[c]

-

-

-

+109

-

R E F .

S-818

S-820

H-385

S-830

S-830; S-829

C-102

S-881

H-336

H-381

D-166

D-163 ; D-167; D-168

D-163 ; D-168

D-165

D-165

H-399

H-399

D-163; D-167; D-168

H-399

H-399

H-399

H-399

F-288

C-97

C-97

106

TABLE I

T ransformat ions by Product

EMPIRICAL FORMULA

C19H2603


6/3-hydroxy-4-androstene -3,17-dione

6/3 -hydr oxy -4 -androstene -3 ,17-d ione-6a ,7£-H 3

la-hydroxy-4-androstene -3,17-dione

7/3 -hydroxy -4 -androstene -3,17-dione


TRANSFORMATION

6/3-OH

3 /3 -OH^3-C=0; Δ 5 - Δ 4 ; 6/3-OH

17/3-Ac->17-C=0

17/3-Ac->17-C=0; 6/3-OH

17/3-(20-C=O-21-OH) - 1 7 - C = 0 ; 6/3-OH

17/3-(20-C=O-21-OAc) ^ 1 7 - C = 0 ; 6/3-OH

17α-ΟΗ-17β-(20-C=0-21-OH) — 1 7 - C = 0 ; 6/3-OH

6/3-OH

la -OH

7β-ΟΗ

9α-OH

9α-OH; 17/3-OH-17-C=0

17/3-Ac->17-C=0

YIELD %

13

4

8(cr0)

-

-

2(cr0)

< 1

-

-

1

-

-

-

-

"

12(cr„)

4

10

< 1

-

10

10

31

17

52

ORGANISM

Fusa r ium solani


Haplosporel la sp.



Rhizopus ref lexus

Wojnowicia graminis



Pénici l l ium ci t r inum



Gliocladium del iquescens

Gliocladium luteolum




Diplodia nata lens is

Neurospora sp.

Haplosporel la sp .

Pseudomonas sp.

Rhizopus stolonifer

Xylar ia sp.


Nocardia sp.

Ascochyta linicola

Circinel la muscae


CONSTANTS m . p . ° [of]D

192-19305 +107[cj

183-187

191-194 + 9 9 f c |

-

-

~

194-195 +11505[c]

-

-

190-192 +107[c]

-

-

-

-

~ ~

185-187

255-256.5 +164[c]

225.5-22805

221-225

220.5-222.5 +186

218-223

-

223.5-224.5 +183[c|

218-220

223-224

R E F .

C-97

U-1043

D-165

E-201

E-201

E-201

H-381

T-1027; Ï-420

M-633

M-637

M-633 ; P-726

M-633

M-633

M-633

M-633

M-633

B-32

T-997

T-1037

D-165

D - 1 7 1 ; M-597

T-1037

D-165

S-898; P-740

D-170; D-172; M-597

S-828

R-748

D-172

107

TABLE I


EMPIRICAL FORMULA

^ 1 9 " 2 6 ^ 3



1 la -hydroxy-4 -andros tene -3,17-dione

1 la -hydroxy-4 -andros t ene -3 ,17-d ione-6a ,7£-H 3

1 Iß-hydroxy -4 -andr ostene -3,17-dione

14a-hydroxy-4-andr o s t ene -3,17-dione

15a -hydroxy -4 -andros tene -3,17-dione

TRANSFORMATION

9a-OH; 17j3-Ac-»17-C=0

11a-OH

1 7 ß - A c - 1 7 - C = 0

A 1 6 -17-Ac->17-C=0; l l a - O H

1 7 a - O H - 1 7 ß - A c -1 7 - C = 0

17a-OH-17ß-(20-C = 0 - 2 1 - O H H 1 7 - C = 0

l l a - O H

1 7 ß - O H - 1 7 - C = 0

17a-OH-17ß- (20-- C = 0 - 2 1 - O H H 1 7 - C = 0

14a-OH; 17/3-OH-* 1 7 - C = 0

14a-OH; 3/3-OH—3-C=0;

17ß-Ac->17-C=0

17ß- (20 -C=O-21-OH)->17-C=0

17a-OH-17ß-(20-C = 0 - 2 1 - O H H 1 7 - C = 0

15a-OH

YIELD %

7

< 1

19-23

-

-

20

-

-

-

-

19

-

-

2

4

5-11

-

—

-

-

33-50

ORGANISM


Pseudomonas sp.



Rhizopus ref lexus




Pénic i l l ium thomii






Wojnowicia g ramin is






Fusa r ium la t e r i t i um

Fusa r ium lini


220-222

212-216

226-227

-

-

-

-

-

-

-

216-225

-

—

246-252

260-261.5

252-258

-

~

-

-

190-198

-

-

+162[c]

-

-

-

-

-

-

-

-

-

—

+166[c]

+162[c]

-

-

—

-

-

+217[cl

R E F .

S-885

D - 1 7 1 ; M-597

M - 6 0 1 ; M-604; E-201

M - 6 0 1 ; E-201

E-201

C-102

S-832

V-1048; S-835

M-637

M-637

M-637

B-32

S-829

N-648

H-381

1-420; S-792; T-1027

M-637; E-204

M-637

M-637

C-97

C-97

G-319; T-980

108

TABLE I

T r a n s f o r m a t i o n s by P roduc t

EMPIRICAL FORMULA

Ο , , Η , Α


15o-hydroxy-4 androstene -3,17-dione

15^-hydroxy-4-andros tene-3,17-dione

16a-hydroxy-4-androstene -3,17-dione

19-hydroxy-4-androstene -3.17-dione

17a -oxa-D-homo-4 -andros tene-3 .17-d ione

TRANSFORMATION

15a-OH

15ö-OH:

17/3-OH >17-C=0

Ι7α-ΟΗ-Ι7β-(20-C=0-21-OH) > 1 7 - C = 0

15,3-OH

16Q-OH

19-OH

17-C=0-> 17a -oxa -17 -C=0

17j3-OH-> 17a -oxa -17 -C=0

17ß-OAc-> 17a -oxa -17 -C=0

YIELD %

~

2

21

-

—

4

-

-

-

25

-

-

-

-

-

-

80

34

-

-

-

-

-

-

ORGANISM

Fusa r ium oxysporum

Fusa r ium solani

Gibberella baccata

Gibberel la saubinetti

Fusa r ium lini


Xylar ia sp.

Staurophoma sp.

St reptomyces argenteolus

St reptomyces calii 'ornicus

Streptomyces olivaceus


St reptomyces v i r id i s

Cort ic ium mic rosc l e ro t i a




Fusa r ium solani



Pythium ul t imum




Fusa r ium solani

Fusa r ium sp.


-

-

195-196

-

-

192-197

180-183

185-187

-

-

185-187

-

165

-

-

-

-

211-212

203-208

-

-

-

-

-

—

-

-

-

-

-

+136[c]

+194[c|

-

-

+194[c]

-

+180[c]

-

-

-

-

-

+ 51[c]

-

-

-

-

-

—

R E F .

M-599

C-97

U-1043

U-1043

G-319

N-648

D-165

H-397

F-265

L-491

F-265

F - 2 6 5 ; F - 2 8 8 '

F-265

H-350

H-398

C-97

C-97

C-97

P-737

S-846

S-846

P-737

C-97

C-97

C-97

C-97

109

TABLE I


EMPIRICAL FORMULA

Cl 9H2 e03


17 a-oxa -D-homo -4 -andro -s t ene-3 ,17-d ione

TRANSFORMATION

1 7 0 - O P r -17a -oxa -17 -C=0

17/3-OFo-17a -oxa -17 -C= 0

17/3-Ac-1 7 a - o x a - 1 7 - C = 0

17a-OH-17/3-Ac— 17a -oxa -17 -C= 0

17/3-(20-C=O-21-OH) —17a-oxa-17-C=0

YIELD %

-

-

-

-

60-65

73

-

-

50

-

-

-

70

-

-

-

-

-

-

-

-

60

-

ORGANISM

Fusa r ium sp .

F u s a r i u m sp.

Aspergi l lus flavipes

Aspergi l lus flavus

Aspergi l lus cheval ier i



Aspergi l lus sp.

Cephalosporium ac remonium

Cephalosporium subver t ic i l la tum

Collybia dryophila

F u s a r i u m sp.

Pénic i l l ium adametzi





Pythium ul t imum

Plutus granular is

Asperg i l lus flavus



Pythium ul t imum



Pythium ul t imum

Rhizopus suinus

Γ CONSTANTS

π ΐ · Ρ · 0 [<*]ρ|

-

-

207-209

210-212

-

202-206

-

-

-

-

-

-

-

207-209

-

-

-

-

-

-

-

~

-

203-206

-

+ 43[cl

+ 43fc]

-

+ 42|c]

-

-

-

-

~

-

-

+ 43[cl

-

-

-

-

-

-

-

-

—

-

+ 40[c]

R E F .

C-97

C-97

F-270

P-726

C-102

K-461

C-102

C-104

H-398

B-67

S-825

C-97

P-726

F-284

S-846

S-832; P-726

C-99 ; C-102

S-846; S-849

S-825

P-726

C-102

S-846

S-846; S-849

K-461

S-846

S-846; S-849

W-1095

110

TABLE I


EMPIRICAL FORMULA

C 1 9 H - 6 0 3

C19H2G°1


17a-oxa-D-homo-4-andro-s tene-3 ,17-d ione

3/3-hydr oxy -5 - andros tene -7,17-dione

1,3,5(10) - e s t r a t r i ene -3,6/3,17/3-triol 3-methyl ether

13a-hydroxy-13 ,17-seco-1,4 -androstadiene -16 -carboxylic acid

1/3,6 j3-dihydroxy-4-andro-s t e n e - 3 , 17-dione

6/3, 9Ö-d ihydroxy-4-andro-s tene-3 ,17-d ione

6/3,11/3-dihydroxy-4-andro-s tene-3 ,17-d ione

6/3, X-dihydroxy-4-andro -s tene-3 ,17-d ione

9a, 12a -dihydroxy -4 -andro -s tene-3 ,17-d ione

9a, 14a-dihydroxy-4-andro -s tene-3 ,17-d ione

9a, 15/3-dihydroxy-4~andro-s tene-3 ,17-d ione

9a, 18-dihydroxy-4-andro -s tene-3 ,17-d ione

11a, 14a-dihydroxy-4-andro-s tene-3 ,17-d ione

11/3,14a-dihydroxy-4-andro -s tene-3 ,17-d ione

11/3,15a-dihydroxy-4-andro -s tene-3 ,17-d ione

TRANSFORMATION

3/3-OH-3-C = 0 ; Λ 5 -> Δ-i ;

17ß-(20-C=O-21-OAc) ->17a-oxa~17-C = 0

7-C = 0

6/3-OH

17a-oxa-17-C=0-> 17 ,17a-seco-13a-OH-16-COOH

1/3-OH; 6/3-OH

6/3-OH

6/3-OH

6/3-OH

6/3-OH; X-OH; 3/3-OH-»3-C = 0 ; Δ 5 - Δ 4

9a-OH

12a-OH

9a-OH; 12a-OH

9a-OH

14a-OH

9a-OH; 14a-OH

9a-OH

15/3-OH

9a-OH; 15/3-OH

18-OH

9a-OH; 18-OH

11a-OH

11/3-OH

l l ß - O H

YIELD %

35

5

15

-

2

-

t r .

20

t r .

-

-

-

-

-

-

-

-

-

-

-

-

ORGANISM


Rhizopus spc

Fusa r ium moniliforme


Xylar ia sp.



Rhizoctonia solani


Cercospora melonis

Cercospora melonis

Cercospora melonis

Cercospora melonis

Cercospora melonis

Pe l l i cu l a r i a f i lamentosa

Cercospora melonis

Cercospora melonis

Cercospora melonis

Cercospora melonis

Cercospora melonis

Cercospora melonis

Pe l l i cu la r ia f i lamentosa


Cunninghamella elegans

Pe l l i cu la r i s f i lamentosa


243-24405

190-192

-

237-239

225-227 [

275-284

271-273

-

253-257

—

243-247

241-244

-

236-238

224-226

-

-

218-220

215-216.5

—

- 83[c]

+ 45[m|

-

+ 68[c]

+ 77 c -m, 1:1]

+132

+ 86 [m]

-

+214[c]

—

+ 137[c]

+139[c]

-

+ 138[c]

+144[d]

-

-

-

+217 c - m , 1:1]

R E F .

K-461

D-175

C-139

H-398

D-165

T-955

U-1043

U-1043

T-1027; S-792

K-473

K-473

K-473

K-473

K-473

T-955

K-473

K-473

K-473

K-473

K-473

K-473

T-955

T-955

U-1043

T-955

I l l

TABLE I


EMPIRICAL FORMULA

C19H2604

^19"28^2


11/3,15a-dihydroxy-4-andro-s tene-3 .17-d ione

2 ß - hy dr oxy -17a - oxa - D -_homo -4 -andros tene -3 ,17-d ione

6j3-hydroxy-17a-oxa-D-homo-4 -andr ostene -3 ,17 -dione

7a-hydroxy-17a-oxa-D-homo-4 -andr ostene -3 ,17 -dione

l l a - h y d r o x y - 1 7 a - o x a - D -homo-4-andr o s t e n e - 3 , 1 7 -dione

16a-hydroxy-17a-oxa-D-homo -4 -andr ostene - 3 , 1 7 -dione

5a -andr ostane -3 ,17 -dione

5/3 -andr ostane -3 ,17 -dione

17/3- hy dr oxy - 3a, 5a -cvc lo-andros tan-6-one

17ß -hydroxy-5a - l - and ro -s ten-3-one

17a-hydroxy-4-andros ten-3-one

17/3-hydroxy-4-androsten-3-one ( testosterone)

TRANSFORMATION

15a-OH

2/3-OH

6/3-OH

7a-OH

17ß-Ac-> 1 7 a - o x a - 1 7 - C = 0

16a, 17a -oxido-17/3 -A c - 1 6 a - O H - 1 7 a -o x a - 1 7 - C = 0

Δ4—5α-Η

d,l - 3 a - O H -d - 3 - C = 0 + l - 3 a - O H

17 /3 -Ac-17-C=0

1 7 / 3 - A c - 1 7 - C = 0 ; 3/3-OAc—3-C=0

Δ4 -5/3-H

Δ ->5ß-H

1 7 ß - A c - 1 7 - C = 0

17 -C=0-17 /3 -OH

1 7 - C = 0 - 1 7 / 3 - O H

3/3-OH—3-C=0; Δ 5 - * Δ 4

17-C=0^17/3-OH

YIELD %

28

5

27

30

—

-

~

-

-

-

-

-

76

-

-

50

83

80

-

-

8.5

ORGANISM




Coniothyrium helleborine

Coniothyrium hel leborine



St reptomyces g r i seus

Pseudomonas sp.


Fusa r ium solani



Bacil lus putr if icus

Clos t r id ium paraput r i f icum

Pénic i l l ium canescens





Streptomyces globisporus

St reptomyces v i r idochromogenes

Chlorel la pyrenoidosa

CONSTANTS m . p . " [or]D

221 222

180-182

235-236

275-280

-

_

...

130-132

-

-

-

-

130-131

-

-

182-183

158-159

215-218

-

-

150-152.5

+222|c |

-182 |c |

- 1 3 [ c |

+ 27[c|

-

-

-

+ 109

-

-

-

-

-

-

-

-

- 4 2 l e l

+ 68 |e |

-

-

-

REF.

U-1043

L-496

T-1036

F-282; F -281 ; ! T-994 |

T-994; F-282; ! F-281

S-832

E-195

V-1059

W-1102

V-1056

V-1056; W 1095

V-1056

V-1056

M-545

S-824

M-637

B-81

B-78

H-337

H-337

H-337

H-337

G-321

112

TABLE !


EMPIRICAL FORMULA

C 1 9 H2 8 0 2


17/3-hydroxy -4 -androsten -3-one ( testosterone)

TRANSFORMATION

1 7 - C = 0 - 1 7 ß - O H

5 4

Δ ->Δ ; 17 -C=0-17 j3 -OH

3 j 3 - O H - 3 - C = 0 ; Δ 5 ^ Δ 4

3/3-OAc—3-C=0; Δ 5 - Δ 4 ; 17-C=0^17/3-OH

17|3-Ac—17j3-OH

YIELD %

~

-

-

60-75

-

-

-

91

41(cr0)

-

-

78

-11

64

-

68

7.5

-

-

-

-

-

-

ORGANISM

Euglena grac i l i s

Fusa r ium sp.

Hydrogenomonas facilis

Pénici l l ium sp.

Rhizobium sp.



Saccharomyces fragil is




Acetobacter pas teur ianum


Corynebacter ium sp„

Flavobacter ium carboni l icum



Proac t inomyces ery thropol is

St reptomyces globisporus

St reptomyces vi r idochromogenes


Cephalospor ium ac remonium



F u s a r i u m sp.


CONSTANTS m . p . ° [ûf]D

-

-

-

-

150-151

152-154 +109[e|

-

-

144-147

151

152 +108[el

152-154 +109[e]

-

151

151

-

-

152-154 +109[e]

-

-

-

-

-

-

R E F .

G-322

C-97

F-228

H-336

C-114

M-543; M-550

H-335; H-337

M-572

S-829; S-830

H-381

M-551

K-457

H-337

Z-1133

M-592

E-217

H-337

T-1032

H-335

H-335

C-102

H-398

F-254

S-880

C-97

S-881

113

TABLE I


EMPIRICAL FORMULA

C19H2802

C19H2803


Tes tos te rone

3/3-hydroxy-5-androsten-17-one

17/3-hydroxy -5a -androstane -3,6-dione

l a -hydroxy - 5a -androstane -3,17-dione

1 l a - hydroxy - 5a -androstane -3,17-dione

11a-hydroxy-5/3-androstane -3,17-dione

9 , 1 0 - s e c o - l , 3 , 5 ( 1 0 ) - a n d r o -s ta t r iene-3 ,9ß ,17 /3- t r io l

l a , 17ß-dihydroxy-4-andro-s ten-3-one

2a, 17ß-dihydroxy-4-andro-s ten-3-one

2/3,17ß-dihydroxy-4-andro-s ten-3-one

TRANSFORMATION

17ß-Ac-17ß-OH

1 7 a - O H - 1 7 ß - A c -17ß-OH

17ß-(20-C=O-21-OH) - 1 7 ß - O H

17/3-(20-C = O - 2 1 -OAc)-»17/3-OH

17ß-(20-C = O - 2 1 -O P r H 1 7 ß - O H

3ß-OAc->3ß-OH

1 7 ß - A c - 1 7 - C = 0

1 7 ß - B u - 1 7 - C = 0

3-C = 0 - A 4 -5 a - H - 3 , 6 - d i - C = 0 ; (via 6/3-OH; Δ4 —► Δ5 ; ketoniz. )

l a -OH

l a - O H ; Δ 4 - 5 α - Η

l l a - O H

l l a - O H

17-C=0—17/3-OH; 9a -OH; Δ 1 ; rev . aldol.; enol. ; 9 - C = 0 -9/3-OH

la -OH

2a-OAc -2a-OH; 17ß-OAc -17/3-OH

2ß-OH

YIELD %

-

62

--

—

-

69

-

-

-

-

-

6

7

1

-

-

t r .

t r .

-

—

ORGANISM





Pénic i l l ium spc

Cylindrocephalum au reum

Neocosmospora vasinfecta


C y lindr o c ep halu m au reum



Fusa r ium solani


Rhizopus ref lexus


Pénic i l l ium sp0

Sporotr ichum epigaeum

Sporotr ichum sul furescens




Septomyxa affinis


CONSTANTS m . p . ° [ a ] D

-

154-155

—

:

-

153.5-155.5

-

-

-

-

-

233-234

211-21305

204-206

-

-

171.5-172.5

239-240

-

-

-

+110[el

-

-

-

+108[c|

-

-

-

-

-

- 9[c]

+110[c]

+114[cl

-

-

+ 19[el

-

-

R E F .

S-832

H-336

H-336; C-102; C-99

C-102

H-336

S-880

S-881

S-881

S-880

S-829

V-1056

V-1056; W-1095

M-633

E-201; M-623

D-163

D-163

M-582

M-582

W-1063

T-1036

H-399

H-399

L-496

114

TABLE I


EMPIRICAL FORMULA

^ 1 9 " 2 8 * ^ 3


2/3,17ß-dihydroxy-4-andr ei-s ten-3-one

6ß, 17/3-dihydroxy-4-andro-s ten-3-one

9a, 1 7/3- dihydr oxy -4 -andr o-s ten-3-one

1 l o , 17/3 -dihydr oxy -4 -andr o -s ten-3-one

11/3,17/3-dihydr oxy-4-androsten -3-one

12/3,17/3-dihydr oxy-4-andros ten-3-one

14a, 17/3-dihydr oxy-4-andros ten-3-one

TRANSFORMATION

2/3-OAc^2/3-OH; 17/3-OAc-17ß-OH

6/3-OH

9a-OH

9a-OH; 17/3 -Ac — 17j3-OH 11a-OH

17-C = 0 -17 j3 -OH

17/3-Ac^ 17/3-OH

11a-OH; 17/3-Ac—17/3-OH

11a-OH; 17a-OH-17/3-(20-C = 0-21-OH)— 17/3-OH

17-C=0-17 /3 -OH

12/3-OH

1 7 - C = 0 -17/3-OH

14a-OH

YIELD %

-

-

11

-

-

6

3

14

10

-

1

—

-

11

43

90

45

-

-

50

50

86

-

38

ORGANISM



Septomyxa affinis

F u s a r i u m r o s e u m




Rhizopus ref lexus

Wojnowicia graminis

Ascochyta linicola

Bac te r ium cyclooxydans

Circ inel la muscae

Nocardia sp0




Rhizopus ref lexus

Tr ichomonas gaLlinae









Mucor gr iseocyanus

CONSTANTS m . p . ° [o?]D

-

-

212-214

-

-

216-222

205;215-218

196-197

209-211

197-199

—

-

181-181.5

181-181.5

-

-

-

-

178-182

-

121-125°d

117-119

183.5-186

-

-

+ 30[c]

-

-

+ 32[c]

+ 29[c]

+ 79[dl

+103[c]

+104[c'

—

-

+ 93[c]

+ 93[c]

-

-

-

-

+ 90[c]

-

+120[c]

+124[c]

R E F .

H-399

H-399

H-399

R-747

T-1036

E-201

E-201

E-201; M-618

H-381

S-828

S-898; P-740

R-748

D-172

V-1048; S-835

E-201

E-201; M-601

E-201

S-830; S-829

C-102

S-832

H-336

M-582

M-582

S-830; S-829

T-1036

R-749

E-204; M-610

115

TABLE I


EMPIRICAL FORMULA

C 1 9 H2 8 0 3

C1 9 H2 8 0 4


14a, 17ß-dihydroxy-4-andr ei-s ten-3-one

15a, 1 7/3 -dihydr oxy -4 -andr o -s ten-3-one

15/3,17/3-dihydroxy-4-andro-s ten-3-one

16a, 17ß-dihydroxy-4-andro-s ten-3-one

16/3,17/3-dihydroxy-4-andro-s ten-3-one

3ξ, 19-d ihydroxy-4-andro-s ten-17-one

l a , 3ß -d ihyd roxy -5 -and ro -s ten-17-one

3β, 7α-dihydroxy-5-andro-s ten-17-one

3ß, 7/3-dihydr oxy-5-andr o-s ten-17-one

11a, 17/3-dihydr oxy-17a-me thy l -4 -e s t r en -3 -one

l a , 6 ß , 1 7 ß - t r i h y d r o x y - 4 -andros ten-3-one

13a-hydroxy-3-ke to-13 ,17-seco -4 -and ros t ene -16 -car boxy lie acid

TRANSFORMATION

17/3-Ac^ 17/3-OH

15a-OH

15/3-OH

17-C=0->17ß-OH

16a-OH

1 6 a - 0 H ; 1 7 - C = 0 - 1 7 ß - O H

3ß-OH-->3-C = 0 ; Δ 5 - Δ 4

17ß-Ac-17ß-OH

16/3 -OH

16/3-OH; 1 7 - C = 0 - 1 7 ß - O H

19-OH

la -OH

7a-OH

7/3-OH

11a-OH

l a - O H ; 6/3-OH

17a-oxa -17-C=0-+ 13 ,17 - seco -13a -OH-16-COOH

YIELD %

-

8

-

-

4

40(cr.)

-

-

42

-

-

-

-

5

7(cr.)

-

24

-

18

12

-

t r .

-

ORGANISM


Fusa r ium lini

F u s a r i u m udum

Pénici l l ium ur t icae



Pes ta lo t ia funer ea


St reptomyces sp.

Wojnowicia graminis

Wojnowicia graminis

Corynebacter ium mediolanum



Wojnowicia graminis

Cort ic ium centrifugum

Hypochnus sasaki i



Fusidium sp.

Rhizopus sp„

Rhizopus sp.


Penci l l ium sp.




-

102-110; 204-206

199-201

199-201

216-218

220-222

183-184

183-184

-

183-187

-

191-192

182-184

183-184

179-182

183.5-185.5

-

288-290

275-277

181.5-183.5

214-216

-

256-260

-

-

+136fm|

+153[c]

+155[c]

+ 67(el

+ 57[e|

+ 76[c]

+ 76

-

+ 63[dl

~

+ 80[c|

+ 66[c]

+ 76

+101[c] + 94[d]

+103[cl

-

+ " M +31.5[e

+ H[c l

- 71[cl

+67.5[c]

-

+ 19[m|

REF.

S-881

T-980; G-319

M-599

M-639

T-1036

H-382

F-266

F-288

S-788

H-381

H-381

A-\

F-271

F-288

H-381

D-166

S-869

D-163; D-168

G-293

D-175

D-175

D-175

M-608

T-1036

H-398

H-398

116

TABLE I


EMPIRICAL FORMULA

ί C1BH,80,

C1 9 H: i 0 O2

^ 1 9 ^ 3 0 ^ 3

C19H30U4

C19n32U2


13a-hydroxy-3-ke to-13 .17-seco-4-andros tene-16 -carboxylic acid

17/3-hydroxy-5/3-andr ostan -3-one

3a-hydroxy-5a-andros tan -17-one

3/3 -hydroxy -5a -andr ostan -17-one

3a -hydr oxy -5/3 -androstan -17-one

5 -androstene -3 ß, 17ß-diol

1α, 3/3-dihydr oxy -5α -andro -s tan-17-one

3α, l la -d ihydroxy-5/3-andro-stan-17-one

δξ-andros tane-X, 16α, 17/3-t r io l

X, 16α, 17/3-trihydroxy-4-androsten -3-one

5a-andros tane-3a , 17ß-diol

5a-androstane-3/3,17/3-diol

TRANSFORMATION

1 7 - C = 0 - 1 3 , 1 7 -seco-13a-OH-16-COOH

17/3-OH-13,17-s e c o - 1 3 a - O H - 1 6 -COOH

17/3-Ac-13 ,17-seco-13a-OH-16-COOH

Δ -»5/3-H

17/3-Ac-17/3-OH

Δ 4 - 5 α - Η ; 3-C = 0 - 3 a - O H

3-C = 0 - 3 / 3 - O H

Δ 4 - 5 α - Η ; 3-C = 0 -3/3-OH

17a-OH-17/3-(20a-OE-21-H)—17-C = 0

Δ ' - Η ; Δ 4 - 5 / 3 - Η ; 3 - C = 0 - 3 a - O H

17-C=0-17 /3 -OH

1 7 - C = 0 - 1 7 / 3 - O H ; 3ß-OAc-*3/3-OH

l a - O H ; Δ —5a-H; 3-C=0->3ß-OH

17a-OH-17/3-Ac-17-C = 0

16a-OH; Δ 4 - 5 ξ - Η ; 3 - C = 0 - > ?

16a-OH; X-OH

Δ 4 - 5 α - Η ; 3 - C = 0 — 3 a - O H ; 1 7 - C = 0 - 1 7 / 3 - O H

3 - C = 0 - 3 / 3 - O H ; 17 -C=0-17 /3 -OH

YIELD %

2

-

-

-

-

70

-

-

-

-

4

18

86

-

-

1

-

3

-

ORGANISM



Pénici l l ium li lacinum




Pénici l l ium sp0

Bacil lus putrif icus




Streptomyces g r i seus

Gliocladium ro seum

Clostr idium paraputr i f icum

Fusidium sp„


Tr ichomonas foetus





Wojnowicia graminis

Pes ta lo t ia funerea




138.5-139.5

-

-

-

-

139

-

-

-

-

180,5-183

178-179

-

-

-

200-201

-

196-199

279-286

-

163-164

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

+ 93[c]

-

+ 10[d] + 10[c]

-

-

R E F .

H-398

H-398

P-737

P-737

H-398

H-398

H-398

M-545

S-881

G-322

V-1059

V-1059

M-633

S-824

D-175

M-549; M-543

S-830

S-829

S-829

D-163

M-637

H-381

F-266

G-322

V-1046; M-543

117

TABLE I


EMPIRICAL FORMULA

^19"32^2

C^H^OaF

C20 H24°3

1 ^20"24^4

C20H24O5

C 2 0 H 2 5 O 2 F

C20H25O3F

^20 "26^2



5ß-andros tane-3a , 17/3-diol

5j3-androstane-3a, 17ß-diol

1 la -ethinyl -6a -f luor 0 -l , 3 , 5 ( 1 0 ) - e s t r a t r i e n e -3,17/3-diol

6 a - m e t h y l - l , 4 - a n d r o s t a d i e n e -3 ,11 ,17 - t r ione

1 6 ß - m e t h y l - l , 4 - a n d r o s t a -d i ene -3 ,11 ,17 - t r i one

3-hydroxy-19-nor - l ,3 ,5 (10)~ p regna t r i ene-11 ,20-d ione

3 ,1 la -dihydroxy -19 -nor-1,3,5(10) -pregnat r iene -11,20-dione

3 ,21 -dihydroxy -19 -nor-1 ,3 ,5(10)-pregnat r iene -11,20-dione

3 ,1 la, 21 - tr ihydroxy -19-nor -1,3,5(10) -pregnat r iene -11,20-dione

6a-f luoro-17ß-hydr o x y - H a -rne t hy l -1 ,4 ,9 (11 ) - and ro -s t a t r i en -3 -one

9a -f luor 0 -1 Iß -hy dr oxy -16a -methyl -1 ,4 -andr ostadiene -3,11-dione

2 -methyl -1 ,4 -androstadiene -3,17-dione

16a-methyl-17j3-hydroxy-l , 4 , 9 ( l l ) - a n d r o s t a t r i e n -3-one

17ß-hydroxy-17a-methyl-l , 4 , 9 ( l l ) - a n d r o s t a t r i e n -3-one

TRANSFORMATION

Δ 1 - Η ; 3-C=0-+3ß-OH

Δ ' - Η ; 3 - C = 0 - 3 ß - O H ; 17-C=0->17ß-OH

Δ 5 - 5 α - Η ; 3 - C = 0 - 3 ß - O H ; 17-C=0-»17j3-OH

Δ*—5/3; 3 -C=0-*3a-OH

17-C=0-»17ß-OH

1 Δ j enol.

1 Δ ;

1 7 ß - A c - 1 7 - C = 0 1

Δ

1 Δ ; enol.

1 Δ ; enol.

1 Δ j enol.

1 Δ ; enol.

1 Δ

17-C=0->17ß-OH

Δ (2a-methyl) ; 17/3-OH — 17-C = 0

1 7 - C = 0 - 1 7 ß - O H

1 Δ

YIELD %

6

24

73

-

-

~

9

-

-

43

—

-

-

-

-

-

—

37

ORGANISM





Clost r id ium t e r t ium

Tr ichomonas vaginalis

Septomyxa affinis

Septomyxa affinis


Corynebacter ium hoagii












163

163

163-164

229-230

-

-

—

274-276d

-

-

229-232

~

—

—

"

—

-

172-174

136-139 (solvate)

-

—

+ 4

+ 24[el

-

-

-

+230[c]

-

-

+324[dl

—

-

-

~

-

-

- 46[d

- 52[dl

R E F .

B-80

B-80

M-551

S-823

S-823

S-830

C-93

R-780

R-752

H-386

B-73

H-386

H-386

H-386

G-308

R-752

H-373

R-775

R-775

G-308

118

TABLE I


EMPIRICAL FORMULA

C20H26O2

^ 2 θ " 2 6 ^ 2 ^ I2

^ 2 0 " 26^3

C2 0 H2 6 O4

^ 2 0 " 26^5

C 2 0 H 2 7 O 2 F

C^H^OgF


16 -méthylène -4 -andr ostene -3,17-dione

D-nor-1 ,4 -pr egnadiene -3,20-dione

3 -hydroxy-19-nor - l ,3 ,5 (10) -pr e gnatr ien - 2 0 - one

9a, l l /3-dichloro-17/3-hydroxy -1 la -methyl - 1 , 4 -androstadien-3 -one

17/3-hydroxy-6a-methyl - l ; 4 -androstadiene -3 ,11 -dione

1 l a -hydroxy - 16a - methyl -l , 4 - a n d r o s t a d i e n e - 3 , 1 7 -dione

11/3,17/3-dihydroxy-17a-methy 1 - 1 , 4 , 6 - andr 0 -s t a t r i en-3-one

l , 3 ,5 (10 ) -e s t r a t r i ene -3 ,17 /3 -diol 17-acetate

11a -hydroxy-D-nor -1 ,4 -pr e gnadiene - 3 , 2 0 - dione

3 , l l /3 -d ihydroxy-19-nor -1,3, 5(10) -pre gnatr i en -20-one

3 , l l / 3 ,17a - t r ihydroxy-19-n o r - 1 , 3 , 5(10) -p regna t r i en -20-one

3 , l l j 3 ,21 - t r ihydroxy-19-nor -1,3,5(10) -p regna t r i en-20-one

3 ,7 ,12- t r iketo-5/3-andro-stane-17/3-car boxy lie acid

3 , l l j 3 ,17a ,21- t e t r ahydroxy-1 9 - n o r - l , 3 , 5(10)-pregna-t r i en -20-one

17a, 21 - dihy dr oxy -18 - nor- 4 -pre gnene -3 ,11 ,20 - t r ione

6a -fluoro-17/3 -hydroxy -17a-methyl-l ,4-androstadien-3-one

9a-f luoro- l l /3 ,17ß-dihydroxy-16a-me thy 1-1,4-andr 0 -s tadien-3-one

21 -f luor 0 -11 j3 -hydroxy - 1 9 -nor-4 -pre gnene -3 ,20 -dione

TRANSFORMATION

3/3-OH-*3-C = 0 ; Δ 5 - Δ 4

1

Δ

1

Δ ; enol.

Δ 1

1 Δ ;

17/3-Ac^ 17/3-OH 1

Δ

l l / 3 - O A c - l l / 3 - O H ; 17/3-OAc-17/3-OH

1

Δ ; enol.

l i a - O H

1

Δ ; enoL

1

Δ ; enol.

1

Δ ; enoL

17/3-CH(CH3)CH2-C H 2 C O O H -17j3-COOH

1

Δ ; enol.

21-OH

1

Δ

17-C=0-+ 17/3-OH

l l ß - O H

YIELD %

63

-

62

20

—

26

—

-

59-79

-

—

-

-

t r .

-

-

-

~

ORGANISM

Flavo bacter ium dehydrogenans


Coryne bacter ium simplex



Septomyxa affinis


Flavobacter ium dehydrogenans






P roac t inomyces erythropol is


Colletotr ichum lindemuthianum

Septomyxa affinis


Curvular ia lunata


161-162

193-194

238-240

242-244

-

209-210

-

-

218-222

227-230

-

-

-

240

-

-

-

—

-

+110[d]

+164[c]

-

-

+148[cl

-

-

-

+ 7 7 W

-

-

-

-

-

-

—

R E F .

B-76

R-763

B-73

G-317

G-308

R-780

R-752

G-305

K-487

R-763

H-386

H-386

H-386

T-1034

H-386

A-10; A-13

C-93

R-752

R-755

119

TABLE I


EMPIRICAL FORMULA

^ 2 0 " 2 8 ^ 2

C2 0 H2 8 O3


17 ß - hydroxy-17a-methyl -1,4 -andr ostadien -3 -one

1 -methyl -1 -5a -and ros t ene -3,17-dione

D-nor-4 -pregnene -3 ,20 -dione

1 l a , 17/3 -dihydroxy -1 la -m e t h y l - l , 4 - a n d r o s t a d i e n -3-one

11/3,1 7/3 -dihydroxy -17a-methy l -1 ,4 -andros tad ien -3-one

3 -keto -4 -andr ostene -17/3 -carboxylic acid

17/3-hydroxy~17a-methyl-4-andros tene-3 ,16-d ione

6β-hydroxy-A-nor -3-pregnene-2 ,20-d ione

la -hydr oxy -A -nor-3 -p regnene-2 ,20-d ione

9a - hy dr oxy - A - n o r - 3 -pregnene-2 ,20-d ione

1 l a -hydr oxy -A -nor-3 -p regnene-2 ,20-d ione

TRANSFORMATION

ϊ Δ

M l / 3 - C H 3 ) ; 17/3-OH— 17-C = 0

3/3-OH-*3-C=0; Δ 5 - * Δ 4

l i a - O H

1

Δ

17j3-CH(CH3)CH2-CH2COOH — 17/3-COOH

17j3-CH(CH3)CH2 CH2CH2CH(CH3)2 - 1 7 ß - C O O H

1 6 - C = 0

6ß-OH

7a-OH

9a-OH

11a-OH

YIELD %

21

-

-

-

39

-

-

-

75(cr0)

-

-

-

-

33

_

t r0

tr .

-

6(cr0)

27

44

5

28

ORGANISM


Baci l lus lentus



Flavobacter ium sp0

Hypomyces solani

Ramula r i a robus ta


Septomyxa affinis

S te reum fasciatum

Volutella ci l iata





Septomyxa affinis



Curvular ia lunata

Aspergi l lus nidulans

Cokeromyces r ecu rva tus

Diplodia na ta lens is




-

162-163

-

163-164

-

-

-

164-166

169-171

164-166

-

-

153-155

250-253

262-265

-

245

-

217-219

214-215

161-161.5

227-229

183-184

-

0

-

0|c]

-

-

-

- 3 | c |

0 | c |

0[c|

-

-

+ 209|c]

- 33[c]

+ 40|cl

-

-

-

+ 24|c]

+ 65 | c |

+ 94|cl

+ 93|c]

REF .

M-536

R-750

N-665; N-667a

V-1052; W-1096

1-430

L-525

L-525

L-508

W-1072; E-205

T-959

L-525

H-373

R-763

E-205; M-582

G-305

E-206

T-1034

T-1034

S-950

T-1006; W-1076

L-503a

W-1078; L-502

W-1079

W-1076; T-1006

120

TABLE I


EMPIRICAL FORMULA

| C2 0 H2 8 O3

C 2 0 H2 8 O4

^ 2 0 " 2 8 ^ 5

C 2 0 H 2 9 O 2 C 1

C 2 0H 3 0O 2

C 2 0H 3 0O 2 S

^ 2 0 " 3 0 ^ 3


16a -hydroxy -A -nor-3 -pregnene-2 ,20-dione

21 -hydr oxy -A -nor- 3 -pregnene-2 ,20-dione

9a-hydroxy-19-nor-4 -pregnene-3 ,20-dione

l l a - h y d r o x y - 1 9 - n o r - 4 -pregnene-3 ,20-d ione

l l /3-hydroxy-19-nor-4-pregnene-3 ,20-d ione

14a-hydroxy-19-nor -4-pregnene-3 ,20-d ione

21-hydroxy-19-nor-4-pregnene-3 ,20-d ione

11/3,17a-dihydroxy-19-nor-4-pregnene-3 ,20-d ione

X-hydroxy-3-ke to -4 -andro-stene-17/3 -car boxy lie acid

I4 ,17/3-dihydroxy-4-es t ren-3-one 17-acetate

l l / 3 ,17a ,21- t r ihydroxy-18-nor -4-pregnene-3 ,20-d ione

3/3-chloro-16a-hydroxy-19-nor-5-pregnen-20-one

17/3-hydroxy-17a-methyl- l -5α -andr osten -3 -one

17/3-hydroxy -1 la -methyl-4 -andros ten-3-one

17a-methylsul f inyl-4-andro-s ten-3-one ( s t e reochemis t ry at S uncertain)

17a - methylsulf iny 1-4-andr 0-s ten-3-one (opposite s t e reochemis t ry at S from preceding compound)

6/3,17/3-dihydr oxy -4 -methyl -4-andr osten -3-one

la, 17/3-dihydr oxy-4 -methyl -4 -andros ten-3-one

7/3,17ß-dihy dr oxy-4-methyl -4 -andr osten -3 -one

J-Λ J

TRANSFORMATION

16a-OH

21-OH

9a-OH

l l a - O H

11/3-OH

14a-OH

21-OH

d l - d - 2 1 - O H + 1

11/3-OH

17j3-CH(CH3)-CH2CH2COOH -17ß-COOH; 3/3-OH-3-C = 0 ; Δ 5 - Δ 4 ; Χ-ΟΗ

1ξ-ΟΗ

21-OH

16a-OH

1 Δ

3 /3-OH-+3-C=0; Δ 5 - Δ 4

17a-SCH3-> 17a-S(0)CH3

17a-SCH 3 ^ 17a-S(0)CH3

6/3-OH

7a-OH

7/3-OH

YIELD %

59

25

-

66

20

15

46

-

-

1

25

-

-

-

-

-

tr0

2

12

ORGANISM


Aspergi l lus niger



Curvular ia lunata

Helicostylum pi r i forme

Aspergi l lus niger

Ophiobolus herpot r ichus

Curvular ia lunata

Streptomyces gelat icus


Colletotr ichum linde muthianum


Actinoplanes mis sour i ens i s


Rhizopus stolonifer

Rhizopus stolonifer




CONSTANTS m . p . ° [ot]D

213-214

148-149

-

171-173

215-217

202-204

—

-

-

255-258d

149-151

-

-

-

-

—

218-220

190-192

189-190.5

+ 32[c]

+ 76[c]

-

+ 62[cl

+158[c]

+166[c]

-

-

-

-

-

-

-

-

—

+ 10[c]

+105[d]

+106[c]

R E F .

L-506; L-502

W-1077; L-502

S-898; P-740

B-73; C-117

B-73

B-73

Z-1124; Z-1123; R-783

W-1102

R-773

H-364

K-487

A-12

Z-1128

M-536

M-546

D-174

D-174

K-445

K-445

K-445

121

TABLE I


EMPIRICAL FORMULA

^20'"30*-'3

C 2 0H 3 0O 3 S

C 2 0 H 3 0 O 4 S

1 ^ 20^32^3

1 ^ 2 l "22^3


11a, 17ß-dihydroxy -4 -methyl -4 -andros ten-3-one

l a , 17/3 -dihydr oxy -17a -methy l -4 -andros ten-3-one

2/3,17/3-dihydroxy-17a-methy l -4 -andros ten-3-one

6/3,17/3-dihydroxy-17a-methy l -4 -andros ten-3 -one

9a, 17/3-dihydr oxy-17a-methyl -4 -an dr osten -3 -one

11a, 17ß-dihydroxy-17a-methyl -4 -androsten -3 -one

16/3,17/3-dihydr o x y - H a -rne thy l -4 -andros ten-3-one

17/3- hydr oxy -7a -methyl -su l f inyl -4-andros ten-3-one

1 la -hydr oxy -17a -methyl -sulf inyl -4 -androsten -3 -one ( s te reochemis t ry at S unknown)

1 la-hydroxy-17/3-methyl -su l f inyl -4-andros ten-3-one ( s t e reochemis t ry at S unknown)

l la -hydroxy-17/3-methyl -sulf iny 1 -4 -andros ten -3 -one (opposite s t e r eochemis t ry at S from preceding compound)

11a-hydr oxy-17/3-methyl-su l fonyl -4-andros ten-3-one

3/3,16a-dihydroxy-19-nor-5a-pregnan-20-one

17a-ethinyl-17/3-hydr oxy-1 ,4 ,6 -andros t a t r i ene -3,11-dione

TRANSFORMATION

l l a - O H

3j3-OH-3-C = 0 ·

2/3-OH

6/3-OH

9a-OH

l l a - O H

16/3-OH

7a-SCH3—7a-S(0)CH3 17/3-OAc-17/3-OH

l l a - O H ; 1 7 a - S C H 3 -17a-S(0)CH3

l l a - O H

l l a - O H ;

l l a - O H

16a-OH

Δ*

YIELD %

7.5

-

-

90

4

-16

47

-

49-70

-

29

-

-

-

ORGANISM




Gibberella saubinetti



Rhizopus ref lexus

Ascochyta linicola



Rhizopus ref lexus

Sporotr ichum sul furescens

Curvular ia lunata

Calonectr ia decora

Rhizopus stolonifer

Rhizopus stolonifer

Rhizopus stolonifer

Rhizopus stolonifer


St reptomyces sp„



179.5-180.5

-

-

-

252-253

-

190-191

160-161.5

-

154-156

-

189.5-190

225-226

223-224

297-299d

267-268

-

-

+ 7 2 [ c |

-

-

-

+ 3|c]

-

-

+ 66[c] + 59[e|

-

-

-

+ l l [m]

- 88[c]

+105

-

-

REF.

K-445

G-293

L-496

U-1043

E-201

E-201; M-613

E-201

S-828

E-201

E-201; M-608

E-201

M-582

S-950

H-405

D-174; D-176

D-176

D-176

D-176

W-1093

W-1093

G-304

122

TABLE I


EMPIRICAL FORMULA

C21H2306C1

C21H2306F

C21H2402C12F2

^ 21 ** 24 ®2 ̂ ^2 ■*■ ^

C^iH^C^FI

* " 2 l " 2 4 ^ 3

C 2 1 H2 4 0 4

C 2 1 H 2 4 0 5

C 2 1 H 2 4 0 5 F 2

^ 2 1 ^ 2 4 ^ 6

C21H2406C1F

C2iH2502F

C21H2503Br


9a-chloro -14α,17α,21-t r ihydroxy-1 ,4 ,6 -p regna-t r iene-3 , 11,20-trione

9a-fluoro-14α, 17α, 21-t r ihydroxy-1 ,4 ,6 -p regna-t r iene-3 , 11,20-trione

9a, l l /3-dichloro-6a,21-dif luor o -1,4 -pr egnadiene -3,20-dione

9a, l l /3-dichloro-6a-fluoro-21- iodo- l ,4-pregnadiene-3,20-dione

6a- f luoro-21- iodo- l ,4 ,9 ( l l ) -p regna t r iene-3 ,20-d ione

17a-ethinyl-17/3-hydroxy-1,4 -andr ostadiene -3,11 -dione

17a-ethinyl-11/3,17/3-dihydroxy-l , 4 , 6 - a n d r o s t a t r i e n - 3 - o n e

l l /3-hydroxy-3,20-diketo-l ,4-pregnadien-18-oic acid (18 41) lactone

17a, 21-dihydroxy-1,4,6-pregnat r iene-3 ,11 ,20- t r ione

6,9a-difluor0-11/3,17a, 21-t r ihydroxy-1 ,4 ,6 -p regna-t r i ene -3 ,20-d ione

9α, 17α, 21- t r ihydroxy-1 ,4 ,6-pregnat r iene-3 ,11 ,20- t r ione

14α, 17α, 21- t r ihydroxy-1 ,4 ,6-pregnat r iene-3 ,11 ,20- t r ione

12a-chloro-6a-fluoro-16a, 17a, 21-trihydroxy-1,4-pregnadiene-3,11, 20-tr ione

17a -ethinyl -6a -fluor 0-17/3-hydroxy -1,4 -andr ostadien -3-one

6/3-fluoro-l, 4,9(11) -pregna-t r i ene-3 ,20-d ione

21-f luoro- l ,4 ,9( l l ) -pregna-t r iene -3 ,20 -dione

9a -b romo-1 ,4 -p r egnadiene -3,11,20-trione

TRANSFORMATION

14a-OH

14a-OH

1

Δ

Δ1

Δ1

Δ1

Δ1

11/3 -OAc^ll/3-OH; 17/3-OAc-17/3-OH

Δΐ

Δ1

2 1 - O A c - 2 1 - O H ; Δ1

Δ1

9a-OH

14a-OH

Δ1

Δ1

Δ1

Δ1

1

Δ

YIELD %

—

—

—

—

-

—

-

75

—

-

-

—

—

-

—

ORGANISM

Curvular ia lunata

Curvular ia lunata




Bacillus sphaer icus


Fla vo bac ter ium dehydrogenans



Eaci l lus sphaer icus


Helicostylum pir i forme


Nocardia aurant ia

Septomyxa affinis





— —

— —

— —

— —

- —

— —

- -

194-195 —

225° d +246|d] 235°d (polymorph)

— —

- -

- -

— —

— —

- -

— —

R E F .

G-302

G-302

R-758

R-758

R-758

G-304

G-304

G-304

U-1044

G-310

G-310

A-7

G-302

G-302

F-261

C-93

R-757

R-773

H-379

123

TABLE I


EMPIRICAL FORMULA

C21H2503C1

C21H2503C12F

C21H2503C12I

C 2 1 H 2 5 ° 3 F

C 2 l H 2 5 0 3 I

C21H2503C12I

C21H2504F

C21H2504FS

1 ^2l"25^4-' : ,3

C21H2505Br

C21H2505C1


9a-ch lo ro -1 ,4 -p r egnadiene -3,11,20-trione

9a, 11/3-die hlor 0-21-fluor o-17α-hydroxy-1,4-pregna-diene-3 ,20-dione

9a,l l /3-dichloro-170-hydroxy-21- iodo- l ,4 -pregnadiene-3 , 20-dione

17a-ethinyl-9a-f luoro-l l /3 , 17/3-dihydroxy-l,4-androstadien-3 -one

6a - f luo ro - l ,4 -p regnad iene -3,11,20-tr ione

6/3-f luoro-l ,4-pregnadiene-3,11,20-tr ione

9a -fluoro-1,4 -pr egnadiene -3,11,20-tr ione

6a -fluor o -17a -hydroxy -1,4,9(11) -p regna t r i ene -3,20-dione

17a-hydroxy-21-iodo-l ,4 ,9( l l ) -pr e gnatr iene - 3 ,2 0 - dione

9a, 11/3-die h loro- 17a -hydroxy -21-iodo-1,4-pr egnadiene-3,20-dione

9a -fluoro -17a -hydroxy -1,4 -pregnadiene-3 ,11,20- t r ione

9a - f luoro -21-hydroxy- l ,4 -pr egnadiene-3,11,20-t r ione

12a-f luoro-21-hydroxy- l ,4-pr egnadiene-3,11,20-tr ione

9a-f luoro-17a-hydroxy-21-mer capto -1,4 -p regna-d i ene -3 , 11,20-trione

6α, 9α, 21-trifluor 0-11/3,17a-dihydroxy-1 ,4-pregna-d iene -3 , 20 -dione

9a-bromo-17a,21-dihydroxy-1,4 -pregnadiene-3,11,20-tr ione

9a-bromo-17a, 21-dihydroxy-1,5-pregnadiene-3,11,20-tr ione

9a-chloro-17a,21-dihydroxy-1,4 -pregnadiene -3,11,20 -t r ione

TRANSFORMATION

1 Δ

Δ1

Δ1

Δ1

Δ1

Δ1

1 Δ

Δ1

1 Δ

Δ1

Δ1

Δ1

A1; 21 -OAc-21-OH

21-SAc ->21-SH

1 Δ

1 Δ

21-OAc-^21-OH

1 Δ

YIELD %

-

—

—

—

-

-

-

—

—

-

-

-

-

—

—

—

—

ORGANISM





Septomyxa affinis

Septomyxa affinis









Septomyxa affinis





- -

— —

— —

— —

- -

- -

- -

— —

- -

- -

- -

- -

- -

— —

267-272 —

— —

— —

REF.

H-379

R-756 j

R-756 !

N-667

C-91

C-91

H-379

H-391

R-756

R-756

H-379

N-668

W-1083

N-685

M-534

N-668

N-690

N-668

124

TABLE I


EMPIRICAL FORMULA

C21H2505C1

C21H2505F

C21H2505N

C21H2506Br

C21ri26U2

C21H2602BrCl

C 2 1 H a 0 2 B r F

C21H2602Br2

C ^ O . C I F


9a-chloro-17a, 21-dihydroxy-1, 5-pregnadiene-3? 11,20-tr ione

2-fluor o-17a, 21-dihydroxy-1,4 -pr egnadiene -3,11,20-tr ione

9a-fluoro-17a, 21-dihydroxy-1,4 -pr egnadiene -3,11,20-tr ione

9a-fluoro-17a, 21-dihydroxy-1, 5-pregnadiene-3,11,20-tr ione

21-hydroxy-17ß, 20a-oxido-16-oximino-1,4-pr egna-diene-3,11-dione

9a-bromo-l l /3,14a,17a,21-t e t r a h y d r o x y - l , 4 , 6 - p r e g n a -t r i ene-3 ,20-d ione

9a - f l uo ro -6£ , I7a ,21 -t r ihydroxy -1,4 -pregnadiene -3,11,20-trione

9a-f luoro-14a ,17a ,21-t r ihydroxy- l ,4 -p regnad iene -3,11,20-trione

9a-fluor0-11/3,14α, 17α, 21-t e t r a h y d r o x y - l , 4 , 6 - p r e g n a -t r iene -3 ,20 -dione

9α-fluor 0-11/3,16α, 17α, 21-t e t r a h y d r o x y - l , 4 , 6 - p r e g n a -t r iene-3 ,20-dione

17a-ethinyl-17j3-hydroxy-1,4 -andros tadien-3 -one

1 ,4 ,9 ( l l ) -p regna t r i ene -3,20-dione

1,4, l l - p r e g n a t r i e n e - 3 , 2 0 -dione

1,4,16 -pregnatr iene - 3 , 2 0 -dione

9a-bromo- l l /3 -ch loro- l ,4 -pr egnadiene-3,20-dione

9a-bromo-l l /3- f luoro- l ,4-pr egnadiene-3,20-dione

9a, 11/3-dibromo-l,4 -pr egna-diene-3 ,20-dione

9a -ch lo ro - l l ß - f luo ro - l , 4 -pr egnadiene -3 ,20 -dione

TRANSFORMATION

21-OAc-21-OH

Al(2aF)

1

Δ

21-OAc-21-OH

1

Δ

14a-OH

6 | -OAc-βξ -OH; 21-OAc->21-OH

14a-OH

14a-OH

16a-OAc^l6a-OH; 21-OAc^21-OH

Δ1

Δ1

Δ1

1

Δ

Δ1

1

Δ

1

Δ

1

Δ

YIELD %

—

23

39

—

—

—

—

—

—

—

-

-

-

—

-

—

—

ORGANISM






Curvular ia lunata


Helicostylum pir i forme

Curvular ia lunata











_ _

232-236 +145[m]

— —

— —

— —

— —

— —

— —

—

— —

135-138; +75[c] 147-150

166-168 +112[a]

— —

— —

— —

— —

R E F .

N-690

H-402; H-401

N - 6 6 8 ; N-669

N-690

N-686

G-302

G-309

N-669

G-302

G-299

N-665

R - 7 7 3 ; R-754

V-1052; W-1096

H-388; O-700

R-754

R-754

R-754

R-754

125

TABLE I


EMPIRICAL FORMULA

C21H260,C1I

C ^ H ^ C l ,

C^H^O.FI

C21 H26°3

1 ^ 21 " 26^4


9a - iodo - l l / 3 - ch lo ro - l , 4 -pr egnadiene -3 ,20 -dione

9 a , l l / 3 - d i c h l o r o - l , 4 - p r e g n a -diene-3 ,20-dione

9a -iodo -11/3- fluor o - 1 , 4 -pr egnadiene -3 ,20 -dione

17a-e th iny l - l lß ,17 /3-d ihydroxy-1 ,4 -andros t a -dien-3-one

17a-ethinyl-11/3,17/3-d ihydroxy-4 ,6-andros ta -dien-3-one

1 ,4 -p regnad iene -3 ,11 ,20 -tr ione

21 -hyd roxy -1 ,4 ,6 -p r egna -t r i ene -3 ,20-d ione

1 7 a - h y d r o x y - l , 4 , 9 ( l l ) -p re gnatr iene -3 ,20 -dione

2 1 - h y d r o x y - l , 4 , 9 ( l l ) -p regna t r i ene -3 ,20-d ione

11a -hydroxy-1 ,4 ,16 -p regna -t r i ene -3 ,20-d ione

l l / 3 - h y d r o x y - l , 4 , 1 6 - p r e g n a -t r i ene-3 ,20-d ione

21 -hydroxy-1 ,4 ,16 -p regna -t r i ene -3 ,20 -d ione

21-hydroxy- l l /3 , 12/3-oxido-1,4 -pr egnadiene - 3 , 2 0 -dione

1 la -hydroxy-16û ,1 la -ox ido -1,4 -pregnadiene - 3 , 2 0 -dione

21-hydroxy-16α,17α-oxido-1,4 -pregnadiene - 3 , 2 0 -dione

21-hydroxy-1 ,4-pregnadiene -3 ,11 ,20 - t r ione

17a,20a-dihydroxy-9j3,11/3-o x i d o - 1 , 4 , 6 - p r e g n a t r i e n -3-one

TRANSFORMATION

Δ1

l

Δ

1

Δ

1

Δ

ll/3,17ß-diOAc-> 11/3,17/3-diOH

1

Δ

1

Δ

1 Δ ;

21-OAc-21 -OH 1

Δ

i

Δ

11a-OH

11/3-OH

2 1 - O A c - 2 1 - O H ; 3/3-OAc->3-C = 0 ; Δ 5 ^ Δ 4 ; Δ '

21-OH

1

Δ

3 /3 -OH^3-C=0 · Δ 5 - ^ Δ 4 ; Δ1

1

Δ

20-C=O->20a-OH

YIELD %

-

-

-

—

—

71

30

-

~

-

-

~

—

—

-

—

—

-

ORGANISM







Septomyxa affinis





Curvular ia lunata


Wojnowicia graminis

Bac te r ium mycoides

Bac te r ium havaniensis

Bacil lus lentus


Calonectr ia decora


Rhodotorulla longiss ima


-

198-208d

-

—

-

156-159

179-181

166-168

233-235

-

-

-

—

—

-

206-208

220-222d

-

-

+ 184[c]

-

—

—

-

+224[cl

+112[a]

- 19[c]

-

-

-

—

—

-

+ 88[dl

—

-

R E F .

R-754

R-754

R-754

G-304

G-304

M-536

E-208; W-1072

W-1096; V-1052

R-773

R-755

H-388; O-700

H-388; O-700

H-388; O-700

D-157

F-240

F-233

R-750

S-942

W-1096

N-665

G-303

126

TABLE I


EMPIRICAL FORMULA

^ 2 1 " 2 6 ^ 4

C^H^aABrCl

C2 1H2 604BrF

C 2 1 H 2 6 0 4 B r2

C21H2604C1F

C21H2604C1I

C 2 1 H 2 6 0 4 C 12

C21H2604FI

^ 2 l " 2 6 ^ 4 ^ 2

C21H2604S


17a, 20/3-dihydroxy-9/3,11/3-ox ido-1 ,4 ,6 -pr egnatr ien -3-one

1 1 a , 2 1 - d i h y d r o x y - l , 4 , 1 6 -pregna t r iene-3 ,20-d ione

11/3,21-dihydroxy-l , 4 , 1 6 -pregna t r iene-3 ,20-d ione

l - l l /3 -hydroxy-3 ,20-d ike to-4-pregnen-18-oic acid (18^11) lactone

9a -b romo- l l /3 -ch lo ro -17a , 21 -d ihyd roxy- l , 5 -p regna -diene-3 ,20-dione

9a -ch loro- l l /3 -bromo -17a, 21-d ihydroxy- l , 5 -pregnadiene-3,20-dione

9 a - b r o m o - l l ß - f l u o r o - 1 7 a , 2 1 -dihydr oxy - 1 , 5 -pr egnadiene -3,20-dione

9a- f luoro- l l /3 -bromo-17a , 2 1 -d ihydroxy- l , 5-pr egnadiene -3,20-dione

9 a , l l / 3 - d i b r o m o - 1 7 a , 2 1 -dihydr oxy - 1 , 5 -pr egnadiene -3,20-dione

9a-chloro- l l /3- f luoro-17a , 2 1 -d ihydroxy- l , 5-pr egnadiene-3,20-dione

9a - f luo ro - l l / 3 -ch lo ro -17a ,21 -dihydroxy -1 ,5 -pr egnadiene -3,20-dione

9a - iodo - l l / 3 - ch lo ro -17a ,21 -dihydr oxy -1 ,5 -pr egnadiene -3,20-dione

9 a , l l / 3 - d i c h l o r o - 1 7 a , 2 1 -dihydr oxy -1 ,5 -p re gnadiene -3,20-dione

9a- iodo-l l /3-f luoro-17a, 2 1 -d ihydroxy- l , 5-pre gnadiene-3,20-dione

9a , l l / 3 -d i f luo ro -17a ,21-dihydroxy-1,5-pregnadiene -3,20-dione

6a ,9a-di f luoro-15a-hydroxy-4 -pr egnene -3 ,11 ,20 - t r ione

17a - hydroxy - 21 - me r capto -1,4 -pr egnadiene - 3 , 1 1 , 2 0 -tr ione

TRANSFORMATION

20-C=O-20/3-OH

21-OH

21-OH

d l - 2 1 - H -d-21-OH + l -21-H

21-OAc-21-OH

21-OAc^21-OH

21-OAc-21-OH

21-OAc 21-OH

21-OAc -21 -OH

21-OAc-21-OH

21-OAC-21-OH

21-OAc - 2 1 - O H

21-OAc-21-OH

21-OAc-21-OH

21-OAC-21-OH

15a-OH

21-SAC-21-SH

YIELD %

-

-

-

—

—

—

—

—

—

—

—

—

—

-

~~

-

ORGANISM















Flavobacter iu m dehydrogenans




-

-

-

-154

— —

— —

— —

- —

— —

— —

— —

- —

— ~

— —

~ ~

-

R E F .

G-303

O-700; H-388

O-700; H-388

V-1055

N-691

N-691

N-691

N-691

N-691

N-691

N-691

N-691

N-691

N-691

N-691

A-31

N-685

127

TABLE I


EMPIRICAL i FORMULA

^ 2 1 " 2 6 ^ 5


l l /3 ,21-dihydroxy-3,20-diketo -1,4 -pr egnadien -18 -a l ( 1 8 - * l l ) hemiaceta l

17a, 21-dihydroxy-9/3,11/3-ox ido- l ,4 -p regnad iene-3,20-dione

16o, 21-dihydroxy-11/3,12/3-ox ido- l ,4 -p regnad iene-3,20-dione

17a,21-dihydroxy-1,4-pregnadiene-3,11, 20-t r ione (prednisone)

TRANSFORMATION

Δ1

d , l - d - A I + 1

21-OAC-21-OH

16α-ΟΗ

Δ1

YIELD %

—

—

-

—

:

62

-

-

—

-

—

58-85 (cr.)

90

—

64

-

-

72(cr.)

-

-

—

—

—

ORGANISM

Calonectr ia decora




Bacillus lentus

Bacillus pulvifaciens

Bacillus sp.


Bacil lus subti l is

Bacter ium cyclooxydans

Calonectr ia decora

Calonectr ia decora





Fusa r ium solani

Fusa r ium solani


Gloeosporium ol ivarum

Graphiola cyl indrica

Helminthospor ium gramineum

Helminthospor ium tu rc icum

Helminthospor ium zizaniae


—

-

—

—

224-225

225-230

-

232-233

-

231-234

-

233-235d

231-234

226-232

229-231d

231-234

229-233

230-234

229-233

-

—

-

—

-

-

—

—

+170[d|

+164[m]

-

+166[d]

-

+169fd]

-

+172[d|

-

—

-

+169[d]

+170[d]

+164[cl

+171[dl

-

-

-

—

REF.

W-1096

V-1055; #-1102

W-1096

D-157

R-750

1-420

S-848

S-942

L-521

K-480

V-1053; W-1096

S-951

N-671; N-665; H-389; H-387

W-1096

V-1052

C-125

V-10 53

K-462

S-857

K-465

K-465

K-465

S-857

K-465

128

TABLE I


EMPIRICAL FORMULA

^ 2 1 " 2 6 ^ 5


prednisone

TRANSFORMATION

Δ1

α , Ι - α - Δ ^ 1

21-OAc->21-OH

21-OH

Δ1'4 (5α-Η)

Δ Μ ( 5 β - Η )

Δ ^ δ / Β - Η ) . 21-OAc->21-OH

3 û - O H - 3 - C = 0 ; Δ 1 ' 4 (5/3-H)

YIELD %

-

—

—

-

75-81

-

-

—

-

-

3

52

-

-

-

—

-

-

-

-

-

-

-

—

ORGANISM

Hypomyces solani

Micromonospora chalcea

Mycobacterium f la vu m


Mycobacter ium sp.


Ophiobolus he te ros t ropus

Pro taminobac te r alboflavum

Pro taminobac te r rub rum

Septomyxa affinis

Septomyxa affinis

Streptomyces olivochromogenus


Bacil lus megater ium



Sclerot inia fructicola

Calonectr ia decora


Nocardia blackwelli



Nocardia blackwelli

Nocardia blackwelli


—

—

-

-

-

-

-

—

-

-

-

-

231-234

-

-

231-233

—

-

—

-

-

-

235-239

—

—

-

-

-

-

-

-

-

-

-

-

-

+170[d]

-

-

—

-

-

-

-

-

-

-

—

R E F .

L-525

S-864; S-867

C-100; C-101

S-873

K-477

H-399

S-857

S-863

S-863

W-1072; K-456

S-901

C-125

V-1055; W-1102

S-948

H-324

W-1101; O-700; H-388

W-1101

W-1096

W-1096

S-943

S-866

S-866

S-943

S-943

129

TABLE I


EMPIRICAL FORMULA

^ 21 " 26^5

1 ^21 "26^6


prednisone

prednisone - 4-C 1

17a,21-dihydroxy-l , 5-pregna-d i e n e - 3 , l l , 2 0 - t r i o n e

11«, 17a, 21 - tr ihydroxy -1 ,4 ,6 -p regna t r i ene -3 ,20-d ione

l l /3 ,17a ,21- t r ihydroxy- l ,4 ,6 -pr egnatr iene -3 ,20 -dione

1 la, 20a, 21 - t r ihydroxy 9 /3 , l l / 3 -ox ido- l ,4 ,6 -p regna-t r i en -3 -one

17a, 20/3,21 - t r ihydroxy-9/3, l l /3-oxido-l ,4 ,6-pregna-t r i en -3 -one

16α, 17α, 21 - t r ihydroxy-1,4,9(11)- p r egna t r i ene -3,20-dione

11/3,14a-dihydroxy-3,20-diketo-4-pregnen-18-oic acid (18—*11) lactone

11/3,21-dihydroxy-3,20-diketo -4 -pr egnen -18 -oic acid (18—»11) lactone

11/3,14a, 21 - t r i hyd roxy-3 ,20 -d ike to - l ,4 -p regnad ien-18-al

6/3,17a, 21 - t r ihydroxy-1 ,4 -p regnad i ene -3 , l l , 20 - t r i one

7α, 17α, 21- t r ihydroxy-1 ,4-pregnadiene -3,11,20-tr ione

14a, 17a, 21- t r ihydroxy-1 ,4 -p regnad iene -3 , l l , 20 - t r i one

15/3 ,17a,21- t r ihydroxy- l ,4-pregnadiene-3 ,11,20- t r ione

9a, 11/3,17a, 21 - te t rahydroxy -1 ,4 ,6-pr egnatr i e n e - 3 , 2 0 -dione

11/3,14α, 17α, 21 - te t rahydroxy-1,4,6-pr egnatr i e n e - 3 , 2 0 -dione

J

TRANSFORMATION

3 a - O H - 3 - C = 0 ; Δ^4(5/3-Η); 21 -OAc-21-OH

Δ1

21-OAc^21-OH

2 1 - 0 - i - B u - 2 1 - O H

11a-OH

Δ1

2 0 - C = O - 2 0 a - O H

20-C=O-20/3-OH

3/3-OAc—3-C=0; 21 -OAc-21 -OH; AS 4 (5a -H)

14a-OH

d, l -»d-21-OH + l

14a-OH

6/3-OH

Δ1; 21-OAc - 21-OH

Δ1

Δ1

9a-OH

14a-OH

YIELD

% j -

54

-

—

—

-

—

—

—

—

—

-

—

-

—

—

ORGANISM

Nocardia blackwelli

Coryne bacter ium s implex



Fusa r ium equiset t i


Rhodotorulla r u b r a



P l eospora gaeumanni

Ophiobolus herpo t r ichus


P leospora gaeumanni

Chaetomium funicolum




Helicostylum p i r i fo rme


CONSTANTS m.p.° [ α ] ρ |

- -

— -

- -

_ _

- -

239-243 +100fd]

_ —

— —

+9[c]

— —

205-222 +117[a]

— —

- -

- -

- ~

- -

— —

R E F .

S-939

C-120

N-690

N-690

M-557

G-310

G-303

G-303

O-705

W-1108

W-1101;

W-1102

W-1102 W-1108

C-108

N-687

S-874; S-873

C-126 1

G-302

G-302

130

TABLE I


EMPIRICAL FORMULA

C21H2606

C21H2G06C1F

C21H2606F2

C21H27Ö3Br

C21H2703C1

C21H2703F

C21H2703N

C21H2704Br

C21H2704C1

i NAME OF REACTION

PRODUCT

l l /3 ,16a ,21- t r ihydroxy-3 ,20-diketo-4-pregnen-18-oic acid (18 —11) lactone

12a-chloro-6a-f luoro-16a, 17a, 21 - tr ihydroxy-4-pregnene-3,11,20-trione

6α, 12α-difluoro-11/3,16a, 17a, 21 - tetr ahydr oxy -1,4 -pr egna -diene-3 ,20-dione

9a-bromo-11/3-hydroxy-1,4-pregnadiene-3 ,20-dione

9a-chloro-l>/3-hydroxy-l ,4-pregnadiéne-3 ,20-dione

6a -fluor o -lia -hydroxy -1,4 -pr egnadiene -3 ,20-dione

6a -fluor o-H/3- hydroxy -1 ,4-pregnadiene -3 ,20-dione

6a-f luoro-17a-hydroxy-1,4-pr egnadiene -3 ,20-dione

6/3-f luoro-l la-hydroxy-l ,4-pr egnadiene -3 ,20-dione

6/3-fluoro-ll/3-hydroxy-l,4-pr egnadiene-3,20-dione

9a-fluor 0-11/3-hydroxy-1,4-pr egnadiene-3,20-dione

9a -fluoro -14a -hydroxy - 4 -pregnene -3,11,20-tr ione

17/3,20a -oxido-16 -oximino -1,4 -pregnadien-3 -one

12a -aza -C-homo- l , 4 -p regna -d iene-3 ,12 ,20- t r ione

9a -bromo -11/3,21 -dihydroxy -1,4 -pr egnadiene - 3 , 2 0 -dione

12a-bromo-16a-hydroxy-4-pregnene -3,11,20-tr ione

9a-chloro-11/3,17a-dihydroxy -1,4 -pregnadiene -3 ,20-dione

9a -chloro -11/3,21-dihydroxy -1,4 -pregnadiene -3 ,20 -dione

12a -chloro -16a -hydroxy -4 -pregnene-3 ,11,20- t r ione

TRANSFORMATION

16a -OH

21-OH

16a-OH

Δ1

Δ1

Δ1

Δ1

Δ1

Δ1

Δ1

1

Δ

Δ1

14a-OH

Δ1

3 / 3 - O H - 3 - C = 0 ; Δ 1 , 4 (5a-H)

21-OAC-21-OH

16a-OH

Δ1

Δ1

Δ1

16a-OH

YIELD %

-

—

—

-

-

—

-

-

-

-

-

_

—

62

—

-

—

—

ORGANISM

Pes ta lo t ia funer a



Nocardia aurant ia



Septomyxa affinis

Septomyxa affinis

Septomyxa affinis

Septomyxa affinis

Septomyxa affinis




Nocardia sp.




Corynebacter ium hoagii Nocardia coral l ina


CONSTANTS m . p . ° [or]D

_ __

- -

- -

- -

- -

- -

- -

- -

- -

- -

- -

- -

183-185 +48[m]

— —

- -

— —

— —

R E F .

W-1091

W-1091

F-261

F-261

H-379

H-379

C-91

C-91

B-34

C-91

C-91

H-379

W-1108a

N-686

M-563

N-668

F-256

H-379

N-668

H-399

F-257

131

TABLE I


EMPIRICAL FORMULA

C 2 1 H 2 7 0 4 F

C21H2704FS

C21H2704N

1 C21H27OsBr

C21H2705C1

C 2 1 H 2 7 0 5 F


9a- f luoro- l l /3 ,17a-d ihydroxy-1,4 -pregnadiene -3 ,20 -dione

9a - f l uo ro - l l ß , 21 -d ihyd roxy -1 ,4-pregnadiene-3 ,20-dione

12a-f luoro- l l /3 ,21-dihydroxy-1,4 -pregnadiene -3 ,20 -dione

6a- f luoro-15a-hydroxy-4-p regnene -3 ,11 ,20 - t r i one

6a- f luoro-16a-hydroxy-4-p regnene -3 ,11 ,20 - t r i one

9a-fluor o-21-hydroxy-4-p regnene -3 ,11 ,20 - t r i one

9a -fluoro-11/3,17a-dihydroxy-21 - m e r c a p t o - 1 , 4 - p r e g n a -diene-3 ,20-dione

12a-aza -17a-hydroxy-C-homo -1 ,4 -pregnadiene -3 ,12 ,20 - t r i one

6 /3 -bromo- l l /3 ,17a ,21- t r i -hydroxy-1 ,4-pregnadiene -3,20-dione

9 a - b r o m o - l l ß , 1 7 a , 2 1 - t r i -hydroxy-1 ,4-pregnadiene -3,20-dione

6a -chloro-11/3,17a, 21 - t r i -hydroxy-1 ,4-pregnadiene -3,20-dione

9 a - c h l o r o - l l / 3 , 1 7 a , 2 1 - t r i -hydroxy-1 ,4-pregnadiene -3,20-dione

2 - f luo ro - l l j 3 ,17a ,21 - t r i -hydroxy-1 ,4-pregnadiene -3,20-dione

6a - f l uo ro - l l j 3 , 17a ,21 - t r i -hydroxy-1 ,4-pregnadiene -3,20-dione

9a-fluoro-11/3,16a, 1 7 a - t r i -hydroxy-1 ,4 -p regnad iene -3,20-dione

9 a - f l u o r o - l l j 3 , 1 7 a , 2 1 - t r i -hydroxy-1 ,4 -p regnad iene-3,20-dione

TRANSFORMATION

Δ1

Δ1;

Δ ; 21 -OAc-21 -OH

15a-OH

16a-OH

21-OH

2 1 - S A C - 2 1 - S H

3i3-OAc-3-C = 0 ; Δ^Μδα-Η)

11/3,17a,21-triOAc - l l / 3 , 1 7 a , 2 1 - t r i O H

1

Δ

11/3-OH

1

Δ

AX(2a-F)

1 Δ ;

21-OAC-21-OH

1

Δ

1

Δ

YIELD %

-

-

—

-

-

-

—

17

—

—

—

—

—

53

-

64

-

-

""*"

ORGANISM




Pénic i l l ium ur t i cae


Cercospore l la herpotr ichoides


Nocardia sp.

F lavobacter ium dehydrogenans


Cunninghamella bainier i



Septomyxa affinis

Septomyxa affinis

Septomyxa affinis



Bacil lus lentus

Baci l lus sphae r i cus

Bac te r ium cyclo-oxydans


CONSTANTS m . p . ° [ûf]D

-

-

—

-

-

-

~

260-262

—

—

195-196

—

-

202-204

202-204

208-213

275-279

265-269

-

—

-

-

—

-

-

-

—

+ 45|c]

_

—

+ 61fdl

—

-

+ 7 3td]

+ 92[d]

+ 92[d]

+ 51

+109[c|

-

~

REF.

H-379; N-668

H-399

T-985; W-1083

A-31

B-35

L-490

N-685

M-563

N-690

N-668 1

R-770

N-668

H-401

S-924

M-647

H-396

F-238

F-238

R-750

S-942; N-669

K-480

F-233

132

TABLE I


EMPIRICAL FORMULA

C21H2705F

C21H2705N

C 2 1 H 2 7 0 6 0

C21H2 706F


9a - f l uo ro - l l / 3 , 17a ,21 - t r i -hydroxy-1 ,4-pr egnadiene -3,20-dione

12a-f luoro- l l /3 , 14α, 1 7 a - t r i -hydroxy-1 ,4-pregnadiene -3,20-dione

12a- f luoro - l l j3 ,17a ,21- t r i -hydroxy-1 ,4-pregnadiene -3,20-dione

1 6 ß - f l u o r o - l l ß , 1 7 a , 2 1 - t r i -hydroxy-1 ,4-pregnadiene -3,20-dione

9 a - f l u o r o - l l ß , 1 7 a , 2 1 - t r i -hydroxy-1 ,5-pregnadiene -3,20-dione

2a -f luor o -17a, 21 -dihy dr oxy -4 -pr egnene - 3 , 1 1 , 2 0 - t r ione

21-hydroxy-17/3,20a-oxido-16-oximino-4-pregnene-3,11 -dione

9 a - c h l o r o - l l / 3 , 1 6 a , 1 7 a , 2 1 -te t r any dr oxy -1 ,4 -pr e gna -diene-3,20-dione

1 2 a - c h l o r o - 1 6 a , 1 7 a , 2 1 - t r i -hydroxy-4-pr egnene-3 ,11 ,20- t r ione

9a-f luoro- l l /3 ,16a , 1 7 a a - t r i -hydroxy-17aß-hydroxy-methyl -D-homo-1 ,4 - and ro -stadiene -3 ,17 -dione

TRANSFORMATION

Δ1

1

Δ ; 21-OAC-21-OH

20/3-OH^20-C=O

14a-OH

1

Δ

1

Δ

Hj3,17a ,21- t r iOAc -11 /3 ,17a , 21-tr iOH

Δ ' - Η

21-OAc->21-OH

1

Δ

16a-OH

1

Δ ; 1 6 a , 1 7 a , 2 1 - t r i - O H -20-C=O— 16a ,17aa-dihydroxy-17a/3-hydr oxy methyl -D -homo-17-C=Q

YIELD %

20

41

-

36

70

-

-

-

-

-

—

—

—

—

8

—

—

—

ORGANISM

Bacter ium mycoides






Nocardia sp.

Bacter ium havaniensis








Streptomyces sp„






265-269d

247-250

263-266

254-256

265-269

-

-

-

263-266

-

—

—

—

—

-

—

—

-

+ l l l [ e ]

—

+ 103[e]

+ 92[m]

+ l l l [ e ]

-

-

-

+108[d]

-

—

—

—

—

-

—

—

—

R E F .

F-240

H-389; N-671

N-668; N-665; N-669

W-1096

H-403; H-399

S-885

T-1005

F-233

F-240

V-1052

G-294

W-1103

H-380

B-51

N-690

H-402

N-686

H-399

F-256

G-297

TABLE I


133

EMPIRICAL FORMULA


9a- f luoro- l l /3 ,16a , 17aa - t r i -hydroxy -17a/3-hydroxy-methy 1-D-_homo - 1 , 4 - andr o-stadiene - 3 , 1 7 - dione

6 a - f l u o r o - l l a , 1 6 a , 1 7 a , 2 1 -t e t r ahyd roxy -1 ,4 -p r egna -die ne -3 ,20 -dione

6 a - f l u o r o - l l / 3 , 1 6 a , 1 7 a , 2 1 -t e t r ahyd roxy-1 ,4 -p regna -d iene-3 ,20-dione

9 a - f l u o r o - 6 | , ll/3,17a,21-tetra-hydroxy - 1 , 4 - p r egnadiene-3,20-dione

9o-f luoro- l l ]3 ,14a , 1 7 a , 2 1 -t e t r ahyd roxy -1 ,4 -p regna -diene - 3 , 20 -dione

9 a - f l u o r o - l l ß , 1 5 j 3 , 1 7 a , 2 1 -t e t r ahydroxy-1 ,4 -pr egna-diene-3 ,20-dione

9a-f luoro- l l /3 ,15/3 ,16a ,21-t e t r ahyd roxy -1 ,4 -p r egna -diene -3 ,20-dione

9 a - f l u o r o - l l j 3 , 1 6 a , 1 7 a , 2 1 -t e t r a h y d r o x y - 1 , 4 - p r e g n a -diene-3 ,20-dione (triamcinolone)

TRANSFORMATION

1

Δ

11a -OH

11/3-OH

16a-OH

6 £ , l l j 3 , 1 7 a , 2 1 - t e t r a -O A c - > 6 | , l l / 3 , 1 7 a , 2 1 -tetraOH

14a-OH

1

Δ

1

Δ

1

Δ

16a-OH

20j3-OH^20-C=O

YIELD

% i ~~

-

-

—

48

5

—

43

10

-

65

—

-

30-70

-

20

-

ORGANISM





Flavo bac ter ium dehydrogenans








Coryne bac te r ium s implex



Nocardia sp .

Nocardia i ta l ica




CONSTANTS m.p.° [e]pl

254-255d

—

-

—

—

—

253-255

-

-

—

-

-

-

248-250

-

—

—

-

—

—

—

-

-

-

—

-

-

-

+ 71[a]

-

R E F .

S-910

R-771

R-771

H-399; M-531

G-309

N-669

W-1108a

N-669

N-669

G-296; G-297; L-505; R-779; S-908

F-233

F-240

B-61 ; S-908; G-296; H-399

T-1002; G-296

B-61 ; H-399; O-704

T-1005

S-918

L-491

T-1002

G-294; 1 G-296

C21H2705F

134

TABLE I


EMPIRICAL FORMULA

C 2 1 H 2 7 0 6 F

^ 2 l " 2 8 ^ 2


tr iamcinolone

12a - f luo ro - l l j 3 ,16a ,17a ,21 -t e t r ahydroxy-1 ,4 -p regna -diene -3 ,20-dione

9a - f l uo ro -16a ,17a , 21 - t r i -hydroxy-4-pregnene-3 ,11 ,20- t r ione

17ß-hydroxy- 17α -methy l -16-methylene -1 ,4 -andr osta -dien-3-one

17/3-hydroxy-17a-vinyl-1,4-andr ostadien -3 -one

17a-ethinyl-17/3-hydroxy-4-andros ten-3-one

1,4 -pregnadiene -3 ,20 -dione

TRANSFORMATION

20/3-OH-20-C=O

20/3-OH-20-C = O; Δ1

16a-OH

16a-OH

1

Δ

1

Δ

3/3-OH-*3-C=0; Δ 5 - * Δ 4

1

Δ

YIELD %

-

-

-

-

—

-

~

51

-

70

-

-

-

-

-

-

-

-

60

-

17

ORGANISM





Streptomyces argenteolus


Streptomyces sp„




Actinoplanes mis sour i ens i s




Calonectr ia decora



Fusa r ium solani

Gloeosporium ol ivarum Mycobacterium smegmat i s




-

-

-

-

—

-

-

145-148

165-166

264-266

144-147

-

-

-

151-152

-

-

151

149-151

150-153

-

150-151

-

-

-

-

—

-

—

-101[d|

-

-

-

-

-

-

+120[e]

~

-

+122[c]

+ 120[e|

-

—

R E F .

G-294; G-296

G-294; G-296

G-294; G-296

G-296

H-380

F-257

S-788

B-76

W-1109 1

C-84

M-536

S-942; H-399

F-233

F-240

V-1053; W-1096

H-399

P-733

N-663

K-465

S-820; S-873

H-399

S-885

135

TABLE I


EMPIRICAL FORMULA

C2iH2802

^ 2 l " 2 8 ^ 3


1 ,4-pregnadiene-3 ,20-dione

1,4 -pregnadiene -3 ,20 -dione -7ö-H3

1,4 -pregnadiene -3 ,20 -dione -I60-H3

1,4 -pregnadiene -3 ,20 -dione -l l a - H 3 , 12ö-H3

l l o - h y d r o x y - 1 , 4 - p r e g n a -diene -3 ,20-dione

11/3-hydroxy-l, 4 -p regna-diene -3 ,20 -dione

17o-hydroxy-1 ,4 -pregna-d iene-3 ,20-dione

21-hydroxy-1 ,4 -p regna-diene -3 ,20 -dione

TRANSFORMATION

Δ1

1,4 Δ (5α)

Δ1,4(5/3)

3 j 3 - O H ^ 3 - C = 0 ; Δ1

3 j3-OH-3-C = 0 ; Δ 5 - ^ Δ 4 ; Δ1

3 ß - O A c ^ 3 - C = 0 ; Δ 5 - Δ 4 ; Δ1

2 0 ß - O H ^ 2 0 - C = O ; 3j3-OH^3-C = 0 ; Δ 5 - > Δ 4 ; Δ1

Δ1

1

Δ

Δ1

1

Δ

Δ1

Δ1

Δ1

YIELD

% ι 20

—

-

-

45

49

50

1

41

-

-

-

-

-

-

8(cr.)

73

-

49

66(cr.)

-

—

ORGANISM

Nocardia sp.

Septomyxa affinis

S t reptomyces lavendulae

Nocardia sp.

Nocardia sp.








Bacter ium cyclo-oxydans


Bacter ium mycoides


Septomyxa affinis


Septomyxa affinis

Septomyxa affinis


Baci l lus sp.



CONSTANTS m.p.° [<*]D

150-151

—

-

-

150-152

150-152

150-155

-

152-153

-

-

-

228-230

-

-

228-230

232.5-234

232-234

-

179-180

183-187

-

-

-

—

-

-

-

-

+112[e]

-

+122[cl

-

-

-

+ 93[c]

-

-

+ 93[c]

+117[cl

—

-

-

+108[a]

-

-

R E F .

S-897; S-888

W-1072; H-399; V-1048

P-733

S-888

S-888

N-665

T-1027; 1-420

T-1027; 1-420

N-665; C-128

G-323

G-323

G-323

K-480

F-233

F-240

T-995

E - 2 0 8 ; W-1072; K-456

S-942

W-1072

W-1072

M-536

S-848

S-942

F-233

136

TABLE I


1

EMPIRICAL FORMULA

C21H2803


21 -hydroxy-1,4-pregnadiene -3,20-dione

21-hydroxy- l , 4 -p regnad iene -3,20-dione

1 l a -hyd roxy -4 ,6 -p regna -diene-3,20-dione

15a -hydroxy-4 ,9 ( l l ) -p regna -diene-3 ,20-dione

16a - hydr oxy -17/3 - methyl -18 -nor-4 ,13-17a-pregnadiene -3,20-dione

16/3-hydroxy-17ß-methyl-18-nor -4 ,13-17a-pregnadiene-3,20-dione

21-hydroxy-4 ,14-pregna-diene-3,20-dione

21-hydroxy-4 ,16-pregna-diene-3 ,20-dione

3 -hydroxy-9 ,10-seco-1,3, 5(10) -p regna t r i ene-3,20-dione

TRANSFORMATION

Δ1

1

Δ ; 21-OAC-21-OH

Δ 1 ' 4 (5ß-H)

21-OH

11a-OH

15a-OH

3 ß - O H - 3 - C = 0 ; Δ 5 -*Δ 4

3 ß - O H - 3 - C = 0 ; Δ 5 - Δ 4

21-OH

21-OH

1

Δ ; 9a-OH; rev . aldol.; enol.

YIELD %

ca. 100

-

88

60(cr.)

-

-

26

-

—

-

-

-

68(cr0)

22-51

-

7

27

-

—

—

<1

ORGANISM

Calonectr ia decora

Calonectr ia decora



Gliocladium ro seum

Helminthosporium turc icum



Septomyxa affinis

My co bacter ium smegmat i s

Mi cromonospor a chalcea








Ophiobolus herpotr ichus

Cercospore l la herpotr ichoides

Kabatiella phoradendr i



189-195d

185-192

-

185-195

185-191

-

-

184-189

-

-

-

-

-

185-192

160-162

-

138-140

128-129

182-184

—

-

+120[c]

-

-

+110[m]

-

-

+110[al

-

-

-

-

-

+120[c]

+ l l l [ c l

-

+187[d] + 82[c]

+ 141[d] +136[c]

-

—

—

R E F .

V-1053

W-1096

N-665

W-1096

S-857

S-857

S-857

S-848

W-1072

S-873

S-867

S-866

S-866

W-1101

P-730; M-601

M-599

S-839

S-839

M-576

L-490

L-498

S-820

137

TABLE I


EMPIRICAL FORMULA

^21 " 2 8 ^ 3

C 2 1 H 2 8 0 3 BrF

C2 1 H2 8 0 4


l l /3 ,21 -d ihydroxy- l ,4 ,17 (20) -p regna t r i en -3 -one

11/3,12/3-oxido-4-pregnene-3,20-dione

17a -b romo-6a - f luo ro - l l / 3 -hydroxy-4 -p regnene -3 ,20 -dione

17/3-hydroxy-4-androstene-3,11 -dione aceta te

6/3,1 la -dihydroxy -1 ,4 -pr egnadiene-3 ,20-dione

11/3,21-dihydroxy-1,4-pr egnadiene -3 ,20 -dione

16α ,21-d ihydroxy-1 ,4-pr egnadiene -3 ,20 -dione

17a, 21-d ihydroxy-1 ,4 -pr egnadiene-3,20-dione

TRANSFORMATION

Δ1

Δ 1 Χ - 1 1 ^ , 1 2 ^ -oxide

llj3-OH

17/3-Ac^l7/3-OAc

6/3-OH

1

Δ

Δ1

1

Δ

YIELD %

80(cr.)

1

—

12

-

—

-

42

-

33(cr.)

44

-

-

-

-

3

-

—

—

33

-

~

42

ORGANISM

Septomyxa affinis

Curvular ia lunata

Curvular ia lunata



Chaetomium succineum


Bacil lus sp.


Calonectr ia decora



Helminthospor ium tu rc icum

Mycobacter ium phlei





Bacter ium mycoides


Azotomonas f luorescens

Bacillus lentus

Bacillus pulvifaciens



149-153

-

—

167.5-169

-

—

-

210-218

-

216-220

227.5-230.5

208-218

-

217-218

-

-

207-211

-

-

—

-

240-242

-

217.5-219

-

—

-

-

—

-

+150[el

-

+158[e]

+173 [m]

+140[e]

-

+154[el

-

-

+136[e]

-

-

-

-

+80[dl

-

+70[cl

R E F .

W-1072; M-647; K-456; R-766

K-484

R-759

F-250

C-108

C-108

1-420

S-848

S-942

V-1053; W-1096 H-389; N - 6 7 1 ; N-665 S-857

S-857

S-873

H-399

S-857

S-848

F-233

F-240

H-376

T-989

R-750

1-420

T-1027 i

138

TABLE I


EMPIRICAL FORMULA

^2 l "28^4


17ö ,21 -d ihydroxy- l , 4 -pregnadiene -3 ,20-dione

TRANSFORMATION

Δ1

YIELD %

56

43

-

-

-

-

-

53

—

32

65

-

-

-

-

60(cr.)

-

-

-

—

—

-

-

24

—

ORGANISM

Bacil lus sp. Bacil lus sphaer icus


Bacillus subti l is



Bacter ium mycoides

Calonectr ia decora




Flavobacter ium sp.


Fusa r ium solani

Fusa r ium solani

Fusa r ium solani




Helminthosporium gramineum

Helminthosporium sp.

Helminthospor ium zizaniae

Hypomyces solani

Mycobacterium f la vu m

Mycococcus sp.



234-238

226-230

-

-

-

-

227-233d

246-250d

—

240-242

-

242-244

229-233

-

226-230

232-236

225-230

-

—

—

224-229

-

—

-

—

+75|c |

+77[e|

—

-

—

-

+76[e|

+76[c|

—

+57[c|

-

—

+76[e]

-

+77[e]

+80[cl

+77lel

-

—

—

+ 77[e |

-

—

-

—

REF.

S-848 S-942; i H-399 K-444

L-522

K-480

F-233

F-240

W-1096; V-1053

H-389; N - 6 7 1 ; N-665

H-399; L-522

F-275

1-430

F-275

V-1053

V-1048; S-835

K-462

S-857

K-464; K-465

K-465

K-460

S-857

K-460

L-525

C-100

1-429

H-399

139

TABLE I


EMPIRICAL FORMULA

("21 " 2 8 * Λ


1 la, 21 - dihy dr oxy -1 ,4 -pregnadiene-3 ,20-d ione

6/3,12a-dihy dr oxy -4 ,9 (11 ) -pr e gnadiene - 3 , 2 0 - dione

TRANSFORMATION

^

A 1 ; 2 1 - O A c - 2 1 - O H

Δ 1 ' 4 (5αΗ)

Δ1,4(5/3Η)

3 J 3 - O A C — 3 - C = O;

2 1 - O A C - 2 1 - O H

6j3-OH; 12a-OH

YIELD %

-

—

—

12

-

—

-

-

20

70-80

-

-

-

—

-

-

-

-

-

-

10-15

25

51(cr.)

—

ORGANISM


Pseudomonas boreopolis

Pseudomonas chlor or aphis


Pseudomonas oleovorans

Pseudomonas sp.

Rhizoctonia solani

Septomyxa affinis

Septomyxa affinis

Septomyxa affinis

Se r r a t i a m a r c e s c e n s

S te reum fasciatum

St reptomyces flaveolus

S t rep tomyces lavendulae

St reptomyces sp .

Volutella ci l iata



Nocardia blackwellii





Col le totr ichum phomoides

Thamnidium elegans

CONSTANTS m . p . ° [ a ] p |

-

—

—

220-231

-

—

221

-

238-242

-

~

233-234

235-239d

-

-

-

-

235-236

-

-

238-240

246-249

231-232

—

-

-

—

+8205[mj

-

—

+72[cl

-

+70[cl

-

-

+80[cl

+75[el

-

-

-

-

+72[al

-

-

-

+76[c]

+107[c]

—·

R E F .

S-857

T-960

N-648

S-848

T-960

N-652; U-1039; 1-414

T-956

S-835; V-1048

W-1072

S-901

T-960

T-959

K-470

S-835; V-1048

K-470

L-525

F-275

S-873

S-943

S-943

C-128; C-115

N-665

F-277

F-277

F-277

140

TABLE I


EMPIRICAL FORMULA

^ 2 1 " 2 8 ^ 4


6 /3 ,X-d ihydroxy-4 ,9 ( l l ) -pr egnadiene -3 ,20 -dione

17a,21 -dihydroxy-4,9(11) -pr egnadiene -3 ,20 -dione -l l , 1 2 a - H 3

6/3,21 -dihydroxy-4,17 (20)-pregnadiene-3 ,11 -dione

9a ,21-dihydroxy-4 ,17(20)-pr egnadiene-3,11-dione

21-hydroxy-ll /3,12/3-oxido-4-pregnene-3 ,20-d ione

7/3-hydroxy-16a, 17a-oxido -4-pregnene-3 ,20-d ione

1 la-hydroxy-16a ,17a-oxido -4-pregnene-3 ,20-d ione

9a-hydroxy-4-pregnene-3 ,11 ,20- t r ione


17a-hydroxy-4-pregnene-3 , 1 1 , 2 0 - t r ione

21-hydroxy-4-pregnene-3 ,11 ,20- t r ione


TRANSFORMATION

6/3-OH; X-OH

2 1 - O A c - 2 1 - OH

6/3-OH ; 11/3-OH - 11-C=0

9a-OH; 1 1 / 3 - O H - 1 1 - C = 0

21-OH

7/3-OH

11a-OH

9a-OH

15a-OH

17a-OH

21-OH

15a-OH; 12a-OH - 1 2 - C = 0

YIELD %

-

—

14-29

-

59

—

32

19

—

9

31-73

78

-

-

-

—

-

-

38

-

51(cr.)

ORGANISM

Colletotr ichum p ho mo ides

Cur uvular ia lunata


Cunninghamella blakesleeana


Cercospore l l a herpotr ichoides


Pénic i l l ium sp„

Botryodiplodia theobromae

Didymocladium te rna tum




Rhizopus ref lexus

Ascochyta linicola

Calonectr ia decora

F u s a r i u m concolor


Aspergi l lus sp.

Cephalothecium r o s e u m

Aspergi l lus niger

Aspergi l lus niger


Calonectr ia decora

CONSTANTS m . p . ° [<*]D

250-252

—

252-254

-

219.5-221

—

164-166

229-232

—

246-247

247-249

235-237

238-238.5

-

—

224-228

227-229

-

178-179

-

170-176

235-239

+23[c]

—

+107[dl

-

+173[dl

—

+179[c]

+158.5[cl

—

—

+136[c]

+146[c]

+137[c]

-

-

+289[c]

+257[el

-

-

-

—

+261[c]

R E F .

F-277

K-484

H-344; H-341

H-344; H-342

H-344; H-342

L-490

D-157

T-1036

P-746

P-746

P - 7 2 7 ; M-644

E-223

B-52 ; D-161

M-644 |

S-828

S-810

M-599

B - 4 4 ; A-31 T-1010

M-600

Z-1124; Z-1123

R-783

M-584; W-1101

S-810

141

TABLE I


EMPIRICAL FORMULA

C21H2804

C21H2804C12

C 2 1 H 2 8 ° 4 F 2

C 2 1 H 2 8 0 4 S

C 21 H 28 0 5


6/3 -hydr oxy -4 -pr egnene -3 ,15 ,20 - t r i one

7£,20/3-dihydroxy-3-keto-4-pregnen-18-o ic acid (18-^20) lactone

l l a ,20 /3 -d ihydroxy-3-ke to -4-pregnen-18-o ic acid (18->20) lactone

9 a , l l / 3 - d i c h l o r o - 1 7 a , 2 1 -d ihydroxy-5-pregnene-3,20-dione

9a , l l / 3 -d i f l uo ro -17a ,21 -d ihydroxy-5-pregnene-3,20-dione

l l /3 ,17a-d ihydroxy-21-m e r c a p t o - 1 , 4 - p r egnadiene -3 ,20-dione

1 7 a , 2 0 a , 2 1 - t r i h y d r o x y - l , 4 -pr egnadiene-3 ,11-dione

17a, 20/3,21 - t r i h y d r o x y - 1 , 4 -pr egnadiene - 3 , 1 1 -dione

6 /3 ,17a ,21 - t r i hydroxy- l , 4 -pr egnadiene -3 ,20 -dione

la, 1 la, 21 - t r ihydr oxy - 1 , 4 -pregnadiene-3 ,20-d ione

TRANSFORMATION

6/3-OH; 1 5 - C = 0 ; (via 15/3-OH)

7ξ-ΟΗ

11α-OH

21-OAc^21-OH

21-OAc^21-OH

2 1 - S A c - 21-SH

2 0 - C = O - 2 0 a - O H

20-C=O^20/3-OH

1 Δ

1

20-C=O^20/3-OH

Δ1

6/3-OH

7a-OH

YIELD %

0.5

—

—

—

—

22

—

-

69

75

60

-

-

-

-

-

-

-

ORGANISM






F lavobac ter ium dehydrogenans

Rhodotorula longiss ima

Calonectr ia decora

F u s a r i u m sp.


Streptomyces albus


St reptomyces hydrogenans

Calonect r ia decora

F u s a r i u m sp.



F u s a r i u m sp.



Baci l lus lentus




280-286

—

—

—

—

238-240d

—

-

184-185

184-185

—

-

-

177-180

-

-

-

229-231

+122[e]

—

—

—

—

+117[d]

;

-

+117[d]

+118[d]

—

-

-

-

-

-

-

-

R E F .

T-1036

L-488; L-489

L-488; L-489

N-691

N-691

N-685

C-110

S-951

S-951

C-100

K-459

C-110

L-522

S-951

S-951

S-951

H-389

S-951

K-465

C-100

R-750

C-108

T-997

142

TABLE I


EMPIRICAL FORMULA

C 2 1 H2 8 0 5


l l ö , 17α, 21 - t r i hyd roxy -1 ,4 -pr egnadiene -3 ,20 -dione

l l / 3 , 1 7 a , 2 1 - t r i h y d r o x y - l , 4 -pr egnadiene -3 ,20 -dione (prednisolone)

TRANSFORMATION

Δ1

11a-OH

11a-OH; 21-OAc^21-OH

1

Δ

YIELD %

25-50

~

-

61(cr.)

-

—

12

-

42

70

-

46

-

62

—

-

—

—

-

-

—

80

94(cr.)

90

—

ORGANISM



Beauveria sp.

Fusa r ium equiset i

Glomere 11a cingulata

Glo mere 11a lagenar ium

unidentified fungus


Glomere l la lagenar ium

Azotobacter agi l is

Azotobacter indicus

Azotomonas f luorescens

Bacil lus lentus



Bacil lus sp.



Bac te r ium cyc lo-oxydans


Bacter ium mycoides

Calonectr ia decora







246-247d

-

-

206-208

-

-

222-223

-

—

-

235-237

220-222

~

228-231

—

233-236d

—

-

-

238-241

-

239-241d

240-241d

235d

-

+ 73 [m]

-

-

+ 76[d]

-

-

+ 76[m]

-

—

-

+100[d]

+ 99[d]

-

+ 98[m]

-

+100[d]

—

—

-

-

—

+107[dl

+102[d]

+100[d]

—

R E F .

H-389; H-384; N-665

V-1048; S-835

1-421

M-557

C-109

C-109

T-990

C-109

C-109

T-989

T-989

T-989

R-750

T-1027

1-420

S-848

S-942; H-399

K-468

K-480

F-233

F-240

W-1096

N-665

N-665

H-389; N-671

K-467

H-399

TABLE I


EMPIRICAL FORMULA

C21H2805


Prednisolone

TRANSFORMATION

Δ1

α , Ι - α - Δ ^ 1

Ij4

Δ (5α-Η)

Δ1,4(5β-Ή)

YIELD %

-

84

75

-

-

46-68

-

-

77-80

55-62

—

-

-

-

-

—

-

-

-

-

-

-

-

-

ORGANISM



Flavobacter ium sp„



Micrococcus sp .



Mycobacter ium sp.

Mycococcus sp0


Nocardia sp.




Septomyxa affinis

Se r r a t i a plymuthica

Streptomyces flaveolus


St reptomyces sp.


Calonectr ia decora



Pro taminobac te r rub rum


234-236 + 98[d]

238-241 —

- ~

~ -

236 +100[d]

- -

- -

196-198 +108[e|

- -

- -

- -

- -

- -

- -

- -

— —

- -

232-236d +100[d]

235-237 —

- -

234-236 + 98[d]

— -

- -

- -

R E F .

V-1052

W-1096

1-430

K-465

K-465

1-431

S-864; S-867

S-873

K-476

1-429

H-399

S-939

S-863

S-863

N-648

W-1072; M-647; K-456

T-960

K-470

F-272

K-470

W-1102

W-1096

S-943

S-866

S-866

143

144

TABLE I


EMPIRICAL FORMULA

CMH„805


Prednisolone

12 /3 ,17a ,21- t r ihydroxy- l ,4 -pr egnadiene -3 ,20 -dione

14a, 1 7 a , 2 1 - t r i h y d r o x y - l , 4 -pr egnadiene - 3 , 20 -dione

15 /3 ,17a ,21- t r ihydroxy- l ,4 -pregnadiene-3 ,20-dione

16a, 1 7 a , 2 1 - t r i h y d r o x y - l , 4 -pr egnadiene -3 ,20 -dione

l l / 3 , 1 7 a , 2 1 - t r i h y d r o x y - l , 5 -pregnadiene-3 ,20-dione

17a ,20/3 ,21- t r ihydroxy-4 ,6-pregnadiene -3 ,11 -dione

14a, 1 la, 21 - t r ihydr oxy -4,9( 11)-pr egnadiene - 3 , 2 0 -dione

17a, 21-dihydroxy-l/3,11/3-oxido -5 ,9 -cyclopr egnane -3,20-dione

l l /3 ,21-d ihydroxy-3 ,20-dike to-4-pregnen-18-a l (18-^11) hemiaceta l (aldosterone)

TRANSFORMATION

3a-OH >3-C = 0 ; Δ1,4(5/3-Η)

11/3-OH

21-OH

Δ 1 ; 11/3-OH

1

Δ

1

Δ

14α-OH 1

Δ

1

Δ

21-OAC-21-OH

11/3,17α, 21-tr iOAc — 11/3, 17α, 21- t r iOH

20-C=O-+20/3-OH

14α-OH

11/3,21-diOAc-11/3,21-diOHj Δ ' - Ι Ι ^ - Ο Η - Ι / Β , 11/3-oxide

11/3-OH

d,l->d-21-OH + 1

YIELD %

-

-

19

11

—

-

-

20-30

-

2

10

—

-

-

—

—

26

—

-

ORGANISM


Coniothyrium hel leborine

Cort ic ium sasaki i

Unidentified fungus

Ophiobolus herpotr ichus



Pseudomonas sp.

Bacil lus lentus


Bacil lus lentus


Unidentified fungus



Bacter ium mycoides



Curvular ia lunata

Curvular ia lunata






-

-

232-236d

230-231

—

227-231

-

-

232-234

232-234

229-230

217-218

234-234.5

-

-

-

—

-

208-209; 204-205 (polymorph)

191-194

208-213

200-206

165-168

162-168

-

-

-

-

—

-

-

-

-

+132[cl

+107[ml

-

-

-

-

—

+126 [d]

—

- 14

- 14

+142[a]

R E F .

S-943

T-1004

H-350

T-990

W-1101; H-388; O-700

H-327

T-960

T-961; U-1040

R-750

R-749

R-750

S-872; S-873

T-990

C-126; C-127

F-233

F-240

N-690

N-690

G-306

B-65

G-292

R-777

W-1100

w-1102; V-1055

145

TABLE I


EMPIRICAL FORMULA

^ 2 l " 2 8 ^ 5


17a ,21-dihydroxy-9a , 11a-ox ido-4 -p regnene -3 ,20 -dione

17a ,21-dihydroxy-9a , 11a-ox ido-4 -p regnene-3 ,20-dione-11/3,12a-H3

6/3,12a-dihydroxy-9j3, 11/3-ox ido-4 -p regnene -3 ,20 -dione

17a,21-dihydroxy-9/3, l l /3-ox ido-4 -p regnene-3 ,20-dione

17a,21-dihydroxy-9/3 , l l /3-ox ido-4 -p regnene -3 ,20 -d ione - l l a , 12a -H3

16a, 21-dihydroxy-l l /3,12/3-ox ido-4 -p regnene -3 ,20 -dione

17a,21-dihydroxy-14a, 15a-ox ido-4 -p regnene -3 ,20 -dione

2/3,21-dihydroxy-16a,17a-ox ido-4 -p regnene -3 ,20 -dione

1 l a , 21 -dihy dr oxy -16a, 17a -ox ido-4 -p regnene-3 ,20-dione

17a ,21 -d ihydroxy- l -5ß -pregnene - 3 , 1 1 , 2 0 - t r ione

6/3,21-dihydroxy-4-pregnene-3 , 1 1 , 2 0 - t r ione

14a, 21-dihy dr oxy-4-pr egnene - 3 , 1 1 , 2 0 - t r ione

TRANSFORMATION

A 9 ( l l ) - 9 a , l l a - o x i d e

9 ( i l )

Δ -*9a, 11a-oxide; 2 1 - O A c - 2 1 - O H

9(11) Δ - 9 / 3 , 1 Iß -oxide; 6/3-OH; 12a-OH

9(11) Δ '->9|3,ll/3-oxide

9 (n ) Δ — 9/3,1 Iß-oxide; 21-OAc-* 21-OH

16a-OH

14

Δ —14a, 15a- oxide

2/3-OH

11a-OH; 21-OAC-21-OH

Δ4-5/3-Η

6β-ΟΗ; l l / 3 - O H - l l - C = 0

14a-OH

14a-OH; l l ß - O H - l l - C = 0

1

YIELD %

20

46

41(cr0)

-

—

11

26

-

—

-

~

—

—

14(cr.)

16(cr.)

36(cr.)

40(cr.)

ORGANISM

Nocardia sp.

Curvular ia sp.

Colletotr ichum p ho mo ides


Curvular ia brachyspor ia

Curvular ia lunata

Curvular ia lunata



Curvular ia lunata


Mucor gr iseocyanus

Mucor pa ras i t i cus

Phycomyces blakesleeanus



St reptomyces sp.

Sclerot ium hydrophilum

Absidia r e g n i e r i


CONSTANTS m . p . ° [ûi]D

213-215

223

202-204

210-211

—

208-211

212-214

230-232

-

—

-

-

—

218-220

-

195-200

208-214

210-215

+ 85fd]

—

+ 5 I C 1

+ 13[d]

—

—

+158[cl

+135[dl

-

—

-

-

—

+127[m]

~

+146.5 [m]

+ 69[m]

R E F .

S-886

K-484

F-277

B-66

S-865

B-66; S-865; B-65

K-484

D-157

B-66; S-865

B-66; S-865

B-66; S-865

B-66; S-865

B-66; S-865

S-865

L-496

A-8

G-314

S-856

S-841

S-841; S-851

146

TABLE I


EMPIRICAL FORMULA

C21 H28°5

C 2 l H 2 8 U 5 r 2


15/3, 21 -d ihydroxy-4-pregnene-3 ,11 ,20- t r ione

17a, 21 -dihydroxy -4 -pregnene-3 ,11 ,20- t r ione (cortisone)

17a, 21 -dihydroxy -16a-methyl -18-nor -4-pregnene -3 ,11 ,20- t r ione

6a ,21-d i f luoro- l l j3 ,16a ,17a-t r ihydroxy-4-pregnene-3,20-dione

TRANSFORMATION

15/3-OH; l l / 3 - O H - l l - C = 0

Δ1—H

21-OAC-21-OH

l l j 3 - O H - l l - C = 0

l l ß - O H - > l l - C = 0 ; 21-OAc-»21-OH

17a-OH

17a-OH; l l j3-OH-»l l -C = 0

11)3 -OH; l l j 3 - O H - l l - C = 0

21-OH

16a-OH

YIELD %

28(cr.)

21(cr.)

1

-

59

—

3

-

-

~

—

-

-

13

-

~

-

-

—

ORGANISM

Botryt is c inerea





Cunninghamella e legans

Cunninghamella e legans


Trichothecium r o s e u m



Absidia sp0

Botryt is c inerea




Cunninghamella sp0

Curvular ia lunata

Rhizoctonia sp.

St reptomyces fradiae




189-195

195-200

215-220d

-

211-213

-

-

206-216

~

-

-

-

226-227

-

—

-

-

-

—

+180[m]

+190[m]

—

-

-

—

-

-

-

-

—

-

-

-

-

-

-

—

—

R E F .

S-842

S-856

H-382

S-948

H-344

E-225

E-225

M-600

M-584

M-600

M-584

C-98; H-334

C-98

H-327

M-601

M-556; 0 -696; H-339; M-555; M-641; S-919

C-98

C-98

G-312; G-313

H-328

A - l l

M-532

147

TABLE I


EMPIRICAL FORMULA

C21 H28°6


11/3,16a, 17aa- t r ihydroxy-17a/3-hydroxymethyl-D-homo - 1 , 4 -andr ostadien - 3 , 17-dione

*6/3, 11/3,17α ,21- te t rahydroxy-1,4 -pr egnadiene -3 ,20-d ione

7a, 11/3,17a, 21- te t r ahydr oxy -1,4 -pr egnadiene -3 ,20-dione

11/3,14a, 17a, 21 - te t r ahydr oxy-1,4 -pr egnadiene -3 ,20-dione

1 l a , 15/3, 17a, 21 - te t r ahydr oxy-1,4 -pr egnadiene -3 ,20-dione

11/3,15/3,17a, 21-tetrahydroxy-1,4 -pr egnadiene -3 ,20-d ione

11/3,16a,17a,21 - te t r ahydr oxy-1,4 -pr egnadiene -3 ,20-dione

11/3,14a,21-tr ihydroxy-3 ,20-d ike to -4-pregnen-18-al (18 — 11) hemiaceta l

11/3,17a, 21 - tr ihydroxy - 3 , 2 0 -diketo -4 -pr egnen -18 -al (18 - 11) hemiace ta l

14a, 17a,21-tr ihydroxy-9/3, l l /3-oxido-4-pregnene-3 , 20-dione

11/3,17a, 21- t r ihydroxy-14a , 15a-ox ido-4-pregnene-3 , 20-dione

2/3 ,17a ,21- t r ihydroxy-4-p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e (tentative)

6/3,17a, 21 - tr ihydroxy -4 -p r egnene -3 ,11 ,20 - t r i one (tentative)

7α, 17α, 21- t r ihydroxy-4-p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e

La t e r , unpublished work has £

TRANSFORMATION

16a-OH ; 17a-OH-17/3-(20-C = 0 - 2 1 - O H ) -17aa-OH-17a/3-CH 2 OH-17-C=0

6/3-OH

7α-OH

Δ1

Δ1

Δ1

Δ1

16α-OH

14α-OH

d , l - d-17a-OH + 1

14a-OH; ΔΚ11) - , 9β, 11/3-oxide

11/3-OH; Δχ4-> 14a, 15a-oxide

11-C = 0 (via 11/3-OH); 2/3-OH

6/3-OH; 11-C = 0 (via 11/3-OH)

7a-OH

ihown this product to b

YIELD %

—

-

—

—

—

-

-

28

10

-

-

—

—

—

—

—

—

e 6/3,17

ORGANISM


Chaetomium cochliodes


My co bacter ium smegmat i s



Bac te r ium havaniensis Bac te r ium mycoides






Tr ichothecium r o s e u m

Curvular ia lunata


Curvular ia lunata

Rhizoctonia solani

Rhizoctonia solani


a , 2 1 - t r i h y d r o x y - l , 4 - (


—

—

227-229

—

—

-

-231-232

229-231

-

-

—

—

—

181-200

210-215d

—

regnadiene

—

-

+103.5['d|

—

—

-

-

+77 [m|

—

-

-

—

—

—

:

—

+113|d|

-

-3 ,11 ,20 -

REF.

G-297

C-108 !

T-997

S-873; S-874

C-126; C-127

C-127; C-126

F-233

F-240

B-61; B-59; B-54

B-61 ; H-399

L-491

G-297; F-257

W-1108

W-1102

B-65

S-865

S-865

G-312

G-312

T-997

t r ionea

148

TABLE I


EMPIRICAL FORMULA

C 21 " 2 8 ^ 6

^ 2 1 " 2 8 ̂ 6 * 2

C21H2903Br

C21H2903F

C21H2903N

C21H2904Br

C 2 1 H 2 9 0 4 F

C21H2905C1


15a, 1 la, 21 - t r ihydr oxy -4 -p regnene -3 ,11 ,20 - t r i one

15j3,17a,21- t r ihydroxy-4-pr egnene - 3 , 1 1 , 2 0 - t r ione

6a, 9a-di f luoro- l l /3 ,16a , 17a, 21 - te t r ahydr oxy-4-pr egnene 3,20-dione

5a, 12a-difluoro-11/3,16a, 17a, 21- te t r ahydr oxy - 4 -pregnene-3 ,20-d ione

17a -bromo -1 l a -hydroxy -4-pregnene-3 ,20-d ione

17a-bromo- l l /3-hydroxy-4-pregnene-3 ,20-d ione

6a - f luoro -17a-hydroxy- l -5a-pregnene-3 ,20-d ione

6a-fluor o -17a -hydroxy-1 -5/3-pregnene-3,20-dione

6a -f l u o r o - 1 l a - h y d r o x y - 4 -pregnene-3 ,20-d ione

12a -aza -C -homo -1 - 5a -p r egnene -3 ,12 ,20 - t r i one

12a -b romo- l l /3 ,16a -dihydr oxy -4 - pr egnene -3,20-dione

6a-f luoro- l l /3 ,16a-dihydroxy-4-pregnene-3 ,20-d ione

6a-fluor o - l l a , 17a-dihydroxy-4-pregnene-3 ,20-d ione

6/3-f luoro-l la , 17a-dihydroxy-4-pregnene-3 ,20-d ione

6/3-fluoro-ll/3,17a-dihydroxy-4-pregnene-3 ,20-d ione

9a-fluor 0-2/3, 11/3-dihydroxy-4-pregnene-3 ,20-d ione

9a-fluoro -11/3,21-dihydroxy-4-pregnene-3 ,20-d ione

12a-f luoro- l l /3 ,14a-d ihydroxy-4-pregnene-3 , 20-dione

12a-f luoro- l l /3 ,16a-d ihydroxy-4-pregnene-3 , 20-dione

6 a - c h l o r o - l l a , 1 7 a , 2 1 -t r ihydroxy-4-pregnene-3 , 20-dione

TRANSFORMATION

15a-OH; 21-OAc-+21-OH

15/3-OH

16a-OH

16a-OH

11a-OH

11/3-OH

Δ1

Δ1

11a-OH

3/3-OAc - 3-C = O; Δ '

16a-OH

16a-OH

11a-OH

11a-OH

11/3-OH

2/3-OH

d , l ^ d - 2 1 - O H + l

14a-OH

16a-OH

11a-OH

YIELD %

-

—

18

—

—

—

—

—

—

26

—

-

—

—

—

—

—

—

—

ORGANISM

Fusa r ium oxysporium

Bacil lus megather ium




Curvular ia lunata

Septomyxa affinis

Septomyxa affinis







Chaetomella oblonga







-

—

242-248

—

—

—

—

—

—

206-207o5

211-212

-

—

—

—

—

—

—

—

-

—

+58[d]

—

-

-

—

—

—

+32[m]

+101[c]

~

—

—

—

—

—

—

—

R E F .

M-599

C-126

M-586

F-261

V-1048; S*835

R-756; R-773

B-34

B-34

V-1048; S-835

M-563

F-256

B-35

F-268

H-391

H-391

L-496

W-1102

W-1103

F - 2 5 6 ; F-257

F-268

149

TABLE I


EMPIRICAL FORMULA

C21H2905C1

C 2 1 H 2 9 ° 5 F

C21H2906C1

C 2 1 H 2 9 0 6 F


6 a - c h l o r o - l l / 3 , 1 7 a , 2 1 -t r i hyd roxy-4 -p regnene -3 , 20-dione

6a- f luoro-2 /3 ,17a ,21-t r ihydroxy-4-p regnene-3 , 20-dione

6a- f luoro- l l /3 ,16« , 17a-t r i hydroxy-4 -p regnene -3 , 20-dione

6 a - f l u o r o - l l a , 17a, 2 1 -t r ihydroxy-4-pregnene-3,20-dione

6a- f luoro-15/3 ,17a ,21-t r ihydroxy-4-pregnene-3 , 20-dione

9 a - f l u o r o - l l / 3 , 1 6 a , 2 1 -t r ihydroxy-4-p regnene-3 , 20-dione

9 a - f l u o r o - l l / 3 , 1 7 a , 2 1 -t r ihydroxy-4-pregnene-3,20-dione

12a -fluor o -11/3,14a, 17a-t r ihydroxy-4-pregnene-3,20-dione

9a -chlor o -2/3,11/3,17a, 2 1 -t e t r ahydroxy-4 -p regnene -3,20-dione

9a -ch lo ro - l l / 3 ,16a , 17a, 2 1 -t e t r ahydroxy-4 -p regnene -3,20-dione

9a- f luoro- l l /3 ,16a , 17aa-t r ihydroxy -17a/3 -hydr oxy -methyl-D-homo - 4 -andr ostene -3 ,17 -dione

9a- f luoro- l l /3 ,16α, 17α, 20/3, 21 -pentahydroxy -1 ,4 -pregnadien-3-one

TRANSFORMATION

11/3-OH; 21-OAc - 21-OH

2/3-OH

16a-OH

11a-OH

15ß-OH

16a-OH

2 1 - C = 0 — 21-OH

21-OAc-> 21-OH

14a-OH

2/3-OH

16a-OH

16a-OH; 17a-OH-17ß-(20-C = 0 - 2 1 - O H ) ^ 17aa-OH-17a/3-CH 2 OH-17-C=0

Δ1

2 0 - C = O ^ 20ß-OH

1

2 0 - C = O — 20/3-OH

YIELD %

-

—

—

32

—

24

~

—

—

—

-

—

< 1

ORGANISM








St reptomyces ol ivochromogenus








Mycobacter ium rhodochorus




-

—

—

201-203

225-228

241.5-244.5

-

—

—

—

252-254

~

—

—

—

262-264

-

—

—

+100[e]

+79 [e]

+127[m]

—

—

—

—

+84[m]

-

—

—

—

-

R E F .

R-770

L-496

M-530

F-268

F-268

H-403

S-907

S-941

W-1103

S-913

S-913

S-910; S-912; G-297; G-295

G-296; G-294

G-296; S-908

G-296; S-908

G-296

S-908

S-908

150

TABLE I


EMPIRICAL FORMULA

^ 21 " 2 9 ^ 6 **


6a-f luoro- l l /3 ,16α, 1 7 a , 2 1 -te t rahydroxy-4-pregnene-3,20-dione

9a-f luoro- l4 ,11/3 ,17a, 2 1 -te t rahydroxy-4-pregnene-3,20-dione

9a- f luoro-2 /3 , l l j3 ,17a ,21-te t r ahydroxy-4-pregnene-3,20-dione

9a- f luoro-6 j3 , l l /3 ,17a ,21-te t rahydroxy-4-pregnene-3,20-dione

9 a - f l u o r o - 7 a , l l / 3 , 1 7 a , 2 1 -te t rahydroxy-4-pregnene-3,20-dione

9 a - f l u o r o - l l / 3 , 1 4 a , 1 7 a , 2 1 -te t rahydroxy-4-pregnene-3,20-dione

9a-f luoro- l l j3 ,15/3 ,16a ,21-te t rahydroxy-4-pregnene-3,20-dione

9a- f luoro- l lß ,15 j3 ,17a ,21-te t rahydroxy-4-pregnene-3,20-dione

9a - f l uo ro - l l j 3 , 16a ,17a ,21 -te t rahydroxy-4-pregnene-3,20-dione

12a - f luo ro - l l / 3 ,16a ,17a ,21 -te t rahydroxy-4-pregnene-3,20-dione

TRANSFORMATION

16a-OH

1ξ-ΟΗ

Ι ξ - Ο Η ; 21 -OAc-21 -OH

2/3-OH

6/3-OH

6/3-OH; 21 -OAc-21-OH

7a-OH

14a-OH

15/3-OH

15j3-OH

Δ1 - H

16a-OH

16a-OH; 21 -OAc-21-OH

16a-OH

YIELD %

26(cr.)

38

5

2

—

-

—

—

—

—

-

30-70

-

50

-

-

-

ORGANISM


Mor t ie re l la sp.

St reptomyces antibioticus

Streptomyces ruber



St reptomyces r i m o s u s








Nocardia i tal ica

Streptomyces californicus


Streptomyces sp.

St reptomyces halstedi i

S t reptomyces argenteolus



234-236

-

248-254

247-252

245-249

224-227

—

—

—

—

-

-

-

250-252

-

235-238

-

+ 95[d]

-

+122[m|

-

+ 1.5[ni|

+ 56[m|

—

—

—

—

-

-

-

+ 97[pl

-

+ 94.5[p]

-

R E F .

M-586; M-533

F-237

F-234

F-234

M-569; S-941

S-912; S-913

S-909

M-569; S-941

T-997

W-1108a

N-669

N-669

G-296

G-296

S-918

L-491

T-1002; G-297; G-295; L-505; S-913

S-788

K-447

H-380

F-256; F-257

151

TABLE I


EMPIRICAL FORMULA

C21H2907C1

C21H2907F

^ 2 1 " 3 0 ^ 2

L21 n30U3


9a-chloro-2/3,11/3,16a, 17a,21-pentahydroxy-4-pregnene-3,20-dione

9a - f luo ro - l£ , 11/3,16o, 17«, 21 -pentahydroxy-4-pregnene-3,20-dione

9a-fluoro-2/3,11/3,16α, 17a,21-pentahydroxy-4-pregnene-3,20-dione

17a -ethyl -17/3-hydr oxy -1 ,4 -andros tadien-3 -one

17/3-hydroxy -1 7a -methyl-16 -méthy lène -4 -andros t en -3 -one

4-pregnene-3 ,20-d ione

17a-ethyl-11/3,17/3-dihydroxy-1,4 -andros tadien-3 -one

17/3 -hydr oxy -4 -androsten -3-one acetate

5 -androstene -3 ,17 -dione 3-ethylene ketal

TRANSFORMATION

2/3-OH

16a-OH

1ξ-ΟΗ

16a-OH

2/3-OH; 16a-OH

1

Δ

3/3-OH -*3-C = 0 ; Δ 5 - Δ 4

3 / 3 - O H - 3 - C = 0 ; Δ 5 - Δ 4

d,l-3/3-OH-> d - 3 - C = 0 + l ; ά , 1 - Δ 5 - α - Δ 4 +1

3/3-OAc-3-C = 0 ; Δ 5 ^ Δ 4

11/3-OH

17ß-Ac-17ß-OAc

17-C=0-*17/3-OAc

17 /3-OH-17-C=0

YIELD %

-

—

3(cr.)

—

24

-

30

-

-

82

-

-

2

—

10-15

-

88

ORGANISM



Mor t ie re l la zonata





Asper gillus sp0



Eremothec ium ashbyii



Streptomyces sp0

Ustilago zeae

Asper gillus niger

St reptomyces fradiae


Curvular ia lunata

Cladosporium r e s i n a e

Saccharomyces fragi l is



-

—

220-223

-

144-146

-

129-130

_

-

127-128

-

-

123-126

125-127

-

-

138.5-140

-

196-198

-

—

- 26.5[m|

—

- 5 [ d |

-

+ 175|d|

-

-

—

-

-

+191

+190

-

-

+ 85 |a |

-

+ 16[c]

REF.

S-913

S-913

F-237

S-912

S-912; S-913

N-667a

B-76

C-104; P-710

T-1027; 1-420

M-546

P-710

E-214

P-710

P-710; P-712; P-716; F-267

P-710

W-1102

W-1102

T-1027; 1-420

N-667a

F-254; F-250

M-572

S-885

152

TABLE I


EMPIRICAL FORMULA

^21 "30^3


11a, 20/3-dihydroxy -1 ,4 -pr egnadien-3 -one

16a, 20/3-dihydroxy-1,4-pr egnadien-3 -one

16a, 20a -dihydroxy -17/3 -m e t h y l - 1 8 - n o r - 1 7 a - 4 , 1 3 -pr egnadien -3 -one

3,9ξ -dihydroxy - 9 , 1 0 - s e c o -1,3,5(10) -p regna t r i en -20-one

20a-hydroxy-4-pregnene-3,11-dione

1 la -hydroxy-17a-4 -p regnene-3,20-dione

1/3 -hydroxy -4 -pregnene -3,20-dione

1ξ-hydroxy-4-pregnene-3,20-dione

2/3-hydroxy-4-pregnene-3,20-dione




(Footnote) r ev i s e to 7/3- r e

TRANSFORMATION

1

20-C=O-*20/3-OH

1

20-C=O->20/3-OH

2 0 - C = O ^ 2 0 a - O H ; 13-Me-16a ,17a-oxido->A13-16a-OH-17/3-Me

Δ 1 ; 9a-OH; r ev . aldol. ; enol. ; 9 - C = 0 - 9 ^ - O H

2 0 - C = O - 2 0 a - O H

11a-OH; A 1 6 -17 -Ac-17a -Ac

3 / 3 - O H - 3 - C = 0 ; Δ5 - Δ 4

1|-OH

2/3-OH

6/3-OH

7a-OH

7/3-OH

. T-1037

YIELD %

~

57

—

34

< 1

-

24

-

35

—

t r .

—

-

-

10

—

18

4(cr.)

15

ORGANISM







Aspergi l lus niger




Cladosporium sp.



Mor t ie re l la pusi l la


Streptomyces aureofaciens

Streptomyces sp.

Çephalosporium sp. (see footnote) Diplodia na ta lens is

Helminthosporium sp.


Cladosporium sp.


227-229

227-229

226-227

172-175

—

-

209-211.5

153

154-156

-

184-186

:

-

175-176

172-173

—

227-231

229-230

188-191

+ 41[c]

+ 41[c]

- 15[cl

- 15[c]

—

-

- 12[c]

+192[c]

+142[cl

—

-

:

-

+108

+ 98[c]

:

+154[d]

+167[c]

+141[c] +158[d]

R E F .

K-480

T-995

F-288; F -271 ; F-273

C-88; C-90

S-820

C-122

M-603

M-579; M-601; M-605

B-77

N-689

S-941

T-1036

F-239

F-239

E-202

F-288; P-713

S-854; S-847

B-56

T-997

M-570

F-288; F-285; F-286

M-570; S-941

153

TABLE I


EMPIRICAL FORMULA

^21 "30^3



1 lö -hydroxy-4-p regnene-3,20-dione

TRANSFORMATION

7ß-OH

7ß-OH; 3j3-OH->3-C=0; Δ 5 - ^ Δ 4

9ö-OH

l i a - O H

YIELD %

17-36

6-12

31

49

—

—

~

13-17

33

—

-

—

35

—

9

90

15

ORGANISM

Diplodia tuber icola


Ascochyta l inicola


Circ inel la sp.

Coryne bac te r ium s implex




Nocardia sp.


S t rep tomyces aureofaciens

Absidia sp.

Aspergi l lus niger

Asperg i l lus niger




Asperg i l lus sai toi


190.5-192.5 +144[d]

— —

191-194 -

190-192 +204[c]

- -

- —

193-194.5 +185

190-191 +188[cl

193-194.5 +185[cl

- -

189-191 +202[cl +150[a]

- -

166-167 +178[c]

— —

165-168 —

- -

168-170 +169[c]

R E F .

T-1023; T-1025; A-28

T-1025; A-28

S-828

S-885

S-815

S-885; P-740

S-885

D-173

S-898; S-885; P-740; S-897

D-172

S-885

P -713 ; F-288

C-98; N-682

F-283

W-1121; W-1120

D-190

W-1067; W-1065

D-193; K-436; M-562; S-797; V-1048; D-182; S-835; S-900; D-181; W-1066; K-454

1-417

9o-hydroxy-4-pregnene-3,20-dione

154

TABLE I


EMPIRICAL FORMULA

^ 2 1 " 3 0 ^ 3


1 lö -hydroxy-4-pregnene-3,20-dione

TRANSFORMATION

11« -OH

YIELD %

3

-

34

-

-

34(cr.)

—

-

>25

-

—

17

16-28

12

50(cr.)

15

80-83

68-82

50

—

70

ORGANISM

Aspergi l lus sp0

Bacil lus ce reus

Botryt is c ine rea

Cunninghamella echinulata

Cunninghamella sp.

Dactylium dendroides

Gloeosporium kaki

Glomerel la lagenar ium

Pénici l l ium sp0

Pes ta lo t ia foedans

Pes ta lo t ia royenae

Psi locybe cae ru lescens



Rhizopus cambodjae

Rhizopus chinensis

Rhizopus javanicus





Rhizopus sp.

Rhizopus stolonifer


161-165

-

165-166

-

-

164-167

-

-

-

-

166-168

166-167

164-165

168.5-169.5

165-167

166-167

166-168

168-170

—

-

-

-

—

-

-

+ 180|c |

-

-

-

-

+ 176 |c |

+176[c]

-

+178[c)

+ 177[c]

+ 180[c]

+176-180[cl

+ 169[c]

—

-

REF.

D-190; M-603; C-104; 1-417; W-1081;l T-1010

M-568

C-98 |

Z-1125

C-98

D-189

S-855

S-855

D-190; C-99

S-882

S-882

C-113 1

P-729

M-601; N-649

C-84

A-29; A-26

N-682

P-729; M-601

T-1028; T-1009; B-42; T-1011

A-26

C-103; R-766; W-1066

M-554; T-1010; A-29; N-682; K-433

T-1011

155

TABLE I


EMPIRICAL FORMULA

C2 1 H3 0 O 3


1 la -hydroxy-4 -p regnene -3,20-dione

1 lß -hydroxy-4-p regnene-3,20-dione

12/3 -hydroxy -4 -pregnene -3 ,20-dione


TRANSFORMATION

l l a - O H

d , l - d - l l a - O H + l

3/3-OH^3-C = 0 ; Δ 5 ^ Δ 4 . i i ö _OH

l l ß - O H

12/3-OH

14a-OH

YIELD %

-

—

2

-

-

-

—

-

-

-

-

-

-

-

-

-

-

4

15(cr.)

33

-

3

7-12

—

19

ORGANISM


Stachylidium theobromae

Tr i chode rma vi r ide



Aspergi l lus niger

Ps i locybe cae ru l e scens

Absidia sp.

Botryt is c ine rea

Coniothyrium hel lebori


Cunninghamella sp.

Curvular ia lunata

Curvular ia lunata

Curvular ia sp„

Pycnospor ium sp.


Absidia r egn i e r i

Bacil lus c e r e u s

Circ inel la sp .


Curvular ia lunata

Curvular ia sp.




Mucor pa ra s i t i cus


166-168

-

153-161

-

169-171

-

—

-

-

-

185-187

-

185-188

-

-

192.5-194

191-193

185-188

187-191

190-192

198-200

191-199

180-187

-

195-200

+180[cl

—

-

-

+176[cl

-

:

-

-

-

+214[a]

-

+217[a]

-

—

+197.5[c] +186[e]

+190

+190[c]

—

-

+190[cl

+215[cl

+200[c]

-

+188[c]

R E F .

M-582

V-1048; S-835

W-1119

W-1122

W-1102

F-288

C-113

C-98

C-98

R-749

E-202; C-98

C-98

S-871

C-98; Z-1130

Z-1132

D-147

R-749

T-982

F-288

S-815

N-661

N-661

Z-1132

M-614; E-204

M-614; E-204

S-835; V-1048

M-614; E-204

156

TABLE I


EMPIRICAL FORMULA

C 2 J H 3 0 O 3




15 j3 - hy dr oxy - 4 -pr e gne ne -3,20-dione

TRANSFORMATION

14a -OH

15a-OH

15/3-OH

YIELD %

24

-

23

24-34

-

-

-

-

-

-

7

-

-

-

7

3

1

—

9

2

18

-

9(cr.)

ORGANISM




Stemphylium botryosum

Colletotr ichum ant i r rh in i

F u s a r i u m lini

Fusa r ium lini

F u s a r i u m lycopers ic i


Fusa r ium r o s e u m

Fusa r ium sp.


Helminthosporium sat ivum

Hypholoma sp.

Nigrospora oryzae

Nigrospora sp.


Pénic i l l ium sp„


St reptomyces sp .



He 1 mintho sp or iu m sat ivum





184-195

-

187-192

231-232

220-228

230-234

231-232

-

-

-

219-221

228-230

231-232

228-230

-

233-235

231-232

230-234

-

195-199

203-205

202-204

198-202

-

204-205

+200[cl

-

+186[a]

+219

+220[c]

+224[cl

+218[cl

-

-

-

+190[c]

+213[c]

+219

+226[c|

-

+235fe]

+219[c]

+224[c]

-

+158[cl

+155

+149[cl

-

~

+151[cl

R E F .

1-424

N-682

S-835; V-1048

N-661

F-288; F-285; F-287

G-319; T-980

M-599

K-452

S-858

R-747

K-452

S-858

T-1022

M-568; D-191

M-596

M-596

C-86

F-285; F-287

M-576; M-602; E-202

F-285; F-287

H-382

M-568; D-191

T-1022

T-1036

C-99

F-288; F-285; F-286; F-287

157

TABLE I


EMPIRICAL FORMULA

^21 " 3 0 ^ 3



1 la -hydroxy-4-pre gnene-3,20-dione

1 la -hydroxy-4-pr egnene-3,20-dione 17-0 1 8

19-hydroxy-4-pregnene-3,20-dione

21-hydroxy-4-pregnene-3,20-dione (desoxycort icosterone)

TRANSFORMATION

16a-OH

3 /3 -OH^3-C=0 ; Δ 5 _ Δ 4 . 16α-OH

17α-OH

3 / 3 - O H - 3 - C = 0 ; Δ 5 ->Δ 4

17α-ΟΗ(0*8)

19-OH

21-OH

YIELD %

25

—

19

—

-

13

-

—

~

68(cr.)

-

-

50

—

~

-

—

58-77

—

—

ORGANISM

Pes ta lo t i a funera



St reptomyces globosus

St reptomyces ol ivaceus


St reptomyces sp.

S t reptomyces sp0

S t reptomyces v i r id i s


Sporormia minima

Tr i chode rma vir ide

Flavobacter ium androstenedionicum


Cor t ic ium mic rosc l e ro t i a

Aspergi l lus niger

Cercospore l l a herpot r ichoides

Coniothyrium sp .

Hendersonia rubi

Kabatiel la phoradendr i

Ophiobolus herpo t r ichus

Sclerot inia fructicola

Wojnowicia g ramin i s


224-225

225-226

225-226

215-219

225-226

223-225

214-218

223-225

—

210-214

214-215

—

170-171

142-143

—

-

-

-

140-142

-

138-141

+126[c|

+158[c]

+170[c]

+155[c]

+158[c]

+152[c]

+160[c]

+152[c]

—

-

-

—

+175[e]

+185[e]

—

-

-

-

+175

-

—

R E F .

F-266

F-267; P-718

P-716; P-719

V-1060

F-267

F-267

S-847

V-1060; S-847; S-788; L-491

F-267

P-716; F-267

D-182a

M-565; D-185

E-222

H-374

H-350

Z-1123; Z-1124; R-783

L-490

D-186

D-183

L-498

M-584; W-1101; W-1081

W-1101

M-564; D-183; D-184

158

TABLE I


EMPIRICAL FORMULA

^ 2 1 " 3 0 ^ 3

C2 1 H3 0 O4



21-hydroxy-4-p regnene-3 ,20-dione 21-O18

X -hydroxy -4 -pr egnene - 3 , 2 0 -dione

20S-lla,20-dihydroxy-4-18,20-cyclopregnen-3-one

16a-hydr oxy-17/3-methyl-18-n o r - 1 3 - δ ξ , 1 7 a - p r e g n e n e -3,20-dione

16/3 - hydr oxy -17/3 - methyl -18 -nor -13 -5ξ ,17a -p regnene -3,20-dione

11a, 17a£-d ihydroxy-17a | -methyl-D-homo - 4 - a n d r o -s tene-3 ,17-d ione

1 7 a , 2 0 a , 2 1 - t r i h y d r o x y - l , 4 -pregnadien-3 -one

17a, 20/3,21-trihydr oxy - 1 , 4 -pregnadien-3 -one

TRANSFORMATION

d,l-*d-21-OH + 1

21-OAc-^21-OH

3/3-OH^3-C = 0 ; Δ 5 - ^ Δ 4

21-OAC-21-OH; 3j3-OH-3-C = 0 ; Δ 5 - Δ 4

Δ4(5ξ-Η)

21 -OHiOf)

X-OH

l i a - O H

3 /3 -OH^3-C=0 ; Δ 5 ->5ξ-Η

3 /3 -OH^3-C=0 ; Δ 5 - 5 ξ - Η

11α-OH; 17a-OH-17/3-Ac — D-homo-17a£-OH-17a£ -Me-17 -C=0

20-C = O ^ 2 0 a - O H

20-C=O-^20/3-OH

1

Δ ; 20-C=O-20j3-OH

YIELD %

—

—

-

34

-

-

-

-

4

63

—

17

25

55

71(cr.)

29

26

25-60

—

-

ORGANISM



Flavobacter ium sp.






Neurospora sitophila




Aspergi l lus niger

Rhodotorula glutinis

Candida pu lche r r ima

Sporotr ichum gougeroti

Alcaligenes sp.






CONSTANTS m.p.° |>]D

140-143

-

-

139-140

-

-

-

~

165-172

205-206

151.5-153

172-173

261-262

212-213

193-195

192-193

190-193

195-196

—

193-194

+180[e]

-

-

—

-

-

-

-

-

+113[dj

+145[dj + 37[cl

+ 93fcl +104[d]

+ 46[c]

+ 13[c"|

+ " M

—

+ 33[m]

—

+ 27[cl

REF.

W-1102

S-948

P-742

M-541; M-544

S-867

S-866

S-866

H-374

M-624

W-1071

S-839

S-839

F-283

T-958

T-958

T-958

S-945

L-522

H-389; N-665

L-522

F-275

C-100

159

TABLE I


EMPIRICAL FORMULA

C21 H30O4


17a ,20 /3 ,21- t r ihydroxy- l ,4 -pregnadien-3 -one

l l a - h y d r o x y - 1 6 a , 1 7 a - o x i d o -5a -pr egnane -3 ,20 -dione

l l a - h y d r o x y - 1 6 a , 1 7 a - o x i d o -5/3-pr egnane-3 ,20-dione

15a -hydr oxy - 5/3 -pre gnane -3 ,11 ,20 - t r ione

16ö -hydroxy-5/3-pr egnane -3 ,11 ,20 - t r i one

1 la, 20a -dihydroxy -4 -pregnene-3 ,11-d ione

1ξ ,15 | -d ihydroxy-4 -pregnene-3 ,20-d ione

2 β, 15/3 -dihydr oxy -4 -pregnene-3 ,20-d ione

2/3,16a-dihydroxy-4-pregnene-3 ,20-d ione


2/3,21 -dihydroxy -4 -pregnene -3,20-dione

2/3,X-dihydroxy-4-pregnene-i 3 ,20-dione

TRANSFORMATION

Δ 1 ; 20-C=O->20ß-OH

3 /3 -OAc^3-C=0 ; Δ 5 - + Δ 4 ; Δ1 ; 20 -C=O-20 /3 -OH; 21-OAc^21-OH

11a-OH

11a-OH

15a-OH

16a-OH

2 0 - C = O - 2 0 a - O H

1ξ-ΟΗ; 15ξ-ΟΗ

2/3-OH; 15/3-OH

2/3-OH

2β-ΟΗ; 16α-ΟΗ

2/3-OH

2/3-OH

2β-ΟΗ; Χ-ΟΗ

YIELD %

-

—

—

-

—

-

35

-

60

30-40

24-44

-

19

—

—

1

37(cr.)

-

6

-

3(cr0)

L

ORGANISM

My co bac ter ium lact icola



Pseudomonas sp .

S tereum fasciatum

Streptomyces flaveolus

Streptomyces sp0






Fusa r ium vasinfectum

Sepedonium ampul losporum


Rhizoctonia solani


Sclerot inia l iber t iana







-

-

—

-

-

-

-

205-207

-

170-172

-

220-225

-

217-222

217-219

206-216

215.5-216.5

219-221

196-198

210-216

-

-

—

-

-

-

-

+ 49[c]

-

+ 57[c]

-

-

-

-

51.5[c]

- 67[cl

- 39[c]

-125[c|

22.5[c]

- 65[c]

REF .

S-945

T-960

T-960

N-652; U-1038; U-1039; U-1040

T-959

K-470

K-470

C-115

K-439

K-439

K-440; W-1066

K-440; W-1066

M-599

F-252

C-122

G-312

T-1036

T-983

L-496

P-718; P-716; F-267

T-983

L-496

T-983

160

TABLE I


EMPIRICAL FORMULA

C21 H30O4


6/3,9ö-dihydroxy -4 -pregnene -3,20-dione

6/3, 11α-dihydroxy-4-pregnene-3 ,20-d ione

TRANSFORMATION

6/3-OH; 9a-OH

6/3-OH

6/3-OH; l l a - O H

YIELD %

-

—

—

10

20

30

50-60

3

—

-

-

10

-

-

—

7

30

12

10

< 1

-

ORGANISM

Streptomyces aureofaciens



Sy ncephalas t r u m r a c e m o s u m

Aspergi l lus niger




Aspergi l lus sai toi

Aspergi l lus sp.

Boletus luteus

Dermoloma sp.

Gloeosporium kaki


Hygrophorus conicus

Leucopaxillus paradoxus


Rhizopus cambodjae

Rhizopus javanicus

Rhizopus kansho



Rhizopus sp.


208-211

—

-

245-247

250-253

-

-

232-234

—

-

-

238-242

-

-

-

245-248

250-254

246-248

232-234

-

-

+ 79[cl

-

-

+152[cl

+100[cl

+100[m]

-

+152[cl

—

-

-

+130[pl

-

-

-

+ 144[pl

+ 155[p] +114[dl

+142[p]

+152[c]

-

-

R E F .

P-714

V-1048

E-202

A-27

F-283

D-190

K-436

D-193; D-181; M-562; S-797; V-1048; D-182; S-900

1-417

1-417; T-1010; D-190

S-825

S-825

S-855

S-855

S-825

S-825

P-729; M-601; M-616

C-84

N-682

A-26

P-729

T-1009

N-682; T-1010

161

TABLE I


EMPIRICAL FORMULA

^ 2 1 "scr-M


6)3,11a -dihydr oxy - 4 - ι p regnene-3 ,20-d ione


6/3,15a-dihydr oxy-4 -pregnene-3 ,20-d ione

6/3,16a-dihydr oxy-4-pregnene-3 ,20-d ione

6β, 17α -dihydr oxy -4 -pregnene-3 ,20-d ione

J

TRANSFORMATION

6ß-OH; l l a - O H

3 ß - O H - 3 - C = 0 ; Δ 5 - Δ 4 ; 6/3-ΟΗ; l l a - O H

6/3-OH

6/3-OH; 14α-ΟΗ

15a-OH

6j3-OH; 15a-OH* * (cor rec ted structur<

r e t Ap-18)

6/3-OH

6/3-OH

YIELD

% 1 40

36

-

-

—

-

-

-

14

-

-

-

-

20

-

-

-

-

—

8 - 12β,

-

30

29(cr .

30

ORGANISM


Streptomyces sp.

Tr ichoderma sp.


Aspergi l lus niger

Naematoloma subla ter i t ium

Absidia r egn ie r i

Absidia sp„

Achromobacter kashiwasakiens is



Curvular ia lunata

Curvular ia sp.

Mucor corymbifer

Mucor h iemal is

Mucor mucedo

Naematoloma subla ter i t ium



Fusa r ium lini 15a -dihydr oxy -4 -pr eg



Botry t i s c ine rea


Gibber ella saubinett i

CONSTANTS m.p.° [ e ] p |

236-241

234-240

-

-

—

-

242-246

-

245

246-249

~

-

246-249

255-265

~

-

~

-

-

192-203 kene-3,20

-

230-232

237-240

230-242

+100[m|

+110[ml

-

-

—

—

+132[p] + 114[c]

-

+125[c]

+124[c]

-

-

-

+142[d]

-

-

-

-

-

+130[cl -dione

-

+ 75

+ 15[c]

+ 10[a]

R E F .

S-856

S-854; S-847

T-1010

T-1010

F-288

S-811

T-982

N-682

T-1026

S-811

S-811

S-811

Z-1132

C-82

D-177

S-811

S-811

S-811

M-599

G-319; T-980

R-747

F-267; F-288

S-842

S-858

S-858

162

TABLE I


EMPIRICAL FORMULA

^ 2 1 " 3 0 ^ 4


6j3,17a-dihydroxy-4-pregnene-3 ,20-dione

6/3,21-dihydroxy-4-pregnene-3 ,20-dione

6/3,21-dihydroxy-4-pregnene-3 ,20 -dione-6/3-Οΐ8

7a, 14a-dihydroxy-4-pregnene-3 ,20-dione

7a, 15j3-dihydroxy-4-pregnene-3 ,20-d ione

7a, 21 -dihydr oxy -4 -pregnene-3 ,20-dione

TRANSFORMATION

6j3-OH

6j3-OH. 17a-OH

6/3-OH

6/3-OH. 21-OAc - 21-OH

21-OH

18 6/3-OH (0 2 )

7a-OH

7a-OH; 14a-OH

7a-OH;15j3-OH

7a-OH

d , l - d - 7 a - O H + l

YIELD %

46

17(cr.)

-

29(cr.)

6

5

1

2-3

34

9

13

8(cr . )

25

—

-

-

-

-

< i

—

-

58

60

-

ORGANISM




Naucoria confragosa

Botryt is c inerea

Gibber ella saubinett i

Lenzi tes abietina


Streptomyces fradiae

Streptomyces sp.

Trichothecium ro seum Rhizopus a r rh i zus


Aspergi l lus niger


Curvular ia sp.

Curvular ia lunata

Curvular ia lunata

Curvular ia sp.

Mucor hiemal is

Helminthospor ium sat ivum

Cephalosporium sp. *(revise to 7/3 - ref0 Curvular ia sp.


Helminthospor ium sp„

Pez i za sp.

Pez iza sp .


244-246

256-258

238-240

-

198-205

-

190-192

181-183

198-202

198-202; 206-210 (solvate)

190-198

198-200

-

252-255

280

252-255

234-238

250-253

T-1037)

-

216-225

216-226

-

+6[cj

+4[cl

+8[cl

-

+96fc]

-

-

+110[el

+115[cl

+97[c]

+97[cl

+105[m|

—

—

+175[cl

+177[m]

+175[c]

-

+121[ml

-

+144[c]

+158

+155

R E F .

M-580

M - 6 0 1 ; M-607

S-856

S-825

S-842

U-1043

M-585

M-601

H-328

S-847

M-584

E-203

S-856

Z-1124; Z-1123; R-783

H-374

S-813

Z-1130; Z-1132

D-187

S-813

D-177

T-1022

B-56

M-585

T-997

M-570

M-585

W-1102

163

TABLE I


EMPIRICAL FORMULA

^ 2 1 " 3 0 ^ 4


7/3, 14a-dihydroxy-4-pregnene-3 ,20-d ione (revised s t ruc tu re - ref. T-1037)

7/3,15/3-dihydroxy-4-pregnene-3 ,20-d ione

7/3,21-dihydroxy-4-pregnene-3 ,20-d ione

9a, 14a-dihydroxy-4-pregnene-3 ,20-d ione

9a ,15a-dihydfoxy-4 -p regnene-3 ,20 -dione

9a, 17a - dihydr oxy - 4 -pregnene-3 ,20-d ione

9a ,21-d ihydroxy-4-pregnene-3 ,20-d ione

TRANSFORMATION

7/3-OH; 14a-OH

15/3-OH

7/3-OH ;15j3-OH

3/3-OH-3-C = 0 · Δ5 - Δ4; 7/3-OH; ' 15/3-OH

7/3-OH

9a-OH

14a-OH

9a-OH; 14a-OH

15a-OH

9a-OH

9a-OH

9a-OH; 21-OAc - 21-OH

YIELD %

5

6

8

1

5

10

19-25

21-42

32

3

44

10

-

—

10-20

7(cr.)

-

10

44

t r .

1

ORGANISM








Syncephalast rum r a c e m o s u m


Cladiosporium sp.

Circinel la sp.

Circinel la sp.

Absidia r egn ie r i (assignment of

s t ruc tu re is doubtful )

Circ inel la sp.

Calonectr ia decora

Nocardia sp.


Neurospora c r a s s a

Nocardia sp.

Nocardia sp.


Ascochyta linicola




208-214

231-233

231-232

231-233

231-232

230-232

232-234

225-226

178-181.5

—

249-253d

272-273

240-242

—

182-184

182-184

180-182

-

-

187-188

180-183

+154[cl

+136|c |

+122[c|

+136|c |

+122|c |

+130[c|

+122[c|

+122[c|

+151|c |

—

+149[c|

+179[c]

+212[cj

—

+167[c]

+163[c]

+168[c]

-

-

-

+167[cl

R E F .

T-982

T-1025

A-28

T-1025

A-28

T-1022

T-1036; T-1037J D-177 Ί

T-1020; A-26; A-27'

T-1025; A-28

M-570

S-815

S-815

T-982

S-815

S-810

D-173

S-937

S-937

S-796

D-173

S-898; P-740

S-828

E-204

E-204; M-640

164

TABLE I


EMPIRICAL FORMULA

C21H30O4



11a, 15/3-dihydroxy-4-pregnene-3 ,20-d ione


1 l a , 17a -dihydroxy -4 -pregnene-3 ,20-d ione

11a, 18-dihydroxy-4-pregnene-3 ,20-d ione

TRANSFORMATION

15a-OH

11a-OH; 15/3-OH

11a-OH

11a-OH

17a-OH

11a-OH; 17a-OH

11a-OH

YIELD %

—

6(c r . )

*(revis 42(cr.)

15

-

41

22

-

30(cr.)

—

2

75

ca. 14

21(cr.)

—

27

6

8-15

—

—

ORGANISM

Calonectr ia decora

Gibberel la zeae

Aspergi l lus giganteus

Nigrospora oryzae le to 12/T-OH; Γ5α-ΟΗ

Aspergi l lus niger

Aspergi l lus niger

Aspergi l lus niger





Gloeosporium kaki







Sepedonium ampul losporum

Aspergi l lus sp .



Tr ichothecium r o s e u m Aspergi l lus ochraceus



182-183

173-175

+180[ml

+134[c]

202-203 +134ÎC1 - ref0 Ap-18) L ' 213-215

219-221

-

216-221

215-217

-

219-222

—

220-223

220-222

218-221

214-224

—

210-214

218-222

224-227; 248-251

195-197

~"~

+128[c]

+87[cl

—

+80[c]

—

—

+80[c]

—

-

+76[c]

+73[cl

+80[c]

—

—

+74[c]

+74[m]

—

-

R E F .

S-814

M-599

D-179; D-180

M-596

F-267; F-283

F-283

M-603

V-1048; S-835

S-841

Z-1125

D-189

S-855

S-855

M-601

M-580; M-601; M-607; H-391

T-983

S-856

D-189

M-646

D-190

M-600

D-189; D-188

T-1010

W-1110

W-1100

165

TABLE I


EMPIRICAL FORMULA

1 C21H30O4


l l a , 2 1 - d i h y d r o x y - 4 -pregnene-3 ,20-d ione

l l a , 2 1 - d i h y d r o x y - 4 -pr e gnene -3 ,20 -dione -l lö -Oie


TRANSFORMATION

11a-OH

11a-OH; 21-OAc - 21-OH

21-OH

11a-OH; 21-OH

3/3-OH-*3-C = 0 ; Δ5 - Δ4; 11a-OH; 21-OH

11a-OH (O")

11/3-OH; 14a-OH

YIELD %

67

-

28

-

-

40

-

17

16

-

6

65

9(cr.)

28

-

-

—

-

—

—

—

ORGANISM

Aspergi l lus niger

Aspergi l lus niger





Gloeosporium kaki


Rhizopus sp„

St reptomyces sp.


Aspergi l lus us tus




Aspergi l lus niger

Hendersonia a b e r r a n s

Wojnowicia graminis

Aspergi l lus niger

Psi locybe cae ru le scens

Psi locybe cae ru le scens


Curvular ia lunata

Curvular ia lunata


153-154

-

150-152

-

-

153-161

158-159

153-156

153-158

-

154-158

153-155

156-160

147-150

-

—

153-154

-

—

—

224-229

+168[c]

-

—

-

-

+180[m]

+171[e]

+165[c]

+166[c;

-

~

+166[c] +165[e]

+173[m]

—

~

—

+163[e]

-

—

—

+211[m]

R E F .

F-283 1

M-603

D-193 ; D-182; V-1048; S-835

T-1003

Z-1125

D-189

S-855

S-855

K-433

S-847

M-603

M-603

E-203

E - 2 0 3 ; M-601

S-856

Z-1124; Z-1123

D-183

D-183; D-184

W-1121; W-1120; W-1081

C-113

C-113

H-374

D-187

Z-1130

166

TABLE I


EMPIRICAL FORMULA

C 2 1 H 3 0 ° 4



11/3,15a-dihydroxy-4-pregnene-3 ,20-dione

l l ß , 17a-dihydroxy-4-pregnene-3 ,20-dione

l l /3 ,21-dihydroxy-4-pregnene-3 ,20-d ione (cort icosterone)

l l /3 ,21-dihydroxy-4-p regnene-3 ,20-d ione-11/3-018


TRANSFORMATION

11/3-OH; 14a-OH

15a-OH

11/3-OH

17a-OH

11/3-OH

21-OH

11/3-OH; 21-OH

d , l - » d - l l ß - O H + 1

11/3-OH (O28)

12/3-OH

YIELD

% 1 _

-

32

—

-

-

— —

~

29

—

28

-—

10(cr . )

—

19

~

— -

-

-

—

ORGANISM

Curvular ia sp.

Calonectr ia decora

Curvular ia lunata

Rhodoseptoria sp.

Spondylocladium aus t r a l e



Sporormia minima Tr ichoderma vir ide

Colletotr ichum sp.


Cort ic ium sasak i i

Cunninghamella blakesleeana Curvular ia lunata

Pycnospor ium sp.

Rhodoseptoria sp.

Stachylidium bicolor


Aspergi l lus niger

Coniothyrium sp.

Hendersonia acicola

Wojnowicia graminis

Curvular ia lunata

Curvular ia lunata


Calonectr ia decora

CONSTANTS m.p.° [ e ] p |

224-227

173-175

226-228

-

-

~

— —

-

178-180

—

178-180

-—

177-179

—

179-182

-

— -

-

178-181

—

240-242

J

+219[m]

+230[c]

+135.5[a]

-

-

-

— —

-

+216[e]

—

+210.5[e]

-—

+220[el

—

—

-

--

~

+220[e]

—

+129[c]

R E F .

Z-1132

S-817

S-871

K-446

H-391

D-146

M-600

D-182a D-185

T-1003

T-1003

H-350

M-555

S-871; S-875 D-147

K-446 S-843

T-1003

Z-1124; Z-1123; R-783 D-186

D-183

D-184

R-783

W-1102

H-374

S-810

167

TABLE I


EMPIRICAL FORMULA

^21 "30^4


12ß, 15α -dihy dr oxy -4 -p regnene-3 ,20-d ione

12ß, 15α -dihydroxy -4 -p regnene -3 ,20 -d ione -1 l a 12a-H3

12/3,15a-dihydroxy-4-pr eg -nene-3 ,20-dione-12/3 ,15a-O 1 8

14a, 15β-dihydroxy-4-pregnene-3 ,20-d ione



TRANSFORMATION

12/3-OH

12/3 -OH; 15a-OH

3 / 3 - O H - 3 - C = 0 Δ 5 - * Δ 4 ; 12/3-OH; 15a-OH

12β-ΟΗ; 15a-OH

12β-ΟΗ; 15α-ΟΗ(Οχ

28)

14a-OH; 15/3-OH

14a-OH

14a-OH; 2 1 - O A C - 2 1 - O H

21-OH

d , l - » d - 1 4 a - O H + 1

15a-OH

YIELD %

—

77

10

—

—

1

—

32

44(cr„ )

-

36(cr„ )

17

26

—

-

—

83-87

-

81

20-70

ORGANISM

Calonectr ia decora

Calonectr ia decora

(cor rec ted structurels 15/3-diol ent r ies)


Calonectr ia decora

Calonectr ia decora


Cunninghamella b lakes leeana





Helicostylum p i r i forme

Mucor gr iseocyanus


Aspergi l lus niger


Fusa r ium lini

Fusa r ium lycopers ic i


Gibberel la bacca ta


— —

218 +139[c] +186[m]

; - see 6/3,15a-diol a

— —

— —

259-263 +136[mj

__ —

174-179 —

166-169

172-177 —

170-175 +171[c]

167-17305 —

175-176 +190[c] (solvate) 167-170o5 (unsolvated)

— —

— —

_ —

198-214 +202.5[c)

- -

222-227 +212[c]

216-222 +196[e]

REF .

S-814

S-814; G-319; M-596*

id 11a,

S-816

H-370

K-485

T-1022

M-555

E-204

T-980

S-843

S-841

E-204

E-204;

S-873

Z-1123

W-1102

G-319; T-980; W-1074

S-858

M-599

M-585; U-1043

168

TABLE I


EMPIRICAL FORMULA

C2 1 H3 0 O4


15a, 21 -dihydroxy -4 -pregnene-3 ,20-dione

15/3, 17α-dihydroxy-4-pregnene-3 ,20-dione

15/3, 21 -dihydroxy-4 -pregnene-3 ,20-d ione

16a, 21 -dihydroxy - 4 -pregnene-3 ,20-dione

17a, 21-dihydroxy-4-pregnene-3 ,20-d ione (Reicnstein's Compound S)

TRANSFORMATION

15a-OH

15a-OH; 21-OAc - 21-OH

d , l - d -15a -OH+l

15/3-OH

15/3-OH

d , l — d -15ß-OH+l

16a-OH

16a-OH; 21-OAc — 21-OH

d, 1 - d - 1 6 a - O H + l

17a-OH

21-OH

YIELD %

25

50

—

-

—

-

—

2

10(cr.)

19

-

—

—

-

15

4

-

-

—

27(cr. )

17

-

—

—

~~~

ORGANISM

Gibberella saubinett i


Gibberel la zeae


Nigrospora oryzae

Gibberel la baccata

Nigrospora oryzae


Botryt is c inerea

Lenzi tes abietina

Lenzi tes abietina



Streptomyces sp0

St reptomyces sp.



St reptomyces sp.

Sporormia minima

Tr ichoderma vir ide


Aspergi l lus niger

Coniothyrium sp .

Hendersonia phragmi t i s


Wojnowicia graminis


215-220

~

-

215-220

210-213

-

213-215

258-259d

202-209

206-216

—

201-203

-

203-205

202-203

-

-

__

202-213

204-207

-

—

—

"~"

+217[c]

-

-

+186[e]

+214[c]

+195

+74[c]

+54[c]

+147[c]

+141.5

+141

—

+129[c]

-

+114.5[e]

+130[c]

~

+144

—

+132[c]

-

-

—

—

" * ■"

R E F .

S-858

U-1043

M-599

C-86

M-596

W-1102

M-596

T-983

S-842

M-585

W-1102

F-288

F-288; F-267

F-267

V-1054

F-267

L-491

W-1102

D-182a

D-185

M-584

Z-1124; R-783

D-186

D-183

M-584; W-1101

D-184

169

TABLE I


EMPIRICAL FORMULA

C21H30O4

C21 H30 O5


Reichstem' s Compound S

19,21-dihydroxy-4-pregnene-3,20-dione

3/3, lla-dihydroxy-5-pregnene-7,20-dione

3/3, lla-dihydroxy-16a, 17a-oxido-5-pregnen-20-one

Products of unknown or questionable structure

11/3,17a, 20/3,21-tetrahydroxy -1,4-pr egnadien-3-one

12/3,17a, 20/3,21-tetr ahydroxy-1,4-pr egnadien-3-one

TRANSFORMATION

21-OAC-21-OH

3/3-OHr 3-C = 0 ; Δ5 - Δ4

3/3-OH-> 3 - C = 0 ; Δ5 — Δ4 ; 21-OAc-,21-OH

3/3-OAc-> 3-C = 0 ; Δ5 — Δ4 · 21-OAc — 21-OH

3/3-OH^ 3- C = 0 ; Δ5 - Δ4 ; 20/3-OH — 20-C=O

19-OH

11a-OH; 7 - C=0

11a-OH

Substrate Progesterone

desoxycorticosterone 21- acetate

20-C = O^20/3-OH

20-C=O-^ 20/3-OH

YIELD %

—

—

87

93

—

—

18

-

,,

-

10

5

0.5

0.2

0.3

0.5

0.3

1

26(cr.)

4(cr.)

-

ORGANISM

Bacillus megaterium

Flavobacterium sp.

Flavobacterium dehydrogenans

Flavobacterium dehydrogenans

Acetobacter suboxydans

Corticium microsclerotia

Rhizopus arrhizus

Fusarium solani

Myrothecium roridum

Absidia regnieri

Absidia regnieri

Curvularia sp.

Mucor corymbifer

Mucor corymbifer

Mucor corymbifer

Mucor corymbifer

Mucor corymbifer

Mucor corymbifer

Mucor corymbifer

Pénicillium sp.

Sclerotinia libertiana


Mucor parasiticus

Streptomyces griseus



—

—

208-210

209

—

153-156

228-230

-

212-213.5

227-228.5

~

270-275

218-223

275-280

217-220

240-250

275-280

210-215

251-253

216-224

228-238d

180-197; 200-225

-

245-247

-

—

+110[c]

+110[c]

—

—

—

-

+154[e]

+88[p]

-

-

-

-

-

-

-

~

+202

-18[P]

+190[c]

+152[c]

-

REF.

S-948

P-742

H-378

H-378

L-523

H-350

E-202-M-630; M-601 Ί

P-746

P-746

T-982

T-982

Z-1132

C-82

C-82

C-82

C-82

C-82

C-82

C-82

F-285; F-287

T-983

T-983

T-980

C-110

R-749

170

TABLE I


EMPIRICAL FORMULA

C2 1 H3 0 O5


17a,21-dihydroxy-5/3-pregnane -3 ,11 ,20 - t r ione

11/3,17a, 20/3,21 - tetrahydroxy-1,4 -pr egnadien -3 -one

1 Ία, 20a, 21 - t r ihydroxy -4 -p regnene-3 ,11 -dione

17a,20/3,21-tr ihydroxy-4-pregnene-3 ,11-d ione

1 la, 2 0 | , 21 - tr ihydroxy - 4 -pregnene-3 ,11-d ione

l /3 ,17a ,21- t r ihydroxy-4-pregnene-3 ,20-d ione

2/3,11/3,21 - tr ihydroxy - 4 -pregnene-3 ,20-d ione

2/3,15/3,21 - t r ihydroxy - 4 -pregnene-3 ,20-dione

2β, 17a, 21- t r ihydroxy-4-p r e gnene-3,20-dione

TRANSFORMATION

Δ 4 ^ 5 / 3 - Η

20-C=O^20/3-OH

1 Δ ;

20-C=O->20/3-OH

2 0 - C = O ^ 2 0 a - O H

20-C=O^20/3-OH

2 0 - C = O - 2 0 4 - O H

1/3-OH

l ß -OAc^ l /3 -OH; 21 -OAc^21-OH; 3/3-OAc-»3-C=0; Δ 5 ^ Δ 4

2/3-OH

2/3 -OH; 15/3-OH; 21-OAc^21-OH

2/3-OH

YIELD %

~

95

—

32

;

-

-

-

-

57

50(cr.)

68

40-60

5

-

68

19(cr.)

20(cr.)

< 1

35

< 1

ORGANISM

Al te rnar ia bataticola

Streptomyces albus


St reptomyces sp.


Calonectr ia decora

Fusa r ium solani

Fusa r ium sp.


Hydrogenomonas facil is

Mycobacter ium sp.

St reptomyces albus



Rhizobium sp.


Rhizoctonia sp.


Sclerotinia l iber t iana


Conidiobolus sp.


Helminthosporium t r i t ic i -vulgar i s



214-217

-

-

240-242d

—

-

-

-

-

202.5-205.5

206-207

190; 204

-

193-207d

-

203-207

183-186

210-219

232-235

208-213

225.5-228d

+ 92

-

-

+158[dl

—

-

-

-

-

+137[dl

-

-

-

+ 89[d]

—

-7[m]

- 47[ml

- 88[el

- 59[d]

- 58[d]

R E F .

S-852

K-459

L-522

K-470

C-110; C-122

S-951

S-949

S-951

K-465

F-228

S-917

K-459

C-110

L-522

C-114

G-315; G-312; G-313

S-793b; G-313

N-689

S-840; S-853

S-849; S-853

W-1073

L-496

K-460

G-313

171

TABLE I


EMPIRICAL FORMULA j

CaiH,0O5

!


2/3 ,17a ,21- t r ihydroxy-4-pregnene-3 ,20-d ione

6/3,11a, 21 - tr ihydroxy - 4 -pregnene-3 ,20-d ione

6/3,11/3, 21- t r ihydroxy-4-pregnene-3 ,20-d ione

6/3,17a, 21 - t r ihydroxy - 4 -pregnene-3 ,20-d ione

TRANSFORMATION

2/3-OH

2/3-OH; 21-OAc-*21-OH

6/3-OH; l l a - O H ; 21-OAC-21-OH

6/3-OH

11/3-OH

6ß-OH

YIELD %

3

-

~

-

6

—

19(cr.)

1

3

33

4-6

30

5(cr.)

—

-

-

-

-

35-40

-

-

-

-

39

26

-

1 -

ORGANISM


Rhizoctonia sp.


Sclerot inia sc l e ro t io rum

Streptomyces sp0

S t reptomyces argenteolus



Curvular ia lunata

Absidia spc

Achromobacter kashiwasakiens is

Ar throbot rys super ba

Bacil lus ce r eus

Botryt is c inerea

Coniothyrium hellebori

j Cor iolus vers ico lor

Cor t ic ium sasak i i


Cunninghamella sp.

Curvular ia lunata

Curvular ia sp0

F u s a r i u m d imerum


F u s a r i u m r o s e u m



Gloeosporium foliicolum

Glomer ella cingulata


220-222

209-211

215-222

-

22505-228

224-227

220-226

225-227

225-227

224-226

-

222

228-235

-

-

223

-

-

229-232

-

228-232

-

—

230-236

1 -

-

-

—

-

- 64[d]

-

- 58fd]

—

+105[ml

+118jdl

+ 118[dj

+ 60.5[e]

-

+ 58[m]

+ 42[c]

-

-

-

-

-

+ 57[e]

-

+ 55[d]

-

-

+ 72[ni|

-

-

-

R E F .

G-315; G-312

G-312

S-860; T-983

S-860

H-383

P-716; F-267

S-856

N-654

N-654

N-682

T-1026

E-226

S-944

S-842

R-749

B-63

H-327

S-919

C-98; N-682

K-469

K-469

K-462

S-858

R-747

S-858

U-1043

K-464

K-464

172

TABLE I


EMPIRICAL FORMULA

C 2 1 H 3 0 O 5


6/3,17a,21-tr ihydroxy-4-pregnene-3 ,20-d ione

7a ,14a ,21 - t r ihydroxy-4 -pregnene-3 ,20-d ione

7a, 17a, 21 - t r ihy dr oxy -4 -pregnene-3 ,20-d ione

TRANSFORMATION

6/3-OH

6/3-OH; 17a-OH

6/3-OH; 17a-OH; 21-OAc - 21-OH

7a-OH

7a-OH; 14a-OH

7a-OH

YIELD %

2

—

-

-

-

—

-

-

-

-

30

3

-

-

24 (cr.)

30

35-40

40

36

-

< 1

20

24

19

> 3 0

ORGANISM


Helminthosporium l ee r s i i

Mucor sp.

Pe l l i cu la r ia fi lamentosa

Phoma sp.

Polyporus tulipiferus

Po r i a cocos

Rhizoctonia solani

Rhizoctonia solani

Rhizoctonia sp.



Rhizopus sp.

Scenedesmus sp.


Streptomyces sp.

Streptomyces sp.

Vert ic i l l ium malthousi

Vert ic i l l ium niveos t ra tosum


Cephalothecium ro seum

Mucor gr iseocyanus

Mucor gr iseocyanus



CONSTANTS m . p . ° [o?]p

228-232

225-231

-

219-221

-

-

-

233-234

-

-

230-233

230-234

-

-

231-238

230-235

-

230-233

-

234-236

—

245-248

248-240

228-230

-

+55[d|

-

-

-

-

-

+67[aj

-

-

+58.5|e]

-

-

-

+62|cj

+51 [m]

-

+57[e]

-

+53

—

+146[dl

+97[e]

+146[m]

REF .

E-204 . M-60l '

K-460

N-682

T-957

1-422

B-63

B-63

T-956

S-793b

G-312

P -725 · M-601; Μ-βΙδ '

P - 7 2 5 ; M-615*

N-682

L-527

S-856

S-854; S-847

C-112

K-468

K-468

M-581

M-600

C-94

C-94

T-997; T-999; T-998

T-1023; A-28

173

TABLE I


EMPIRICAL FORMULA

C2 1 H3 0 O5


7/3,14a, 15/3-trihydroxy-4-pregnene-3 ,20-d ione

7/3 ,17a,21- t r ihydroxy-4-pregnene-3 ,20-d ione

7^ ,17a ,21 - t r ihydroxy-4 -pregnene-3 ,20-d ione

8 j3 ,17a ,21- t r ihydroxy-4-pregnene-3 ,20-d ione

9 a , l l | 3 , 2 1 - t r i h y d r o x y - 4 -pregnene-3 ,20-d ione

9a, 17a ,21- t r ihydroxy-4-pregnene-3 ,20-d ione


TRANSFORMATION

14a-OH

7/3 -OH; 14a-OH; 15/3-OH

7/3-OH

7 | -OH

8/3-OH

9a-OH

9a-OH

11a-OH

1

YIELD %

38(cr.)

8

5

—

16(cr. )

-

-

—

10

10

60(cr. )

8-15

10

-

21

-

37

44

70

—

4 0 - 5 0

70

25

—

ORGANISM

Syncephalas t rum r a c e m o s u m


Syncephalas t rum r a c e m o s u m

Syncephalast rum sp.

Cephalosporium a s p e r u m

Cephalosporium sp.


Rhizoctonia sp.

Cercospora melonis

Ascochyta l inicola

Ascochyta linicola

Curvular ia lunata


Nocardia aurant ia



St reptomyces aureofaciens

Absidia glauca

Absidia orchid is


Absidia sp.

Ar throbot rys superba


Aspergi l lus niger

Aspergi l lus niger


-

267-269

263-265

263-265

—

209-211

-

-

219-223

—

235-240

231-235

248-252

-

-

236-238

218-220

205-209

206-209

—

-

-

217-219

—

-

+75[pl

+103[mj

+170[ml

—

+94[ml

-

-

+109[dl

—

+103[d]

+107[dl

-

-

+103[d]

+120[e]

+110[cl

+120[ml

—

-

-

+117[el

—

R E F .

T-1021

T-982

T-1021; A-27

A-26

B-56

B-56; B-55

T-1037; T-1036

G-312

K-472

S-828

S-828

K-469

E-204; M-601; M-609

S-898; P-740

D-173

P-740

P - 7 1 5

N-682

H-334

S-841

N-682; C-98; S-801

E-226

F-288

F-283

M-603

174

TABLE I


EMPIRICAL FORMULA

C21H30O5


l l û , 1 7 û , 2 1 - t r i h y d r o x y - 4 -pregnene-3 ,20-dione

TRANSFORMATION

l l a - O H

YIELD %

60-85

50

28

88

> 7 0

-

-

-

2

-

-

3

-

13(cr.)

88

30

-

—

3-5

-

-

30

70(cr.)

—

ORGANISM



Aspergi l lus sp.

Bacil lus ce reus

Beauveria sp.

Cercospora melongenae

Cercospora sc i rpicola

Cercospora zinniae

Colletotr ichum sp.

Conidiobolus sp .

Coniothyrium hellebor ine

Conocybe si l igenoides



Cort ic ium vagum

Coryneum cardinale



Cunninghamella sp.

Curvular ia lunata

Curvular ia sp.



Fusa r ium equiset i

Fusa r ium sp .

CONSTANTS m . p . ° [α]Ώ

-

-

203-209

212-214

215-218

211-216

-

-

206-209

-

—

212-216

-

212-216

219-220

216-217

-

-

213-215

-

-

210-212

210-213

—

-

-

+110[ml

-

+120[el

—

-

-

+82[ml

-

-

+120[e]

-

+120[e]

—

-

-

-

+120[e]

-

—

—

+117[el

—

R E F .

K-436

D-193; D-182; V-1048; S-835

D-190

S-944

1-421

K-472

K-472

K-472

T-1003

W-1073

T-1003; T-1004

C-113

H-325

H-347

H-350

T-991

Z-1125

K-466

N-682

K-469; K-443

K-469

D-189

S-836; S-835; V-1048

M-557

M-557

175

TABLE I


EMPIRICAL FORMULA

^ 2 1 " 3 0 ^ 5



TRANSFORMATION

l la-OH

YIELD %

—

38

88

49

—

tr.

> 7 0

-

-

-

-

—

55

30

-

—

-

23 (cr.)

61

15

—

11

-

27

ORGANISM

Gloeosporium foliicolum

Gloeosporium kaki



Glomerel la sp.


Helminthosporium sigmoideum

Mucor sp„


Phoma sp.

Psi locybe sp .

Rhizoctonia sp.

Rhizopus nigr icans

Rhizopus sp.

Rhizopus sp.

Sclerotinia l iber t iana






St reptomyces sp.

St rophar ia cubensis

Sycephala s t r u m r a c e m o s u m


214-218 +120rej

204-208 + 115fej

212-214 —

200-209 +110[mj

- -

206-211 —

210-213 +120jej

- -

210-212 +112[dl

- -

- -— —

209-212; +113[c] 217-219 +113[mj (polymorphs)

207-211 +115[e]

- -

205-209 +115[el

- -

205-210 +112fml

205-210 -

- -

- -

205-210 +117|m!

- -

208-210 +107lc|

REF.

K-464

S-859; S-855

C-109

S-855

C-109; K-464

E-204; M-601

K-460

N-682

T-957

1-422

C-113

G-313; G-312; S-793b

P-725 ; M-601; M-641

K-433

N-682

S-860

S-860

S-856

M-582

K-468

D-146

S-854; S-847

C-113

A-27

176

TABLE I


EMPIRICAL FORMULA

C21 H30 O5


lla,17a,21-trihydroxy-4-Pregnene-3,20-dione

l lß , 12ß, 15a-trihydroxy-4-pregnene-3,20-dione

l lß , 14α, 17ö-trihydroxy-4-pregnene-3,20-dione

llß,14a,21-trihydroxy-4-pregnene-3,20-dione

llß,15a,21-trihydroxy-4-pregnene-3,20-dione

llß,15ß,21-trihydroxy-4-pr egnene -3,20 -dione

l lß , 16a,21-trihydroxy-4-pregnene-3,20-dione

llß,17a,21-trihydroxy-4-pregnene-3,20-dione (hydrocortisone)

TRANSFORMATION

11a-OH

11a-OH; 21-OAc -*21 -OH

11a-OH; 17a-OH

21-OAc^ 21-OH; lla-OH; 17a-OH

12ß-OH; 15a-OH

llß-OH; 14a-OH

llß-OH

15a-OH

15ß-OH

16a-OH

llß-OH

YIELD %

—

9

—

—

—

—

1

—

caQ 20

37

—

20

—

—

—

—

6-8

33(cr0)

2(cre)

—

19

—

—

—

ORGANISM

Trichothecium roseum

Verticillium theobromae

Coryneum cardinale

Rhizopus nigricans

Cephalothecium roseum



Calonectria decora

Curvularia lunata


Fusarium moniliforme

Botrytis cinerea



Absidia glauca

Absidia orchidis

Absidia sp.

Arthrobotrys superba

Botrytis cinerea

Botrytis cinerea

Botrytis cinerea

Botrytis fabae

Botrytis peoniae

Cercospora zinniae

Chaetomella oblonga


-

213-215

—

—

206-211

—

—

229-231

247-250

206-215

—

235-244

230-235

—

206-210

—

—

213-216

201-209

—

200-208

—

207-210

—

—

+120[e]

—

—

+121[m]

—

—

+148[c]

+181[e]

+180[m]

—

+180[p]

+180[p]

—

+163[e]

—

—

+162[e]

+156[m]

—

+155[e]

—

+160[e]

—

REF.

T-1003; M-600

K-468

T-991

M-601; M-641

M-581

D-189; D-188

M-600

S-817

S-876

S-841; S-843; S-851

M-599

S-842

S-853; S-840

H-399

N-682

H-334; N-682

S-801; C-98

E-226

F-229

S-842

C-98

S-859

F-229

K-472

S-789

177

TABLE I


I EMPIRICAL FORMULA

C2 1 H3 0 O5


hydrocortisone

TRANSFORMATION

11/3-OH

YIELD %

—

—

—

—

—

37

19

65

5-20

—

—

39

40-55

—

—

—

—

—

<10

ORGANISM

Chaetomella raphigera

Colletotrichum sp0

Coniothyrium hellebori(ne)

Corticium microsclerotium

Corticium practicola

Corticium sasakii

Corticium vagum



Cunninghemella blakesleeana

Cunninghamella sp.

Curvularia falcata

Curvularia lunata

Curvularia lunata

Curvularia lunata

Curvularia lunata

Curvularia pallescens

Dothichiza ferruginosa

Epicoccum sp.

Helminthosporium sigmoideum

Pellicularia filamentosa

Phoma sp.

CONSTANTS ™.p.° [β ] ρ |

— —

— —

205-207 +162[e]

— — — —

205-207 —

208-210 +160[a]

— —

— —

— —

208. 5-20a 5+166[e]

— —

212-215d +160[e]

— —

— —

— ■ —

208-212 +160[e]

204-207 +178[e]

REF.

S-789

T-1003

T-1003; T-1004; T-993; F-288; R-749

H-350

H-350

H-350; H-347; H-325

H-350

H-339

M-556

M-601; M-641; M-555; 0-696; S-919

C-98

S-878

S-871; S-875

K-443; K-466

K-469

D-192; C-98

S-875

,K-449

R-782

K-460

T-957

1-422

178

TABLE I


EMPIRICAL FORMULA

C 2 i H 3 0 O 5


hydrocort isone

TRANSFORMATION

llj3-OH

d , l ^ d - l l / 3 - O H + l

llj3-OH; 21-OAc-»21-OH

17a-OH

YIELD %

—

—

—

—

—

—

— ·

20(cro;

—

46

50(cro)

—

—

—

1

5-10

—

28

—

—

—

—

—

—

ORGANISM


Pseudomonas spD

Pycnospor ium sp0

Rhizoctonia sp.

Rhodoseptor ia sp„



Spondylocladium aus t r a l e

Spondylocladium xylogenum









Vert ic i l l ium theobromae

Curvular ia lunata

Botry t i s c ine rea

Cort ic ium mic ros l e ro t ium

Curvular ia lunata



CONSTANTS m.p.° [e]D

—

—

—

—~

—

201-206

—

—

—

—

202-208

—

201

—

202-204

—

—

210-213

209-212

—

—

—

—

—

—

—

—

—

—

+160[e]

—

—

—

—

+162[m]

—

+163[c]

—

+16405[e]

-

—

+160[e]

+171[e]

—

—

—

—

—

R E F .

T-960

N-652; U-1038

D-147

G-312; G-313; S-793b

K-446

S-860

S-860

S-790

S-790

K-468

S-843

D-146

D-146

S-835

C-134; C-135; H-328

C-112

S-878; T-1003

K-468

W-1102

F-229

H-3&)

Z-1131

D-146

M-600

179

TABLE I


EMPIRICAL FORMULA

^ 2 1 ^ 3 0 ^ 5


hydrocort isone

11/3,18, 21- t r ihydroxy-4-pregnene-3 ,20-d ione

l l / 3 ,19 ,21 - t r i hyd roxy-4 -pregnene-3 ,20-d ione

12/3 ,17a,21- t r ihydroxy-4-pregnene-3 ,20-d ione

14a ,15a ,21 - t r i hyd roxy-4 -pregnene-3 ,20-d ione

14a ,17a ,21 - t r i hyd roxy-4 -pregnene-3 ,20-d ione

TRANSFORMATION

17a-OH

21-OH

Δ Α - Η

2 1 - O A c ^ 2 1 - O H

11/3-OAc-» 11/3-OH; 21-OAc-*21-OH

Δ4 (5/3-H)

11/3-OH

d , l - » d -21 -OH+l

11/3-OH

12/3-OH

15a-OH

14a-OH

YIELD %

—

—

—

—

—

2

—

90

—

—

—

21

7

25

29

—

—

—

—

15-20

—

—

3-6

—

—

—

—

ORGANISM

Sporormia minima


Coniothyrium sp.

Hendersonia herpot r icha

Wojnowicia graminis

Baci l lus mega te r ium



Nocardia a s t é ro ïdes




Curvular ia lunata


Fusa r ium lini

Absidia r egn i e r i

Coriolus ve r s i co lo r


Curvular ia lunata

Curvular ia lunata

Curvular ia lunata

Curvular ia sp .


Helminthosporium avenae

Mucor sp.

P o r i a cocos

Polyporus tul ipiferus

CONSTANTS m.p.° [<*]D|

—

202-210

—

—

—

210-215

—

—

—

—

—

163-164

—

179-181

208-222

213-218

—

—

229-233d

227-230

—

—

.234-237

227-230

—

—

—

—

—

—

—

—

—

—

—

—

—

—

+210[c]

—

—

+172[c]

+155[mj

—

—

+147[d]

+150[d]

—

—

+155[m]

+148[m]

—

—

—

REF.

D-182a

M-584

D-186

D-183

D-184

H-382

E-225

C-129

S-939

W-1100

W-1102

B-40

N-654

R-749

T-980

S-841

B-63

E-202; S-919

K-469

K-469

K-443

K-469

E-204; M-601

K-460

N-682

B-63

B-63


EMPIRICAL FORMULA

C21 H30°5


14α , 17a, 21- t r ihydroxy-4-pregnene-3 ,20-d ione

15a, 17a, 21 -tr ihy dr oxy -4 -pregnene-3 ,20-dione

15/3,17a, 21- t r ihydroxy-4-pregnene-3 ,20-d ione

16a, 17a, 21- t r ihydroxy-4-pregnene-3 ,20-d ione

17a, 19 ,21- t r ihydroxy-4-pregnene-3 ,20-d ione

TRANSFORMATION

14a-OH

14a-OH; 21-OAc-+21-OH

15a-OH

15a-OH; 2 1 - O A c - 2 1 - O H

15/3-OH

16a-OH

16a-OH; 2 1 - O A c - 2 1 - O H

19-OH

YIELD %

5 ( c r 0 )

—

—

2-4

5

42(cr . )

29(cr . )

—

3

15

50

—

2

—

—

—

15(cr„)

30-70

—

—

—

42

3

8 ( c r J

ORGANISM

Stemphylium botryosum


Calonectr ia decora


Gibberel la baccata



Hormodendrum olivaceum

Rhizoctonia sp.

Fusa r ium Uni

Aspergi l lus niger (our ass ignment - que Baci l lus mega te r ium

Coriolus vers ico lor


Phoma sp0

P o r i a cocos

Polyporus tulipiferus Spicaria s impl i c i s s ima

Nocardia i tal ica

Pes ta lo t ia funarea


Streptomyces v i r id is


Cort ic ium mic rosc le ro t ium Cort ic ium sasak i i

Cort ic ium vagum


227-228d

226-228

225-227

—

—

216-218

227-230

—

176-178

248-250 stionable)

+144[m]

+130[a]

+146[m)

-

-

+145[mj

+146[m]

-

+146[mj

+97[e]

218-220d; +103[e] 240-241d (polymorphs)

—

219-222

—

—

—

240-242

—

—

—

—

235-236

233-236d

233-236

-

+88[e]

—

—

—

+96[m]

—

—

—

—

+121[e] +123[e| +127[d] +144[e]

+143[e] + 128[d]

R E F .

N-661

S-873

S-810

R-747

U-1043

U-1043

T-1024

ß - 5 8 ; A-9

G-312

T-980

F-283

H-382; C-127; C-126

B-63

T-1036

1-422

B-63

B-63

B-58; A-9

S-918

S-835

H-399; V-1048; S-835

V-1048; S-835

L-491

H-350

H-325; H-326; H-347 H-350

TABLE I 180

TABLE I


181

EMPIRICAL FORMULA

C2 1 H3 0 O5

^ Ι ^ ο ^ β


17a ,19 ,21 - t r i hyd roxy-4 -pregnene-3 ,20-d ione

X , 1 7 a , 2 1 - t r i h y d r o x y - 4 -p regnene ,3 ,20 -d ione

11a, 16a, 17aa- t r ihydroxy-17a/3-hydroxy methy l -D-homo-4 -andr ostene - 3 , 1 7 -dione

11/3,16a, 17aa- t r ihydroxy-17a/3-hydroxymethyl-D-homo -4 -andr ostene - 3 , 1 7 -dione

1ξ, 11/3,17α, 21- te t rahydroxy-4-pregnene-3 ,20-d ione

6/3,11/3,17a, 21- te t rahydroxy -4 -pregnene-3 ,20-d ione

6/3,14a, 17a ,21- te t rahydroxy-4-pregnene-3 ,20-d ione

7a, 11/3,17a, 21- te t rahydroxy-4-pregnene-3 ,20-d ione

7α, 14α, 17a ,21- te t rahydroxy-4-pregnene-3 ,20-d ione

11α, 16α, 17a,21- te t rahydroxy-4-pregnene-3 ,20-d ione

11/3,14a, 17a, 21- te t rahydroxy-4-pregnene-3 ,20-d ione

11a, 15/3,17a,21-tetrahydroxy-4-pregnene-3 ,20-d ione

TRANSFORMATION

19-OH

19-OH; 21-OAc - 21-OH

X-OH

16a-OH; 16a,17a-diOH-17/3 (-20-C=O-21-OH) -D-homo-16a, 17aa-diOH-17a/3-CH2OH-1 7 - C = 0

16a-OH; 16a,17a-diOH-17/3 (-20-C = O - 2 1 - O H ) -D-homo-16a, 17aa-diOH-17a/3-CH2OH-1 7 - C = 0

1 | -OH

6/3-OH

6/3-OH; 11/3-OH

6β-ΟΗ

14α-OH; 6β-ΟΗ

7α-OH

7α-OH; 11/3-OH

7α-OH

7α-OH; 14α-OH

16α-OH

11/3-OH; 14a-OH

15/3-OH

YIELD %

33

-

—

17(cr.)

-

10

5

-

-

40

5

-

—

—

-

-

ORGANISM

Hypochnus sasaki i


Cor t ic ium mic rosc l e ro t ium




St reptomyces antibioticus

Mor t ie re l l a sp .

S t reptomyces sp.

Curvular ia lunata

Curvula r ia lunata

Curvular ia sp.


Curvular ia lunata

Curvular ia lunata

Curvular ia lunata

Curvular ia lunata

Curvular ia sp .


Curvu la r ia lunata

Curvula r ia lunata

Curvula r ia lunata

Baci l lus mega te r ium


234-235

-

219-225d

210-212.5

-

216-220d

-

-

231-234d

238-240d

-

-

241-242

232-233 solvate

-

+123[e"|

-

-

+136[m]

-

+87[d]

-

-

+146[d]

+48[c]

-

-

+183[e] +152[d]

+188[e]

-

R E F .

S-869

T-957

H-350

T-983

G-297

G-297

F-234

F-239

C-112

K-469

K-469

K-469

T-997

K-443

K-469

K-469

S-879

K-469

G-297

A-2 S-877

S-877 S-879

K-443

C-126

182

TABLE I


EMPIRICAL FORMULA

^21 "30^6

(^21H31(-)5F

C 2 1 H 3 1 0 6 F

C2 1n32W2


11/3,15β,17α, 21 -tetrahydroxy-4-pregnene-3 ,20-d ione

11/3,16a, 17a ,21 - te t rahydr oxy-4-pregnene-3 ,20-d ione

11 β, 17α, 19,21 - te t rahydr oxy-4-pregnene-3 ,20-d ione

X, 11 β, 15α, 21 - te t rahydr oxy-4-pregnene-3 ,20-d ione (X is 8/3,9a or 14a)

Unknown

9a- f luoro- l l /3 ,17a , 20/3,21 -t e t rahydroxy-4-pregnene-3-one

9a-f luoro- l l /3 ,16a , 17a, 20/3, 21-pentahydroxy-4-pregnen-3-one

5a-pregnane-3 ,20-d ione

TRANSFORMATION

11/3-OH

15/3-OH

16a-OH

19-OH

X-OH; 15a-OH

Substrate proges te rone

20 -C=O-20 /3 -OH

20-C = O --+ 20/3-OH; 21-C = 0-+ 21-OH

20-C=O — 20/3-OH; 21-OAc - 21-OH

Δ ' - Η

20-C=O-> 20/3-OH

Δ1 — H; 20-C=O - 20/3-OH

16a-OH; 20-C=O^20/3-OH

Δ4 -> 5a-H

YIELD %

-

30-70

—

29

2

-

—

-

—

—

—

-

—

—

—

-

ca. 30

—

ORGANISM

Curvular ia lunata

Bacillus Megater ium

Nocardia i tal ica

Strep to my ce s roseochromogenus

Hypochnus sasak i i

Fusa r ium lycopers ic i


Mucor corymbifer



Streptomyces olivochromo genus










Cor t inar ius evernius




- -

- -

- -

180-182 +216[m]

225 —

- -

- -

- -

_ _

- -

— —

- -

132-145; +49.5[ml 227-231d (hydrate )

— —

— —

■ - -

197-200 —

— —

REF.

C-126

C-127; C-126

S-918

G-297; H-399

S-870

S-858

S-858

C-82

S-907

S-907

M-569; S-941

G-296

G-296

G-296

G-296; S-908

G-296

G-296

G-296; S-908

G-296

S-907

S-825

S-820

W-1081

183

TABLE I


EMPIRICAL FORMULA

^ 2 l " 3 2 ^ 2

1 ^ 2 l " 3 2 ^ 3



5ß-pregnane-3 ,20-dione

20a-hydroxy-4-pregnen-3-one

20ß-hydroxy-4-pregnen-3-one

17a-ethyl-17/3,19-dihydroxy-4-andros ten-3-one

5-androstene-3/3,17/3-diol-3-acetate

3/3,16a, 20a- t r ihydroxy-17ß-m e t h y l - 1 8 - n o r - 1 7 a - 5 , 1 3 -pregnadiene

1 l a -hydroxy-5a -p regnane -3,20-dione

1 la-hydroxy-5/3-pr egnane-3,20-dione

1 la -hydroxy-5ß-pregnane-3 ,20-dione-12a-H 3

15a-hydroxy-5a-pregnane-3,20-dione

15a-hydroxy-5ξ-pregnane-3,20-dione

16a -hydr oxy- 5/3-pr egnane -3,20-dione

TRANSFORMATION

Δ4 — 5a-H

Δ — 5ß-H

5 4 Δ - > Δ ; 3/3-OH ■--» 3 - C = 0

20-C=O * 20a-OH

20-C=O > 20/3-OH

19-OH

17-C = 0 - 17β-ΟΗ

16a, 17a-oxide -» 16a-OH ; 13/3-CH3 — 17ß-CH3; 20-C = O — 20a-OH ; Δ13

11a-OH

11a-OH; Δ4 - 5a-H

11a-OH

l l a - H 3 -» 11a-OH

15a-OH

15a-OH; Δ4 - 5 | - H

16a-OH; Δ4 -» 5/3-H

YIELD %

9

-

-

87

> 3 9

—

2

-

—

67

71

20(cr.) - 6 0

26

t r .

40

-

—

-

t r . -8

ORGANISM

Pénici l l ium ur t icae


Alter na r i a bataticola

Bacil lus putr if icus

Fla vo bac te r ium dehydrogenans




Hypochnus sasaki i





Rhizopus nigr icans

Aspergi l lus niger




F u s a r i u m sulphureum




185-198

204-206

120-122

119-120

—

—

151-152

170-172

—

146

-

202-204

197-200

198-200

102-106

-

123-125

-

219-229

199-200

—

-

+ 124

-

—

—

-

+81[c]

-

-

-

-189[e]

+82[c]

+84[c]

+83[cl

—

—

-

+8405[cl

+90.5[c|

REF .

M-602 1

V-1059; W-1097

S-852

M-545

N-693

C-122

M-637; S-832

F -284 ; F-271

S-869

M-539

S-829 ; S-830

C-88 ; C-90

E-209 ; M-601

P-729

M-603

E-209; M-601

M-582

H-371

M-599

G-319; T-980

P - 7 1 8 ; P - 7 1 6 ; F-267

184

TABLE I


EMPIRICAL FORMULA

C-2l"32^3


21 -hydroxy-5a-pregnane-3,20-dione

21-hydr oxy-5/3-pr egnane -3,20-dione

3a-hydroxy-5a-pregnane-11,20-dione

3a-hydr oxy-5/3-pr egnane-11,20-dione

6/3, l l a -d ihydroxy-3a , 5a-çyçlopregnan-20-one

6/3, l l /3-dihydroxy-3a, 5a-cyclopregnan-20-one

11a, 20a-dihydroxy-4-pregnen-3-one

11a, 20/3-dihydr oxy-4-pregnen-3-one

11/3,20a-dihydr oxy-4-pregnen-3-one

16a, 20/3-dihydroxy-4-pregnen-3-one

17a, 20a -dihydr oxy -4 -pregnen-3-one

2 0/3,21-dihydr oxy-4-pre gnen-3-one

(revision of s t ruc tu re at 2 0 - see réf. S-832)

3/3, 7/3-dihydroxy-5-pregnen-20-one

3/3, l l a -d ihydroxy-5 -p regnen-20-one

3/3,21-dihydroxy-5-pregnen-20-one

3/3, 16a-d ihydroxy-5a-9( l l ) -pregnen-20-one

TRANSFORMATION

Δ 4 ^ 5 α - Η

Δ4 - 5/3-H

3 - C = 0 - 3a-OH

3-C = 0 - 3a-OH

11a-OH

11/3 -OH

11a-OH

20-C=O - 20a-OH

11a-OH

20-C=O - 20/3-OH

2 0 - C = O - 20a-OH

20-C=O - 20/3-OH

20-C = O — 20a-OH

20-C=O -» 20/3-OH

2 0 - C = O ^ 20/3-OH; 21-OAc - 21-OH '

7/3-OH

11a-OH

21-OH

16a-OH; 3/3-OAc - 3/3-OH

YIELD %

-

-

40-44

60

-

16

82-85

2

-

-

-

—

-

—

—

14

—

ORGANISM

Streptomyces gr i seus

Alter nar ia bataticola

Saccharomyces cerev is iae



Metar rh iz ium anisopliae


Curvular ia lunata



Rhizopus nigr icans





Pénici l l ium sp.

Streptomyces sp.



Metar rh iz ium anisopliae

Aspergi l lus niger

Streptomyces sp.


162-164

-

160-165

169-171

-

208-212

211.5-217

243.5-249.5

-

178-179

-

212-213

-

-

—

181-183

—

-

-

+93[cl

+103[c]

-

-

+92[c]

—

-

+73[c]

-

+44[c)

-

-

—

—

—

REF.

V-1059; W-1097

S-852

C-83; C-89

C-83; C-89

S-835

K-483

W-1069; W-1070

W-1070

S-832

C-122

S-832

S-832

C-122

F-271 ; F-273; F-288

C-122

M-637

E-202

M-637

E-202

K-483

R-783

W-1092

185

TABLE I


EMPIRICAL FORMULA

j C a i H 3 2 0 3

C21H3204


16a, 20a-dihydroxy-17/3-methy l -18-nor - 5/3,17a-13-pregnen-3-one

11a ,15a-d ihydroxy-5a-pregnane-3 ,20-d ione

11a, 15a -dihydr oxy -5/3 -p regnane-3 ,20-d ione

l l /3,21-dihydroxy-5/3-pregnane-3 ,20-d ione

12/3,15a-dihydr oxy-5a-pregnane-3 ,20-d ione

12/3,15a-dihydroxy-5/3-pregnane-3 ,20-d ione

15a, 21-dihydroxy-5/3-pregnane-3 ,20-d ione

16a, 21 -dihydroxy-5/3-pregnane-3 ,20-d ione

17a,21 - dihydroxy-5a -pregnane-3 ,20-d ione

17a, 21 - dihydr oxy - 5/3 -p regnane-3 ,20-d ione

3/3,16a - dihydr oxy -5a-pregnane-11 ,20-d ione

6/3,15£,20ξ - t r ihydroxy-4-pregnen-3-one

11/3,17a,20a-tr ihydroxy-4-pregnen-3-one

17a, 20a, 21 - t r ihydr oxy -4 -pregnen-3-one

17a,20/3 ,21- t r ihydroxy-4-pregnen-3-one

TRANSFORMATION

16a, 17a-oxido —* 16a-OH; 13j3-CH3 - 17/3-CH3; 20-C=O - 20a-OH; Δ13

15a-OH

15a-OH

Δ 4 - 5/3-H

12j3-OH; 15a-OH

12/3-OH; 15a-OH

15a-OH; 21-OAc -» 21-OH

16a-OH; 21-OAc -> 21-OH; Δ4->5/3-Η Δ4 - 5a-H

Δ4 - 5/3-H

16a-OH

6β-ΟΗ; 15ξ -OH; 2 0 - C = O - 20 4 -OH

2 0 - C = O - 20a-OH

20-C=O -» 20a-OH

20-C=O - 20/3-OH

YIELD %

20

60

40

—

40

40

—

—

—

—

—

—

40

-

65(cr.)

27(cr.)

—

—

62(cr.)

-

-

-

ORGANISM


Calonectr ia decora

Calonectr ia decora


Calonectr ia decora

Calonectr ia decora




Al te rna r ia bataticola

Pes ta lo t ia funera

Rhizoctonia solani






Bacil lus sp.


Candida pu l che r r ima

Chlorel la sp.


Demat iacea sp.


223-225

208-210

175-177

—

253-257

225-231

—

215-217

—

185-190

—

237-240

209-210

—

220-222

221-225

—

—

188-190

-

-

-

-58[e]

+105[cl

+108.5 [cj

—

+70 [m]

+56[cl

—

+44[cl

—

+40

—

+70[dl

+94[cl

—

+60[el

+55[dl

—

—

+77[cl

-

-

-

R E F .

C-88; C-90

S-816

S-816

S-852

S-816

S-816

M-599

F-267

V-1059

S-852

W-1092

G-312

T-958

C-122

T-958

C-110

C-122

V-1045

L-522

T-958

V-1045

L-522

V-1045

186

TABLE I


EMPIRICAL FORMULA

C21 H32°4

^21 "32^5


17a,20/3,21-tr ihydroxy-4-pregnen-3-one

17a ,20£ ,21- t r ihydroxy-4-pregnen-3-one

3/3, 7/3, l l a - t r i h y d r o x y - 5 -pregnen-20-one

Unknown

l l a ,17a ,21 - t r i hydroxy-5 /3 -pregnane-3 ,20-d ione

l l /3 ,17a,21- t r ihydroxy-5/3-pregnane-3 ,20-d ione

3/3 ,17a,21- t r ihydroxy-5a-p r e g n a n e - l l , 2 0 - d i o n e

TRANSFORMATION

2 0 - C = O - 20/3-OH

d , l - 2 0 - C = O -d-20/3-OH + 1

20-C=O ^ 20ξ -OH

7ß-OH ; 11a-OH

Substrate

desoxycor t icosterone

desoxycor t icosterone acetate

l l a - O H

11a-OH; Δ4 - 5/3-H

Δ4-> 5/3-H

3-C = 0 - 3/3-OH; Δ4 — 5a-H

YIELD %

5

—

—

32

-

—

-

54

64

-

—

48

-

-

-

40-60

18

6(cr.)

12

8 (c r . )

-

17

ORGANISM


Diplodia tuber icola Epicoccum sp.

Hydrogenomonas facilis

Pénic i l l ium ci t r inum


Pseudomonas f luorescens

Pythium ult imum

Streptomyces albus

Streptomyces dias ta t icus

Streptomyces hydrogenans


Streptomyces sp.

St reptomyces sp.

Streptomyces coelicolor


Rhizobium sp.






Catena bacter ium sp.

CONSTANTS m . p . ° [ot]O

189-190

-

-

172-177

-

—

-

191-193

188-189

183. I 9 4 '

-

175. 19θ '

-

193-194

-

-

247-248

196-206

218-222

190-196

192-198

195-200

—

-

-

+71[d |

-

—

-

+65[d|

+65.5fd|

-

-

+65[d]

-

+74[e]

-

-

-41[m|

+121[c|

+57M

+94

—

REF.

V-1048; S-836; S-835 A-28

R-782

F-228

S-846

M-637

N-652 . T - 9 6 0 ' U-1030

S-846

K-458

K-470

L-522

S-835

C-110

K-470

W-1094

W-1094

C-114

M-601-E - 2 0 2 '

T-980

P-725

P-725 ; M-606

S-852

T-973

187

TABLE I


EMPIRICAL FORMULA

^21 "32^5

C 2 1 H 3 3 ° 4 F

1 ^ 2 l " 3 4 ^ 2


3a, 17a, 21- t r ihydr oxy - 5/3-p regnane-11 ,20-d ione

l l a , 1 7 a , 2 0 a , 2 1 - t e t r a -hydroxy-4-pregnen-3-one

11a, 17a, 20/3,21 - t e t r a -hydroxy -4 -pregnen-3-one

11/3,17a, 20a, 21 - t e t r a -hydroxy-4-pregnen-3-one

11/3,17a, 20/3,21-tetra-hydroxy-4-pregnen-3-one

11/3,17α, 20έ, 2 1 - t e t r a -hydroxy-4-pregnen-3-one

17a, 19,20a, 21 - tetrahydroxy -4-pregnen-3-one

X ,17a ,21 - t r ihydroxy-5 f -pregnane-3 ,20-d ione (X probably is l l a -OH)

9 a - f l u o r o - 3 ß , l l ß , 1 6 a -t r ihydroxy-5a-pregnan-20-one

3a -hydroxy-5a-pregnan-20-one

3/3-hydroxy-5a-pregnan-20-one

TRANSFORMATION

3 - C = 0 ^ 3 a - O H ; Δ*-»5/3-Η

2 0 - C = O - 2 0 a - O H

2 0 - C = O - 2 0 ß - O H

11/3-OH

2 0 - C = O - 2 0 a - O H

20-C=O->20ß-OH

2 0 - C = O - 2 0 £ - O H

19-OH

20-C=O-*20a-OH

X-OH; Δ 4 - ^ 5 ξ - Η

16a-OH

3 - C = 0 - > 3 a - O H ; Δ 4 - 5 α - Η

3-C=0-»3ß-OH

YIELD %

56

< 1

-

74

5

—

—

—

-

59

—

16(cr.)

80

-

40-60

10

—

—

—

-

ORGANISM

Al te rna r ia batat icola

Clost r id ium paraput r i f icum

Streptomyces sp.


Streptomyces hydrogenans



Hydrogenomonas facil is



St reptomyces a lbus

St reptomyces d ias ta t icus



St reptomyces sp.

Rhizobium sp .

Pe l l i cu l a r i a f i lamentosa


Ce rcospo ra sc i rp icola

St reptomyces sp .

Mycobacter ium smegma t i s



188-191

187-189

186-190

—

205-206

250-252

—

—

-

—

124-126.5; 141-143; 177.5-179 (solvates)

125-126

133-135

145

-

-

217-220

-

199-204

—

173-175

+ 60

+ 88[c]

+ 85.5[el

—

+ 58[e]

+ 73[c]

—

—

—

-

+ 86[d]

+ 92[d]

+ 85[dl

-

-

-

+ 62[pl

-

—

—

-

"

R E F .

S-852

S-823

B-41

C-122

L-522

T-954

C-122

F-228

S-873

T-954

K-459

K-470

C-110

L-522

K-470

C-114

T-954

T-958

K-472

W-1092

S-820

V-1059

188

TABLE I


EMPIRICAL FORMULA

C21H3402

^ 2 l " 3 4 ^ 3

C 2 1 H 3 4 0 4



3a-hydroxy-5/3-pregnan-20-one

3/3-hydroxy-5/3-pregnan-20-one

3)3, 7/3-dihydroxy-5a-pregnan-20-one

3/3, l l a -d ihyd roxy-5a -pregnan-20-one

3/3,16a-dihydroxy-5a-pregnan-20-one

3/3,16a-dihydroxy-5/3-pregnan-20-one

3/3,21-dihydroxy-5a-pregnan-20-one

3a, 21 -dihydroxy-5/3-pregnan-20-one

3/3,21-dihydroxy-5/3-pregnan-20-one

3/3,16a,20a-tr ihydroxy-17ß-me thy l -18 -no r -5a ,17q -13 -pregnene

3ß,4/3,5a- t r ihydroxy-pregnan-20-one

3/3, 5a, 6/3-trihydroxy-pregnan-20-one

3a, 6a, l l a - t r i h y d r o x y - 5 ß -pregnan-20-one

TRANSFORMATION

3 - C = 0 - 3 / 3 - O H ; Δ4-+5α-Η

3 - C = 0 - + 3 a - O H ; Δ 4 ^ 5 β - Η

3-C = 0 ^ 3 / 3 - O H ; Δ4-*5/3-Η

7/3-OH

l i a - O H

3 - C = 0 ^ 3 ß - O H

16a-OH

16a-OH; 3/3-OAC-3/3-OH

3-C = 0 - 3 / 3 - O H ; Δ4 - 5 a - H

16a-OH

3 - C = 0 - 3 / 3 - O H

3-C = 0 -3/3-OH; Δ4-+5α-Η

3 - C = 0 - 3 a - O H ; Δ 4 -5 /3 -Η

3-C=0—3/3-OH; Δ 4 -5 /3 -Η

16a, 17a -oxide -♦ 16a-OH; 13/3-CH3->17/3-CH3; 2 0 - C = O - 2 0 a - O H ; Δ13

4/3, 5/3 - oxide — 4/3,5a-diOH; 3-C = 0 - 3 / 3 - O H

5a, 6a-oxide—» 5a,6/3-diOH

l i a - O H

YIELD %

8

80

-

-

5

23

60-70

~

-

-

-

-

53

~

-

92

40

44

ORGANISM




Clost r id ium paraputr i f icum

Clost r id ium te r t ium



Rhizopus nigr icans


Streptomyces sp„



Streptomyces sp.




Clost r idium paraputr i f icum

Clost r id ium te r t ium





Calonectr ia decora


200

192-195

142

149-150

-

188-192

194-195

178-181

179-181

258-260

258-260

-

198-199

168-174

139-145

149-151

-

-

200-201

235-237

248-251

223-225

+ 94[c]

+ 96

+108[cl

-

+ 90

+ 78[cl

+ 70[c]

+ 62[cl

-

-

-

-

-

+ 99[cl

-

-

+ 79[c]

—

+ 61 [m]

R E F .

C-86

V-1059; W-1097

S-852

S-823

S-823

S-852

M-601; E-202

M-601

C-83; C-89

N-653; W-1092

W-1092

V-1059

W-1092

V-1059

V-1059; W-1097

S-852

S-823

S-823

S-852

C-88

C-87; C-90

C-87

S-812

189

TABLE I


EMPIRICAL FORMULA

C21 H34°4

C21H3405

C21 H36°4

1 C22H2402C1F

C 22 H 24°2 C 12

C22H2502C1

C22H2503F

C22H2504F3

C22H2505N


3/3,7/3,11a - t r ihydroxy- 5a -pregnan-20-one

3/3,7/3,21 - tr ihydroxy-5/3-pregnan-20-one

3ß, l l ß , 16α-tr ihydroxy-5α-pregnan-20-one

3ß, l l ß , 21- t r ihydroxy-5α-pregnan-20-one

3α, l l ß , 21- t r ihydroxy-5β-pregnan-20-one

3ß ,17a ,21 - t r i hyd roxy-5a -pregnan-20-one

3α, 17α, 21- t r ihydroxy-5ß-pregnan-20-one

3ß, 17α, 21- t r ihydroxy-5ß-pregnan-20-one

3 ß, l l ß , 17a ,21- te t rahydroxy-5a-pregnan-20-one

3a, l l ß , 17a ,21- te t rahydroxy-5ß-pregnan-20-one

3ß, 4ß , 5a, 20ß- te t rahydroxy-pregnane

17a -chlor ethinyl -6 -f luor o -1 7 ß - m e t h o x y - l , 4 , 6 -andros ta t r ien -3 -one

6-chlor o-17α-chlor ethiny 1-1 7 ß - m e t h o x y - l , 4 , 6 -andros t a t r i en -3 -one

17α-chlor e thinyl-17ß-hydr oxy -6 -methyl - 1 , 4 , 6 -andros ta t r ien -3 -one

17α -ethiny 1 -9α -fluor o -17β -hydr oxy -16α - methyl - 1 , 4 -androstadiene - 3 , 1 1 -dione

6α, 9α, 21 - t r i f luoro-17a-hy d r o x y - 2 - m e t h y l - 1 , 4 -p regnad iene -3 ,11 ,20 - t r ione

7a-cyano-17a , 21 -dihydroxy-1 ,4 -p regnad iene -3 ,11 ,20 -t r ione

TRANSFORMATION

7β-ΟΗ; 11α-ΟΗ

7β-ΟΗ

16α-OH

3 - C = 0 - * 3 ß - O H ; Δ 4 - + 5 α - Η

3 - C = 0 ^ 3 a - O H ; Δ 4 ^ 5 β - Η

3 - C = 0 - » 3 ß - O H

3 - C = 0 - 3 ß - O H ; Δ 4 - 5 α - Η

3 - C = 0 ^ 3 a - O H ; Δ 4 - 5 β - Η

3 - C = 0 - ^ 3 ß - O H ; Δ 4 - 5 β - Η

3-C=0->3ß-OH; Δ 4 ^ 5 α - Η

3 - C = 0 - > 3 a - O H ; Δ 4 ^ 5 β - Η

4ß ,5ß-ox ide-» 4ß,5a-diOH

Δ1

1

Δ

1

Δ

1

Δ

Δ 1 (2a-CH3)

1

Δ

1

YIELD %

9 .5

—

—

—

—

49

—

—

18

—

43

—

—

—

—

—

ORGANISM


Rhizopus sp.

Didymella vodakii

Streptomyces gr i seus



Streptomyces au reus


Al t e rna r i a batat icola

Al te rna r ia bataticola

Catenabacter ium sp0

A l t e rna r i a batat icola


Septomyxa affinis

Septomyxa affinis

Septomyxa affinis


Septomyxa affinis



268-270

205-213

257-260

—

196-197

226-230d

203-205

215-225

184-186

—

276-280

—

—

—

—

—

+103[m]

+106[e]

—

—

+ 88

+440 5[d]

+ 62

+ 48

-

—

—

—

—

—

—

—

REF.

M-601

K-433

W-1092

V-1059

S-852

V-1059

K-471

V-1059

S-852

S-852

T-973

S-852

C-87

0-694

0-694

0-694

O-701

B-43

B-75

190

TABLE I


EMPIRICAL FORMULA

C22H2506N

C2 2H2 602Bra2F

C22H26O2CIF

^ 2 2 ^ 2 6 ^ 4

P^22"26^4^2

^ 2 2 " 2 6 ^ 5

C 2 2 H 2 6 0 5 F 2

^ 2 2 " 26^6

C22H27O2CI

C22H2702C12F

C22H2702C12I

ρ-/22"27^2·^


6a-cyano-16a ,17a , 2 1 - t r i -hy dr oxy -1 ,4 -pre gnadiene -3 ,11 ,20- t r ione

17a-bromo-9a , 11/3-dichloro-2 1 - f l u o r o - 6 a - m e t h y l - l , 4 -pre gnadiene -3 ,20 -dione

17a -chlor ethinyl -6a -fluor 0 -17ß-methoxy - 1 , 4 - a n d r o -Stadien-3-one

3,14/3-dihydroxy-l ,3,5(10), 20(22) -cardate t raenol ide

6a, 9a -difluoro -17a -hydroxy -2 -methy l -1 ,4 -p regnad iene-3 ,11 ,20- t r ione

6a, 21 -difluoro-17a -hydroxy -2 -me thy l -1 ,4 -pregnadiene -3 ,11 ,20- t r ione

17a,21-dihydroxy-16-methylene -1 ,4 -pr egna -d i e n e - 3 , l l , 2 0 - t r i o n e

17a ,21-dihydroxy-6-methyl -1,4,6 -pr egnatr iene -3 ,11 ,20- t r ione

6a ,9a -d i f l uo ro - l l j 3 , 17a ,21 -t r ihydroxy -16 -méthylène -1,4 -pre gnadiene - 3 , 2 0 -dione

3,17α, 21 -tr ihydroxy -19 -nor -1,3,5(10) -pregnatr iene -11,20-dione 21-aceta te

17a -chlor ethinyl -17/3 -methoxy-1 ,4 -andros tad ien-3-one

17a-chlorethinyl-17/3-hy dr oxy - 6a - methyl - 1 , 4 -androstadien-3 -one

9a, l l ß -d i ch lo ro -21- f luo ro -6a -methy l -1 ,4 -pregnadiene -3 ,20-dione

9a, l l ß - d i c h l o r o - 6 a - m e t h y l -21 - iodo -1 ,4 -pre gnadiene -3,20-dione

21-fluor 0 -6a -methy l -1 ,4 ,9(11)-pregnatr iene -3,20-dione

TRANSFORMATION

16a-OH

1

Δ

1

Δ

1

Δ ; enol.

Δ 1 ; 10 /3 -HC=O-10/3-H; enol.

3 / 3 - O H - 3 - C = 0 ; 5/3-ΟΗ^Δ4; Δ 1 ; 10/3-HC=O-10/3-H; enol.

Δ ' ^ α - ^ )

A1(2a-CH3)

1

Δ

1

Δ

1

Δ

A 1 ; 21-OPr—21-OH

1

Δ ; enol.

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

YIELD %

—

—

—

-

—

—

—

—

-

—

—

—

—

—

ORGANISM



Septomyxa affinis




Septomyxa affinis

Septomyxa affinis


Septomyxa affinis

Nocardia opaca

Mycobacter ium phlei


Septomyxa affinis

Septomyxa affinis




CONSTANTS m . p . ° [ÛÎ]D

— —

— —

— —

- -

263-265d + 78[p]

— —

— —

218-219 +103[dl

— —

- -

— —

— —

— —

— —

— —

R E F .

B-74

R-759

0-694

K-481

K-481

K-481

B-43

B-43

M-558

H-395

A-7

A-7

H-386

0-694

0-694

R-755

R-755

R-755

191

TABLE I


EMPIRICAL FORMULA

^-'22"27^2·'·

C 22H27O3 B r

C22H2703C1

C22H2703C12F

C22H2703C12I

C22H2703F

^22-"27^3^

C 2 2 H 2 7 0 4 F

C22H2704F3

C22H2705Br

C22H2705C1

C22H2705F


2 1 - i o d o - 6 a - m e t h y l - l , 4 , 9(11) - p r e g n a t r i e n e - 3 , 2 0 -dione

9 a - b r o m o - 1 7 a - e t h i n y l - l l ß , 17ß-dihydr oxy-16a-methyl -1,4 -andr ostadien -3 -one

9a -ch lo ro-17a-e th iny l - l l /3 , 1 7ß -dihydr oxy -16a -methyl -l , 4 - and ros t ad i en -3 -one

9a, 1 Iß -dichlor o-21 -fluor 0-17a -hydroxy -6a -methyl -1,4 -pr egnadiene -3 ,20 -dione

9a, l lß -d ich loro-17a-hydroxy-2 1 - i o d o - 6 a - m e t h y l - l , 4 -pr egnadiene -3 ,20 -dione

17a -e th iny l -9a - f luo ro - l lß , 17ß-dihydroxy-16a-methyl -1,4 -andr ostadien -3 -one

6a- f luoro-17a-hydroxy-21-methyl-1 ,4 ,9(11) -pregna-t r iene -3 ,20 -dione

17a-hydroxy-21- iodo-6a-methy l -1 ,4 ,9 (11) -p regna-t r i ene -3 ,20 -d ione

9a -f luor 0 -1 I ß , 17a -dihydr oxy-16-méthy lène-1 ,4 -p r egna-diene-3 ,20-dione

6a- f luor0-17a-hydroxy-2-me thy l -1 ,4 -p r egnadiene-3 ,11 ,20 - t r ione

6 a , 9 a , 2 1 - t r i f l u o r o - l l ß , 1 7 a -dihydroxy -2 -me thy l -1 ,4 -pregnadiene -3 ,20-dione

9a -b romo- 17a, 21 -dihydroxy -1 6 a - m e t h y l - l , 5 - p r e g n a -diene - 3 ,11 ,20 - t r ione

9a-bromo-17a ,21-d ihydroxy-16/3 - methyl - 1 , 5 -pr egna -d i e n e - 3 , l l , 2 0 - t r i o n e

16 -ch lo rome thy lene - l l ß , 17α, 21 - t r i hyd roxy - l , 4 -p regna-diene-3 ,20-dione

9 a - f l u o r o - l l ß , 1 7 a , 2 1 - t r i -hydr oxy -16 - méthylène -1 ,4 -pregnad iene-3 ,20-dione

16- f luoromethy lene- l lß , 17α, 21 - t r ihydroxy-1 ,4 -p regna -diene-3,20-dione

TRANSFORMATION

I1

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

Δ1 (2α - CH3)

Δ1 (2a - CH3)

21-OAc - 21-OH

21-OAc - 21-OH

1

Δ

1

Δ

1

Δ

YIELD %

—

—

—

—

—

—

—

—

—

—

—

48

67

ORGANISM







Mycobacterium phlei



Septomyxa affinis

Septomyxa affinis







— —

— —

— —

— —

— —

— —

271-275 +30fe]

— —

— —

— —

— —

223-224 -34[d|

246-248 +27jd]

263-264 +25fd]

REF .

R-755

O-701

O-701

R-759

R-759

O-701

H-391

R-759; R-756

B-68

B-43

B-43

N-690; N-692

N-690; N-692

W-1084

M-558

W-1084

192

TABLE I


EMPIRICAL FORMULA

C 2 2 H 2 7 0 5 F

C22H2705N

^ 2 2 " 2 7 ^ 6 ^

C22H2707N

^ 2 2 " 2 8 ^ 2

C22H2802C12

^ 2 2 · " 2 8 ^ 3

1 ^ 2 2 " 2 8 ^ 3 · ^ 2


6a-f luoro-17a,21-dihydroxy-2-methyl -1 ,4-pregnadiene -3 ,11 ,20 - t r ione

6j3-fluoro-17a, 21 -dihydroxy-2 - methy l -1 ,4 -pr egnadiene -3 ,11 ,20 - t r ione

9a-f luoro-17a,21-dihydroxy-16a -me thy l - l , 5-pregna -diene -3 ,11 ,20 - t r ione

9a-f luoro-17a ,21-dihydroxy-16/3-methyl - l ,5 -pregna-d iene -3 ,11 ,20- t r ione

16- f luoromethy l - l l /3 ,17a ,21-t r i hyd roxy -1 ,4 ,15 -p regna -t r i ene-3 ,20-d ione

7a - cyano - l l / 3 , 17a ,21 - t r i -hydroxy-1 ,4-pregnadiene -3,20-dione

7 ß - c y a n o - l l ß , 1 7 α , 2 1 - t r i -hydroxy-1 ,4-pregnadiene -3,20-dione

9ö-fluoro-15j3,17α, 21 - t r i -hydr oxy -15a - methyl -1 ,4 -pr egnadiene -3 ,11 ,20 - t r ione

17a, 21 - dihydr oxy -16a -n i t romethy l -1 ,4 -pr egna -d iene -3 ,11 ,20 - t r ione

6 a - m e t h y l - l , 4 , 9 ( l l ) -p regna t r i ene-3 ,20-d ione

6 / 3 - m e t h y l - l , 4 , 9 ( l l ) -pregnat r iene -3 ,20-dione

6j3-methyl-9a, l l ß - d i c h l o r o -1,4 -pr egnadiene - 3 , 2 0 -dione

17a-[2 ' - car boxy ethyl]-17/3-hydroxy -1 ,4 -andr ostadien -3-one lactone

17a-hydroxy -16-méthylène-1,4 -pr egnadiene -3 ,20 -dione

17a-hydroxy-21-methyl -1 ,4 , 9 ( l l ) - p r e g n a t r i e n e - 3 , 2 0 -dione

l l a - h y d r o x y - 1 6 a , 1 7 a , 2 1 -[ 3 , 1 , 1 - (2-pyrazol ino)]-4-pregnene-3 ,20-d ione

TRANSFORMATION

Δ1 (2α - CH3)

Δ1 (2a - CH3)

21-OAc - 21-OH

21-OAc - 21-OH

1 Δ

1

Δ

1 Δ

1

Δ

1 Δ

1 Δ

1

Δ

1 Δ

1 Δ

1

Δ

1

Δ

l l a - O H

YIELD %

-

—

—

—

68

—

—

-

—

—

—

—

—

67

ORGANISM

Septomyxa affinis

Septomyxa affinis





Septomyxa affinis


Septomyxa affinis

Septomyxa affinis


Cor ynebacter ium s implex



Ar throbac te r sp.


Nocardia opaca

Metar rh iz ium sp.



-

—

—

—

224-225

—

—

-

—

—

134-136; 179-180

—

—

245-247

245-247

-

—

—

—

+23[d]

—

—

—

—

—

—

—

—

+392[cl

R E F .

B-43

B-43

N-690; N-692

N-690; N-692

W-1084

B-75

B-75

B-75

B-75

B-44

R-751

R-755

R-754

R-754

C-121

B-68

H-391

M-593

W-1113

193

TABLE I


EMPIRICAL FORMULA

^ 2 2 " 28^3-N 2

^ 2 2 ^ 2 8 ^ 4

C22H2804Br2

C22H2804FI

1 ^ 2 2 " 2 8 ^ 4 - ' : ,2

1 C22H28U5

1


l l j3 -hydroxy-16a ,17a ,21-[ 3 , 1 , 1 - (2 -pyrazolino)] -4 -pregnene-3 ,20-d ione

3 .12-d ike to -b i snor -4 , 6-choladienic acid

11/3,17a-dihydroxy-16-methylene -1 ,4 -pr egnadiene -3 ,20-dione

17a ,21-dihydroxy-16-methy lene -1 ,4 -pre gnadiene -3,20-dione

17a -hy dr oxy - 16a - me thy l -1 ,4 -p r e ^ n a d i e n e - 3 , 1 1 , 2 0 -t r ione

21-hydroxy -16a -me thy l -1 ,4 -pr egnad iene -3 ,11 ,20-tr ione

21-hydr oxy -17a -me thy l -1 ,4 -pregnadiene - 3 , 1 1 , 2 0 -t r ione

9 a , l l / 3 - d i b r o m o - 1 7 a , 2 1 -d ihydroxy-6-methy l -1 , 5-pr egnadiene -3 ,20 -dione

l l /3- f luoro-9a- iodo-16a-me thy l -1 , 5-pre gnadiene -3,20-dione

6a ,9a -d i f luoro - l l /3 ,17a-dihydroxy -2 - me thy l -1 ,4 -pr egnadiene-3,20-dione

6a ,21-d i f luoro- l l /3 ,17a-dihydroxy-2 - m e t h y l - 1 , 4 -pregnadiene-3 ,20-d ione

l l a , 1 7 a , 2 1 - t r i h y d r o x y - 1 6 -methylene -1 ,4 -pr egnadiene -3,20-dione

l l / 3 ,17a ,21- t r ihydroxy-16-methy lene -1 ,4 -pr egnadiene -3 ,20-dione

17a,21-dihydroxy-16j3-m e t h y l - 9 a , l l a - o x i d o - l , 4 -pr egnadiene -3 ,20-dione

17a, 21 -dihydr oxy -6a -methyl -1,4-pr egnad iene -3 ,11 ,20-t r ione

TRANSFORMATION

11/3-OH

7 α - Ο Η - Δ 6 ; 3 a - O H - 3 - C = 0 ; Δ4(5/3-Η); 17^-CH(CH3)-(CH2)2-COOH-17j3-CH(CH3)-COOH

1

Δ 11/3-OH

1 Δ

1 Δ

1 Δ

1

Δ ; 21-OAC-21-OH

21-OAC-21-OH

21-OAC-21-OH

Δ (2a-CH3)

Δ1(2a-CH3)

11a-OH

1 Δ

9(11) Δ —»9a, 11a-oxide; Δ 1 ; Δ4(5α-Η); 21-OAC-21-OH

1

Δ

YIELD %

6

—

—

—

—

—

—

—

—

—

—

—

—

-

ORGANISM

Cunninghamella sp.

Curvular ia lunata

St reptomyces gelat icus


Curvular ia lunata


Bacil lus lentus

Bacil lus lentus




Septomyxa affin is

Septomyxa affin is






Septomyxa affinis


255-258

255-258

238-241

222-226

219-220

179-181

183-186d

—

—

—

—

—

225-226

210-211

196-198

230-232

+450[cl

- 37.5[c]

- 16[c]

—

—

+120[el

—

—

—

—

—

+ 22

+ 67[d]

-

R E F .

M-593

W-1113

H-359

B-68

B-68

M-558

R-750

R-750

V-1052; W-1096

N-691

N-691

B-43

B-43

M-558

M-558

T-981

C-138

G-300

L-512; S-833

194

TABLE I


EMPIRICAL FORMULA

^ 2 2 " 2 8 ^ 5

C 2 2 H 2 8 0 5 F I

^ 2 2 ^ 2 8 ^ 6

C22H2806FN

C22H28OgF2

C22.n29U2r

C 2 2 H 2 9 ° 3 F

C22H2904 F


17a, 21-dihydr oxy-6/3-methyl-1 ,4 -p regnad iene-3 ,11 ,20-tr ione

17a,21-dihydroxy-16a-methyl -1 ,4 -pr egnadiene -3 ,11 ,20- t r ione

17a,21-dihydroxy-16/3-me thy l -1 ,4 -pr egnadiene -3 ,11 ,20- t r ione

17a,21-dihydroxy-16a-methy l -1 ,5 -pr egnadiene -3 ,11 ,20- t r ione

1 la, 21 - dihydr oxy -16/3 -methy l -1 ,5 -pregnadiene -3 ,11 ,20- t r ione

l l /3 ,17a ,21- t r ihydroxy-6-methyl - 1 , 4 , 6 -pr egnatr iene -3,20-dione

l l j3 ,17a ,21- t r ihydroxy-16-me thy l -1 ,4 ,15 -p r egna-t r iene-3 ,20-dione

l l j3 - f luoro-6ß ,17a ,21- t r i -hydr oxy- 9a - iodo -16a -methyl -1 ,4 -pregnadiene -3,20-dione

6/3,17a, 21 - t r ihydroxy-16a-methy 1-1,4 -pr egnadiene -3 ,11 ,20- t r ione

15/3,17a,21-tr ihydroxy-15a-methy 1-1,4 -pr egnadiene -3 ,11 ,20- t r ione

6a-cyano-9a-f luoro-l l / 3 , 1 6 a , 1 7 a , 2 1 - t e t r a -hydroxy-4-pregnene-3 ,20-dione

6a, 9a-difluoro-ll/3,16a,17a,21 -te t rahydroxy-12a-methyl -1,4 -pregnadiene - 3 , 2 0 -dione

21 - f l uo ro -17a -me thy l - l , 4 -pre gnadiene -3 ,20 -dione

6a-f luoro-17a-hydroxy-16a-methy 1 -1 ,4 -pre gnadiene -3,20-dione

9a-f luoro- l l /3-hydroxy-6a-methyl -1 ,4 -pregnadiene -3,20-dione

6a-f luoro- l l /3 ,17a-dihydroxy-2 - methy l -1 ,4 -pregnadiene -3,20-dione

TRANSFORMATION

Δ1

1

Δ

Δ 1 ; Δ (5α-Η)

Δ 1 ; Δ4(5α-Η); 21-OAC-21-OH

21-OAC-21-OH

21-OAC-21-OH

1

Δ

1

Δ

6/3-OH

6β-ΟΗ

1

Δ

16a-OH

1

Δ

1

Δ

1

Δ

1

Δ

Δ1(2α-ΟΗ3)

YIELD %

—

—

46

—

—

—

57

—

—

60

—

—

ORGANISM

Septomyxa affinis

Bacil lus lentus





Septomyxa affinis




Septomyxa affinis


Nocardia aurant ia

Septomyxa affinis

Calonectr ia decora

Septomyxa affinis

Septomyxa affinis


— —

199-202 -

200-205 +198[d|

— —

— —

221-222 —

250-251 + 18[c]

— —

— —

- -

— —

— —

R E F .

S-833

R-750

K-451

K-451

N-690; N-692

N-690; N-692

H-395

W-1084

N-691

N-690; N-692

B-44

B-74

F-260

S-901

W-1090a

S-927; S-923

B-43

195

TABLE I


EMPIRICAL FORMULA

^ 2 2 " 29^4 '

C22H2905Br

C22H2905C1

C2 2H2 905F


6a-f luoro-17a ,21-dihydroxy-1 6 a - m e t h y l - l , 4 -p regna-diene-3 ,20-dione

9a- f luoro- l l /3 ,17a-d ihydroxy-6a - methyl -1 ,4 -pr egnadiene -3,20-dione

9a - f luor 0 -15a - hy dr oxy - 6a -methyl-4 -pr egnene -3 ,11 ,20 - t r i one

9 a - b r o m o - l l / 3 , 1 7 a , 2 1 - t r i -hydr oxy -16a -me thy l -1 ,4 -pr egnadiene -3 ,20 -dione

9 a - b r o m o - l l / 3 , 1 7 a , 2 1 - t r i -hy dr o x y - 1 6 a - m e t h y l - 1 , 5 -pre gnadiene -3 ,20 -dione

9 a - b r o m o - l l / 3 , 1 7 a , 2 1 - t r i -hydroxy -16/3-methyl - 1 , 5 -pr egnadiene-3,20-dione

9 a - c h l o r o - l l / 3 , 1 7 a , 2 1 - t r i -hydr oxy -16a -me thy l -1 ,4 -pr egnadiene-3 ,20-dione

16 -chlor o m e t h y l e n e - l l ß , 1 7 a , 21- t r ihydroxy-4-pregnene-3,20-dione

9 a - c h l o r o - l l / 3 , 1 7 a , 2 1 - t r i -hydroxy-16a -me thy l -1 ,5 -pregnadiene -3 ,20 -dione

9 a - c h l o r o - l l / 3 , 1 7 a , 2 1 - t r i -hy dr oxy-160-methy l -1 , 5-pregnadiene -3 ,20 -dione

6a - f l uo ro - l l j 3 , 17a ,21 - t r i -hy dr oxy - 2 - methy 1 - 1 , 4 -pregnadiene-3 ,20-d ione

6 a - f l u o r o - l l ß , 1 7 a , 2 1 - t r i -hydr oxy-16α-methy l -1 ,4 -pregnadiene-3 ,20-d ione

6 j3- f luoro- l l /3 ,17a ,21- t r i -hydroxy - 2 - methyl - 1 , 4 -pregnadiene -3 ,20 -dione

9 a - f l u o r o - l l / 3 , 1 7 a , 2 1 - t r i -hydr oxy - 6a - methyl - 1 , 4 -p r egnadiene-3 ,20-dione

9 a - f l u o r o - l l / 3 , 1 7 a , 2 1 - t r i -hy dr oxy -16a - methy 1 - 1 , 4 -pregnadiene-3 ,20-d ione (dexamethasone)

9a - f l uo ro - l l j 3 , 17a ,21 - t r i -h y d r o x y - 1 6 a - m e t h y l - l , 5 -pr egnadiene-3 ,20-dione

TRANSFORMATION

Δ1

1

Δ

15a-OH

1

Δ

21-OAC-21-OH

21-OAC-21-OH

1

Δ

llj3-OH

21-OAC-21-OH

21-OAC-21-OH

A1(2a-CH3)

1

Δ

A1(2a-CH3)

1

Δ

1

Δ

21-OH

21 - O A c - 2 1 -OH

YIELD %

67

—

—

—

—

—

—

58(cr.)

—

—

—

75-85

—

32

-

ORGANISM


Septomyxa affinis






Curvular ia lunata



Septomyxa affinis


Septomyxa affinis


Septomyxa affinis

Bacil lus lentus

Colletotr ichum lindemuthianum


CONSTANTS m . p . ° [oi]D

177-179 —

292-303 -

— —

— —

— —

— —

— —

228 + 40[d]

— —

— —

— —

— —

— —

243-250 + 93 [a]

221-223 —

R E F .

M-536

L-513

A-31

R-752

N-690; N-692

N-690; N-692

R-752

W-1084

N-690; N-692

N-690; N-692

B-43

U-1042

B-43

G-300

S-921

R-750

M-598

N-690; N-692

196

TABLE I


EMPIRICAL FORMULA

C22H2905F

C 2 2 H 2 9 ^ 6 F

C22H2906N

C22H2907N

^ 2 2 · " 3 0 ^ 2

1 ^-/22"30^'3


9a - f luo ro - l l / 3 ,17a ,21 - t r i -hydroxy-16/3-methyl-1, 5-pregnadiene-3 ,20-dione

16- f luoromethyl - l l /3 ,17a ,21-t r ihydroxy-4 ,15-p regna-diene - 3 , 20-dione

6 a - f l u o r o - l l a , 1 7 a , 2 1 - t r i -hydroxy -16 - méthylène -4 -pregnene-3 ,20-dione

16-f luoromethylene-l l /3 , 17a, 21 - t r ihydroxy -4 -pregnene -3,20-dione

6a-fluor o-9a-methy 1-11/3,16α, 17α, 21 - t e t r a -hydroxy-1,4-pregnadiene -3,20-dione

6a-f luoro- l l /3 ,14a , 17a, 2 1 -te t r ahy dr oxy -16a - methy 1-1,4 -pregnadiene - 3 , 20 -dione

9a - f l uo ro - l l / 3 , 16a ,17a ,21 -t e t r ahyd roxy -2 -me thy l - l , 4-pregnadiene-3 ,20-dione

9 a - f l u o ro - l l / 3 , 16a ,17a ,21 -te t rahydroxy-6a-methyl -1,4 -pr egnadiene - 3,20 -dione

6 a - c y a n o - 1 6 a , 1 7 a , 2 1 - t r i -hydroxy-4-pregnene-3 ,11 ,20- t r ione

l l /3 ,17a ,21- t r ihydroxy-16a-nitr omethy 1-1,4 -pre gna -diene-3 ,20-dione

17a-al ly l -17j3-hydroxy- l ,4-androstadien-3 -one

17a-isopropenyl-17/3-hydr oxy -1 ,4 -andr ostadien -3-one

16a-methyl -1 ,4-pregnadiene -3,20-dione

17a-methy 1-1,4-pregnadiene-3,20-dione

20-methoxy- l ,4 ,17(20) -pregna t r i en-3 -one

3 -keto -bisnop-1,4 -chola-dienic acid

21-hydr oxy-17a-methy 1-1,4-pregnadiene -3 ,20 -dione

TRANSFORMATION

21-OAc -21-OH

11/3-OH; 21-OAc - 2 1 -OH

l l a - O H

11/3-OH

1

Δ

1

Δ

16a-OH

16a-OH

16a-OH

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

3 / 3 - O H - 3 - C = 0 ; Δ5 — Δ 4 ; Δ 1 ; 17/3-[2T-isooctyll— 17j3-[2' -propionic acid]

1

Δ ; 21-OAc—21-OH

YIELD %

—

19

—

48

80-85

—

—

—

—

-

—

-

55

-

62(cr.)

ORGANISM


Curvular ia lunata


Curvular ia lunata

Nocardia aurant ia








Bacil lus lentus

Septomyxa affinis

Septomyxa affinis

Nocardia sp.

Septomyxa affinis


— —

210-211 + 70[d]

— —

239-241 + 85[dl

— —

— —

— —

— —

- —

— —

116-117 —

160 + 38[c]

- -

154.5-156.5 -

R E F .

N-690; Ί N-692

W-1084

A-7

W-1084

F-260

U-1042

H-380

F-257

B-74

R-751

W-1109

W-1109

R-750

S-901

F-251

W - l l l l

S-901

197

TABLE I


EMPIRICAL FORMULA

^22 " 3 0 ^ 3

1 C 22™ 3QPA

C22H30O4ClF

C 22H30O4 C l 2


l l ß , 2 1 - d i h y d r o x y - 2 - m e t h y l -1,4,17(20) - p r e g n a t r i e n - 3 -one

lljS, 21 - dihy dr oxy - 6a - methyl -1,4,17(20) -pr egnat r ien-3 -one

16/3-methyl-16a, 17a-oxido-4-pregnene-3 ,20-d ione

1 7 ß - h y d r o x y - l ß , l l ß - o x i d o -5 ,9-cyc loandros tan-3-one 17-propionate

17a-[2 ' -carboxyethyl]-7a, 17β -dihy dr oxy - 4 -androsten - ' 3-one spirolactone

1 7 a - [ 2 ' - c a r boxy ethyl]-9a, 17ß-dihydroxy-4-andros ten-3 -one spirolactone

11/3,17a-dihydroxy-16a-m e t h y l - l , 4 - p r e g n a d i e n e -3,20-dione

l l ß ,21 -d ihyd roxy-16a -methyl -1 ,4 -pr egnadiene -3,20-dione

17a, 21-dihy dr oxy-16a-methyl -1 ,4 -pr e gnadiene -3,20-dione

11a ,17a-dihydroxy-16-methylene-4-pregnene -3,20-dione

l l ß , 17a-dihydroxy-16-méthylène-4-pregnene -3,20-dione

17a ,21-dihydroxy-16-méthylène -4 -pregnene -3,20-dione

15a-hydr oxy-6a-me thy 1-4-pr egnene -3 ,11 ,20 - t r ione

16a - hydr oxy - 6a - methyl - 4 -pregnene -3 ,11,20 - t r ione

21-hydroxy-12a-methy l -4 -p regnene -3 ,11 , 20- t r ione

9 a - c h l o r o - l l ß - f l u o r o - 1 7 a , 2 1 -d ihydroxy-2a-methy l -5 -pregnene-3 ,20-d ione

9 a , l l ß - d i c h l o r o - 1 7 a , 2 1 -dihy dr oxy - 6 - methyl - 5 -p regnene-3 ,20-d ione

TRANSFORMATION

A ^ a - C H g )

1

Δ

3 ß - O H - 3 - C = 0 ; Δ 5 - Δ 4

A ' - l l ß - O A c -Ι β , Ι Ι β - o x i d e

7a-OH

9a-OH

1

Δ

1

Δ

1

Δ

l l a - O H

l l ß - O H

3 ß - O A c - 3 - C = 0 ; 21-OAC-21-OH; Δ 5 - Δ 4

15a-OH

16a-OH

21-OH

21-OAC-21-OH

21-OAC-21-OH

YIELD

% 1 -

-

42

—

—

—

—

—

—

—

—

-

—

—

49(cr.)

—

ORGANISM

Septomyxa affinis

Septomyxa affinis



Gelas inospora t e t r a s p o r a

Nocardia sp.

Bacil lus lentus

Bacil lus lentus

Bacil lus lentus

F u s a r i u m sp.

Curvular ia lunata




Cercospore l l a herpotr ichoides

Kabatiel la phoradendr i


F lavobac te r ium dehydrogenans

CONSTANTS m . p . ° [of]D

-

-

164

268-270

228-230

212.5-213

192-193.5

209-212

208-210

216-217

207

-

-

-

149-151

—

—

-

-

"

+ 44

+ 76[c]

—

—

+ 46[d]

- 8 [ c ]

+ 42[c]

+ 47.5[c]

-

-

-

+207.5[c

—

R E F .

M-573; H-394

M-573; S-928

S-837

R-777

T-1035

D-173

R-750

R-750

R-750

B-68

B-68

T-981 ; M-558

A-31

S-834

L-490

L-498

N-691

N-691

198

TABLE I


EMPIRICAL FORMULA

^ 2 2 " 3 0 ^ 5


la - hy dr oxy - 3 ,12 - diketo -bisnor-4-cholenic acid

l l a , 1 7 a , 2 1 - t r i h y d r o x y - 6 £ -methyl -1 ,4 -pr egnadiene -3,20-dione

l l a , 1 7 a , 2 1 - t r i h y d r o x y - 1 6 a -methyl -1 ,4 -pregnadiene -3,20-dione

l l a ,17a ,21- t r ihydroxy-16 /3 -methy 1 -1 ,4 -pr e gnadiene -3,20-dione

l l /3 ,17a ,21- t r ihydroxy-2-methyl -1 ,4 -pr egnadiene -3,20-dione

11/3,17a, 21- t r ihydroxy-6a-metl iyl-1,4 -pr egnadiene -3,20-dione

l l /3 ,17a,21- t r ihydroxy-6/3-methyl -1 ,4 -pregnadiene -3,20-dione

l l /3 ,17a ,21- t r ihydroxy-16a-methy 1 -1 ,4 -pr egnadiene -3,20-dione

11/3,17a, 21-trihydroxy-16/3-methy 1 -1 ,4 -pr e gnadiene -3,20-dione

TRANSFORMATION

7-C=0->7a-OH; Δ4(5/3-Η) ; 17ß-CH(CH3)-(CH2)2-COOH^17/3-CH(CH3)-COOH

3a-OH->3-C=0; 1 2 a - O H - 1 2 - C = 0 ; Δ4(5/3-Η); 17/3-CH(CH3)-(CH2)2-COOH-17/3-CH(CH3)-COOH

1

Δ

l l a - O H

11a-OH

1

Δ

A(2a-CE3)

A1(2a-CH3); 21 -OAc-21-OH

1

Δ 1

Δ

1

Δ

1

Δ

11/3-OH 1

Δ ; 21-OAC-21-OH

11/3-OH

YIELD %

1

—

—

-

-

-

-

-

2

46(cr.)

—

—

-

-

ORGANISM

Streptomyces gelaticus

Streptomyces gelaticus

Septomyxa affinis

Beauveria sp.


Pesta lot ia foedans

Phoma sp .

Beauveria sp.

Glomerel la sp.

Phoma sp.


Septomyxa affinis



Septomyxa affinis

Septomyxa affinis

Bacillus lentus


Phoma sp.


Phoma sp.


278-280

280-282d

—

—

236-238

—

-

-

-

270-272

245-247

—

219-220

-

-

+ 77fe]

—

—

+ 2 4 i d l

—

-

-

-

-

+ 83[d]

—

—

-

-

REF.

H-363

H-354

S-833

1-421

C-109

Ü-702

1-422

1-421

C-109

1-422

1-421

H-394; M-573

H-399

G-300

L-512; S-833; W-1072; M-647; M-573; K-456

L-512; S-833

R-750

H-392

1-422

T-986

1-422

199

TABLE I


EMPIRICAL FORMULA

^ ■ ^ " β θ ^

I ^ 2 2 " 3 0 ^ 6

C2 2Hs l03Br

C 2 2 H 3 1 0 3 F

C 2 2 H 3 1 0 4 F

C 2 2 H 3 1 ° 5 F


l l ß , 1 7 a , 2 1 - t r i h y d r o x y - 1 6 a -m e t h y l - l , 5 - p r e g n a d i e n e -3,20-dione

l l ß , 1 7 a , 2 1 - t r i h y d r o x y - 1 6 ß -methy 1-1 ,5-pregnadiene-3,20-dione

l l ß , 1 7 a , 2 1 - t r i h y d r o x y - 1 6 -methy l -4 ,15-pregnad iene-3,20-dione

17a,21-dihydroxy-16ß-methyl-1 - 5α-pr egnene -3 ,11 ,20 - t r i one

17a ,21-dihydroxy-16a-methy 1 -1 - 5ß-pregnene -3 ,11 ,20 - t r ione

l l a , 1 7 a , 2 1 - t r i h y d r o x y - 1 6 -methylene -4 -pregnene -3,20-dione

l l ß , 1 7 a , 2 1 - t r i h y d r o x y - 1 6 -methylene -4 -pr egnene -3 ,20-dione

17a,21-dihydroxy-16ß-methyl-9a , l l a - o x i d o - 4 -pregnene-3 ,20-d ione

11/3,15/3,17a, 21-tetrahydroxy-15a-methyl - 1 , 4 - p r egna-diene-3 ,20-dione

11/3,16a, 17a, 21 - tetrahydroxy-6a -me thy l -1 ,4 -p regnad iene -3,20-dione

1 7 a - b r o m o - l l ß - h y d r o x y - 6 a -methyl -4-pr egnene -3 ,20 -dione

6a-fluoro-11/3-hydroxy-17a-me thy l -4 -p regnene -3 ,20 -dione

6 ß - f l u o r o - l l a , 17a-dihydroxy-21-methy l -4 -pregnene-3,20-dione

6/3-f luoro-l lß, 17a-dihydroxy-21-methy l -4 -pregnene-3,20-dione

6 a - f l u o r o - l l a , 1 7 a , 2 1 - t r i -hydroxy-16a-methyl -4-pregnene-3 ,20-d ione

6 a - f l u o r o - l l ß , 1 7 a , 2 1 - t r i -hy dr oxy -16a - methy 1 - 4-p regnene-3 ,20-d ione

TRANSFORMATION

21-OAc^21-OH

21-OAC-21-OH

l l ß - O H

1 Δ

1

Δ ; 21-OAc^21-OH

Δ 4 ^ 5 β - Η

l l a - O H

l l ß - O H

9(11) Δ - 9 a , 1 l a - o x i d e ; Δ4(5α-Η); 21-OAC-21-OH

Δ1

16a-OH

l l ß - O H

l l ß - O H

l l a - O H

l l ß - O H

l l a - O H

l l a - O H ; 21-OAC-21-OH

l l ß - O H

YIELD

% 1

27

-

4

—

-

—

—

—

—

—

—

-

70-75

ORGANISM



Curvular ia lunata

Cor ynebacter ium s implex


Streptomyces sp .

F u s a r i u m sp.

Curvular ia lunata


Septomyxa affin is


Curvular ia lunata

Curvular ia lunata


Curvular ia lunata

Epicoccum oryzae



Curvular ia lunata

CONSTANTS m.p.° [a]p|

— —

245-247 + 53[c]

- -

206-212 +116[d]

199-201 + 42[d]

224-225 + 69[d]

— —

— —

— —

— —

— —

— —

216.5-218.5 —

REF.

N-690; 1 N-692

N-690; N-692

W-1084

K-451

K-451

G-314

M-558

M-558; T-981

C-138

B-44

F-257

R-756; R-759

R-759

H-391

H-391

H-391

W-1098

W-1098

U-1042

200

TABLE I


EMPIRICAL FORMULA

C 2 2 H 3 1 0 5 F

C22H3106F

^ 2 2 ^ 3 2 ^ 2

C22H3203


6a - f luo ro - l l / 3 ,17a ,21 - t r i -hydr oxy - 21 - me thyl -4 -pregnene-3 ,20-dione

6a - f luo ro -14a ,17a ,21 - t r i -hydroxy -16a - me thyl - 4 -pregnene-3 ,20-dione

21- f luo ro - l l / 3 ,16a ,17a - t r i -hydroxy-6a-methyl -4-pregnene-3 ,20-dione

6 a - f l u o r o - l l a , 1 4 a , 1 7 a , 2 1 -te t rahydroxy-16a-methyl -4-pregnene-3 ,20-dione

6a- f luoro- l l /3 ,14a , 1 7 a , 2 1 -te t r ahydr oxy -16a - methyl -4-pregnene-3 ,20-dione

6a- f luoro- l l /3 ,16a , 17a, 21 -te t r ahydr oxy -9a - methyl -4-pregnene-3 ,20-d ione

9 a - f l u o r o - l l / 3 , 1 6 a , 1 7 a , 2 1 -te t r ahydr oxy -2 ξ -methyl -4-pregnene-3 ,20-dione

9a-fluor o-11/3,16a, 17a, 21 -te t rahydroxy-12a-methyl -4-pregnene-3 ,20-d ione

17/3-hydroxy-4-androsten-3-one 17-propionate

3 - k e t o - 2 0 - M i s o " - b i s n o r - 4 -cholen-22-al

15a -hydroxy -3 -keto - bisnor -4-cholen-22-a l

3 -keto-bisnor -4-cholenic acid

7/3-hydroxy-7a-methyl-4-pregnene-3 ,20-d ione

11a-hydroxy-16a-methyl -4-pregnene-3 ,20-d ione

11a -hydroxy - 17a-methyl -4-pregnene-3 ,20-dione

Hj3-hydroxy-6j3-methyl-4-pregnene-3 ,20-d ione

s t e reochemis t ry a t 20- of sta

TRANSFORMATION

11/3-OH; 21-OAc^21-OH

14a-OH

16a-OH

11a-OH

11/3-OH

16a-OH

16a-OH

16a-OH

3 / 3 - O H - 3 - C = 0 ;

Δ 5 - Δ 4

20-HC=O-> 20-" i so"-HC=O*

15a-OH

3/3-OH-*3-C = 0 ; Δ 5 - + Δ 4 ; 17j3-(2' -isooctyl)-» 17j3-(2' -propionic acid)

3/3-OH-*3-C = 0 ; Δ 5 - Δ 4 ; 20 /3-OH-20-C = O

l l a - O H

l la -OH

11/3-OH

rung mater iaLnot cjef]

YIELD %

—

0.5-2

—

1

15-25

—

—

"

—

9

-

35

-

—

ned

ORGANISM

Curvular ia lunata

Curvular ia lunata







Acetobacter pas teur ianum


Fusa r ium solani

Nocardia sp.





Curvular ia lunata


— —

247-251 +124[dl

— —

— —

— —

— —

— —

"

121 + 87[e]

— —

— —

154-157 +121[dl

161-163 +149[cl

— —

— —

R E F .

H-390

U-1042

L-510

U-1042

U-1042

F-260

H-380

F-260

K-457

W-1068

M-599

W - l l l l

R-776

S-804; L-515; L-517; C-141

V-1048; S-835

L-520

R-754; R-757; R-773

TABLE I


201

EMPIRICAL FORMULA

C22H32O4

^ 2 2 " 3 2 ^ « î


1 l a - hydr oxy - 3 -keto - bisnor -4-cholenic acid

11a, 17a-dihydroxy-16a-methyl-4 -pregnene -3 ,20 -dione

11a ,17a-d ihydroxy-21-me thy l -4 -p regnene -3 ,20 -dione

11/3,16a-dihydroxy-6a-methyl-4 -pregnene -3 ,20 -dione

11/3,16a-dihydroxy-12a-m ethyl -4 -pre gnene -3 ,20 -dione

11/3,17a-dihydroxy-21-methyl-4 -pregnene - 3 , 2 0 -dione

17a, 21-dihydroxy-16a-me thy l -4 -p regnene -3 ,20 -dione

17a, 21 - dihydroxy -16/3 -me thy l -4 -p regnene -3 ,20 -dione

2ß ,17a ,21- t r ihydroxy-16a-me thy l -4 -p regnene -3 ,20 -dione

l l a , 1 7 a , 2 1 - t r i h y d r o x y - 1 6 a -me thy l -4 -p regnene -3 ,20 -dione

l l a , 17a ,21 - t r i hyd roxy-16 /3 -me thy l -4 -p regnene -3 ,20 -dione

11/3,16a, 17a- t r ihydroxy-6a-methyl-4 -pregnene - 3 , 2 0 -dione

l l / 3 ,17a ,21- t r ihydroxy-2a -methyl-4 -pregnene - 3 , 2 0 -dione

l l ß , 1 7 a , 2 1 - t r i h y d r o x y - 1 6 a -methyl-4 -pregnene - 3 , 2 0 -dione

l l /3 ,17a ,21- t r ihydroxy-16ß-me thy l -4 -p regnene -3 ,20 -dione

TRANSFORMATION YIELD

l l a - O H

11a-OH; 17a-OH

l l a - O H

16a-OH

16a-OH

l l ß - O H

3/3-OH—3-C=0; Δ5 - Δ 4 ; 21-OAC-21-OH

3 ß - O A c - 3 - C = 0 ; Δ 5 - > Δ 4 ; 21-OAc-»21-OH

2β-ΟΗ

l l a - O H

l l a - O H

l l a - O H ; 21-OAc^21-OH

16a-OH

21-OAC-21-OH

l l ß - O H

11/3-OH

55

ORGANISM






Curvular ia lunata




Beauver ia sp .

Glomere l la cingulata

Phoma sp.

Beauver ia sp.


Phoma sp.

Beauveria sp.




Curvular ia lunata

Phoma sp .

Phoma sp.


219-220

196-198

fl30[d]

- 61[c

R E F .

220-222 +110[d]

M-582

M-571

H-391

S-834

F-257

H-391

C-109; 1-421; 1-422

C-109; 1-421; 1-422

L-496

1-421

C-109

1-422

1-421

C-109

1-422

1-421

C-109

L-511

H-399

C-96

1-422

1-422

202

TABLE I


EMPIRICAL FORMULA

^22"32^5

^22"32^6

C22H33ON

^22"34^2

^22^34^3

C22 H34°4

C 22H34O5


15α, 17α, 21- t r ihydr oxy-16a-methy l -4 -p regnene-3 ,20-dione

l l /3 ,14a ,17a ,21- te t rahydroxy-16a-methy l -4-pregnene-3,20-dione

4-conenin-3-one

22 -hy dr oxy - bisnor -4 -cholen -3-one

2 2 - hy dr oxy - 2 0/3-bisnor-4-cholen-3-one

Γ7/3, 19-dihydroxy-17a-propyl -4-andros ten-3-one

1 l a , 22 -dihydr oxy - bisnor - 4 -cholen-3-one

15α, 22 -dihydr oxy -bisnor - 4 -cholen-3-one

6/3, l i a , 22 - t r ihydr oxy -bisnor -4-cholen-3-one

3a ,7a -d ihydroxy-12-ke to -bisnor - 5j3-choIanic acid

l l a , 1 7 a , 2 1 - t r i h y d r o x y - 1 6 a -methyl-5a -pregnane -3 ,20 -dione

l l a ,17a ,21- t r ihydroxy-16 /3 -methyl- 5a -pregnane - 3 , 2 0 -dione

11/3,17a, 21 - t r ihydr oxy -16a -me thy l -5a -p regnane -3 ,20 -dione

11/3,17a, 21-tr ihydr oxy-16ß-methyl-5a -pregnane - 3 , 2 0 -dione

TRANSFORMATION

15a-OH

11/3-OH; 14a-OH

3 /3 -N(CH 3 ) 2 -3 -C=0 ; Δ 5 ^ Δ 4

20-HC=O-^ 20a-CH2OH

2 0 - H - C = O ^ 20/3-CH2OH

19-OH

l l a - O H

l l a - O H ; 22-C=0->22-OH

15a-OH; 2 2 - C = 0 ^ 2 2 - O H

6/3-OH

6ß-OH; l l a - O H ; 22-C = 0-»22-OH

12a-OH->12a-C = 0 ; 17/3-CH(CH3)-CH2-CH 2 -COOH-17ß-CH(CH3)-COOH

l l a - O H

l l a - O H

11/3-OH

11/3-OH

YIELD %

—

—

35

-

20

8

-

-

15

—

4

30

2-12

-

—

-

—

ORGANISM

Curvular ia lunata

Curvular ia lunata

Gloeosporium cyclaminis

Hypomyces haematococcus


Pénici l l ium l i lacinum

Hypochnus sasaki i








Beauveria sp.


Phoma sp.

Beauveria sp .

Glomerel la sp.

Phoma sp.

Phoma sp .

Phoma sp.


—

—

108-110

-

133-146

143-145

-

-

130-133

-

222-228

238-240

232-238

:

-

—

-

—

—

—

+160[d]

-

-

+ 98[cl

-

-

+ 78[cl

-

-

+ 22[c]

-

:

-

—

R E F .

C-96

C-96

D-148

D-148

W-1068

W-1068; E-202

S-869

M-582

M-578; M-601

E-202

M-578

M-578

M-578; M-601

H-359

1-421

C-109

1-422

1-421

C-109

1-422

1-422

1-422

203

TABLE I I I


EMPIRICAL FORMULA

C23H2403C1F

C 2 3 H 2 4 0 3 C 12

C23H2603C1F

1 C23H2603C12

C23H2703C1

1 ^23^27^3-k

C 2 3 H 2 7 0 4 I

C23H2709C1S

|C23H28Ü3

C 2 3 H 2 8 0 4 C 12

|C23H2805

IC23H2806


17a-chlore th inyl -6-f luoro-17 /3-hydroxy- l ,4 ,6 -andro-s t a t r i en -3 -one aceta te

6-ch loro-17a-chlore th inyl -17 j3-hydroxy- l ,4 ,6 -andro-s t a t r i en -3 -one aceta te

17a - chlor ethiny 1 - 6a - fluor o -17/3 - hy dr oxy -1 ,4 - andr o -Stadien-3-one aceta te

6a - chlor o- 17a -chlor ethiny 1-17/3-hydr oxy-1 ,4 -andr o-s tadien-3-one ace ta te

17a-chlorethinyl-17ß-hydr oxy -1 ,4 -andr ostadien -3-one aceta te

17a - ethiny 1 -16a - ethyl - 9a -f luoro-17/3-hydroxy- l ,4-androstadiene -3 ,11 -dione

17a-hydroxy-21-iodo-1,4,9 ( 11) -pre gnatr iene -3,20-dione aceta te

1 2 a - c h l o r o - l l j 3 , 1 6 a , 1 7 a , 2 1 -t e t r ahyd roxy-1 ,4 -p regna -d iene-3 ,20-dione 16 ,17-cyclosulfate 21-acetate

17a - ethiny 1 -16a - ethyl -17/3-hydroxy-9/3, l l ß - o x i d o - 1 , 4 -andros tadien-3 -one

17ß-hydroxy-16a-methyl-17a-(l f -propinyl)-9/3,11/3-oxido-1,4 -andr os tadien-3 -one

17/3-hydroxy-16a -methyl - Ha-il' -pr opiny 1)-1 ,4-andr o-stadien - 3 , 1 1 - dione

9a, l l j3-dichloro-17a-hydroxy-1,4 -pr egnadiene -3 ,20 -dione aceta te

14/3-hydroxy-3,19-dioxo-4,20(22)-cardadienolide

21-hydroxy-16a ,17a-oxido-1,4-pr egnad iene-3 ,20-dione aceta te

17a, 21-dihydr oxy - 1 , 4 -pr egnad iene-3 ,11 ,20- t r ione 21 -acetate

1 7 a , 2 1 - d i h y d r o x y - l , 4 -p regnad iene -3 ,11 ,20 - t r ione 21-aceta te 4-Ci*

TRANSFORMATION

Δ^

1

Δ

1

A

1

Δ

l

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1 9 - O H - 1 9 - C = 0

3/3-OH-3-C = 0 ; 5 /3 -ΟΗ-Δ 4

1

Δ

1

Δ

1

Δ

YIELD

% 1

1̂ —

—

—

—

—

—

—

—

—

—

8

-

—

11

6

ORGANISM













Pénic i l l ium thomii

Chaetomium globosum

No cardia r e s t r ictus





"

— —

— —

— —

— —

— —

— —

— —

— —

— —

230-235 +129[c]

222-224 —

- -

— —

230-233d —

- -

R E F .

0-694 1

0-694

0-694

0-694

0-694

O-701

R-756

F-262

O-701

O-701

O-701

G-307

S-892

S-891

K-481

F-233

N-665

C-120

204

TABLE I


EMPIRICAL FORMULA

C23H2902C12I

C 23 H29O3F

^ 2 3 H 2 A B r

C23H 2 90 5 F

C23H2906F

^ 2 3 " 3 ( Γ Λ

^23 " 3 0 ^ 4

C 2 3 H 3 0 ° 4 C 12

C2 3 H3 0 O5


9 a , l l ß - d i c h l o r o - 2 1 - i o d o -6 a , 1 7 a - d i m e t h y l - l , 4 -pregnadiene-3 ,20-dione

1 la - ethiny 1 -16a - ethyl - 9a -f luoro-l lß ,17/3-di hydroxy -l , 4 - andros t ad ien -3 -one

9 a - b r o m o - 1 6 a - e t h y l - 1 7 a , 2 1 -dihydroxy-1, 5-pregnadiene -3 ,11 ,20- t r ione

16a-e thy l -9a- f luoro-17a ,21-dihydroxy-1,5-pregnadiene -3 ,11 ,20- t r ione

9 a - f l u o r o - l l ß , 1 7 a , 21 - t r i -hydroxy -1 ,4 -pr egnadiene -3,20-dione 21-acetate

6 , 1 7 a - d i m e t h y l - l , 4 , 6 -pregna t r iene-3 ,20-d ione

14/3 -hydroxy -3 -keto -4,20(22)-cardadienolide

21 -hydroxy -1 ,4 -pre gnadiene -3,20-dione aceta te

9a, l l ß - d i c h l o r o - 6 , 1 6 a -dimethyl-17a, 21-dihydroxy-1,5 -pr egnadiene - 3 , 2 0 -dione

9a, l lß -d ich lo ro-6 ,16 /3-dimethyl-17a, 21-dihydroxy-1,5 -pr egnadiene - 3 , 2 0 -dione

14/3,19-dihydroxy-3-keto-4,20(22)-cardadienolide

14/3-hydroxy-3,16-diketo-5ß-20(22)-cardenolide (tentative)

11/3,17a, 21 -tr ihydroxy -6a-methy l -16-méthy lène-1 ,4 -pregnadiene-3 ,20-dione

17a ,21-dihydroxy-6a ,16a-dimethyl -1 ,4 -pregnadiene -3 ,11 ,20- t r ione

16a - ethyl -17a, 21 - dihy dr oxy -1, 5 -p regnad iene-3 ,11 ,20-t r ione

11/3,17a, 21 -tr ihydroxy -6a, 16-d i m e t h y l - l , 4 , 1 5 - p r e g n a -t r i ene -3 ,20-d ione

TRANSFORMATION

Δ1

1 Δ

21-OAc^21-OH

21-OAC-21-OH

1 Δ

1 Δ

5/3-Η-Δ4

(via 5ß-OH)

3/3-OH-3-C = 0 ; 5 ß - H - Δ 4 ( v i a 5ß-OH)

1 Δ

21-OAC-21-OH

21-OAc->21-OH

1 9 - C = 0 - 1 9 - O H

3 ß - O H - 3 - C = O j 16ß -OH-16-C = 0

1 Δ

1

Δ

21-OAc^21-OH

1 Δ

YIELD %

—

—

—

—

79

—

<1

67(cr.)

55

—

—

ORGANISM







Septomyxa affinis

Absidia orchid is


Absidia orchid is





Pénici l l ium thomii

Gibberel la fujikuroi





CONSTANTS \m.y.° [e]p

— —

— —

— —

— —

121-121.5 + 13[c]

— —

229-236 —

202-204 +143[cl +152[el

247-251 —

— —

236-237 + 5[d]

"

— —

246-248 + 10[d]

R E F .

R-759

O-701

N-692

N-690; N-692

F-233

F-240

S-901

N-682

N-682

N-679

N-678

H-389; N-671

N-691

N-691

S-892

K-434

B-69

A-24; A-25

N-690; N-692

B-69

205

TABLE I


EMPIRICAL FORMULA

r^23"30^5

C23H30O5NF

IC23H30Ue

| ^ 2 3 " 3 0 ^ 7

C23H3105Br

C 2 3 H 3 1 ° 5 F

1 C23H3202

1 ^23 " 3 2 ^ 3


l l /3 ,16a ,21- t r ihydroxy-1 ,4 ,17(20) -c i s -p regna t r i en-3-one 21-aceta te

21-hydroxy-16a ,17a-oxido-4-pregnene-3 ,20-d ione aceta te

21 - (N-acetylamino) -9a -f luor o -l l / 3 , 1 7 a - d i h y d r o x y - l , 4 -pregnadiene-3 ,20-d ione

Π β , 17α, 21 - t r i hyd roxy-1 ,4 -pregnadiene-3 ,20-d ione 21-aceta te

l l /3 ,21-d ihydroxy-16a ,17a-ox ido-4 -p regnene-3 ,20-dione 21-aceta te

14a ,21-d ihydroxy-16a ,17a-ox ido-4 -p regnene-3 ,20-dione 21-aceta te

11/3,14a,21-tr ihydroxy-16a, 17a-oxido-4-pregnene -3,20-dione

9a -b romo-16a-e thy l -l l ß , 1 7 a , 2 1 - t r i h y d r o x y - l , 5 -pregnadiene-3 ,20-d ione

9 a - f l u o r o - l l / 3 , 1 7 a , 2 1 - t r i -hydroxy-6a, 16a-dimethyl-1,4 -pregnadiene -3 ,20 ~ dione

16a - ethyl - 9a -fluoro-11/3,17a, 21 - t r ihydroxy - 1 , 5 -pregna-diene-3 ,20-dione

17a-e thy l -1 ,4 -pregnad iene-3,20-dione

6α, 17α-d imethy l -1 ,4 -pregna-diene-3 ,20-dione

1,4-pregnadiene -3 ,20-dione 20-cycloethylene ketal

TRANSFORMATION

^

3/3-OH-3-C = 0 ; Δ 5 - Δ 4

1 Δ

21-OH^21-AcNH

1 Δ

11/3-OH

14a-OH

l l ß - O H ; 14a-OH

21-OAC-21-OH

1 Δ

21-OAC-21-OH

1 Δ

1 Δ

1 Δ

YIELD %

—

—

—

13

—

—

—

—

—

25

27

-

-

—

—

ORGANISM

Septomyxa affinis

F lavobacter ium sp.





Curvular ia lunata

Curvular ia lunata

Curvular ia lunata




Septomyxa affinis

Septomyxa affinis



Corynebac ter ium hoagii



CONSTANTS m.p.° MD[

—

—

252-255 (ethanol solvate)

—

237-239d

—

—

—

—

—

150-151

118-119

-

-

—

—

—

—

+107[ml

—

-

—

—

—

—

—

-

+ 14[c]

-

-

—

-

R E F .

M-529

P-742

S-911

S-911

K-480

N-665

A-3 ; A-5

A-3 ; A-5

A-3 ; A-5

N-690; N-692

A-24; A-25

N-690; N-692

S-901

S-901

F-251

F-251

F-251

F-251

F-251

206

TABLE I


EMPIRICAL FORMULA

C^HggOg

^ 2 3 " 3 2^4

^ 2 3 Η 3 2 ϋ 5


1 ,4-pregnadiene -3 ,20-dione 20-cycloethylene ketal

3/3,14/3-dihydroxy-5/3-16, 20 (22) -cardadienolide (tentative)

3/3-hydroxy-14a, 15a-oxido-5/3-20(22) -cardenolide

14/3-hydroxy-3-keto-5/3,17a-20(22)-cardenolide

14/3-hydroxy-3-keto-5/3-20(22)-cardenolide

5 / 3 - 1 - p r e g n e n e - 3 , 1 1 , 2 0 -tr ione 20-cycloethylene ketal

21-hydroxy-4-pregnene-3 ,20-dione acetate

7/3,14/3-dihydroxy-3 -keto-5/3-20(22)-cardenolide

12/3,14/3-dihydroxy-3-keto-5/3-20(22) -cardenolide

TRANSFORMATION

3/3-OH-*3-C = 0 ; Δ5—>Δ4· Δ1

Δ 1 6

3j3-OAc^3/3-OH

3/3-OH-*3-C = 0

3 a - O H - 3 - C = 0

3/3-OH-3-C = 0

1

Δ

3/3-OH->3-C = 0 ; Δ 5 - Δ 4

7/3-OH

3/3-OH-*3-C = 0

7/3-OH; 3/3-OH-3-C = 0

7/3-OH; 3/3-OAc-3-C = 0

12/3-OH

YIELD %

-

1

93

:

4

-

—

10

-

-

2

-

2

-

2

-

-

44

-

5

-

1

13

-

ORGANISM

Septomyxa affinis

Tr ichothecium roseum

Rhizopus shanghaiensis

Calonectr ia decora


Nigrospora sphaer ica

Rhizopus a r rh i zus

Calonectr ia decora




Absidia sp.


Cunninghamella sp.


Mucor sp.

Psi locybe mexicana

Rhizopus sp.

Tr ichothecium roseum

Septomyxa affinis

Flavobacter ium sp0

Psi locybe mexicana



Psi locybe mexicana



Calonectr ia decora


-

—

-

—

219-223

-

—

198-204

-

-

-

-

197-205

-

205-207

-

-

204-206

—

266-273

-

259-269

261-275

—

-

—

-

—

-

-

—

-

-

-

-

-

-

-

-

-

-

—

—

+ 56[cl

-

:

—

"

REF.

F-251

T-1013

M-576

N-681

N-681

N-681

N-681

N-681

N-681

N-681

N-681

N-682

J-432

N-682

N-678

N-682

W-1075

N-682

J-432

F-253; F-249; F-251

P-742

W-1075

N-678

N-678

W-1075

N-678

N-678

N-677

207

TABLE I


EMPIRICAL FORMULA

*-'23"32^'5


12)3,14/3-dihydroxy-3-keto-5/3-20(22)-cardenolide

14/3,16/3-dihydroxy-3-keto-5)3-20(22) -cardenolide

1 6 a - e t h y l - l l a , 1 7 a , 2 1 - t r i -hydroxy-1 ,4-pregnadiene -3,20-dione

1 6 / 3 - e t h y l - l l a , 17a ,21 - t r i -hydroxy-1 ,4-pregnadiene -3,20-dione

16j3-e thyl - l l /3 ,17a ,21- t r i -hydroxy-1 ,4-pregnadiene -3,20-dione

l l /3 ,17a ,21- t r ihydroxy-6α, 16α -dimethyl - 1 , 4 -pregnadiene -3 ,20 -dione

1 6 a - e t h y l - l l / 3 , 1 7 a , 2 1 - t r i -hydroxy-1 ,5 -p r egnadiene -3,20-dione

l l ß , 1 7 a , 2 1 - t r i h y d r o x y -6α, 16 -d ime thy l -4 ,15 -pr egnadiene-3,20-dione

11 β, 17α -dihydr oxy -1 - 5a -p regnene-3 ,20-d ione 17-aceta te

TRANSFORMATION

12j3-OH

3 ß - O H - 3 - C = 0

12/3-OH; 3 a - O H - 3 - C = 0

12/3-OH; 3j3-OH - 3 - C = 0

12/3-OH; 3/3-OAc >3-C=0

3/3-OH-*3-C = 0

3/3-OAc->3-C=0

3 ß - O A c - 3 - C = 0 ; 16j3-OAc-16j3-OH

l l a - O H ; 21 -OAc-21 -OH

l l a - O H

11/3-OH

1

Δ

21-OAC-21-OH

11/3-OH

11^-OH

YIELD %

5

50

-

13

10

-

10

10

-

8

-

—

—

—

-

—

—

—

—

ORGANISM




Calonectr ia decora


Calonectr ia decora


Calonectr ia decora

Calonectr ia decora

F u s a r i u m sp.

Gibber ella fujikuroi


Calonectr ia decora




Pes ta lo t ia foedans

Beauver ia sp.

Glo me r e l i a cingulata

Phoma sp.

Phoma sp.

Nocardia a s t é ro ïdes


Curvular ia lunata

Curvular ia lunata

CONSTANTS m.p.° [ a ] p |

247-252 (hydrate)

251-254

-

243-248

242-253

254-256

-

201-209

199-202; 215-220

-

195-198

-

—

221-222

-

—

—

—

238-240

+ 41[m]

+ 32 [lm: lc]l

-

—

—

-

-

-

-

—

+ 21[d]

-

—

—

—

+ 51[d]

R E F .

G-320; T-978

0-699

N-677

N-681

N-681

N-677

N-677

N-677

N-677

K-434

K-434

N-677

N-677

N-677

N-677

N-677

O-703

1-421

C-109

1-422

1-422

A-24; A-25

N-690; N-692

B-69

R-773

208

TABLE I


EMPIRICAL FORMULA

C23 H32 0 5

C23H3205NF

C23 H32°6

C23H3206NF

^ 2 3 " 34^2

^23"34^3

C23 H34 04

C23 H34°5


l l /3 ,17a ,21- t r ihydroxy-6a-methy 1 -16 - méthylène -4 -pregnene-3 ,20-d ione

17a,21-dihydroxy-4-pregnene-3,20-dione 21-acetate

21-[N-acetylamino]-9ö-f luoro-11/3,17û-dihydroxy-4-pregnene-3 ,20-d ione

3/3, 5/3,14/3-trihydroxy-19-oxo-20(22) -cardenolide (strophanthidin)

21- |N-acetylaminoj-9a-f l u o r o - 2 ß , l l ß , 1 7 a - t r i -hydroxy-4-pregnene-3 ,20-dione (tentative)

16 ,16-d imethyl -4-pregnene-3,20-dione

l la-hydroxy-6a,16û!-d imethy l -4 -p regnene-3 ,20-dione

l l /3-hydroxy-6a ,16a-d imethy l -4 -p regnene-3 ,20-dione

l l /3-hydroxy-6a ,17a-d imethy l -4 -pregnene-3 , 20-dione

3a,14/3-dihydroxy-5/3-20(22)-cardenolide

3j3,14/3-dihydroxy-5/3-20(22)-cardenolide (digitoxigenin)

6ß-hydroxy-4-pregnene-3 ,20-dione 20-cycloethylene ketal

1 la -hydroxy-4-pregnene-3 , 20-dione 20-cycloethylene ketal

l/3,3/3,14/3-trihydroxy-5/3,17a-20(22)-cardenolide (tentative)

TRANSFORMATION

11/3-OH; 21-OAc—21-OH

3/3-OH^3-C = 0 ; Δ 5 - Δ 4

3/3-OAc-*3-C=0; Δ 5 —Δ 4

21-NH2->21-AcNH

21-OH—21-AcNH

3/3-D-glucoside-^ 3/3-OH

3ß-D-glucoside tetraacetate—3/3-OH

2/3-OH

3/3-OH-3-C = 0 ; Δ 5 ->Δ 4

Πα-ΟΗ

11/3-OH

11/3-OH

3 - C = 0 ^ 3 Ö - O H

3 - C = 0 - 3 ß - O H

6ß-OH

l l a - O H

lß-OH

YIELD %

—

—

3-11

-

51

57

53

—

—

12-15

4

-

—

ORGANISM

Curvular ia lunata

Flavobacter ium sp .




Fusa r ium lini

Fusa r ium lini




Cunning hamella blakesleeana

Curvular ia lunata

Absidia orchidis

Fusa r ium lini




Psi locybe semperv iva



Absidia orchidis


218

-

213-215

263-264

135-140; 198-201

133-135

168-169

—

269-282

280-284

-

"

+ 50[d]

—

-

+132[ml

-

+ 88[d] +104[cl

"

"

-

-

-

:

R E F .

B-69

P-742

C-128; N-665

S-911

S-911

T-978

T-978

S-911

S-837

S-923

S-923

R-759

N-682

T-978; G-320

0-699

N-678; N-682 N-678

W-1075

F-251

F-251

N-681

209

TABLE I


EMPIRICAL FORMULA

C-23 H 3 4 0 5


3/3, 5/3,14/3-trihydroxy-17a-20(22)-cardenolide

I ß , 3/3,14/3- t r ihydroxy- 5/3-20(22)-cardenolide

3a, 7/3,14/3 - tr ihydroxy -5/3-20(22)-cardenolide

3a, 12/3,14/3 - tr ihydroxy -5/3-20(22)-cardenolide

3a, 14/3,16/3-trihydroxy-5/3-20(22)-cardenolide

3/3,5/3,14/3-trihydroxy-20(22)-cardenolide

3/3,7/3,14/3-trihydroxy-5/3-20 (22)-cardenolide

TRANSFORMATION

5/3-OH

1/3-OH

3 - C = 0 - 3 a - O H ; 7/3-OH

3-C = 0 - 3 a - O H ; 12/3-OH

3-C=0->3a-OH

5/3-OH

7/3-OH

YIELD %

3

17

-

-

-

-

4

1

-

-

37-40

-

24

-

22(cr.)

-

—

4

! 25

l l ( c r . )

ORGANISM

Absidia orchid is


Absidia orchid is

Absidia sp.

Mucor sp.


Rhizopus sp.


Fusa r ium lini

Gibberel ia saubinett i

Fusa r ium lini

Absidia orchidis



Absidia orchidis

Absidia sp .


Cunninghamella sp .

Mucor sp.

Ps i locybe mexicana




232-241d

276-282d

-

-

-

-

255-259

249-262

-

-

245-248

-

266-275

-

275-280

-

-

263-266

267-272

275-280

+ 35[m]

+ 3[m]

-

-

-

-

+ 48[ml

+ 27[m]

-

-

+ 25[cj + 28.5[ml

-

+ 37[m]

-

+ 39[m]

-

—

+ 39[m]

+ 34.5

+ 39[m]

R E F .

N-681

N-681

N-679; N-680; 1-426; N-683

N-682

N-682

N-683

N-682

N-678

G-320; T-978

0-699

T-977

N-679; N-680; N-683; 1-426

1-423; N-678; N - 6 8 3 ; N-682

N-678; N-682

N-680; N-679; 1-426; N-683; N-681

N-682

J-432

N-682

N-682; N-683

W-1075

N-678; 1-425

J-432

210

TABLE I


EMPIRICAL FORMULA

C 23 H 34 0 5


3/3, 7/3,14/3-trihydroxy-5/3-20(22)-cardenolide

3/3,11a, 14/3-trihydroxy-5/3-20(22)-cardenolide

(sarmentogenin)

3/3,12/3,14/3-trihydroxy-5/3-20(22)-cardenolide (digoxigenin)

3/3,14/3,16/3-trihydroxy-5/3-20(22)-cardenolide (gitoxigenin)

3/3,14/3,X-trihydroxy-5/3-20(22)-cardenolide

17/3-methyl-18-nor-17a-5,13-pregnadiene-3/3,16α, 20α, 21 -t e t ro l 21-acetate

TRANSFORMATION

7/3-OH

l l a - O H

12/3-OH

12/3-OH; 3/3-OAc-3/3-OH

12/3-OH; 3-C = 0 - 3 / 3 - O H

16/3-OH

16/3-OAc-16ß-OH

3/3-OAc-3/3-OH; 16/3-OAc-16/3-OH

X-OH

20-C=O-»20a-OH; 13/3-CH3-16a,17a-oxide—17/3-CH3-18-nor -16a -OH; Δ13

YIELD %

l l ( c r . )

-

8

-

4.5

35

-

43

—

-

2

—

25

-

-

-

—

-

9(cr.)

40

ORGANISM

Rhizopus dele mar

Rhizopus sp.

St reptomyces aureofaciens


Trichothecium ro seum


Calonectr ia decora

Fusa r ium lini

Gibberel la fujikuroi




Psi locybe mexicana

Psi locybe semperviva


Psi locybe semperv iva




Calonectr ia decora

Fusa r ium lini





266-274d

-

268-275

-

—

207-209

-

206-209

-

197-208

-

-

210-213

-

—

-

—

-

268-276

205-210

-

-

+ 37[mj

-

—

+ 22.5[ml

-

-

-

-

-

-

-

-

—

-

+ 18[m] •

R E F .

N-682

N-682; N-683

T-1013

T-1013

J-432

T-1013

N-677

T-978; G-320; W-1074

N-651

0-699

N-651

N-677

W-1075

W-1075

T-978; G-320

W-1075

N-651

N-651

0 -699

N-677

T-977

N-677

J-432

C-90

211

TABLE I


EMPIRICAL FORMULA

C23H3405

C^H^Og

1 C23H3604

1 ^23 "36^5

CMH2904C12F


l l j3 ,17a ,21- t r ihydroxy-6a , 16Ö -dimethyl -4 -pregnene -3 ,20-dione

1/3,3/3, 7/3, 14/3 - t e t r any droxy-5/3-20(22) -cardenol ide

3/3, 5/3, 7/3, 14/3-tetr any droxy-20(22)-cardenolide

3/3,12/3,14/3,16/3-tetr ahydroxy-5/3-20(22)-cardenolide (diginatigenin)

3/3,5/3,14/3,19/3-tetrahydroxy-20(22)-cardenolide

3a ,17a ,21- t r ihydroxy-5 /3-p r e g n a n e - l l , 2 0 - d i o n e 2 1 -aceta te

3a,21-dihydroxy-5/3-pregnan-20-one 21-aceta te

16/3-ethyl- l lö , 17α, 21 - t r i -hydroxy-5a -p regnane -3 ,20 -dione

16/3-e thyl - l l /3 ,17a ,21- t r i -hydroxy-5a -p regnane -3 ,20 -dione

9a, 11/3-dichloro-21-fluor o-17a-hydroxy-6a-methyl -1,4 -pr egnadiene -3 ,20-d ione aceta te

9a, l l /3-d ichloro-17a-hydroxy-21 - i odo -6a -me thy l -1 ,4 -pr egnadiene -3 ,20 -dione ace ta te

TRANSFORMATION

11/3-OH; 21-OAC-21-OH

1/3-OH; 7/3-OH

5j3-OH; 7/3-OH

12/3-OH

12β-ΟΗ; 16/3-OAc-16/3-OH

1 9 - C = 0 ^ 1 9 - O H

3 - C = 0 — 3 α - Ο Η ; Δ 4 - 5 β - Η

3 - C = 0 - 3 a - O H ; Δ4 -5/3-H

l l a - O H

11/3-OH

1 Δ

1 Δ

YIELD %

—

6-10

-

-

-

4-7

-

-

-

6

2

-

53

57

-

—

-

—

ORGANISM

Curvular ia lunata

Absidia orchid is

Absidia sp.

Mucor sp.

Rhizopus sp.

Absidia orchid is

Absidia sp .

Mucor sp.

Rhizopus sp.

Fusa r ium lini

Fusa r ium sp.

Gibber el la saubinett i


Ps i locybe semperviva


Clos t r id ium t e r t i u m


Clos t r id ium t e r t i um

Beauveria sp.

Glomere l la sp.

Phoma sp .

Phoma sp.



CONSTANTS m . p . ° [a]D

—

244-254d

-

-

-

249-250

-

-

-

155-156

154-156

153-156

-

216

176-178

-

—

-

—

—

+ 19[m| + 22.5[m]

-

-

-

+ 49[ml

-

-

-

—

+ 34[ml

-

-

+ 73 [a]

+100[c|

-

—

-

—

—

R E F .

S-805

N-679; N-680; 1-426; N-682

N-682

N-682

N-682

N-679; 1-426; N-682

N-682

N-682

N-682

T-977

K-434

0-699 !

0-699

W-1075

S-823

S-823

S-823

S-823

1-421

C-109

1-422

1-422

R-759

R-759

212

TABLE I


EMPIRICAL FORMULA

C24H30O4

C^HaoOgBrF

^ 2 4 ^ 3 0 ^ 6

C^HaPeClF

^ 2 4 ^ 3 0 ^ 6 1*2

^■24"30^7

C 2 4 H 3 1 0 6 F

C24H3107F

C24H3204

1 ^ 2 4 " 32^5


17a-hydroxy-16-méthylène 1,4 -pr egnadiene -3 ,20 -dione acetate

9 a - b r o m o - l l ß - f l u o r o - 1 6 a , 1 7 a , 2 1 - t r i h y d r o x y - l , 5 -pr egnadiene-3,20-dione 16,17-acetonide

17a, 21 -dihydroxy -16a -methyl-1,4 -pregnadiene - 3 , 1 1 , 2 0 -tr ione 21-acetate

17a, 21 -dihydroxy -16/3-methyl -1 ,4 -pregnadiene 3 ,11 ,20- t r ione 21-acetate

6 a - c h l o r o - 1 2 a - f l u o r o - l l ß , 16a, 17a, 21 - te t r any droxy-1,4 -pregnadiene - 3 , 2 0 -dione 16,17-acetonide

2 , 9 a - d i f l u o r o - l l ß , 16α, 17α, 21 - te t r ahydr oxy - 1 , 4 -pr egnadiene-3,20-dione

16,17-acetonide

3, l l ß , 17a, 21- te t r ahydr oxy-19-nor - l , 3,5(10) -pregna-t r ien-20-one 1 1 , 2 1 -diacetate

9 a - f l u o r o - l l ß , 1 6 a , 1 7 a , 2 1 -t e t r ahydroxy-1 ,4 -p regna -diene-3 ,20-dione 16 ,17-acetonide

9 a - f l u o r o - 2 , l l ß , 1 6 a , 1 7 a , 2 1 -pen tahydroxy-1 ,4-pregna-diene - 3 , 20-dione 16 ,17 -acetonide

9a-f luoro-6ß, l l ß , 16α, 17α, 21-pen tahydroxy-1 ,4-pregna-diene - 3 , 20-dione 16 ,17-acetonide

9a-f luoro-6ß, 16α, 17α, 21 -t e t rahydroxy-4-pregnene-3 ,11 ,20- t r ione 16 ,17 -acetonide

3,12 -diketo - 4 , 6 - choladienic acid

12/3,14/3 -dihydroxy -3 -ke to-5ß-20,22-bufadienolide

TRANSFORMATION

Δ1

2 1 - O A c - 2 1 ~ O H

Δ1*4 (5/3-H); 3 a - O H - > 3 - C = 0

Δ 1 ' 4 (5ß-H); 3a -OH-*3-C = 0

1

Δ

A ^ a - F )

Δ ; enolo

Δ1

2-OH

1 Δ

6ß-OH; 11/3-OH—11-C=0

7 - C = 0 - Δ6

3 a - O H - 3 - C = 0 ; 7 α - Ο Η - Δ 6 ; 12a -OH-*12-C=0 ; 5/3-H— Δ4

12ß-OH

YIELD %

22

—

—

18

6

1

ORGANISM



Nocardia blackwelli i

Nocardia blackwelli i

Nocardia aurant ia






Phycomyces sp„



Streptomyces rubescens Fusa r ium lini


222-223

—

—

277-282

243-24505

205-208

228-237

-90[d]

"

—

—

"

+72[p]

+94[m)

—

+l[m]

R E F .

S-837

N-691

S-902

S-905

F-261

H-401

H-386

H-399

F-235; F-236

H-400

H-400

T-975

H-359

H-365

T-979

213

TABLE I


EMPIRICAL FORMULA

^ 2 4 " 3 2 ^ 5

C 2 4 H 3 2 U 6

1 ^24 "32^7

L 2 3 n 3 2 U 7 . r 2

C 2 4 H 3 3 0 6 F

C 2 4 H 3 3 0 7 F

C 2 4 H 3 4 0 4

C 2 4 H 3 4 0 5

C24H3 30 6F


2 1-hydroxy-16/3- methyl -16a, 17a-oxido-4-pregnene -3,20-dione aceta te

l l /3 ,17a ,21- t r ihydroxy-16a-me thy 1-1 ,4-pregnadiene-3,20-dione 21-aceta te

l l /3 ,17a ,21- t r ihydroxy-16/3-methoxy - 1 , 4 - p r egnadiene-3,20-dione 21-aceta te

6a, 9a-difluor 0-2/3,11/3,16a, 17a, 21 -pentahydroxy-4-pregnene-3 ,20-d ione 16 ,17-acetonide

6a - fluor 0-2/3,16a, 17a, 21 -t e t r ahydroxy-4-p regnene-3,20-dione 16,17-acetonide

6 a - f l u o r o - l l a , 1 6 a , 1 7 a , 2 1 -t e t r ahydroxy-4-p regnene-3,20-dione 16,17-acetonide

9a- f luoro-2 j3 , l l j3 ,16a ,17a ,21-pentahydroxy-4-pregnene-3,20-dione 16,17-acetonide

9a-f luoro-6ß, 11/3,16α, 17α, 2 1 -pentahydroxy-4-pregnene-3,20-dione 16,17-acetonide

12a-hydroxy-3-keto - 1 , 4 -choladienic acid

12a-hydroxy-3-keto - 4 , 6 -choladienic acid

3/3,12/3,14/3-trihydroxy-5/3-20,22-bufadienolide

3 ,7 ,12- t r ike to-5 /3-cholan ic acid

7a -hydroxy-3 ,12-d ike to -4 -cholenic acid

6 a - f l u o r o - l l ß , 16α, 17α, 2 1 -te t r ahydr oxy-4-pr egnene -3 ,

| 20-dione 16,17-acetonide

TRANSFORMATION

3 / 3 - O H - 3 - C = 0 ; Δ 5 - Δ 4

11/3-OH

1 Δ

2/3-OH

2/3-OH

l l a - O H

2/3-OH

6/3-OH

3 a - O H - 3 - C = 0 ; 7a-OH-*H; Δ 1 ; Δ4(5β-Η)

3 a - O H - 3 - C = 0 ; 7α-ΟΗ->Δ6; Δ4(5/3-Η)

12/3-OH

3 a - O H - 3 - C = 0 ; 7a-OH->7-C = 0 ; 1 2 a - O H - 1 2 - C = 0

7-C = 0 - 7 a - O H ; Δ4(5/3-Η)

3 a - O H - 3 - C = 0 ; 12a -OH—12-C=0 ; Δ4(5/3-Η)

11/3-OH

YIELD

% 1 —

—

—

14

24

24

—

15

—

3

—

50(cr.)

65-99

-

15

2

1

—

ORGANISM

Flavobacter ium sp .

Curvular ia lunata

Cor yne bac ter ium s implex



Col le totr ichum phomoides



Phycomyces sp.



Corynebac te r ium sp.

S t reptomyces rubescens


Alcal igenes faecal is

Esche r i ch ia coli

Corynebac te r ium sp„

St rep tomyces gelat icus

S t rep tomyces rubescens

Cunninghamella b a i n i e n

CONSTANTS m . p . ° [o?]D|

—

—

—

240-242

264-266

260-261

240.5-243.5

—

249-252

-

240-246

236-237

-

246-249d

224-226d

248-252d

—

—

—

—

- 53[c]

+102[cl

+ 13[m]

+ 72[m]

—

-

- 16[m]

—

-

-

—

—

R E F .

P-742

S-904

R-760

F-235; F-236

L-496

D-159

D-159

F-235; F-236

H-400

H-358; H-367

H-367

T-974

H-362

T-979

S-799; S-800; H-393

S-799

T-975

H-363

H-365

R-771 ,

214

TABLE I


EMPIRICAL FORMULA

C 2 4 H3 4 0 7

^24 " 3 6 ^ 3

C2 4 H3 6 0 4

C 2 4 H3 6 0 5

^ 2 4 ^ 3 8 ^ 4

^ 2 4 " 3 8 ^ 5

C2 4 H4 0 O4

C 2 5 H 3 0 O 5 S


2/3,11/3,16α, 17α, 21-penta-hydroxy-4-pregnene-3 ,20-dione 16,17-acetonide

3-keto-4-cholenic acid

12a-hydroxy-3-ke to-4-cholenic acid

3a-hydroxy-7,12-diketo-5/3-cholanic acid

7a-hydroxy-3 ,12-d ike to-5ß-cholanic acid

la, 12a -dihydroxy -3 -keto -4 -cholenic acid

3a-hydroxy-6-keto-5/3-cholanic acid

3a-hydroxy-7-keto-5/3-cholanic acid

3a-hydroxy-12-ke to-5ß-cholanic acid

3a, 7a-dihydroxy -12 -keto-5/3-cholanic acid

3a, 12a-dihydroxy-7-keto-5/3-cholanic acid

7a, 12a-dihydroxy-3-keto-5/3-cholanic acid

3a, 7a-dihydroxy-5/3-cholanic acid

21-hydroxy-16a-mercap to-1,4,9(11) -p regna t r i ene -3,20-dione 16,21-diaceta te

unidentified gram-pos i t ive co

TRANSFORMATION

2/3-OH

3/3-OH^3-C = 0 ; Δ 5 - Δ 4

3 a - O H - 3 - C = 0 ; 7 a - O H ^ H ; Δ4(5/3-Η)

7 a - O H - 7 - C = 0 ; 1 2 a - O H - ^ 1 2 - C = 0

7-C=0-*7a-OH

3 a - 0 H - 3 - C = 0 ; 1 2 a - O H - 1 2 - C = 0

3a -OH->3-C=0; Δ4(5/3-Η)

3 - C = 0 - 3 a - 0 H

7a-OH->7-C = 0

3 - C = 0 - 3 a - 0 H

12a-OH->12-C=0

7a-OH->7-C=0

3 a - O H - 3 - C = 0

3 - C = 0 — 3a-OH; 7 - C = 0 - 7 a - O H

Δ1

2CUS

YIELD %

—

37

—

-

10

-

-

-

-

-

60

-

-

-

-

-

-

4

ORGANISM




Alcaligenes faecalis

Bacillus coli

St reptomyces gelat icus

Bacter ium sp.



St reptomyces rubescens


Escher ich ia coli




Alcaligenes faecalis

Clost r idium perfr ingens

Escher ich ia coli



Bacil lus coli

Corynebacter i urn s implex


-

185

—

-

195-196

-

-

-

-

-

165

162

-

-

-

-

-

110-115

-

-

—

-

+ 72[ml

-

-

-

-

-

-

+ l l l [ e ]

-

-

-

-

—

+ 12[e]

R E F .

F-235

T-1032

H-367

H-393

F-289

H-366

E-194

H-367

T-974

H-365

E-221

N-675

M-543

K-441

H-366

H-393

N-675

N-675

H-367

H-366

S-899

R-764

215

TABLE I


EMPIRICAL FORMULA

C 2 5 H 3 1 0 8 F

^ 2 5 " 3 2 θ 3

C25 H32°5

C25H3205C1F

I ^25"32^7

C 2 5 H 3 4 0 5

C25H3405C1F

C25 H34°6

C 25 H36°5


9 a - f l u o r o - l l ß , 1 6 a , 1 7 a , 2 1 -te t r ahy droxy -1 ,4 -pr e gna -d iene-3 ,20-dione 1 6 , 2 1 -diacetate

16a-n-butyl-17a-ethinyl-17/3-hydroxy -1 ,4 -androstadiene -3,11-dione

16/3-n-butyl-17a-ethinyl-17/3-hy droxy -1 ,4 -androstadiene -3 , 1 1 , dione

17a,21-dihydroxy-6/3,16a-dimethyl -1 ,4 ,9(11) -p regna-t r i ene -3 ,20 -d ione 2 1 -aceta te

9a -chloro -11/3 -fluor o- 16α, 17a, 21 - t r ihydroxy -6 -methyl - 1 , 5 -pr egnadiene -3,20-dione 16,17-acetonide

l l ß , 1 7 a , 2 1 - t r i h y d r o x y - l , 4 -pregnadiene -3 ,20 -dione 11,21-diaceta te

16a -n -bu ty l -17a ,21 -dihydr oxy -1 ,4 -pr egnadiene -3 ,11 ,20- t r ione

16ß-n -bu ty l -17a ,21-dihydroxy -1 ,4 -pr egnadiene -3 ,11 ,20 - t r ione

16a -n -bu ty l -17a ,21 -dihydroxy -1 ,5 -pr egnadiene -3 ,11 ,20 - t r ione

16j3-n-butyl-17a,21-dihydroxy-1 , 5-pr egnadiene-3 ,11 ,20- t r ione

9a -chloro -11/3 -f luoro- 16a, 17a, 21 - tr ihydroxy -2a -methyl - 5 -p regnene -3 ,20 -dione 16,17-acetonide

14/3,16ß-dihydroxy-3-keto-5/3-20(22)-cardenolide 16-aceta te

16a- t -butyl -11a , 17a, 21 - t r i -hydroxy -1 ,4 -pr egnadiene -3,20-dione

16a- t -bu ty l - l l /3 ,17a , 21 - t r i -hydroxy -1 ,4 -pr egnadiene -3,20-dione

TRANSFORMATION

Δ1

1 Δ

1 Δ

1 Δ

21 -OAc-21 -OH

1 Δ

1 Δ

1 Δ

21-OAc->21-OH

21-OAc-21-OH

21-OAc^21-OH

3 ß - O H - 3 - C = 0

3/3-OAc—3-C = 0

l l a - O H

l l ß - O H

YIELD

% 1

—

—

59

—

—

—

—

2

-

-

—

-

ORGANISM














Calonectr ia decora


Beauver ia sp .

Glomere l la sp.

Phoma sp.

Phoma sp.


158-235 + 22[c | (solvate); 186-188; (solvate)

— —

— —

219-221 +152[c|

— —

— —

— —

— —

242-249 —

- -

- -

— —

- -

R E F .

B-60; B-59

O-701

O-701

N-691

N-691

H-389

N-692

N-692

N-690; 1 N-692

N-690; N-692

N-691

N-677

N-677

N-677

N-677

1-421

C-109

1-422

1-422

216

TABLE I


EMPIRICAL FORMULA

^ 2 5 " 3 6 ^ 6

^ 2 5 " 3 6 ^ 7

C2 5 H4 0 O5

^ 2 β " 3 4 ^ 7

C 2 6 H 3 5 ° 7 F

^26 " 3 6 ^ 6

C 2 6 H 4 0 U 2

^ 2 6 ^ 4 2 ^ 5

C26H4403

C27H2905P

C27H30O5FP


3/3,14/3,16/3-trihydroxy-5/3-20(22)-car denolide 16-acetate (oleandrigenin)

3/3,12/3,14/3, 16/3-tetrahydroxy-5/3-20(22) -cardenolide 16-acetate

1 6 a - t - b u t y l - l l a , 1 7 a , 2 1 - t r i -hydroxy-5a-pregnane-3 ,20-dione

16a - t -bu ty l - l l / 3 , 17a ,21 - t r i -hydroxy-5a-pr egnane-3 ,20-dione

3/3,6/3, 8/3,14/3-tetrahydroxy-4,20,22-bufatr ienol ide 6-acetate (scil l irosidin)

9 a - f l u o r o - l l / 3 , 1 6 a , 1 7 a , 2 1 -te t rahydroxy-4-pregnene-3,20-dione 16,17-acetonide 21-acetate

l l / 3 , 1 7 a , 2 1 - t r i h y d r o x y - l , 4 -pr egnadiene -3 ,20 -dione 21 - t r imethylaceta te

2 7 -nor-4 -cholestene - 3 , 2 5 -dione

3a, 12a-dihydroxy-5/3-cholanic acid 12-acetate

A - n o r - 3 , 5 - s e c o - 5 - k e t o -choles tan-3-oic acid

16a, 17a -d ihydroxy-1 ,4 ,6 -pregnat r iene -3 ,20 -dione 16,17-cyclophenylphos-phonate

6a-f luoro-16a, 17a -dihydroxy -1,4-pr egnadiene-3 ,20-dione 16,17-cyclophenyl-phosphonate

TRANSFORMATION

3/3-0 \c-3 /3-OH

12/3-OH

l l a - O H

11/3-OH

3/3-[lf ξ -glucosidel ^3/3-OH

21-OH^21-OAc

ά,Ι^ά-Α +1

3i3-OH->3-C = 0 ; Δ 5 - Δ 4

3-C = 0 - 3 a - O H

cholestenone -> r ing A cleavage

choles terol —» r ing A cleavage

Δ1

Δ1

YIELD %

—

14

—

-

—

15

5-100

85-90

90

60-90

50

15

30

35

70(cr.)

—

14

33(cr.)

t r .

—

ORGANISM

Calonectr ia decora


Gibberella saubinett i

Beauveria sp.

Glomerel la sp.

Phoma sp.

Phoma sp.

Al te rnar ia sp.

Aspergi l lus sp.

Claviceps purpurea

Paec i lomyces sp.

Pénici l l ium sp.

Pul lu la r ia pullulans


Stachybotrys sp.

Stemphylium sp.

Tr ichoderma glauca




Proac t inomyces erythropol is

Mycobacter ium sp.



CONSTANTS m . p . ° [α]Ώ

—

233-238

—

-

—

:

-

-

-

-

-

-

-

239-240

233-236

128

174-175

150

—

—

+ 6[m]

—

-

—

—

-

-

-

-

-

-

-

+136[m]

+103[c]

—

—

—

—

REF.

N-677

N-677

0-699

1-421

C-109

1-422

1-422

S-936a

S-936a

S-936a

S-936a

S-936a

S-936a

S-936a

S-936a

S-936a

H-404

W-1102

E-214

K-442

T-1034

S-930

F-259

F-259

217

TABLE I


EMPIRICAL FORMULA

C 2 7 H3 7 0 6 F

C 27H 3 803

L 2 7 n4o^3

C2 7 H4 0 O5

1 ^27"42^2

1 ^ 2 7 " 4 2 ^ 3

C 2 7 H4 2 0 4

C2 7 H4 2 ° 5

C27H4303N

C27H440


6 ö - f l u o r o - l l ö , 1 6 ö , 1 7 ö , 2 1 -te t r ahydroxy-4-p regnene-3,20-dione 16 ,17-cyc lo-hexanonide

1,4-diosgadien-3 -one

4-diosgen-3-one

9 -dehydromanogenin

1 lö -hydroxy - 7-ketodiosgenin

4 -cholestene -3 ,6 -dione

22a, 25D-5-spirosten-3/3-ol (diosgenin)

hecogenin

manogenin

7/3, l lö-dihydroxydiosgenin

7/3-hydroxy solasodine

9ö -hydroxy s olasodine

1 lö-hydroxy solasodine

5 ,7-chole Stadien-3/3-01

4-choles ten-3-one

•

TRANSFORMATION

l l ö - O H

3/3-OH-3-C = 0 ; Δ 5 ^ Δ 4 . Δ1

3/3-OH-3-C = 0 ; Δ5 —Δ 4

3/3-glycoside (dioscin)—3β-ΟΗ; 3/3-OH-3-C = 0 ; Δ 5 ^ Δ 4

3/3-glycoside (saponinH3/3-OH

l l ö - O H ; 7/3-OH; 7/3-OH^7-C = 0

3 / 3 - O H - 3 - C = 0 ; Δ 5 ^ Δ 4 . 6-C = 0

3ß-glycoside (dioscinH3/3-OH

3/3-glycoside (saponin)->3/3-OH

3/3-glycoside (saponinH3/3-OH

7ß-OH; l l ö - O H

7/3-OH

9ö-OH

l l ö - O H

7

Δ

3/3-OH-+3-C=0; Δ 5 - Δ 4

YIELD %

~Ί -

—

2

—

5-10

—

5

—

-

-

—

10-15

1

27

1

-

-

—

—

ORGANISM

Colletotr ichum phomoides




Aspergi l lus sp.



Mycobacter ium sp.

Aspergi l lus t e r r e u s

Al t e rna r i a sp .

Aspergi l lus sp.

Corynespora casai icola

Pénic i l l ium sp .

Aspergi l lus sp.






Azotobacter oxydans

Acetobacter xylinum

Azotobacter oxydans




'

—

-

180-181.5

—

221-225

-

205.5-208

—

-

-

—

263-266

234-238

213-215

200-203

141-143

80-81

-

-

—

—

- 7[cl

—

-137[e]

-

-118[c]

—

-

-

—

- 47[el

- 82[cj

-138[cl

-110[cl

-

+ 87

-

-

R E F .

D-159

N-665

N-665

R-781

K-479

K-479

H-368

S-930

R-781

H-351

K-479

H-351

K-479

K-479

K-479

H-368

S-791

S-791

S-791

H-406; H-407

K-457

H-406; H-407

T-1005

T-1005

218

TABLE I

T rans format ions by Product

EMPIRICAL FORMULA

C27H440

C27H4403

C27H4404

C27H4405

C27H4503N

C27H4504N

C27H460

1 C27H4602

C27H480

jC^HggUglr


4-choles ten-3-one

ti go gen in

gitogenin

digitogenin

7a-hydr oxytomatidine

9a -hydr oxytomatidine

7a, l la -d ihydroxytomat id ine

5/3-7-cholesten-3/3-ol

5/3-cholestan-3-one

5 -cholestene -3/3,7ξ -diol

5a-c hole s tan-3ß-ol

5/3-cholestan-3/3-ol

16α, 17a-dihydroxy-6ß-methyl -1 ,4 -pr egnadiene -3,20-dione 16,17-(phenyl cyclophosphate)

TRANSFORMATION

3/3-OH->3-C = 0 ;

3/3-glycoside (saponin)^3/3-OH

3/3-glycoside (saponin)^3/3-OH

3/3-glycoside (saponin)->3/3-OH

7a-OH

9a-OH

7a-OH; 11a-OH

Δ5-*5/3-Η

3/3-OH->3-C=0

7ξ-ΟΗ

3-C=0->3/3-OH

Δ5-^5/3-Η

1

Δ

YIELD %

16-44

11-23

-

-

-

34-45

-

-

—

—

-

—

5

< 1

20

50

21

—

65

74

-

ORGANISM


Flavobacter ium m a r i s


Mycobacter ium sp.

Nocardia sp.


Proac t inomyces r o s e u s

Streptomyces sp.

Aspergi l lus sp.

Pénici l l ium sp.

Aspergi l lus sp.


Bacil lus mace rans

Flavobacter ium sp.




" r a t feces a n a e r o b e s "


Proac t inomyces r o s e u s


" r a t feces anae robes"

fecal bac te r ia



80

80

-

-

-

80

-

-

—

—

-

—

238-242d

188-191

266-270d

104-105

61

—

141-142

-

99-101

-

-

-

-

-

-

-

—

—

-

—

- 3.5[c]

—

+ 23[el

+ 54.5

—

—

-

-

-

REF.

C-136

A-21; A-19; A-22 ; B-50

T-1005

S-930

T-1005

T-1031; T-1032

K-474

T-1005

K-479

K-479

K-479

K-479

S-794

S-795

S-791

S-791

S-791

C-133

T-1032

K-474

M-543

C-133

S-914

F-259

219

TABLE I


EMPIRICAL 1 FORMULA

C29H3506C1

C 29 H 44°8

C29H160

C 2 9 H 4 8 °

C29H520

|c3 0H3 4O7ClP

1 ^3θ"46^7

C30 H44 O9

1 ^30^46^8

j ^32"48^9

C36H54°14

C41H64°13


6 ö - c h l o r o - l i a , 1 6 a , 1 7 a , 2 1 -te t rahydroxy-4-pregnene-3,20-dione 16 ,17-ace to -phenonide

3/3,14/3-dihydroxy-5/3-20(22)-cardenolide 3 - (L - rhamno-side)

4,22 -s t igmastadien -3 -one

4 - s t igmas ten -3 -one '

5/3-stigmastan-3/3-ol

1 2 o - c h l o r o - l l ß , 1 6 ö , 1 7 α , 2 1 -t e t r ahyd roxy-1 ,4 -p regna -diene-3 ,20-dione 1 6 , 1 7 -(benzyl cyclophosphonate) 21-aceta te

3/3,14/3 -dihydroxy -5/3 -20(22)-cardenolide 3 - [D-cymaro -side]

3ß,5/3,14/3-trihydroxy-19-oxo-20(22) -cardenolide 3- jD-cymaros ide l

3/3,14/3,16/3-trihydroxy-5/3-20(22)-cardenolide 3 -[D-cymaros ide]

3/3,14/3,16/3-trihydroxy-5/3-20(22)-cardenolide 3 -[D-cymaros ide] 16-aceta te

3/3,5/3,14/3-trihydroxy-19-oxo-20(22)-cardenolide 3 -[D-glucosyl -D-cymaros ide]

3/3,14/3-dihydroxy-5/3-20(22)-cardenolide 3 - [digitoxosy 1 -digitoxosyl-digitoxoside] (digitoxin)

TRANSFORMATION

l l a - O H

2 ' - O A c - 2 ' - O H ; 3 ' - O A c ^ 3 ' - O H ; 4 ' -OAc->4 ' -OH

3/3-OH-3-C = 0 ; Δ5 ->Δ4

3/3-OH-3-C = 0 ; Δ 5 ->Δ 4

Δ 5 - 5 β - Η 1

Δ

4 r - O A c - 4 ' -OH

digitoxigenin --3- [D-glucosyl -D-g lucosy l -D-cymaro-side l^digi toxigenin -3- [D-cymaros ide]

strophanthidin -3 -fheptaacetyl-D-glucosyl-D-glucosyl-D-cymaros ide] — strophanthidin 3 -[D-cymaroside]

4 ' -OAc^4-OH; 16/3-OAc-* 16/3-OH

4 ' - O A c - 4 f -OH

D-glucosy l -D-cymaros ide t e t r a c e t a t e - ^ D -g lucosy l -D-cymaro-side

digi toxosyl-digi-toxosy 1 - digitoxoside t e t r aacetate—>digi -toxosy 1 - digitoxosyl-digitoxoside

glucosy 1 - digitoxosyl -digitoxosyl-digi -toxoside—digitoxosyl digitoxosy 1 -digi -toxoside

YIELD

% i

14

19

36

66

40

28

52

3

47

4

18-100

5-95

30-60

20

5-95

ORGANISM

Trichothecium ro seum




" r a t feces anaerobes '


Fusa r ium lini


Fusa r ium lini


Fusa r ium lini

Fusa r ium lini

Fusa r ium lini

Aspergi l lus sp.

Claviceps purpurea

Paec i lomyces sp .


CONSTANTS m.p.° [Œ]D

212-221 -

125 -

83 -

126-127 + 23

186-197 -

188-200; -140-158

131-133 -

154-195 —

187-207 —

247-250 —

- -

_ —

R E F .

D-159

T-978

T-1032

T-1032

C-133

F-263

T-978

T-978

T-978

T-978

T-978

T-978

T-978; G-320

S-936a

S-936a

S-936a

S-936a

CHAPTER IV

TAXONOMY

SYSTEM OF CLASSIFICATION

The system of classification used here is designed as an aid to determine the taxonomic position and relationships of the genera, active and inactive, that have been used for the transformations of steroids.

Generally, the same groupings or categories have been used for classifications of bacteria and fungi as have been used for plants. For example,

Kingdom: Plant

Phylum: Fungi (Eumycophyta); typically filamentous organisms lacking chloro-phyll (depend for their food either directly or indirectly on green plants )

Class: Ascomycetes; ultimate reproductive spores produced internally in a saclike cell called ascus. Mycelium septate Basidiomycetes; ultimate reproductive spores produced externally upon a special organ called basidium. Mycelium septate Phycomycetes; mycelium usually aseptate and multinucleate Fungi Imperfecti (Deuteromycetes); artificial grouping of fungi whose sexual stages are not known. They are the imperfect stages of the Ascomycetes and Basidiomycetes

Schizomycetes; true bacteria, single cell, reproduction by fission

Order: Subunit of Class

Family: Subunit of Order

Genus: Subunit of Family

Species: Subunit of Genus (may be further broken down into varieties, strains, and physiological or cultural races)

The classes, orders, families, genera, and species in the various tables are listed alphabetically for convenience and, therefore, may not be in the same sequence as would be found in various published systems of taxonomy.

Table II is a taxonomic listing for reference purposes containing all cultures reported in the literature and U.S. patents through January, 1964. This spectrum of genera encompases all five classes of microorganisms, the Ascomycetes, Basidio-mycetes, Fungi Imperfecti, Phycomycetes, and Schizomycetes, twenty-three out of 49 major orders, 292 different genera, and 1216 different species.

220

SYSTEM OF CLASSIFICATION 221

The most widely screened taxonomic class has been the Fungi Imperfecti. In fact, this is the only class in which all of the orders within a class (four) have been studied. One hundred eleven of the 292 genera listed in Table II and five hundred thirty-four of the 1216 species are members of the Fungi Imperfecti.

The tabulation entitled "Classes and Major Orders of Fungi and Bacteria" r e -ported to transform steroids shows that this ability is rather widespread in the micro-bial world.

This is further emphasized in tabulations entitled "Hydroxylation — Taxonomic Distribution According to Order" and "Hydroxylation — Taxonomic Distribution According to Genus," as well as the distribution of cultures capable of Δ1- dehydro-genation classified to taxonomic order and genus.

As a result, it is quite difficult to draw taxonomic inferences of major signifi-cance at the class or order level.

The differences observed at the genus, species, or strain levels are governed more by the nature of the substrates and the environmental conditions of growth than by taxonomic considerations. These differences can be selected readily by checking the species of the genus in question in Table III "Transformation by Genus."

Of the reported cultures, the group with the narrowest spectrum of activity appears to be the yeasts. Only two genera (of 19 tested), Saccharomyces and Rhodotorula, showed any activity and this was limited to their ability to reduce ke-tones to hydroxyl groups and to reduce double bonds.

An extensive discussion of the reactions listed in the aforementioned taxonomic tables is presented in the section on chemical transformations in Chapter II.

222 IV. TAXONOMY

Classes and Major Orders of Fungi and Bacteria M

Ascomycetes

Dothideales Endomycetales Erysiphales Eurotiales Helotiales Hemisphaeriales Hypocreales Hysteriales Laboulbeniales Myriangiales Pezizales Phacidiales Sphaeriales Taphrinales Tuberales

Basidiomycetes

Agaricales Hymenogastrales Lycoperdales Nidulariales Phallales Sclerodermatales Tremellales Uredinales Ustilaginales

0 + 0 + + 0 + 0 0 + + 0 + + +

+ 0 + 0 0 0 + 0 +

Fungi Imperfecti (Deuteromycetes)

Melanconiales Moniliales Mycelia Sterilia Sphaeropsidales

Phycomycetes

Blastocladiales Chytridiales Ento mo phtho rales Hyphochytriales Lagenidiales Leptomitales Monoblepharidales Muco rales Peronosporales Plasmodiophorales Saprolegniales

Schizomycetes

Actinomycetales Beggiatoales Caryophanales Chlamydobacteriales Eubacteriales Hyphomicrobiales Mycoplasmatales Myxobacteriales Pseudomonadales Spirochaetales

+ + + +

0 0 + 0 0 0 0 + + 0 0

+ 0 0 0 + 0 0 0 + 0

* Arranged alphabetically. +, Reported to transform steroids; 0, not mentioned.

Î Other taxonomic groups which have been reported to transform: algae (Chlorophyta), Order: Chlorococcales; plants (Spermatophyta), Orders: Liliiflorae, Rosales; protozoa (Masti-gophora), Orders: Euglenoidina, Polymastigina.

Hydroxylation — Taxonomic Distribution According to Order

Class and Order

Ascomycetes

Eurotiales Helotiales Hypocreales Pezizales Sphaeriales

Basidiomycetes

Agaricales

Fungi Imperfecti (Deuteromy cetes )

Melanconiales Moniliales Mycelia Sterilia Sphaeropsidales

Phy co my cetes

Ento mophtho rales Mucorales Peronosporales

Schizomycetes

Actinomycetales Eubacteriales Ps eudo mo nadales

a

*.

*

1

~ß

*

* * *

*

* *

2

a ß

*

*

*

* *

* * *

5

a ß

* *

6

a ß

*

*

*

*

* * * *

* *

* *

r

a

* *

*

*

*

r ~ß

*

*

* * *

*

*

8

ß

*

9

a ß

*

*

*

*

* * *

10

ß

*

*

11

a

* * * * *

*

* * * *

* *

*

ß

*

*

* * * *

* *

* * *

12

a

* *

*

*

ß

*

*

* *

*

*

14

a

*

*

*

*

*

* *

15

a

*

*

*

* * *

*

*

ß

*

*

*

* * *

*

*

16

a

*

*

* *

*

* *

ß

*

*

* *

*

*

*

17

a

*

*

*

*

*

18 19 21

*

*

* *

* * *

*

SYST

EM

OF

CL

ASSIFIC

AT

ION

223

224 IV. TAXONOMY

Hydro xylation - Taxonomic Distribution According to Genus

Position and class Order Genus

l t t-OH

Ascomycetes Basidiomycetes Fungi Imperfecti

(Deuteromycetes) Phycomycetes Schizomycetes

10-OH Ascomycetes

Basidiomycetes Fungi Imperfecti

(Deuteromycetes)

Phycomycetes

Schizomycetes

Moniliales

Actinomycetales

Sphaeriales

Moniliales

Mycelia Steriiia

Sphaeropsidales Mucorales

Actinomycetales Eubacteriales

Pénicillium

No cardia

Gnomonia Xylaria

Cladosporium

Rhizoctonia Sclerotium Haplospo relia Absidia Cunninghamella Mortierella Streptomyces Co ry nebacter ium

2a-OH Ascomycetes Basidiomycetes Fungi Imperfecti


2/3-OH Ascomycetes

Basidiomycetes Fungi Imperfecti (Deuteromycetes)

Phycomycetes

Schizomycetes

Actinomycetales

Sphaeriales

Agaricales Moniliales

Entomophtho rales Mucorales Actinomycetales Eubacteriales

No cardia

Diaporthe Gnomonia Pyrenophora Sclerotinia Corticium Botrytis H elmintho spo r ium Macrosporium Pénicillium Rhizoctonia Thyrospora Conidiobolus Absidia Streptomyces Bacillus Escherichia Serratia


Hydroxylation - Taxonomic Distr ibut ion According to Genus (continued)

Posi t ion and c l a s s Orde r Genus

5ûf-OH

Ascomycetes Basidiomycetes Fungi Imperfect i

(Deuteromycetes ) Phycomycetes Schizomycetes

Mucora les

5/3-OH


(Deuteromycetes) Phycomycetes

Schizomycetes

6a?-OH



6/3-OH

Ascomycetes

Mucora les

Euro t ia les Hypocrea les

Sphaer ia les

Basidiomycetes Agar ica les

Cokeromyces

Absidia Cunninghamella Mucor Rhizopus

Thielavia Cordyceps Gibberel la Chaetomium Cochliobolus Daldinia Glomere l la Ophiobolus Pyrenophora Xyla r i a Boletus Clavar ia Coriolus Cor t ic ium Dermoloma Hydrophorus I rpex Lenzi tes Leucopaxil lus Naematoloma Naucor ia

226 IV. TAXONOMY

Hydroxylation — Taxonomic Distribution According to Genus (continued)


6/3-OH (continued) Bas idiomyc êtes


Agaricales

Melanconiales

Moniliales

Phycomycetes

Mycelia Sterilia

Sphaeropsidales

Ento mo phtho rales Mucorales

Schizomycetes Actinomycetales

Eubacteriales

Pellicularia Polyporus Polystictus Poria Colletotrichum Gloesporium Acrostalagmus Arthrobotrys Aspergillus Botrytis Cephalothecium Curvularia Fusarium Gliocladium Helminthospo rium Hyalopus Isaria Nigrospora Pénicillium Piricularia Stysanus Tricoderma Tricophyton Tricothecium Virticillium Rhizoctonia Sclerotium Co nio thy rium Haplosporella Phoma Wojnowicia Basidiobolus Absidia Blakeslea Chaetocladium Choanephora Circinella Cokeromyces Cunninghamella Helicostylum Mortierella Mucor Phycomycetes Rhizopus Syncephalastrum Thamnidium Zygorhynchus Actinoplanes Streptomyces Achromobacter Bacillus


Hydroxylation - Taxonomic Distr ibut ion According to Genus (continued)

Posi t ion and c l a s s O r d e r Genus

7 a-OH

Ascomycetes

Basidiomycetes Fungi Imperfect i

(Deute romyc êtes)

Phycomycetes

Schizomycetes

7/3-OH


(Deuteromycetes)

Phycomycetes

Schizomycetes

8/3-OH

Ascomycetes Basidiomycetes Fungi Imperfect i (Deuteromycetes )

Phycomycetes Schizomycetes

9a-OH

Ascomycetes Basidiomycetes

Pez iza les Sphaer ia les

Moniliales

Sphaeropsidales

Mucora les

Sphaer ia les Agar ica les Moniliales

Mycelia S te r i l i a Sphaeropsidales

Mucora les

Ac tino my c é ta les

Monil iales

Pez i za Glas inospora Glomere l la Neurospora

Asperg i l lus Curvu la r ia Fusidium Helminthosporium Coniothyrium Diplodia Hel icostylum Mucor Phycomyces Rhizopus

Xyla r ia Psi locybe Aspergi l lus Cephalosporium Cladosporium Pénici l l ium Tr icothec ium Rhizoctonia Diplodia Haplosporel la Absidia Cunninghamella Helicostylum Mucor Rhizopus Syncephalas t rum Proac t inomyces

(Nocardia) S t reptomyces

Ce rcospo ra

Sphaer ia les Neurospora

228 IV. TAXONOMY

Hydroxylation -Taxonomic Distribution According to Genus (continued)


9Q?-OH (continued) Fungi Imperfecti

(Deuteromycetes)

Phy corny c êtes

Schizomycetes

Moniliales


Actino my c étales

Eubacteriales

Ps eudo mo nadal es

Cercospora Curvularia Cylindrocarpon Ascochyta Absidia Circinella Cunninghamella Helicostylum Mucor My co bac ter ium Nocardia Streptomyces Arthrobacter Bacterium Corynebacterium Pseudomonas

9/3-OH Ascomycetes Basidiomycetes Fungi Imperfecti


10/3-OH Ascomycetes Basidiomycetes Fungi Imperfecti

(Deuteromycetes )


Moniliales

Mucorales

Botrytis Curvularia H elmintho spo r ium Rhizopus

l la-OH Ascomycetes t Eurotiales

Helotiales Hypocreales

Pezizales Sphaeriales

Carpenteles Sclerotinia Calonectria Cordyceps Pyrenema Chaetomium Cochliobolus Daldinia Didymella Glomerella Guignardia Ophiobolus Pyrenophora Xylaria


Hydroxylation-Taxonomic Distribution According to Genus (continued)


11a?-OH (continued) Basidiomycetes Agariales


Melanconiales

Moniliales

Mycelia Sterilia

Boletus Clavaria Conocybe Corticium Cortinellus Der mo lo ma Ganoderma Hygrophorus Leucopaxillus Pellicularia Polyporus Polystictus Psilocybe Stropharia Colletotrichum Coryneum Gloesporium Pestalotia Acrostalagmus Arthrobotrys Aspergillus Beauvaria Botrytis Candelospora Cephalothecium Cercospora Cladosarum Dactylium Didymocladium Fusarium Helminthosporium Hyalopus Isaria Metarrhizium Mycogone Myrothecium Nigrospora Pénicillium Piricularia Scopulariopsis Spicaria Sportrichum Stachylidium Stysanus Tricoderma Trichophton Trichothecium Verticillium Rhacodium Rhizoctonia Sclerotium

230 IVc TAXONOMY

Hydroxylation - Taxonomic Distribution According to Genus (continued)

Position and class

l la-OH (continued) Fungi Imperfecti

(Deuteromycetes)

Phycomycetes

Order Genus

Sphaerops idales

Entomophthorales

Mucorales

Schizomycetes Eubacteriales

Botryodiplodia Coniothyrium Diplodia Phoma Phomopsis Wojnowicia Basidiobolus Conidiobolus E nto mophtho r a Absidia Blakeslea Choanephora Circinella Cunninghamella Lichtheimia Mucor Mycocladus Phy corny ces Rhizopus Syncephalastrum Thamnidium Tieghemella Zygorhynchus Achromobacter Bacillus Escherichia

11/3-OH Ascomycetes Basidiomycetes


Helotiales Agaricales

Melanconiales

Moniliales

Mycelia Sterilia

Sclerotinia Corticium Omphalia Pellicularia Colletotrichium

Arthrobotrys Botrytis Cercospora Curvularia Epicoccum Isaria Pénicillium Spicaria Spondy lo cladium Stachylidium Stigmina Tricophyton Tricothecium Verticillium Rhizoctonia Sclerotium




11/3-OH (continued) Fungi Imperfecti

(Deuteromycetes)

Phycomycetes

Schizomycetes

Sphaeropsidales

Mucorales

Peronosporales Actinomycetales Eubacteriales

Ps eudo mo nadal es

Chaetomella Coniothyrium Dothichiza Phoma Pycnosporium Rhodos eptoria Absidia Blakeslea Choanephora Circinella Cunningham ella Lichtheimia Rhizopus Sync ephalas tr urn Thamnidium Tieghemella Pythium Streptomyces Bacillus E scher ichia Proteus Pseudomonas

12o?-QH

Ascomycetes Bas idiomyc êtes Fungi Imperfecti

(Deuteromycetes)


12/3-OH Ascomycetes

Bas idiomyc êtes Fungi Imperfecti

(Deuter o my c êtes )


14a-OH

Melanconiales

Moniliales


Hypocreales

Agaricales Melanconiales

Moniliales


Colletotrichum

Aspergillus Cercospora Wojnowicia Thamnidium

Calonectria Gibberella Psilocybe Colletotrichum

Fusarium Nigrospora Tricothecium Coniothyrium Helicostylum

Ascomycetes Sphaeriales Pleospora

232 IV. TAXONOMY


Position Order Genus

14Q?-OH (continued) Basidiomycetes


Phycomycetes

Schizomycetes

Agaric ales

Moniliales


Ac tinomyc étales Eubacteriales

Coriolus Naematoloma Pellicularia Polyporus Poria Cercospora Chrysosporium Curvularia Helminthosporium Stachylidium Stemphylium Tricothecium Wojnowicia Absidia Circinella Cunningham ella Helicostylum Mucor Sync ephalast rum Mycobacterium Achromobacter Bacillus

15a?-OH Ascomycetes

Basidiomycetes Fungi Imperfecti (Deuteromycetes)


15/3-OH Ascomycetes

Hypocreales

Sphaeriales Agaricales Melanconiales

Moniliales

Mycelia Sterilia Mucorales Ac tinomyc étales

Helotiales Sphaeriales

Calonectria Gibberella Glomerella Hypholoma Colletotrichum

Aspergillus Curvularia Fusarium Helminthosporium Hormodendrum Nigrospora Pénicillium Rhizoctonia Rhizopus Streptomyces

Sclerotinia Xylaria




15/3-OH (continued) Basidiomycetes

Fungi Imperfecti (Deuteromycetes )

Phycomycetes

Schizomycetes

Agaricales

Moniliales

Mycelia Sterilia Sphaeropsidaies

Mucorales

Eubacteriales

Coriolus Lenzites Polyporus Poria Botrytis Cercospora Crinsporium Helminthosporium Pénicillium Spicaria Sclerotium Diplodia Phoma Absidia Phycomyces Syncephalastrum Bacillus

lto-OH Ascomycetes

Basidiomycetes Fungi Imperfecti

(Deuteromycetes )


Hypocreales Sphaeriales

Melanconiales Moniliales

Sphaeropsidaies

Actinomycetales

Eubacteriales

Hypomyces Didymella Gnomonia Mycosphaerella

Pestalotia C ephalospor ium Sepedonium Staganospora Staurophoma Wojnowicia

Nocardia Streptomyces Bacillus


(Deuteromycetes )

Phycomycetes

Schizomycetes

Helotiales Agaricales Melanconiales Moniliales

Sphaeropsidaies Mucorales

Eubacteriales

Sclerotium Corticium Colletotrichum C ephalospor ium Curvularia Wojnowicia Cunninghamella Helicostylum Bacillus

y>e-0H

234 IV. TAXONOMY



17a-OH

Ascomycetes

Bas idiomyc êtes Fungi Imperfecti

(Deuteromycetes)

Eurotiales Hypocreales Sphaeriales

Agaricales Moniiiales

Phy corny c êtes Schizomycetes

18dQ_H


(Deuteromycetes ) Phycomycetes Schizomycetes

19-OH

Ascomycetes Basidiomycetes



Moniiiales

Agaricales

Thielavia Melanospora Cucurbitaria Leptosphaeria Lophotrichus Sporormia Naucoria Acrospeira Aspergillus Cephalothecium Dactylium Scopulariopsis Sepedonium Tricoderma Tricothecium

Cercospora

Corticium Hypochnus Pellicularia

21rOH

Ascomycetes

Basidiomycetes

Helotiales Sphaeriales Agaricales

Schlerotinia Ophiobolus Psilocybe

IV. TAXONOMY 235



21-OH (continued

.Fungi Imperfecti (Deuter omyc êtes)


Melanconiales

Moniliales

Sphaeropsidales

Colletotrichum

Aspergillus Cercosporella Kabatiella Coniothyrium Hendersonia Wojnowicia

236 IV. TAXONOMY

A1-Dehydrogenation — Taxonomic Distribution According to Genus

Class Order Genus

Ascomycetes

Basidiomycetes



Spermatophyta (plant) Zoomastigina (protozoa) [Mastigophora]

Hypocreales

Sphaeriales

Agaricales

Ustilaginales Melanconiales

Moniliales

Mycelia Sterilia Sphaeropsidales Muco rales Actino my c étales

Eubacteriales

Pseudomonadales

Liliiflorae Polymastigina

Calonectria Hypomyces Chaetomium Didymella Ophiobolus Corticium Stereum Graphicola Gloeosporium Septomyxa Alternaria Cylindrocarpon Fusarium Gliocladium Helmintho spo rium Ramularia Volutella Rhizoctonia Pycnodothis Absidia Actinoplanes Mic ro mo no spo r a Mycobacterium Mycococcus Nocardia Aerobacter Arthrobacter Azotobacter Bacillus Bacterium Corynebacterium Flavobacterium Micrococcus Serratia

Acetobacter Azotomonas Protaminobacter Pseudomonas Xanthomonas Sansevieria Trichomonas

TABLE I I

T a x o n o m y to Spec ies

237

CLASS

Ascomycetes

ORDER

Endomycetales

Euro t ia les

Helotiales

Hypocreales

Myriangiales

FAMILY

Endomycetaceae

Saccharomycetaceae

Eurot iaceae

Gymnoscaceae

Helotiaceae

Hypocreaceae

Myriangiaceae

GENUS

ß y s s o c h l a m y s

Debaryomyces

Dilplodasus

Endomyces

E r e m a s c u s

Eremothec ium

Hansenula

Nadsonia

P ich ia

Saccharomycodes

Schizosaccharomyces

His toplasma

Saccharomyces

Al lescher ia

Thielavia

Carpente les

Sclerot inia

Calonect r ia

Cordyceps

Gibberel la

Hypomyces

Melanospora

Neocosmospora

Elsinoe

SPECIES

nivea 1

hansenii

albidus

l indneri

albus

ashbyii

anomala

fulvescens

membranaefac iens

ludwigii

octosporus

capsulatum

cerev i s iae el l ipsoideus fragi l is lac t is pas to r ianus

boidii

basicola t e r r i c o l a

javanicus

all i i fructicola fluctigena l iber t iana sc l e ro t io rum

decora

mi l i t a r i s

baccata cyanea fujikuroi saubinett i zeae

aurant ius haematococcus solani

pa ra s i t i ca

vasinfecta

ampelina fawcetti

238

TABLE M

T a x o n o m y to Spec ies

CLASS

Ascomycetes

ORDER

Pez iza l e s

Sphaeriales

FAMILY

Hellvellaceae

Pez izaceae

Cera tos tomaceae

Chaetomiaceae

F ime ta r i aceae

Sphaer iaceae

GENUS

Morchella

Pez iza

Py rone ma

Cera tos tomel la

Chaetomium

Neurospora

Cochliobolus

Cucurbi tar ia

Daldinia

Diaporthe

Didymella

Gelas inospora

Glomerel la

Gnomonia

Guignardi

Leptosphaer ia

Lophotrichus

Mycosphaerel la

Ophiobolus

SPECIES

c r a s s i p e s

species

confluens

f imbriate (fimbriata)

cochloides funicolum globosum species succineum

c r a s s a sitophila spec ies

miyabeanus

laburni

concentr ia (concentrica)

numurai

ly coper s ic i vodakii

t e t r a s p o r a

cingulata fluctigena fusaroides glycines gosypii

(gossypii) lagenarium major mume phacidiomorpha rubicola

cingulata e r rabunda e ry th ros toma fimicola f ragar iae

camel l iae

maculans

mar t in i

hori i l a tebrosa

g ramin i s herpo t r ichus he te ros t rophus

TABLE I I

Taxonomy to Spec ies

239

CLASS

Ascomycetes

1 Basid iomycetes

ORDER

Sphaer ia les

Taphr ina les

Agar ica les

FAMILY

Sphaer iaceae

Taphr inaceae

Agar icaceae

GENUS

Ophiobolus

Ophiostoma

P leospora

Pyrenophora

Rosse l l in ia

Sordar ia

Sporormia

Venturia

Xylar ia

Taphrina

Agar icus

Agrocybe

Amanita

Armi l l a r i a

Cantharel lus

Clitocybe

Collybia

Conocybe

Coprinus

Cor t ina r ius

Cort inel lus

Dermoloma

SPECIES

miyabeanus 1 sat ivus 1 spec ies 1

catanianum

gaeumanni

g reminea

neca t r ix

spec ies

fasciculata leporina minima montana pol lacci i

p i r m a (pirina)

polymorpha spec ies

deformans pruni

c a m p e s t r i s edulis rodmani i

ace r ico la

m u s c a r i a porphyr ia

mellae

c ibar ius

adi rondackensis clavipes odor a spec ies

dryophila velut ipes

si l igenoides

a t romenta r ius (a t ramentar ius)

sobil i ferus

evernius

shii take

spec ies

240

TABLE I I

T a x o n o m y to S p e c i e s

CLASS

Basidiomycetes

ORDER

Agar ica ies

FAMILY

Agar icaceae

GENUS

Gymnopilus

Hebeloma

Hygrophorus

Hypholoma

Lentinus

Lentodium

Lepiota

Leucopaxillus

Lyophyllum

Marasmius

Mycena

Naematoloma

Naucoria

Omphalia

Panaeolus

Panel lus

Paxi l lus

Pholiota

P leuro tus

Pluteus

Psi locybe

Russula

Schizophyllum

Stropharia

SPECIES

junenius spec ies

s inapizans

conicus

species

vulpinus

squamosum

molybdites naucina p r o c e r a rachodes

paradoxus

aggregatum

s iccus

strobil inoides

subla tera t ium

confragosa

t ra luc ida

papil ionaceus

st ipt icus

involutus verna l i s

adiposa squar roso ides

japonicus os t r ea tus

granular is

cae ru lescens caeru i ipes mexicana semper viva

del icans

commune

cubensis normandii

TABLE I I


241

CLASS

ßas id iomyce tes

ORDER

Agar ica les

FAMILY

Agar icaceae

Boletaceae

Clavar iaceae

Hydnaceae

Hypochnaceae

Polyporaceae

GENUS

Tr icholoma

Tubar ia

Xeromphal ina

Boletinus

Boletus

Clavar ia

Echinodontium

Irpex

Hypochnus

Coriolus

Fomes

Ganoderma

Lenzi tes

Polyporus

Polys t ic tus

P o r i a

T r a m e t e s

SPECIES

nudum 1 spec ies

conspe r sa

tenuipes 1

p ic tus

acidus 1 amer i canus luteus

mucida 1

tsugicola

consors lacteus

centrifugum sasak i

vers ico lor

pinicola robs tus spec ies

applam (applanatum)

abie t ina bebulina

(betulina) s ty rac ina

abiet inus b ruma l i s caeru leoporus cinnabarinus conchifer frondosus pubescens rad ica ta squamosus sulphur eus tul ipiferus

c innabar ius h i r s tu s polyzonus sanguineus ve r s i co la ve r s ico lo rpus

cocos spec ies vapora r i a

dickinsi i pini

242

TABLE I I


CLASS

Basidiomycetes

Fungi Imperfect i (Deuter omycete s )

ORDER

Agar ica les

Lycoperdales

T r e m e l l a l e s

Ust i laginales

Melanconiales

FAMILY

Thelephoraceae

Lycoperdaceae

Aur icu lar iaceae

Graphiolaceae

Usti laginaceae

Melanconiaceae

GENUS

Cort ic ium

Pe l l i cu la r i a

Stereum

To mente lia

Lycoperdon

Helicobasidium

Graphiola

Ustilago

Colletotr ichum

Coryneum

Gloeosporium

Pes ta lo t i a

Septomyxa

Sphaceloma

SPECIES

centrifugum centrifugus graminum mic rosc le ro t i a prac t ico la roefs i i sa lmonicolar sasaki i soiani species vagium vagum

filamentosa

fasciatum induratum

species

umbrinum

mompa

cylindrica

zeae

ant i r rh in i de r r i d i s gloeosporioides lindemuthianum phomoides p is i s p e c i e s

cardinale

cyclaminis foliicolum kaki laet icola ol ivarum

diospyri foedans funerea royenae

aescui i affinis corni sal ic ina tu lasuei

spec ies

243

TABLE I I


CLASS

Fungi Imperfect i (Deuteromycetes)

ORDER

Moniliales

FAMILY

Cryptococcaceae

Demat iaceae

GENUS

Candida

Pa rendomyces

Pseudomycoderma

Ti l le t iops is

Ac rospe i r a

Alter na r i a

Cercospora

Chala ra

Cladosporium

Corynespora

SPECIES

guil l iermondii k ruse i pu l che r r ima ut i l is

a s t é ro ïdes

l i ' ac ina

levis

batat icola c i t r i kikutiana pass i f lorae spec ies

apii bat icola calotropidis canescens chenopodii c ladosporioides cruenta diazu fusca hibsci-cannabini i ta l ica kaki kikuchii lagenarum mac rospo ra malvacea rum medicaginis melongenae melonis musae m u s a r u m nicotianae oryzae ro s i co l a sc i rp ico la s e s a m i ta iwanensis vaginae violae zebr ina zinniae

my coder ma

c ladospor iodes fulvam

(fulvum) herbarurn r e s i n a e spec ies

casa i icol i

miso

244

TABLE I I


CLASS


ORDER

Moniliales

FAMILY

Demat iaceae

GENUS

Curvular ia

Cylindrocephalum

Dematium

Fumago

Fusic ladium

Hel icoceras

Helminthosporium

Hemispora

Hormodendrum

Humicola

Macrospor ium

Mar gar ino my ce s

SPECIES

brachyspora falcata fallax geniculata inaequalis lunata maculans oryzae pal lescens species t e t r a m e r a trifolii uncinata

aureum

pullulans

spec ie s

diospir i

oryzae 1

avenae 1 br izae buchloes coices

(coicis) gramineum i r r egu l ä r e kusanoi 1 l ee r s i i leptochloae maydis nodulosum oryzae panic i -mel iace i

(miliacei) sat ivum se ta r i ae s igmoideum species t e r e s t r i t i c i -vu lgar is turc icum velur inam

(velutinum) zizaniae 1 zonatum

rogosa

olivaceum pedrosoi vir ide

g r i sea

(grisae)

bataticola

spec ies

TABLE I I


245

CLASS

Fungi Imperfect i (Deuter omycetes)

ORDER

Moniliales

FAMILY

Demat iaceae

,TDermatophytesT'

Moniliaceae

GENUS

Nigrospora

Phialophora

Pul lu la r ia

Spondylocladium

Stachybotrys

Stachylidium

Stemphylium

Stigmina

Thyrospora

Epidermophyton

Acremonium

Acros ta lagmus

Ar throbot rys

Aspergi l lus

SPECIES

oryzae 1 spec ies sphaer ica 1

v e r r u c o s a

pullulans spec ies

aus t r a l e xylogenum

spec ies

bicolor theobromae

bot ryosum spec ies

platani

a s t r aga l i

f loccasum

potronii

albus

conoides dactyloides musi formis superba

aculeatus a l l iaceus amste lodami a s p e r e s c e n s as t ianus a t ropurpureus au reus aur icomus avenaceus awamor i batatae b rev ipes butyracea caes ie l lus caespi tosus candidus ca rbonar ius ca rneus cheval ier i c innamomeus c i t r i c i t r i spo rus clavatus conicus echinulatus effusus elegans f ischer i

246

TABLE I I


CLASS ORDER FAMILY GENUS SPECIES

Fungi Imperfecti (Deuter omycetes)

Moniliales Moniliaceae Aspergi l lus flavipes flavus fonsecaeus fumigatus giganteus glaucus grac i i i s gymnosardae he rba r io rum inuii i taconicus janus japonicus kanagaw -aens is kawachii luchuensis mangini melleus minimus

(minutus) miyakoensis moll is montevidensis nakazawai nidulans niger ni veo-glaucus niveus ochraceus oryzae ost ianus panamens is pa ra s i t i cus penici l loides phoenicis p ro l i fe rans pseudoglaucus pulverulentus quadri l ineatus r ehmi i r epens r e s t r ictus ruber rugulosus sai toi s c l e ro t io rum sojae s p a r s u s spec ies sulphureus sydowi t a m a r i i t e r r e u s t e r r i c o l a unguis usami i us tus va r i ans var iecolor ve r s ico lo r violaceo -fuscus wentii

TABLE I I

Taxonomy to Species

247

CLASS

Fungi Imperfect i (Deuter omycetes)

ORDER

Moniliales

FAMILY

Moniliaceae

GENUS

Beau ver ia

Bot ry t i s

Candelospora

Cephalosporium

Cephalothecium

Cercospore l l a

Chrysospor ium

Cladosarum

Core throps i s

Cr inspor ium

Dactylium

Didymocladium

Fusidium

Geotr ichum

Gliocladium

Hyalopus

Meta r rh iz ium

Monilia

Monosporium

Mycogone

Oidium

Oospora

Paec i lomyces

SPECIES

bass iana 1 spec ies 1

c ine rea fabae 1 paeoniae 1 rep tons 1 spectabi l i s 1 spec ies 1

penici l loides 1

ac remonium a s p e r u m 1 spec ies 1 subver t ic i l la tum 1

r o s e u m 1

herpotr ichoides

luteium

olivaceus (olivaceum)

ho mini s

panorum

dendroides

t e rna tum

spec ies

lact is

catenulatum del iquescens luteolum r o s e u m spec ies

nopporoensis

anisopliae spec ies

spec ies

ap iospe rmum

jaepi i

s p e c i e s

aurant i i l ac t i s

spec ies var i to i

248

TABLE I I




Moniliales Moniliaceae Pénic i l l ium aculeatum adametzi albidum aspe rum a t ramentosum aurant io -violaceum aurant io-v i r ens avellaneum biforme brefeldianum brevi -compactum camember t i canescens casei caseicolum char les i i chermes inum chrysogenum c i t reo-v i r ide ci t r inum claviforme clavigerum commune corylophilum corymbiferum crus tosum cyaneofulvum cyaneum cyclopium daleae decumbens digitatum d iversum duponti egyptaceum ehrl ichi i expansum fellutanum frequentans funiculosum fuscum gladioli godlewskii granulatum helicum herquei humuli implicatum islandicum i tal icum janthinellum javanicum jenseni i kapuscinskii lanoso-coeruleum lanoso-gr i seum lanoso-vir id i lanosum lavendulum lovitum lilacinum lividum luteum

TABLE 11


249

CLASS

Fungi Imperfect i ( Deuter o my c êtes)

ORDER

Moniliales

FAMILY

Moniliaceae

GENUS

Pénic i l l ium (continued)

SPECIES

P i r i c u l a r i a

mar t ens i i melearg inum melinii miczynskii mult icolor nalgiovensis namyslowskii n igr icans notatum novae -zeelandii ochraceum ochro -ch lo rum ol ivino-vir ide oxalicum pal i tans pal l idum parvum patulum phoenicum p i s ca r ium psi t tac inum puberulum pulvi l lorum purpurescens purpurogenum pusi l lum rac ibo r sk i i r a i s t r i c k i i r e s t r i c t u m r e s t r i c u l o s u m rol fs i i roquefort i r o seo -pu rpu r eum r u b r u m rugulosum sc l e ro t io rum s impl i c i s s imum soli tum soppi spec ies sp icul i sporum spinulosum stecki i s toloniferum s t r i a tum subal te r i t ium t a r d u m ter l ikowski t e r r e s t r e thomii t rzeb insk i i turbatum ur t i cae var iabile vermicu la tum ver rucu losum vinaceum vi r id ica tum waksmanni wortmanni

oryzae

250

TABLE I I


CLASS


ORDER

Moniliales

FAMILY

Moniliaceae

Rhodotorulaceae

Sporobolomycetaceae

Stilbaceae

Torulopsidaceae

GENUS

Ramula r i a

Sarc inomyces

Scopulariopsis

Sepedonium

Spicaria

Sporotr ichum

Ster igmatocys t i s

T r i chode rma

Trichophyton

Tr icothecium

Tr i t i r ach ium

Vert ic i l l ium

Rhodotorula

Sporobolomyces

I sa r i a

Stysanus

Kloeckera

SPECIES

robusta

c rus taceum

amer i cana brevicaul is

ampul losporum ch rysospe rmum

s impl ic i s s ima spec ies violacea v i r idans

a s t é ro ïdes bombycinum epigaeum gougeroti sul furescens

japonica

album glaucum koningi l ignorum nigrovi rens spec ies v i r ide

concentr icum

ar rhenopum candi du m cys tospor ium domest icum luteum p lasmoparae polybrochum r o s e u m

pu ru reum

a lbo -a t rum dahliae malthousii nieveostxatosum spec ies theobromae

glutinis g rac i l i s longiss ima

r o s e u m

far inosa

médius

apiculata

TABLE I I


251



Moniliales Torulopsidaceae

Tuber cu la r iaceae

Torula

Toru lops is

Cylindrocarpon

Epicoccum

F u s a r i u m

spec ies

ae r i a Candida

radic icola

humicola neglectum oryzae purpurascens spec ies yuccae

aquaeductum a r t h o c e r a s aspidioti avenaceum bata ta t is bulbigenum buxicoia caucas icum cocophilum coeru leum concolor cu lmorum d imerum d ive r s i sporum equiset i expansum gibosum gigas g raminea rum he rbe rum he te rosporum javanicum la te r i t ium lini lycopers ic i m a c r o c e r a s mer i smoides m i c r o c r e a moniliforme nivale niveum niveus o r thoce ra s oxysporum poae pruni redolens r o s e u m sambucinum sa rcochroum semi tec tum solani spec ies sphaer iae sporo t r iche i la sporot r ichio ides sulphureum udum vasinfectum

252

TABLE I I


CLASS


ORDER

Moniliales

Mycelia Ster i l ia

Sphaeropsidales

FAMILY

Tubercular iaceae

No Family

Sphaerioidaceae

GENUS

Kabatiella

Myrothecium

Volutella

Rhacodium

Rhizoctonia

Sclerot ium

Ascochyta

Botryodiplodia

Chaetomella

Coniothyrium

Diplodia

Dothichiza

Haplosporel la

Hendersonia

Phoma

Phomopsis

Pycnodothis

Pycnospor ium

Rhodoseptoria

Stagonospora

Staurophoma

Wojnowicia

SPECIES

phoradendr i

ro r idum spec ies

ci l iata

ce l la re

ferrugena solani species

coffeicolum hy drop hi lu m oryzae rolfs i i

favae linicola pinadella viciai

theobromae

oblonga raph ige ra

diplodiella hei lebori helleborine spec ies

nata lens is tuber icola

ferruginosa

spec ies

a b e r r a n s acicola herpot r icha phragmi t i s rubi

spec ies

c i t r i

spec ies

species

spec ies

cur t i s i i

spec ies

g ramin i s

TABLE I I


253

CLASS

Phycomycetes

ORDER

Entomophthorales

Mu cor aie s

FAMILY

ßas id iobolaceae

Empusaceae

Entomophthoraceae

Choanephoraceae

Cunninghameoaceae

Mor t ie r ie l l aceae

Mucoraceae

GENUS

ßas id iobolus

Entomophthora

Conidiobolus

Choanephora

Cunninghame 11a

Mort ier e lia

Absidia

Actinomucor

Blakes lea

Circ inel la

Cokeromyces

Lichtheimia

SPECIES

r a n a r u m

coronata 1

spec ies

cucurb i ta rum

africana albidia bainier i b lakes leeana echinata echinulata elegans homothall ica r a m o s a spec ies ver t ic i l la ta

alpina bainier i candelabrum isabel l ina marburgens i s ol igospora polycephala pusi l ia tuberosa zonata

coerulea cyl indrospora glauca hyalospora orchid is r a m o s a r e g n i e r i r epens spec ies

corymbosus r epens

t r i s p o r a

muscae s implex spec ies syndowi umbel la ta

r ecu rva tus

corymbifera r a m o s a

254

TABLE I I



Phycomycetes Mucorales Mucoraceae Mucor

Mycocladus

P a r a s i t e l l a

Phycomyces

Rhizopus

adr ia t icus adventit ius angul isporus berol inens is buntingii chr i s t i anens i s c i rc inel lo ides corymbifer d imorphosporus d i spe r sus dubius e rec tus genevensis globosus glomerula gr iseocyanus guil l iermondii h iemal is humicola

(humicolus) humilis hypochninus javanicus mandshuricus mic rosporus mucedo muro rum pa ras i t i cus p i r i fo rmis plumbeus pusi l lus r a c e m o s u s ramannianus rouxianus rouxii s implex solani spec ies sphaerospora spinosus stolonifer va r ians vuil lemini

hyalinus

s implex

blakesleeanus nitens pi rot t ianus spec ies theobromatus

a r r h i z u s cambodjae chinensis chiuniang cohnii de le mar fo rmosens i s

(formosaensis) japonicus

TABLE I I


255

CLASS

Phycomycetes

1 Schizomycetes

ORDER

Mucorales

Pe ronospo ra l e s

Act inomycetales

FAMILY

Mucoraceae

Pi lobolaceae

Thamnidaceae

Pythiaceae

Act inomycetaceae

GENUS

Rhizopus (continued)

Syncephalas t rum

Syncephalis

Thamnidium

Tieghemel la

Zygorhynchus

P i lair a

Chaetocladium

Helicostylum

Phytophthora

Pythium

Nocardia

SPECIES

javanicus 1 kansho 1 kasanens i s 1 n igr icans 1 niveus nodosus 1 oryzae pseudochinensis pygmaeus ref lexus shangaiens is

(shanghaiensis) spec ies stolonifer 1 suinus ' 1 tonkinensis t r i t i c i

c incereum (cinereum)

r a c e m o s u m spec ies

nodosa ref lexa

elegans

coerulea cyl indrospora hyalospora orchidis r epens spinosa t ieghemii tu rkes tan ica

he te rogamus moe l l e r i

anomala

brefeldi i

p i r i forme spec ies

c i t rophthora p a r a s i t i c a

ul t imum

as t e ro ides aurant ia blackwelli i b raz i l i ens i s coel iaca convoluta coral i ina e ry thropol i s farcinica formica

256

TABLE I I



Schizomycetes Actinomycetales Actinomycetaceae Nocardia (continued)

Proac t inomyces

Actinop lanaceae

Mycobacter iaceae

Actinoplanes

Mycobacter ium

Streptomycetaceae

Mycococcus

Streptomyces

gardner i globerula i tal ica leishmanii maculata madurae mexicanus minima opaca paraffinae polychromogenes r e s t r ictus r u b r a salmonicolor spec ies

act inomorphus a g r e s t i s aquosus coel iacus crystal lophagus erythropol is globerulus minimus paraffinae polychromogenes r e s t r ictus r o s e u s rubroper t inc tus spec ies

mi s sour i ens i s spec ies

album berol inense butyr icum chelonei choles terol icum flavum fortuitum friedmannii hyalinum lact icola luteum phlei r anae rhodochrous rubroper t inc tum rub rum salmonicolor smegmat i s spec ies thamnopheos tuberculos is

spec ies

albidoflavus albidus a lbosporeus albus annulatus

TABLE I I


257

CLASS

Schizomycetes

ORDER FAMILY

Actinomycetales St reptomycetaceae

GENUS

Streptomyces

Micromonospora

SPECIES

antibioticus argenteolus aureofaciens a u r e u s bikiniensis bobilae cal ifornicus celluloflavus c h a r t r e u s i s chrysomal lus coelicolor d ias ta t icus d ias ta tochromogenes endus e ry th r eus exfoliatus f imicar ius flaveolus f lavogriseus fradiae fulvissimus gelat icus globisporus globosus g r i seoca rneus g r i seo lus g r i seus hals tedi i hydrogenans hygroscopius lavendulae l ipmanii mediocidicus microflavus n i t rosporeus ol ivaceus ol ivochromogenus pa rvus purpureochromogenus r i m o s u s roseochromogenus ruber rubescens rub r i r e t i cu l i rubroocyanodiastat icus] r u t g e r s e n s i s scab ies setonii spec ies t anash iens i s tendae thioluteus vinaceus v i r idans vir idifaciens v i r id i s vi r idochromogenus wi l lmore i

chalcea spec ies

258

TABLE I I



Schizomycetes Eubacter ia les Achromobacter iaceae Achromobacter

Alcaligenes

Flavobacter ium

Azotobacter iaceae Azotobacter

Baci l laceae Bacil lus

Bac te r i aceae

Clostr idium

Bac te r ium

cyclocoastes (cycloclastes)

kashiwasakiensis liquidum spec ies

faecalis spec ies

androstenedionicum aquatile aurant iacum buccalis carbonii icum dehydrogenans f lavescens flavotennae fulvum helvoium m a r i s sewanense spec ies

agi l is chroococcum indicus oxydans spec ies vinlandii

alvei b rev i s c e r e u s c i rcu lans c los te ro ides coagulans coli fir mus lentus mac er an s me gâter ium mycoides poly my xa p ro teus pulvifaciens pumilus putr if icus pymilus r o s e u s spec ies sphaer icus subti l is thiaminolyt icus tumescens

bifermentans paraputr i f icum perf r ingens sporogenes t e r t i um welchii

bifidum cyclo -oxydans

TABLE I I


259

CLASS

Schizomycetes

ORDER

Eubac te r ia les

FAMILY

Bac te r i aceae

Cor ynebacter iaceae

Ente robac te r iaceae

Lactobaci l laceae

Micrococcaceae

GENUS

Bac te r ium

Ar throbac te r

Cellulomonas

Corynebacter ium

Aerobacter

Erwinia

Escher ich ia

P ro t eus

Se r r a t i a

Catenabacter ium

Lactobaci l lus

Streptococcus

Micrococcus

Sarcina

SPECIES

havaniensis mycoides spec ies s te ro id ic las ium

s implex spec ies

biazotea

equi fascians helvolum hoagii mediolanum pseudodiphtheri t icum simplex spec ies xe rose

aerogenes cloacae

a ro ideae caro tovora

coli freundii

spec ies vulgar is

m a r c e s c e n s plymuthica

catenaforme spec ies

b rev i s buchneri bulgar icus

pyogenes

candidus c i t reus congloneratus dehydrogenans flava flavus luteus lysodeikt ius pi l tonensis pyogenus-aureus r o s e u s spec ies subflavus u reae va r i ans

a lbida albiden

260

TABLE I I


CLASS

Schizomycetes

ORDER

Eubacter ia les

Pseudomonadales

FAMILY

Micrococcaceae

Rhizobiaceae

Methanomonadaceae

Pseudomonadaceae

GENUS

Sarcina

Staphylococcus

Agrobacter ium

Chromobacter ium

Rhizobium

Hydrogenomonas

Acetobacter

Azotomonas

Mycoplana

Phytomonas

Pro taminobac te r

Pseudomonas

SPECIES 1

aurent iace marginata var iabi l i s

albus aureus

ethanicus radiobacter tumefaciens

violaceum

leguminosarum me li loti phaseol i tr ifoli i

facilis

acet i pas teur ianum suboxydans xylinum

f luorescens

bullata dimorpha

c i t r i e icobatryae malvacearum

albofiavum r u b r u m

aeruginosa aureofaciens azoformicans boreopolis caudata chlor or aphis cohaerens cruciviae dacunhae desmolyt ica f luorescens fragi gaeger i gelidicola graveolens indoloxidans iner t ia j aeger i lacunogenes melanogenes myxogenes n i t roreductans ochracea oleovorans ovalis

TABLE I I

Taxonomy to Species

261

CLASS

Schizomycetes

OTHER TAXONOMIC GROUPS

Algae - Chlor op hy ta

P lan ts -

Spermatophyta Angiosperme Monocotyledonae

Dicotyledonae

Pro tozoa -

Mastigophora

Subclass :

Phytomast igina

Subclass :

Zoomastigina

ORDER

Pseudomonadales

Chlorococcales

Lil i i f lorae

Rosa les

Euglenoidina

Polymast igina

FAMILY

Pseudomonadaceae

Spir i l laceae

Chlorel laceae

Scenedesmaceae

Li l iaceae

Leguminosae

Euglenidae

Trichomonadidae

GENUS

Pseudomonas (continued)

Xanthomonas

Vibrio

Chlorel la

Scenedesmus

Sansevier ia

Medicago

Euglena

Tr ichomonas

Penta t r ichomonas

SPECIES

pavonacea pe r lu r ida p ic torum putida pyocyanea ra thonis riboflavinus r o s e u m schuylkill schuylki l l iensis spec ies s t r ia fac iens s tu tze r i synxantha t ae t ro lens t e s tos te ron i tr ifoli xanthe

c i t r i malvacerum

cyclosi tes metschnikovu perco lans tyrogenes

spec ies

spec ies

zeylanica

s at i va

g rac i l i s

foetus gallinae vaginalis

gal l inarum hominis

CHAPTER V

THE CONSTRUCTION AND USE OF TABLE I I I - TRANSFORMATIONS BY GENUS

ORDER OF THE TABLE

The entries in Table III include all the genera, species, sources, substrates, and reactions reported in the cited references. These include both inactive genera and assignments for reactions based solely on Chromatographie evidence.

Transformations that are documented with specific experimental details are cross-indexed with the product table. The references for those entries are under-lined.

The table entries are recorded in an order determined by the following rules which are applied sequentially.

(a) According to genus (alphabetically) (b) According to species (alphabetically) (c) According to source (alphabetically) (d) According to substrate (using the following systematic stem names

sequentially): estrane androstane pregnane cardanolide bufanolide cholanic acid cholestane stigmas tane sapogenins (common stem name)

Taxonomic names and identifying culture collection numbers, as well as the spellings of the genera, species, and varieties are as given in the cited references. Occasional changes in spelling were made to conform to standard reference texts or culture collection catalogs. In a few instances, to avoid misinterpretation, the prob-able correct spelling is given parenthetically.

SPECIFIC NOTES ON DIVISIONS OF THE TABLE

Genera The taxonomic position by class and order are given for each genus the first

time is appears in the table. A complete list of related families and genera can be found in Table II ("Taxonomy to Species"). Where more than one genus is tabulated on a page, the genus, in capital letters is repeated in the species column and under-lined.

262

SPECIFIC NOTES 263

Species An asterisk indicates that the corresponding entry in Table I ("Transformation

by Product") is recorded by the generic description (e.g. Aspergillus sp. for a list of species which perform the same transformation on a given substrate).

Occasionally, to better identify a species lacking a culture collection number, additional data are supplied, e .g. , Absidia orchidis (Vuill. ) hagem.

Transformations performed with one or more cultures (mixed or sequential) are recorded at the end of the list of substrates for the given species. Only the r e -action carried out by the primary culture is cited in the reaction column.

Transformations carried out by the second or third culture of the mixed group are listed parenthetically in the species column giving the full name of the culture and the particular reaction. The original references should be consulted for the experimental details.

When an organism has simply been identified as species in early work, but fully characterized in later reports, the final assignment is used giving the appropriate reference for the change. For example, Streptomyces argenteolus [Species ATCC-11009 (F-265, H-380, P-716, P-719; identified as argenteolus in F-267) ] .

Sources The source, with rare exceptions, is not related to the source from which the

culture was originally isolated but, wherever possible, to the major culture collec-tion where it can be obtained. The sources are coded and listed alphabetically (in-cluding the addresses) at the end of this chapter.

If the culture is not provided with an identifying number, the source is listed as either the name of the laboratory where the work was done or NG (not given).

All accession or identifying numbers for strains of a species are listed in numerical sequence. All identifying numbers for strains other than those available from the American Type Culture Collection or from the United States Department of Agriculture are enclosed in parentheses.

Different sources for the same species are listed alphabetically.

Substrates Systematic organic chemical nomenclature has been used, in most entries,

excepting for sapogenins and steroidal alkaloids. No more than one class of suffix designation for substituents is affixed to any stem. All remaining substituents are expressed in prefixes, arranged alphabetically.

In general, following the systematic stem name, the order of precedence, once the degree of substitution is established, is as follows.

(a) ane, ene, diene, triene (b) ol, diol, triol (c) one, dione, trione

For example, 5o?-pregnane-3,20-dione 3/3-hydroxy-5-pregnen- 20-one 4-pregnene-3,20-dione 6/3-hydroxy-4-pregnene-3,20-dione 17Œ, 2 l-dihydroxy-4-pregnene-3,20-dione 9a?-fluoro-17û?, 2l-dihydroxy-4-pregnene-3,20-dione 11/3,17a, 21-trihydroxy-4-pregnene-3,20-dione

264 V. CONSTRUCTION AND USE OF TABLE III

4-pregnene-3,11,20- trione 3j3-hydroxy-5,16-pregnadien-20-one

For Uie definition of terms such as nor, homo, and other notations with regard to nomenclature, see the explanations in the section on nomenclature in Chapter III.

Reactions The shorthand notation used to describe the reaction is identical with the nota-

tion used in Table I (cf. Chapter III). Reactions accomplished with cellfree enzymes and enzyme systems or those concerned with special effects of nutrients or environ-mental conditions are carried as notes in the substrate column under the appropriate culture.

A dash (—) in the reaction column indicates generally that no reaction took place or that the reaction was not characterized. Positive, though otherwise unspec-ified reactions are recorded as "oxidation - products not identified" or equivalent nonspecific terminology.

Two categories of entries are recorded in Table III (a) Those for which the ref-erence is underlined correspond to equivalent entries in Table I "Transformation by Product." To determine the structure of the product, thereby gaining access to Table I, the following rules apply. Rule 1: For those entries wherein no more than one hydroxylation appears in the

reaction column, the product is determined by the sum of all the recorded changes applied to the substrate.

Rule 2: For those entries wherein more than one hydroxylation is recorded, each hydroxylation determines a separate transformation product from the given substrate. Exception: A polyhydroxylation expressed as di-OH is read as a single, combined transformation of the substrate.

Examples: Substrate 3/3-hydroxy-5-pregnene-20-one

Reactions 3/3-OH — 3-C=0; Δ5-— Δ4 ; 12/3-OH i

Product 12/3-hydroxy-4-pregnene-3,20-dione

Substrate 3/3-hydroxy-5-pregnen-20-one +

Reactions 3/3-OH-— 3-C=0; Δ5-—Δ4 ; 12/3,15a-diOH

Product 12/3, 15a-dihydroxy-4-pregnene-3, 20-dione

Substrate 4-pregnene-3,20-dione +

Reactions 6/3-OH; l la-OH; 15/3-OH

Products 6/3-hydroxy-4-pregnene-3,20-dione 1 la-hydroxy-4-pregnene-3, 20-dione 15/3-hydroxy-4-pregnene-3,20-dione

Substrate 4-pregnene-3,20-dione +

Reactions 6/3-OH; l la-OH; 6/3, l la-diOH

Products 6/3-hydroxy-4-pregnene-3,20-dione lla-hydroxy-4-pregnene-3, 20-dione 6/3, lla-dihydroxy-4-pregnene-3,20-dione

SPECIFIC NOTES 265

(b) Entries which do not bear underlined reference citations have no equivalents in Table I. The reactions for these entries merely record the variety of transformations which may occur with the indicated substrate. For those instances in which multiple transformations are recorded, these may occur either in concert (to give a single product) or individually (and in combinations) to give multiple products.

References

The references for each entry are given by coded citation in the reference column. These citations are arranged alphabetically in the Bibliography (Chapter VI).

Those transformations for which there are data listed in Table I are identified by underlined references.

SOURCE OF CULTURES

Code Used to Identify Source in Transformation by Genus (Table III)

Code Source

Depar tment of Biochemist ry , R e s e a r c h Division, Abbott Labora to r i e s , North Chicago, 111.

Amer ican Cyanamid Co. (see a lso under LED), Lede r l e Division, P e a r l River , N. Y.

Armour and Co . , Chicago, 111.

Akimov State R e s e a r c h Insti tute (see under IPB)

Amer ican Type Culture Collection, 12301 Parklawn Drive, Rockeville, Md.

Ay e r s t R e s e a r c h Labora to r i e s , Montreal , Canada

Ben May Labora tory for Cancer Resea rch , Universi ty of Chicago, Chicago, 111.

Ciba Pharmaceu t i ca l P roduc t s , I n c . , Summit, N. J . and Basle , Switzerland

Centraa lbureau Voor Schimmelcul tures , Baarn, Nether lands

Microbiological Insti tute of Char les Univ. , Czechoslovakia

Commonwealth Mycological Inst i tute, Kew, Surrey , England

Depar tment of Plant Pathology, Cornel l Universi ty , Ithaca, N. Y.

Czechoslovak Academy of Agr icu l tura l Sciences, P rague , Czechoslovakia

Asterisk indicates major collections.

CZAS

EM

FAHU

FAKU

FARMIT

Czechoslovak Academy of Sciences, P rague , Czechoslovakia

E. Merck A. G. , Darmstad t , West Germany

Faculty of Agr icu l ture , Hokkaido Universi ty , Sapporo, Japan

Faculty of Agr icul ture , Kyushu Universi ty, Fukuoka, Japan

R e s e a r c h Labora to r i e s , Fa rmi ta l i a , Milan, Italy

AL

AMCY

ARMOUR

ASRI

ATCC*

AY

BEN MAY LAB

C

CBS*

CHARLES

CMI*

CORNELL

CZAA


Code Source

Depar tment of Fermenta t ion Chemis t ry , Universi ty of Technical Science, P rague , Czechoslovakia

Fermenta t ion Resea rch Inst i tute, Agency of Indust r ia l Science and Technology, Japan

Hoechst A. G. , Frankfurt , West Germany

Insti tute of Applied Microbiology, Universi ty of Tokyo, Japan

Insti tute for Fermentat ion, 4-54, Juso-Nishinocho, Higashiyodogawa-Ku, Osaka, Japan Institut für Microbiologie und Exper imente l le Therap ie , Jena , W. Germany

R e s e a r c h Insti tute for Pha rmacy and Biochemis t ry , Kour imska 17, P rague , Czechoslovakia

Labora tory of Food Science, Kyoto Universi ty , Japan

Kagawa Universi ty, Japan

Depar tment of Botany, Kansas State College, Manhattan, Kans.

Leder le Labora to r i e s Division, Amer ican Cyanamid C o . , P e a r l River , N. Y. (see AMCY)

Leo Pharmaceu t i ca l Produc ts , Copenhagen, Denmark

R e s e a r c h Labora to r i e s , Lepetit , S . p . A . , Milan, Italy

Lilly R e s e a r c h Labora to r i e s , El i Lilly and C o . , Indianapolis, Ind.

Merck Culture Collection, Merck and C o . , Rahway, N. J .

Nagas Labora to r i e s , 380 Mi-Shuka-Cho, Setagayaku, Tokyo, Japan

National Agr icul tura l R e s e a r c h Inst i tute, Japan

National Collection of Indust r ia l Bac te r ia , Chemical R e s e a r c h Labora tory , Teddington, Middlesex, England

National Collection of Type Cul tures , Centra l Public Health Labora tory , London N .W. 9, England

Source not given

Nagao Insti tute, Tokyo, Japan

National Inst i tutes of Health, Bethesda, Md.

National Inst i tute of Health, Japan Nor thern Regional R e s e a r c h Labora to r i e s , Nor thern Utilization Branch, Agr icul tura l R e s e a r c h Service, U . S . Depar tment of Agr icul ture , Peor ia , 111.

Ohara Insti tute for Agr icul tura l Biology, Kurashiki , Japan

Depar tment of Biochemis t ry , Okayama Medical School, Okayama, Japan

R e s e a r c h Labora to r i e s , N. V. Organon, Nether lands

R e s e a r c h Labora to r i e s , Pa rk , Davis and C o . , Ann Arbor , Mich.

Char les Pf izer and Co . , New York, N. Y.

FCUTS

FRI

HOECHST

IAM

IFO

IMJ

IPB

K

KAG

KSC

LED

LEO

LEPETIT

LRL

MCC

NAGAS

NARI

NCIB*

NCTC*

NG

NI

NIH

NIHJ

NRRL*

OIAB OKAYAMA

OR

PD

P F

SPECIFIC NOTES 267

Source

N.V. Philips Duphar, Apollolaan 151, Amsterdam, Netherlands Research Institute for the Pharmaceutical Industry, Budapest, Hungary Quartermaster Culture Collection, Quartermaster Research and Engineering Command, United States Army, Natick, Mass. Research Institute of the Distillers and Preservation Industry, Prague, Czechoslovakia Research Institute for Natural Drugs, Prague, Czechoslovakia Department of Plant Pathology and Mycology, Rutgers University, New Brunswick, N. J . Sankyo Co., Ltd., Japan Schering A. G., Berlin, Germany Sandoz, Basle, Switzerland Research Laboratories, Schering Corporation, Bloomfield, N. J . G. D. Searle and Co., Chicago, 111. Shionogi Research Laboratory, Shionogi and Co., Ltd., Fukushima-Ku, Osaka, Japan School of Pharmacy, University of Wisconsin, Madison, Wise. Squibb Institute for Medical Research, E. R. Squibb and Son, New Brunswick, N . J . (Division of Olin Mathieson Chemical Corporation, New York, N. Y.) Soviet Union. Includes Institute of Microbiology of the Academy of Sciences of the USSR, Institute of the Chemistry of Natural Products of the Academy of Science of the USSR; S. Ordzhonikidze, All-Union Scientific Research Chemical - Pharmaceutical Institute Research Laboratories, Syntex, S. A., Mexico, D. F . Research Laboratories, Takeda Chemical Industries, Ltd., Juso-Nishino-Cho, Higashiyodogawa-Ku, Osaka, Japan Tokyo Biochemical Research Institute 2-593, Takadaminami-Cho, Toshima-Ku, Tokyo, Japan Tokai-Kinki National Agricultural Experiment Station, Japan Tsurumi Chemical Research Laboratories, Yokohama, Japan Institute of Organic Chemistry, University of Basle, Switzerland UpjohnCo., Kalamazoo, Mich. Department of Fermentation, University of Chemical Technology, Prague, Czechoslovakia University of Minnesota, Minneapolis, Minn. Research Laboratories, VEB Jena Pharm., Jena, Germany Waksman Collection, Institute of Microbiology, Rutgers University, New Brunswick, N. J .

Code

PH PIRI

QM*

RIDPI

RIND RUTGERS

S SAG SANDOZ SCH SEARLE SHIONOGI

S P-WISC SQ

SSSR

SY TAKEDA

TBRI

TNAES TSURUMI UB UC UCT

UM VEB WC*


Ç2ËË Source

WFEB Worcester Foundation for Experimental Biology, Shrewsbury, Mass.

WISC Wisconsin Strain, University of Wisconsin, Madison, Wis.

WURB Western Utilization Research Branch, Agricultural Research Service, U. S. Department of Agriculture, Albany, Calif.

TABLE I I I TAXONOMY

T r a n s f o r m a t i o n s by Genus : ABSIDIA (Phyco. - Mucorales)

SPECIES

coerulea

cyl indrospora *

1 *

1 *

I glauca *

*

1 *

1 * 1 *

1 * 1 * 1 *

1 * 1 *

SOURCE

ATCC-1359b

RIDPI

NI

IPB

OIAB

UCT

SUBSTRATE

19-nor -4 -p regnene -3 ,20 -d ione

4 -p regnene-3 ,20-d ione

17a ,21-d ihydroxy-4-pregnene-3,20-dione 21-ace ta te


17a, 21 -dihydroxy-4-pregnene -3,20-dione

14j3-hydroxy-3-keto-5/3-20(22)-cardenolide

3/3,14/3-dihydroxy-5/3-20(22)-cardenolide

4 -pregnene-3 ,20-d ione

17a, 21-dihydroxy-4-pregnene -3 ,20-dione

17a, 21-dihydroxy-4-pregnene -3 ,20-dione 21-ace ta te


17a, 21-dihydroxy-4-pregnene -3,20-dione




REACTION

unidentified monohydr oxy la -tion

11a-OH; 11/3-OH

11a-OH; 11/3-OH; 1 1 - C = 0 (via 11/3-OH); 2 1 -OAc—21-OH

11a-OH; 14a-OH; 6/3,1 la -d iOH

6/3-OH;l la-OH

7/3-OH

3/3-OH-»3-C=0; lß-OH; 7/3-OH; 1/3,7/3-diOH; 5/3,7j3-diOH

l i a - O H

11/3-OH

6/3-OH;l la-OH

11/3-OH

1 1 - C = 0 (via 11/3-OH)

21-OAc^21-OH

11a-OH

14a-OH; 6/3, l l a - d i O H

11a-OH; 11/3-OH

6/3-OH

7/3-OH

3 /3 -OH-3-C=0 ; 1/3-OH; 5/3-OH; 7/3-OH

l/3,7/3-diOH;5/3, 7/3-diOH

l i a - O H

11/3-OH

R E F .

B-71

C-98

C-98

N-682

N-682

N-682

N-682

C-98

C-98

C-98

C-98

C-98

C-98

N-682

N-682

N-682

N-682

N-682

N-682

N-682

C-98

C-98

269

270

TABLE I I I

T r a n s f o r m a t i o n s by Genus: ABSIDIA

SPECIES

glauca

*

*

*

hyalospora *

*

*

orchidis (-)

orchidis

*

*

*

* *

*

SOURCE

UCT

VEB

NI

CZAA

NG

OIAB

pmi

SUBSTRATE

17a, 21 -dihydr oxy -4 -pr egnene -3,20-dione

17a, 21 -dihydroxy-4 -pr egnene -3,20-dione 21-aceta te



17a, 21 -dihydroxy-4-pr egnene -3,20-dione

14/3-hydroxy-3-keto-5/3-20(22)-cardenol ide

3/3,14/3-dihydroxy-5j3-20(22)-cardenolide

B -nor -4 -androstene -3 ,17 -dione

17a, 21 -d ihydroxy-4-pregnene-3,20-dione


17a, 21-dihydroxy-4-pr egnene -3 ,20-dione



17a, 21 -dihydroxy -4 -pregnene -3,20-dione

REACTION

6/3-OH; l l a - O H

11/3-OH

l l - C = 0 ( v i a 11/3-OH)

21 -OAc-21-OH

l l a - O H

11/3-OH

l l a - O H ; 14a-OH; 6/3,1 la-diOH

6/3-OH; l l a - O H ; 14a-OH

7ß-OH

3/3-OH— 3 - C = 0 ; 7/3-OH; 1/3,7/3-diOH; 5/3,7/3-diOH

6ξ-ΟΗ; l l a - O H

1/3-OH

l l a - O H

11/3-OH

1 1 - C = 0 (via 11/3-OH

l l a - O H

14a-OH; 6/3,11a-diOH

6/3-OH; l l a - O H

11/3-OH

3-C=0—3a-OH

5/3-H -> Δ4

l l a - O H

l l a - O H

11/3-OH

1 1 - C = 0 ( v i a 11/3-OH)

R E F .

C-98

C-98

C-98

C-98

C-98

C-98

N-682

N-682

N-682

N-682

P-741

S-825a

S-825a

S-825a

S-825a

N-682

N-682

N-682

C-98; H-334; N-682

N-682

N-682

C-98

C-98

C-98

271

TABLE I I I


SPECIES

orchidis

*

*

*

*

*

*

*

*

orchid is (Vuill. ) Hagem

*

SOURCE

PIRI

RDDPI

UCT (310)

VEB

OIAB

SUBSTRATE

17a ,21-d ihydroxy-4-pregnene-3,20-dione 21-ace ta te

17α, 21-d ihydroxy-4-pregnene-3,20-dione 21-ace ta te


17a ,21-d ihydroxy-4-pregnene-3,20-dione 21 -aceta te


17a, 21-dihydroxy-4-pregnene -3,20-dione 21-ace ta te

3/3,14/3-dihydroxy-5/3,17a-20(22)-cardenol ide

3/3, 14/3-dihydroxy-5/3-20(22)-cardenolide

REACTION

21-OAc^21-OH

l i a - O H

11/3-OH

1 1 - C = 0 (via 11/3-OH)

21-OAc->21-OH

l i a - O H

l i a - O H

1 1 - C = 0 ( v i a 11/3-OH)

21-OAC-21-OH

l i a - O H

l i a - O H

11/3-OH

1 1 - C = 0 (via 11/3-OH) 21-OAc-+21-OH

1/3-OH; 5/3-OH; 7ß-OH; 3/3-OH-» 3 - C = 0 ; 5/3-H-> Δ4

lß -OH

5/3-OH

7/3-OH

R E F .

C-98

C-98

C-98

C-98

C-98

C-98

C-98; H-334

C - 9 8 ; H-334

C-98

C-98

C-98

C-98

C-98

C-98

N-679; N-681

1-426; N-679; N-680; N-682; N-683; N-684

1-426; N-679; N-680; N-682; N-683; N-684

1-426; N-679; N-680; N-681 ; N-682; N-683; N-684

272

TABLE I I I


SPECIES

orchidis (Vuill. ) Hagem

r a m o s a

r egn ie r i

SOURCE

OIAB

NRRL

IAM

NG

SUBSTRATE

3/3,14/3-dihydroxy-5|3-20(22) -cardenolide

Sarsasapogenin

Diosgenin

4 -dehydrotigogenone


17a-hydroxy-4-pregnene-3 ,20-dione

21-hydroxy-4 -p regnene-3 ,20-dione

11/3,21 -dihydroxy -4 -pregnene -3,20 -dione

17a, 21-dihydroxy-4-pr egnene-3,20-dione


REACTION

1/3, 7/3-diOH

5/3,7/3-diOH

---

14a -OH

15/3-OH

6/3,14a-diOH

7/3,14a-diOH (revised s t ruc t -ure)

9a ,14a-diOH (assignment of s t ruc tu re -doubtful )

Π α - Ο Η

14α-OH

14α-OH

l l / 3 -OH-> l l -C=0

2/3-OH

11α-ΟΗ

14α-OH

6/3,14a-diOH

7/3,14a-diOH (revised s t r u c t -ure)

9a ,14a-diOH (assignment of s t ruc tu re -doubtful)

R E F .

1-426; N-679; N-680; N-682

1-426; N-679; N-682

M-587

M-587

M-587

S-849

S-849

S-849

S-849

S-849

S-849

S-849

S-849

S-849

S-849

S-849

S-120; S-859; T-982

S-844; S-859; T-982

S-844; T-982; T-1037

T-982

TABLE I I I

273

T r a n s f o r m a t i o n s by G e n u s : ABSIDIA

SPECIES

regn ie r i

repens

1 *

spec ies

SOURCE

NG

UCT

NG

SUBSTRATE


17a-hydroxy-4-p regnene-3 ,20-dione

21 -hydroxy-4 -p regnene -3 ,20 -dione

21 -hydroxy-4 -p regnene -3 ,20 -dione ace ta te

11/3,21-dihydroxy-4-pregnene-3,20-dione

1 l a , 21 -dihydroxy -4 -pregnene -3,20-dione

21 -hyd roxy -4 -p regnene -3 ,11 ,20 -t r ione

17a, 21 -dihydroxy-4 -pregnene-3,20-dione

11/3,17a, 21 - t r i hyd roxy-4 -p reg -nene-3 ,20-d ione


1 la, 21 -dihydroxy -4 -pregnene -3,20-dione

17a, 21-d ihydroxy-4-pregnene-3,20-dione ace ta te

17a, 21 -dihydroxy -4 -pregnene -3 ,20-dione

Saponins (sapogenin glycosides)

REACTION

7/3,14a, 15/3-tri-OH (revised s t ruc ture )

l l a - O H

14a-OH

21-OAc-21-OH; 14a-OH

14a-OH

l l / 3 - O H - l l - C = 0

14a-OH;ll /3-OH

-n-c=o -

14a-OH

l l a - O H

14a-OH

-

l l a - O H ; 11/3-OH

l l a - O H ; 11/3-OH; 1 1 - C = 0 ( v i a 11/3-OH)

21-OAC-21-OH

l l a - O H

11/3-OH

R E F .

S-844; T-982; T-1037

S-859

S-841

S-841

S-841

S-851

S-841

S-841; S-851

S-851

S-841; S-851

S-841; S-844; S-859

S-841; S-844; S-859

S-851

C-98

C-98

C-98

C-98; N-682; S-801

C-98; S-801

K-478

274

T r a n s f o r m a t i o n s by Genus:

TABLE I I I

ACETOBACTER ACHROMOBACTER

TAXONOMY

(Schizo. - Pseudomonadales) (Schizo. - Eubacteriales)

SPECIES

acet i

(in mixed cul ture with Mycococcus sp. )

pas teur ianum

suboxydans

xylinum


ACHROMOBACTER

cyclocoastes (cycloclastes)

kashiwasakiensis

liquidum


SOURCE

IFO (3169)

NRRL

IFO ( A j

NG

NG

NRRL

IFOÎ3174)

NG

I F O ( A j

IAM

IAM

IFO (3084)

I F O ( A j

SUBSTRATE

l l / 3 ,17a ,21 - t r i hyd roxy-4 -p reg -nene-3 ,20-d ione

Sarsasapogenin

Diosgenin


11/3 ,17a ,21- t r ihydroxy-4-preg-nene-3 ,20-d ione

5-androstene-3/3,17/3-diol

5-androstene-3/3,17ß-diol 17-propionate


5-pregnene-3/3,17a,20/3,21-t e t r o l

Sarsasapogenin

Diosgenin



5-cholesten-3/3-ol


17a ,21-d ihydroxy-4-pregnene-3,20-dione



11/3,17a, 21 - t r ihydroxy-4-p reg-nene-3 ,20-d ione

REACTION

-

—

-

-

3/3-OH— 3-C = 0 ; Δ 5 - Δ 4

3 | 3 -OH-3 -C=0 ; Δ -^Δ4

3 /3 -OH-3-C=0; Δ5 —Δ4

3 /3-OH^3-C=0; Δ 5 -Δ 4 ;20 /3 -ΟΗ - 2 0 - C = O

-

-

-

-

3/3-OH-*3-C=0; Δ 5 - Δ 4

-

11α-OH

6/3,14a-diOH

6/3-OH

-

Δ1

R E F .

1-428

M-587

M-587

M-587

1-428

K-457

K-457

K-457

L-523

M-587

M-587

M-587

1-428

K-457

1-428

S-849

T-1026

T-1026

1-428

1-428

275


TABLE I I I ACREMONIUM ACROSPEIRA

ACROSTALAGMUS ACTINOMUCOR ACTINOMYCES

ACTINOP LANES

TAXONOMY

(Imperf. - Moniliales) (Imperf. - Moniliales) (Imperf. - Moniliales) (Phyco. - Mucorales) (Schizo. - Actinomycétales) (Schizo. - Actinomycetales)

SPECIES

species

ACREMONIUM

potronii

ACROSPEIRA

levis

ACROSTALAGMUS

albus

ACTINOMUCOR

corymbosus

repens

ACTINOMYCES

(See Streptomyces)

ACTINOPLANES

missour i ens i s

SOURCE

IAM (K-40-5)

FRI

NG

FRI

NG

NRRL

ATCC-14538

SUBSTRATE


17a, 21 -dihydr oxy-4 -pregnene -3,20-dione

17a, 21-d ihydroxy-4-pregnene-3,20-dione

not given



Sarsasapogenin

Diosgenin


17/3- hydroxy- 17a -methyl -5a -andros tan-3-one


REACTION

6/3,14a-diOH

6/3-OH

—

17a-OH

6/3-OH; l l a - O H

-

-

-

-

1

Δ

3/3-OH— 3 - C = 0 ; Δ5 -» Δ4 ; Δ *

3 /3 -OH-3-C=0 · Δ5 — Δ4 ; Δ1

3/3-OH->3-C=0; /5 * 4 . A 1 .

Δ — Δ ; Δ ; 6/3-OH

R E F .

1-418

1-418

S-849

W-1106; W-1107

S-849

E-224

M-587

M-587

M-587

M-536

M-536; M-537

M-536; M-537

M-536; M-537

276


T r a n s f o r m a t i o n s by G e n u s : ACTINOPLANES AEROBACTER (Schizo. - Eubacter ia les)

SPECIES

missour i ens i s

(in sequential fermenta-tion with Curvular ia lunata [11/3-OH])

(in sequential fe rmenta-tion with Curvular ia lunata [11/3-OH])

spec ies

AEROBACTER

aerogenes

SOURCE

ATCC-14538

LRL-431

NCTC

NG

SUBSTRATE

l i a , 17/3-dihydroxy-4-androsten-3-one

17/3-hydroxy -17a - methyl -4 -andros ten-3-one

17/3-hydroxy-4-estren-3-one



4 -p regnene -3 ,11 ,20 - t r i one

21-hydroxy-4-pregnene-3 ,20-d ione

17a, 21 -d ihydroxy-4-pregnene-3 , 11 ,20- t r ione 21 aceta te

6a -f luoro-17a, 21 -dihydroxy-16a -methyl -4 -pregnene -3 ,20-dione

3j3-hydroxy-5-androsten-17-one


4 -androstene -3 ,17 -dione

5-cholesten-3/3-ol

5-cholesten-3/3-ol

3a ,7a ,12a- t r ihydroxy-5/3-cholanic acid

REACTION

Δ1; 17/3-OH — 17-C = 0

Δ1

enol.

Δ1

Δ1

1

Δ

Δ1

Δ1

Δ1; 21-OAc— 21-OH

Δ1

X

Δ

3/3-OH-3-C = 0 ; Δ 5 - Δ4; Δ1

3/3-OH-3-C = 0 ; Δ5 — Δ4 ; Δ *

3/3-OH->3-C=0;

6/3-OH

A1; 1 7 / 3 - O H -17-C = 0

1

Δ

-

—

—

R E F .

M-536

M-536

M-536

M-537

M-536

M-536

M-536

M-536

M-536

M-536

M-536

M-537

M-537

M-537

M-537

M-537

T-1030

S-914; W-1062

N-675

277

T r a n s f o r m a t i o n s by Genus :

TABLE I I I

AEROBACTER AGARICUS

AGROBACTERIUM

TAXONOMY

(Basidio. - Agar icales) (Schizo. - Eubacter ia les)

SPECIES

aerogenes (Izaki)

cloacae

AGARICUS

c a m p e s t r i s

eduiis

rodmani i

AGROBACTERIUM

ethanicus

(in mixed cul ture with Aspergi l lus wentii)

radiobacter

tumefaciens

SOURCE

ATCC-7256

ATCC-8308

ATCC-8329

ATCC-8724

IFO(3321)

IAM(l- l )

IAM(Al-2)

IAM (K-5)

FRI

NRRL-2334

AL(698)

WURB

NG

NRRL

IFO(3058)

SUBSTRATE

3a ,7a ,12a- t r ihydroxy-5 /3-cholanic acid

11/3,17a, 21- t r ihydr oxy -4 -p reg -nene-3 ,20-d ione

1 la, 21 -dihydr oxy -4 -pr egnene -3,20-dione

1 la, 21 -dihydroxy -4 -pregnene -3 ,20-dione




5-choles ten-3ß-ol

5-choiesten-3j3-ol aceta te

24j3-methyl-5 ,7 ,22-choies ta t r ien-3j3-ol

4 , 4 , 1 4 a - t r i m e t h y l - 5 a - 8 , 2 4 -cholestadien-3/3-ol

24-e thyl -5 ,22-choles tadien-3/3-ol

Sarsasapogenin

Diosgenin



REACTION

-

-

-

-

-

-

-1

Δ

-

-

-

-

degradat ion

degradation

degradation

degradat ion

degradat ion

-

-

-

R E F .

S-849

S-849

S-849

S-849

1-428

1-428

1-428

S-849

S-849

R-778

S-825

R-778

T-1015; T-1016

T-1015; T-1016

T-1015; T-1016

T-1015; T-1016

T-1015; T-1016

M-587

M-587

M-587

S-849

278

T r a n s f o r m a t i o n s by G e n u s :

TABLE I I I

AGROBACTERIUM AGROCYBE

ALCALIGENES

TAXONOMY

(Basidio. - Agaricales) (Schizo. - Eubacteriales)

SPECIES

tumefaciens


AGROCYBE

acer ico la

ALCALIGENES

faecalis

SOURCE

IFO(3058)

IFO

AL(SS-14)

IAM (ACC 101)

IAM (ACC 107)

NG

SUBSTRATE



1 la, 21 -dihydr oxy -4 -pr egnene - 3 , 20-dione

l ,3 ,5 (10) -es t ra t r i ene -3 ,17 /3 -d io l

1,3, 5 (10) -es t r a t r i ene -3 ,16a , 17j3-triol

3ß -hydroxy-5-androsten -17-one

3a, la ,12a - t r ihydroxy - 5/3 -cholanic acid

3a, 12a -dihydr oxy- 5/3 -cholanic acid

3a, 6a -dihydroxy - 5/3-cholanic acid

3a-hydroxy-5/3-cholanic acid

5-cholesten-3/3-01

REACTION

-

Δ1

-

-

—

-

-

keto der ivat ive

3 a - O H - 3 - C = 0

7a-OH—7-C=0

12a-OH-^12-C=0

3 a - O H - 3 - C = 0 ; 7 a - O H ^ 7 - C = 0

3a-OH->3-C=0; 12a-OH— 12-C = 0

7a-OH->7-C=0; 12a-OH-* 1 2 - C = 0

3 a - O H - 3 - C = 0 ; 7a-OH->7-C=0; 12a-OH->12-C=0

keto der ivat ive

keto der ivat ive

keto der ivat ive

degradation

R E F .

1-428

1-428

S-825

S-849

S-849

H-411

H-411

H-411

S-799

H-393; S-799

S-799

S-799

S-799

H-393; S-799

H-393; S-799; S-800

H-411

H-411

H-411

T-1030

279


T r a n s f o r m a t i o n s by G e n u s : ALLESCHERIA ALTERNARIA

(Asco. - Eurot ia les) ( Imperf. - Moniliales)

SPECIES SOURCE SUBSTRATE REACTION R E F .

species

ALLESCHERIA

Diodii

ALTERNARIA

bataticola

SCH (ON-1-42)

FRI

FAKU


1 la, 21 -dihydr oxy -4 -pregnene -3,20-dione


17a,21-dihydroxy-5/3-pregnane-3,20-dione


1la -hydroxy-4 -p regnene -3 ,20 -dione




Δ ; 20-C=O 20/3-OH

S-945

S-849

3-C = 0->3/3-OH

5j3-H

Δ -3-C:

Δ -3-C:

Δ 4 -3-C:

• 5/3-H; : 0 -3a

' 5/3-H; :Q->3/3

5/3-H

5/3-H; 0 ^ 3 a

Δ4 - - 5/3-H

Δ* -3-C

OH

OH

OH

OH

Δ -3-C:

Δ -3-C:

Δ -3-C:

> 5/3-H; = 0->3a

5/3-H

> 5/3-H; = 0 ^ 3 a - O H

' 5/3-H; = 0 — 3/3-OH

• 5/3-H

5ß-H; 0 - 3 a - O H

S-849

S-845

S-845; S-849; S-852

S-845; S-849; S-852

S-845; S-849; S-852

S-852

S-845

S-852

S-845; S-849

S-845; S-849; S-852

S-845; S-849; S-852

S-845; S-849; S-852

S-852

S-845; S-849; S-852

s

280

TABLE I I I

Transformations by Genus: ALTERNARIA

SPECIES

bataticola

c i t r i

kikutiana

pass i f lorae

SOURCE

S

FRI

TNAES

TNAES

NG

SUBSTRATE


170,21 -d ihydroxy-4-pregaene-3 ,11 ,20 - t r ione




1 la ,21-d ihydroxy-4-pregnene-3,20-dione



3/3-hydroxy-5-pregnen-20-one

3 ß , 21 -dihydroxy -5 -p re gnen- 20-one


21-hydroxy-4-p regnene-3 ,20-dione

17a, 21-dihydroxy-4-pregnene-3,20-dione

1 l a , 2 1 -d ihydroxy-4-pregnene-3,20-dione

11/3, 21-dihydroxy-4-pregnene -3,20-dione

REACTION

Δ4 -> 5/3-H

Δ4 - 5j3-H; 3-C = 0 - 3 a - O H

Δ4 — 5ß-H; 3-C=0-*3/3-OH

Δ4 - 5/3-H

Δ4 - 5/3-H; 3 - C = 0 -3a -OH

Δ4 - ' 5/3-H

Δ4 - 5/3-H; 3 - C = 0 - 3 a - O H

-

-

-

Δ1

Δ1

Δ1

Δ1

Δ1

Δ

Δ1

Δ1

Δ1

R E F .

S-845; S-849; S-852

S-845; S-849; S-852

S-845; S-849; S-852

S-845; S-849; S-852

S-845; S-849; S-852

S-845; S-849; S-852

S-845; S-849; S-852

S-849

S-849

S-849

W-1105

W-1105

W-1105

W-1105

W-1105

W-1105

W-1105

W-1105

W-1105

281


T r a n s f o r m a t i o n s by Genus: ALTERNARIA

AMANITA (Basidio. - Agaricales)

SPECIES

pass i f lorae

(in sequential fermentat ion with Curvular ia lunata [11/3], Ophiobolus herpotrichus[21-OHl and Leptosphaer ia maculans [17-OH])

AMANITA

mucar ia

porphyr ia

SOURCE

NG

CMI

NG

NRRL

AL(H-26) A L ( F - 6 )

AL(H-104)

SUBSTRATE

11α, 17α, 21 - t r i hyd roxy-4 -p reg -nene-3 ,20-d ione

17a, 21-d ihydroxy-4-pregnene-3 ,11 ,20 - t r i one

l l /3 ,21-d ihydroxy-3 ,20-d ike to-4 -p regnen-18-a l

11/3, 17a ,21 - t r i hyd roxy-3 ,20 -d ike to -4 -pregnen-18-a l


Hecogenin glycoside



l l ß , 21 -dihydroxy -4 -pregnene -3,20-dione


1 la, 21 -dihydroxy -4 -pregnene -3 ,11 ,20 - t r i one

3/3,6/3,8/3,14/3-tetrahydroxy-4, 20,22 -bufatrienolide 6-aceta te 3-glucoside

Sarsasapogenin

Diosgenin




REACTION

Δ1

Δ1

Δ1

Δ1

1

Δ

3/3 - glycoside (saponin) —» 3/3-OH

Δ1; 17/3-Ac -> 17-C = 0

1

Δ

Δ1

Δ1

Δ1

^ - [ l ^ - g l u c o s i d e ] -» 3/3-OH

-

-

-

-

R E F .

W-1105

W-1105

W-1105

W-1105

W-1107

H-351

V-1053

V-1053

V-1053

V-1053

V-1053

S-936a

M-587

M-587

M-587

S-825

S-825

species

282


T r a n s f o r m a t i o n s by G e n u s : ARMILLARIA

ARTHROBACTER (See Corynebacter ium)

(Basidio. - Agaricaies) ;' Schizo. - Eubacter ia les)

SPECIES

ARMILLARIA

mellea

ARTHROBACTER

(See Corynebacter ium)

simplex

SOURCE

WURB (M-6a)

ATCC-6946

UV( mutant)

(enzyme prepara t ion)

SUBSTRATE



4-pregnene-3 ,2C-dione

5-pregnene-3/3 ,17a,21- t r io l -2C-one 3 ,21-diace ta te


17a, 21 -dihydroxy -4 -pregnene -3 ,11 ,20 - t r ione

11/3,17a, 21 - t r ihydroxy-4 -p reg -nene-3 ,20-d ione

3 ,20-d ioxo- l l /3 -hydroxy-4-preg-nen-18-oicacid(18 —»11) lactone


5-pregnene-3/3,17a, 21 - t r i o l -20 -one 3 ,21-diace ta te


REACTION

-

1

Δ ; enol.

1

Δ ; enol. ; 17/3-OH - 17-C = 0

1

Δ 1 5 4

Δ1; Δ - Δ ; 3/3-OH-+ 3-C = 0 ; 20-C = O-> 20/3-OH; 3 , 2 1 -diOAc — 3 , 2 1 -diOH; degradation

Δ1

Δ1

Δ - high concen t ra t ion , 50 gm subs t ra te pe r 100 ml broth

Δ1

Δ ; enol. ; 17/3-OH — 17-C = 0

A l A 5 A 4

Δ ; Δ —► Δ ; 3j3-OH—3-C=0; 3,21-diOAc — 3,21-diOH no degradation

Δ1

R E F .

R-778

K-463

C-116

K-463

C-115

K-463

K-463

K-463; K-467

U-1044

C-116

C-115

K-463

283

TABLE I I I

TAXONOMY

Transformat ions by Genus: ARTHROBACTER (See Corynebacterium)

ARTHROBOTRYS (Imperf. - Moniliales)

SPECIES

simplex

(Jensen) Lochhead

species

ARTHROBOTRYS

conoides

1 dactyloides

1 musiformis

1 superba var . ol igospora

SOURCE

ATCC-13260 (Searle B-22-8)

NG

NG

ATCC-14560

Sear le (20-178)

Sear le (B-20-27)

Sear le (B-22-9)

NG

NG

NG

NG

SUBSTRATE

4 -andros tene -3 ,17 -dione

19-hydroxy-4-andros tene-3 ,17 -dione

9a- f luoro- l l /3 ,16a , H a ^ l - t e t r a -h y d r o x y ^ - p r e g n e n e - S , 20-dione

6 a - f l u o r o - l l ß , 17a ,21- t r ihydroxy-16a -me thy l -4 -p regnene -3 ,20 -dione

6a-f luoro- l l /3 ,14α, 17α, 2 1 - t e t r a -hydroxy-16a-methy l -4 -p re g-nene-3 ,20-d ione

3/3-hydroxy-12a- a z a - C - h o m o -5a-pregnane-12 ,20-d ione aceta te


9a-hydr o x y - 4 - a n d r o s t e n e - 3 , 1 7 -dione

17a[21-carboxyethyl]-17i3-hydroxy-4-andros ten -3 -one lactone

9a -hyd roxy-4 -p regnene -3 ,20 -dione

9a-hydroxy-4-andros tene - 3 , 1 7 -dione

17a, 21-dihydr oxy-4-p regnene-3,20-dione



17a ,21-d ihydroxy-4-pregnene 3,20-dione

REACTION

Δ1

9a-OH; Δ* r e v e r s e aldol

1

Δ ; r e v e r s e aldol (Formaldehyde \ ) enol.

1

Δ

Δ 1

1

Δ

3 ß - O A c -3-c=o; Δ1

1

Δ

Δ ; r e v e r s e aldol; enol.

Δ1

17/3-Ac— 1 7 - C = 0


-

-

-

6/3-OH

11a-OH

11/3-OH

R E F .

D-171; M-597

D-171; M-597

M-597

T-1007

U-1042

U-1042

M-563

D-170

D-170

C-121

D-172

D-172

E-226

E-226

E-226

E-226

E-226; E-227

E-226; E-227

284


Transformat ions by Genus: ASCOCHYTA ASPERGILLUS

(Imperf. - S^haeropsidales) ylmperf. - Moniliales)

SPECIES

ASCOCHYTA

favae

linicola

pinadella

viciai

ASPERGILLUS

aculeatus

a l l iaceus

*

*

amste lodami

*

SOURCE

FAKU

NRRL-2923

FAKU

FRI

IAM

CZAA

IAM

CZAA

IAM

SUBSTRATE


17/3-hydroxy -4 -andr osten -3-one

17j3-hydroxy-l 7a- methyl -4 -andros ten-3-one


4 - p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e

17a, 21 -dihydroxy-4 -pregnene -3,20-dione

21-hydroxy-4 -p regnene-3 ,20-dione aceta te

1 Iß , 21 -dihydroxy-4 -pregnene-3,20-dione









3/3-hydroxy- 5 -pregnen -20 -one



REACTION

-

9a-OH

9a-OH; 17/3-OH - 17-C = 0

9a-OH

9a-OH

9a-OH

9a-OH

9a-OH; 21-OAc - 21-OH

9a-OH

-

-

-

17-C = 0 -*17a -o x a - 1 7 - C - O

Δ5—Δ4; 3/3-OH - 3-C = 0

17j3-Ac-17a-oxa-17-C = 0

11a-OH

-

Δ 5 - Δ 4 ; 3/3-OH - 3 - C = 0

11a-OH; metabo l i t e -X

R E F .

S-849

S-828

S-828

S-828

S-828

S-828

S-828

S-828

S-828

S-849

S-849

1-416; 1-417

C-104

C-104

C-104

1-416; 1-417

C-104

C-104

C-104

1-416; 1-417

TABLE I I I

Transformat ions by Genus·. ASPERGILLUS

285

SPECIES

amste lodami *

a s p e r e s c e n s

as t ianus

a t ropurpureus

*

aureus *

I aur icomus

avenaceus

awamori (Nakazawa) *

awamori

| *

batatae

brevipes

butyracea

caes ie l lus

SOURCE

MCC

IAM

IAM

CZAA

IAM

IAM

IAM

NRRL (An-S)

CZAA

IAM (K-0625, K-0924, K-3532, K-5112)

NG

IAM

IAM

IAM

IAM

SUBSTRATE










Saponins (sapogenin glycoside)






17a -hydroxy-4 -p regnene -3 ,20 -dione

1 la, 21 -dihydr oxy -4 -pregnene - 3 , 20-dione





REACTION

l l a - O H ; 6/3,11a-diOH

l l a - O H

6/3,1 la-diOH

metaboli te - X

Δ5 - Δ4; 3/3-OH - 3 - C = 0

metaboli te - X

Πα-ΟΗ; 6/3, Πα-d iOH

-

-

3/3-glycoside (saponin) —» 3/3-OH

-

Δ5—Δ ; 3/3-OH - 3 - C = 0

l l a - O H

l i a - O H

l i a - O H ; 6/3, l l a - d i O B

-

-

-

-

-

—

R E F .

D-190

1-416; 1-417

1-416

C-104

C-104

C-104

I 416; 1-417

1-416; 1-417

1-416; 1-417

K-478; K-479

C-104

C-104

C-104

1-416; 1-417

S-859

S-859

S-859

1-416; 1-417

1-416; 1-417

1-416; 1-417

1-416; 1-417

286

TABLE I I I

Transformat ions by Genus.· ASPERGILLUS

SPECIES

caespi tosus

* candidus

*

*

carbonar ius

carneus

*

cheval ier i

1 *

SOURCE

IAM

MCC

CZAA

FRI

IAM

MCC

SSSR (28)

IAM

MCC

CBS

IAM

CZAA

SUBSTRATE










4 -pregnene - 3 , 1 1 , 2 0 - t r i o n e



3 -hydroxy -1 ,3 ,5(10) - e s t r a t r i e n -17-one

l , 3 ,5 (10 ) -e s t r a t r i ene -3 ,17 j3 -d io l



3/3 -hydroxy -5 -pregnen-20 -one

REACTION

-

11a-OH

metaboli te - X

Δ 5 ^ Δ 4 ; 3/3-OH - 3 - C = 0

metabolite - X

-

11a-OH

11a-OH,

11a-OH; 6/3, l l a - d i O H

-

-

-

7a-OH

15a-OH

7a-OH; 1 7 - C = 0 - 17/3-OH

15a-OH; 1 7 - C = 0 — 17/3-OH

7a-OH

15a-OH

7a-OH; 17/3-OH — 1 7 - C = 0

15a-OH; 17/3-OH - 1 7 - C = 0

l l a - O H ; 6)3, l l a - d i O H

17-C=0—17a-o x a - 1 7 - C = 0

Δ 5 - Δ 4 ; 3j3-OH - > 3 - C = Q

R E F .

1-416; 1-417

D-190

C-104

C-104

C-104

S-849

1-416; 1-417

D-190

T-1010

T-1010

1-416; 1-417

D-190

L-495; L-497

L-495; L-497

L-495; L-497

L-495; L-497

L-495; L-497

L-495; L-497

L-495; L-497

L-495; L-497

1-416; 1-417

C-104

C-104

TABLE I I I

T ransformat ions by Genus: ASPERGILLUS

287

SPECIES

cheval ier i

*

*

cinnamomeus

*

*

ci t r i

c i t r i sporus *

clavatus

1 *

1 * conicus *

echinulatus *

1 * effusus

1 *

SOURCE

IAM

MCC

NG

NRRL (CZ-43)

CZAA

IAM

FRI

IAM

ATCC-9598

ATCC-10058

CZAA

IAM

MCC

MCC

IAM

MCC

CZAA

SUBSTRATE













4 -andros tene -3 ,17-d ione









3/3-hydroxy- 5 -pregnen -20 -one

REACTION

-

l i a -OH; 6/3, l la-diOH

17/3-Ac^ 17-C = 0

1 7 / 3 - A c ^ l 7 a -o x a - 1 7 - C = 0


metaboli te - X

Δ 5 - * Δ 4 ; 3/3-OH->3-C=0

metaboli te - X

l i a - O H ; 6/3, l l a - d i O H

-

l i a - O H ; 6/3, l l a - d i O H

l i a - O H ; 2 1 -OAc - 21-OH

l i a - O H

-

Δ5->Δ4; 3/3-OH - 3 - C = 0

l i a - O H

l l a - O H ; 6/3, l l a - d i O H

l l a - O H

l l a - O H

l l a - O H ; 6/3, l l a - d i O H

l l a - O H

-

Δ 5 - Δ 4 ; 3/3-ΟΗ - 3 - C = 0

REF.

1-416; 1-417

D-190

C-102

C-102

K-478; K-479

C-104

C-104

C-104

1-416; 1-417

S-849

1-416; 1-417

M-603

M-603

C-104

C-104

C-104

1-416; 1-417

D-190

D-190

1-416; 1-417

D-190

C-104

C-104

288

TABLE I I I

Transformat ions by Genus: ASPERGILLUS

SPECIES

ei iusus

elegans

*

f ischeri

*

flavipes

*

*

*

SOURCE

CZAA

CZAA

IAM

ATCC-1G20

CZAA

IAM

MCC

ATCC-11013

CZAA

IAM

MCC

SUBSTRATE



3/3-hydroxy-5-pregnen-2G-one



21-hydroxy-4-p regnene-3 ,20-dione aceta te


3/3 -hydroxy- 5 -pregnen -20 -one





17a-oxa-D-homo-4-andros tene-3,17-dione



3/3-hydroxy -5 -pregnene -20 -one




REACTION

l l a - O H

metabolite - X

Δ 5 - Δ 4 ; 3β-ΟΗ - 3 - C = 0

metabolite - X

l l ö - O H ; 6,3, l l a - d i O H

21-OAc—21-OH; l l a - O H

17-C = 0 -> 17a-oxa-17-C = 0

no oxidation at 3-C

17j3-Ac-»17a-oxa-17-C = 0

l l o - O H ; 6/3, l l a - d i O H

11a-OH

17-C = 0 - 1 3 , 1 7 -seco-13a-OH-16-COOH

17a-oxa-17-C = 0 — 13 ,17 - seco -13ö-OH-16-COOH

17|3-Ac->17a-oxa-17-C = 0

17/3-Ac—13,17-seco-13a-OH-16-COOH

17-C = 0 - 17a-oxa-17-C = 0

Δ 5 - Δ 4 ; 3/3-OH -> 3-C = 0

17/3-Ac-» 17a -oxa-17-C = 0

l l a - O H ; 6/3, l l ö -d iOH

l l a - O H ; 6/3, l l a - d i O H

R E F .

C-104

C-104

C-104

C-104

1-416; 1-417

M-603

C-104

C-104

C-104

1-416; 1-417

D-190

H-398

H-398

F-270

H-398

C-104

C-104

C-104

1-416; 1-417

D-190

TABLE I I I

Transformations by Genus: ASPERGILLUS

289

SPECIES

fia vu s

*

*

*

1 *

SOURCE

ATCC-9170

ATCC-9807

CZAA

FRI

IAM

IPB

MCC

NG

NRRL

SUBSTRATE




3j3-hydroxy-5-pregnen-20-one




5-androstene-3/3,17a-diol




17a -hydroxy-4 -p regnene-3 ,20-dione



Sarsasapogenin

Diosgenin

REACTION

l i a - O H

hydrolysis of glycosides to aglycones (sapogenins)

17 -C=0—17a-o x a - 1 7 - C = 0

Δ5-*Δ4; 3/3-ΟΗ ^ 3 - C = 0

17/3-Ac—17a-o x a - 1 7 - C = 0

-

l i a - O H ; 6/3, l l a - d i O H

3 /3 -OH-3-C=0; A 5 A 4

Δ —>Δ

3 /3 -OH-3-C=0; Δ 5 ^ Δ 4

l i a - O H

17/3-Ac -> 1 7 - C = 0

17j3-Ac-»17a-o x a - 1 7 - C = 0

17a-OH-17/3-Ac —>17a-oxa-17-C = 0

17j3-(20-C=O-21-OH)-» 1 7 - C = 0

17/3-(20-C = O-2 1 - O H ) - 1 7 a -o x a - 1 7 - C = 0

17a-OH-17/3-(20 -C=O-21 -OH)->17-C = 0

17a-OH-17/3-(20 -C=O-21-OH)-+17a-oxa-1 7 - C = 0

-

-

R E F .

M-603

K-478

C-104

C-104

C-104 1

S-849

1-416; 1-417

H-337

H-337

D-190

P-726

P-726

P-726

P-726

P-726

P-726

P-726

M-587

M-587

290

TABLE I I I

T r a n s f o r m a t i o n s by Genus : ASPERGILLUS

SPECIES

f lavus

*

fonsecaeus

fu mi gat us

*

*

*

*

*

fumigatus F r e s .

giganteus

*

glaucus

*

SOURCE

NRRL

SSSR (27)

IAM

CZAA

IAM

IAM

MCC

NRRL

SSSR (12)

SSSR (14)

NG

ATCC-1005a

IAM

IAM (mutant)

IAM

NRRL (CZ-5)

SSSR

SUBSTRATE


4-pregnene-3,2G-dione

4 -p r egnene -3 ,11 ,20 - tr ione








Sarsasapogenin

Diosgenin




4 -pregnene -3 ,11 ,20 - t r i one

3/3,6j3,8/3,14-tetrahydroxy-4, 20,22 -bufatrienolide 6-aceta te 3-glucoside





4 - p r e g n e n e - 3 , 1 1 , 2 0 - t r ione

REACTION

—

6/3,1 la-diOH

-

-

metabolite - X

Δ5 - Δ 4 ; 3/3-OH -» 3 - C = 0

metabolite - X

l l a - O H ; 6/3, l l a - d i O H

-

11a-OH

11/3-OH

-

-

-

6/3, l la-diOH

6/3,1 la -diOH

-

3/3-fl^-glucosidel — 3/3-OH

lla,15/3-diOH

11a-OH; 6/3, l l a - d i O H

-

—


—

R E F .

M-587

T-1010

T-1010

1-416; 1-417

C-104

C-104

C-104

1-416; 1-417

1-416; 1-417

D-190

H-328

M-587

M-587

M-587

T-ioio

T-1010

T-1010

S-936a

D-179; D-180

1-416; 1-417

D-190

1-416; 1-417

K-478; K-479

T-1010

(mutant)

TABLE I I I

T rans format ions by Genus: ASPERGILLUS

291

SPECIES

grac i l i s *

gymnosardae

he rba r io rum

inuii *

i taconicus

janus

japonicus *

kanagaw-aensis

kawachii

luchuensis

1 *

1 * mangini *

1 mel leus

1 *

I minimus * (minutus)

miyakoensis *

SOURCE

IAM

MCC

IAM

IAM

IAM

ATCC-10021

IAM

IAM

IAM

IAM

IAM

ATCC-10061

CZAA

MCC

MCC

CZAA

IAM

IAM

IAM

SUBSTRATE







4 -p regnene -3 ,2 0-dione














4 -p regnene-3 ,2 0-dione



REACTION

l l a - O H ; 6/3, l l a - d i O H

-

-

-

l i a - O H 5 6/3, l l a - d i O H

l l a - O H

l i a - O H ; 6/3, l l a -d iOH

-

l l a - O H ; 6/3, l l a - d i O H

-

-

l l a - O H

-

Δ5->Δ4; 3j3-OH-> 3 - C = 0

l l a - O H

l l a - O H

l l a - O H

-

Δ5->Δ4; 3/3-OH —3-C=0

l l a - O H

-

l l a - O H ; 6/3, l l a - d i O H

l l a - O H ; 6/3, l l a - d i O H

R E F .

1-416; 1-417

D-190

1-416; 1-417

1-416; 1-417

1-416; 1-417

M-603

1-416; 1-417

1-416; 1-417

1-416; 1-417

1-416; 1-417

1-416; 1-417

M-603

C-104

C-104

C-104

D-190

D-190

C-104

C-104

C-104

1-416; 1-417

1-416; 1-417

1-416; 1-417

292

TABLE I I I


SPECIES

mollis *

montevidensis *

nakazawai *

nidulans

*

*

*

SOURCE

IAM

MCC

IAM (K-2C24)

ATCC-10C74

ATCC-11267

CZAA

IAM

MCC

NRRL

SUBSTRATE


4-pregnene-3,2C-dione

4 -p regnene-3 ,2" -d ione

4 -p regnene -3 , 2·! -dione

I6a-hydroxy -4 -pregnene - 3 , 2.° -dione

21-hydroxy-4-p regnene-3 ,20-dione acetate

1 7ÛÎ , 21 -dihydroxy -4 -pregnene -3, 20-dione

4 , 9 ( l l ) - p r e g n a d i e n e - 3 , 20-dione

A-nor -3 -p regnene -2 ,20 -d ione

6a - fluor o -1 la - hydroxy - 4 -p regnene-3 ,20-d ione

6a - chlor o -17a - hydroxy - 4 -p regnene-3 ,20-d ione

6a - chlor o -17a, 21 -dihydroxy-4 -pregnene-3 ,20-d ione

6a -fluoro -17a, 21 -dihydr oxy - 4 -p regnene-3 ,20-d ione






Sarsasapogenin

Diosgenin


REACTION

l i a - O H ; 6/3, I l a -d iCH

l i a - O H

Ha-OK; 6/3, l l a -d iOH

l i a - O H

6/3 -OH

l i a - O H ; 2 1 -OAc —21-OH

l l a - O H

6/3,12a-diOH

6/3-OH

l l a - O H

l l a - O H

l l a - O H

l l a - O H

l l a - O H

15ß-OH

-

Δ5—Δ4; 3/3-ΟΗ-* 3-C = 0

l l a - O H

l l a - O H ; 6/3, l l a -d iOH

l l a - O H

-

—

R E F .

1-416; 1-417

D-19C-

1-416; 1-417

M - O C J

F-265; F-257; F-288

M-603

F-288

F-277; F-279

T-1006; W-1076

T-1006; W-1076

F-268

F-268

F-268

F-268

F-268

C-104

C-104

C-104

1-416; 1-417

D-190

M-587

M-587

M-587

TABLE I I I


293

SPECIES

nidulans

*

* niger

SOURCE

SSSR

SSSR (13)

SSSR (23)

ATCC-6257

ATCC-9142

ATCC-9145

SUBSTRATE

1 l a - h y d r o x y - 4 - p r e g n e n e - 3 , 2 0 -dione


4 - p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e


4 - p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e


A-no r -3 -p regnene -2 ,20 -d ione

19 -nor -4 -p regnene -3 ,20 -d ione


6/3-hydroxy-4-pregnene-3 ,20-dione





4 - p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e

1 9 - n o r - 4 -pregnene -3 ,20-d ione

3/3-hydroxy - 5-pregnen-20-one


6/3-hydroxy-4-pregnene-3, 20-dione



4 - p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e

REACTION

-

l l a - O H ; 6/3, l l a - d i O H

17a-OH

l l a - O H ; 6/3, l l a - d i O H

17a-OH

l i a - O H

21-OH

21-OH

21-OH

21-OH

21-OH

21-OH

21-OH

21-OH

21-OH

21-OH

21-OH

21-OH

21-OH

21-OH

21-OH

21-OH

R E F .

T-1010

T-1010

T-1010

T-1010

T-1010

M-603

W-1077

Z-1123; Z-1124

Z-1123; Z-1124

Z-1123; Z-1124

Z-1123; Z-1124

Z-1123; Z-1124

Z-1123

Z-1124

Z-1123; Z-1124

R-783

R-783

R-783

R-783

R-783

R-783

R-783

294

TABLE I I I


SPECIES

niger

*

*

*

SOURCE

ATCC-10549

ATCC-10577

CZAA

FRI

IAM

MCC

NG

SUBSTRATE


5/3 -pr egnane -3 ,20 -dione





4 ,16 -pregnadiene -3 ,20-dione









d , l -3 /3-hydroxy-5-pregnen-20-one

3)3-hydroxy-5-pregnen-20-one



(20S)- 20-hydr oxy-18,20-cyclo- 4-pregnen-3-one

REACTION

l i a - O H

l i a - O H

l i a - O H

l i a - O H

l i a - O H

l i a - O H

l i a - O H ; Δ1 6-17-Ac—► 17a-Ac

-

3/3-OH->3-C=0; Δ 5 - Δ 4

l i a - O H

-

l l a - O H ; 6j3, l l a - d i O H

l l a - O H ; 6j3, l l a - d i O H

6/3-OH

21-OH

d,I-3/3-OH-+ d - 3 - C = 0 + 1-3/3-OH

3 / 3 - O H - 3 - C = 0 ; Δ 5 - Δ 4

3 j 3 - O H - 3 - C = 0 ; Δ5->Δ4; l l a - O H

3|3-OH-^3-C=0; Δ 5 - Δ 4 ; 6j3, l l a - d i O H

l l a - O H

l l a - O H

-

R E F .

M-603

M-603

M-603

M-603

M-603

M-603

M-603

C-104

C-104

C-104

S-849

1-416; 1-417

D-190

F-288

L-502

W-1102

P-710

F-288

F-288

M-566

F-265; F-267; F-283

W-1071

TABLE I I I

T ransformat ions by Genus: ASPERGILLUS

295

SPECIES

niger

*

1 *

I niveo-glaucus *

1 niveus *

SOURCE

Sandoz NG

NRRL-3 ,328 , 330,334,1292

ALCA(5 TC-251-4247)

PIRI(47)

PIRI (mutant)

SSSR(3, 10, 25)

SSSR121, 2 2 , 2 4 , 2 9 , 30,31,33)

SSSR(2, 7 ,10 ,29 ,31)

SSSR(3, 4 , 5 , 6 , 8 , 2 1 , 2 2 , 2 4 , 2 5 , 3 0 , 33)

WISC(72-2)

MCC

MCC

SUBSTRATE

3ß, 6/3,8/3,14/3-tetrahydroxy-4, 20,22 -bufatrienolide 6-aceta te 3-glucoside

Saponins (agave)





4 -pregnene - 3 , 1 1 , 2 0 - t r ione

4 - p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e





6a-f luoro-17a, 21-d ihydroxy-4-p regnene-3 ,20-d ione



REACTION

3/3-[ lVghicoside] — 3/3-OH

3/3-glycoside (saponin) —* 3/3-OH

l i a - O H

l l a , 2 1 - d i O H

l i a - O H (only)

l i a - O H

l i a - O H ; 6/3, l l a - d i O H

17a-OH

l i a - O H

6/3,1 la -d iOH

l l a - O H

l i a - O H ; 17a-OH-17/3-Ac -» D - h o m o - 1 7 a | -OH-17a£-Me-1 7 - C = 0

l l a - O H

l l a - O H

l l a - O H

l l a - O H ; 6/3, l l a - d i O H

l l a - O H

R E F .

S-936a

K-479

W-1120

W-1081; W-1120; W-1121

W-1120

T-1010

T-1010

T-1010

T-1010

F-283

F-283

F-283

F-283

F-283

F-283

F-268

D-190

D-190

296

TABLE I I I


SPECIES

ochraceus

ochraceus (Wilhelm)

*

*

SOURCE

ATCC-1009

C

C (924)

CZAA

IAM

IAM (mutant)

MCC

NRRL-405

SUBSTRATE


20S-hydroxy-18,2G-cyclo-4-pregnen-3-one

18-hydroxy-4 -p regne^e -3 ,20-dione

6a - fluor o -1 la, 21 - dihy dr oxy -16a -methy l -4 -p regnene-3 , 20-dione

6a -fluor o -17a, 21 - dihy dr oxy -16a -methy l -4 -p regnene-3 , 20-dione 21-aceta te






16a, 17a-oxido-5a-pregnane-3,20-dione


4 - e s t r e n e - 3 , 1 7 - d i o n e


17ß-hydroxy-4-andros ten-3-one

6/3-hydroxy-3a, 5a-cyclo -pregnan-20-one

16a, 17a-oxido-5/3-pregnane-3, 20-dione

REACTION

l i a -OH

l i a - O H

l i a - O H

l i a - O H

l l a - O H ; 2 1 -OAc—21-OH

-

Δ 5 - Δ 4 ; 3/3-ΟΗ - 3 - C = 0

l l a - O H

l l a - O H ; 6/3, l l a -d iOH

l l a - O H (only)

l l a - O H

l l a - O H ; 6/3, l l a - d i O H

l l a - O H (High concentrat ion 30 - 50 g r a m s per l i ter)

l i a - O H

Πα-ΟΗ; 17/3-ΟΗ -» 1 7 - C = 0

11α-OH

11α-OH

11α-OH

R E F .

Μ-603

#-1071

W-1110

W-1098

W-1098

C-104

C-104

C-104

1-416; 1-417

1-416; 1-417

Κ-439; Κ-440

D-190

W-1067

D-150

D-150

S-835; V-1048

S-835

Κ-440; W-1066

TABLE I I I


297

SPECIES SOURCE SUBSTRATE REACTION REF.

ochraceus NRRL-405 4 -p regnene-3 ,20-d ione

4 ,16-pregnad iene-3 ,20-d ione

6a - f l uo ro -4 -p regnene -3 ,20 -dione

l i a - h y d r o x y - 4 - p r e g n e n e - 3 , 2 0 -dione


1 7 a - b r o m o - 4 - p r e g n e n e - 3 , 2 0 -dione

17a -methyl-4 -pregnene - 3 , 2 0 -dione


l i a - O H ; ( suppress ion of 6j3-OH - effect of zinc )

l i a - O H

l i a - O H (with conidia)

l i a - O H (continuous fermentation)

6j3, l la-diOH

6/3,1 la-diOH (with conidia)

l l a - O H ; 17/3-A c - 1 7 - C = 0

l l a - O H ; 17/3-Ac->17-C=0 (with conidia)

l l a - O H

6/3-OH

l l a - O H

l l a - O H

l l a - O H

l l a - O H

D-181

D-182 D-193 K-435 K-436 S-835 S-900 V-1C48; W-1065; W-1066

K-454; S-797

M-562

D-181 D-182 D-193 K-435 K-436 M-562 S-900 V-1048

S-797

V-1048

S-835

S-835; V-1048

V-1048

S-835; V-1048

S-835; V-1048

S-835; V-1048

D-182; D-193; S-835; V-1048

298

TABLE I I I


SPECIES

ochraceus

oryzae

*

*

*

SOURCE

NRRL-405

SSSR(26)

CBS

CZAA

IAM

IAM (mutant)

IAM (24,31)

IAM ( 1 , 2 , 3 , 11 ,15,82)

IAM(24,31)

IAM( 24 )

IPB

SUBSTRATE


1 7 a , 2 1 - d i h y d r o x y - l , 4 - p r e g n a -d iene-3 ,20-d ione


3j3,14j3-dihydroxy-5/3-20(22)-cardenolide








3/3,21-dihydroxy-5-pregnen-20-one 21 aceta te





REACTION

l l ö - O H

l i a - O H

l l ö - O H ; 6/3, l lö -d iOH

3 / 3 - O H - 3 - C = 0

7/3-OH

17-C=0->17a-o x a - 1 7 - C = 0

Δ 5 - Δ 4 ; 3/3-ΟΗ -» 3-C = 0

17/3-Ac-17a-o x a - 1 7 - C = 0

l l o - O H ; 6/3, l l ö -d iOH

-

17/3 - A c - 17a-o x a - 1 7 - C = 0

17/3-Ac-» 17a-o x a - 1 7 - C = 0

3 /3 -OH-3-C=0; Δ5-»Δ4; 17/3-(20-C=O-21-OAc) —17a-o x a - 1 7 - C = 0

17/3-(20-C=O-2 1 - O H ) - 1 7 a -o x a - 1 7 - C = 0

-

1 7 - C = 0 —17/3-OH

1 7 - C = 0 - 1 7 a -o x a - 1 7 - C = 0

17/3-OH-17-C

=o

R E F .

D-182; D-193; K-435; K-436; S-835; V-1048

S-835; V-1048

T-1010

J-432

J-432

C-104

C-104

C-104

1-416; 1-417

1-416; 1-417

K-461

K-461

K-461

K-461

K-461

C-102

C-102

C-102; H-332

1

TABLE I I I

T r a n s f o r m a t i o n s by Genus : ASPERCILLUS

299

SPECIES

oryzae

1 *

I ost ianus

1 *

SOURCE

IPB

MCC

Sandoz NG

NI

SSSR

SSSR(17)

CZAA

SUBSTRATE



l l a - h y d r o x y - 4 - p r e g n e n e - 3 , 2 0 -dione

17ö-hydroxy-4-p regnene-3 ,20-dione

4 - p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e


3/3, 6/3, 8/3,14/3-tetrahydroxy-4, 20,22 -bufatrienolide 6-aceta te 3-glucoside

3/3,14/3-dihydroxy-5/3-20(22)-cardenolide 3-[glucosyl-digi toxosyl-digi toxosyl-digitoxoside]



4 - p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e



REACTION

17/3-OH-17a-o x a - 1 7 - C = 0

17/3-Ac-17/3-OH

17/3-Ac-17-

c=o 17/3-Ac—17a-o x a - 1 7 - C = 0

17 /3 -Ac-17 -C=0

17/3-Ac-17/3-OH

17a-OH-17/3-Ac - 1 7 - C = 0

17a-OH-17/3-Ac — 17/3-OH

17a-OH-17/3-Ac —17a-oxa-17-c=o 17/3-Ac—17-C=0

17/3-Ac-17/3-OH

l i a - O H

^ - [ l V g l u c o s i d e j — 3/3-OH

glucosyl-digitoxosyl-digitoxosyl-digitoxoside — digitoxosyl-digitoxosyl-digitoxoside

17/3-OH-1 7 - C = 0

l i a - O H ; 6/3, l l ö -d iOH

-

metaboli te - X

Δ 5 - Δ 4 ; 3/3-OH-3 - C = 0

R E F .

C-102

C-102

C-102

C-102; H-332

C-102; H-332

C-102; H-332

C-102

C-102

C-102; H-332

C-102

C-102

D-190

S-936a

S-936a

K-482

T-1010

T-1010

C-104

C-104

300

TABLE I I I


SPECIES

ostianus

*

panamensis

pa ras i t i cus

*

*

penicil ioides

*

*

phoenicis

*

pro lifer ans

pseudoglaucus

*

pulverulentus

quadri l ineatus

*

rehmi i

SOURCE

CZAA

IAM

IAM

CZAA

IAM

MCC

CZAA

IAM

NRRL-1956

IAM

IAM

MCC

IAM

IAM

MCC

CZAA

SUBSTRATE



4 -p regnene -3 , 20-dione







3/3-hydroxy-5-pregnen-2 r -one



plant saponins








REACTION

metabolite - X

11α-ΟΗ; 6/3, ΙΙα-diOH

-

metabolite - X

Δ5 Δ4; 3/3-ΟΗ 3-C = 0

metabolite - X

11α-OK; 6/3, l lo -d iOH

-

1 7 - C = 0 - * 1 7 a -o x a - 1 7 - C = 0

Δ 5 - Δ 4 ; 3/3-OH -3-C = 0

17/3 - A c - 17a-oxa-17-C = 0

-

3/3-giycoside (saponin) —̂ 3/3-OH

3/3-glycoside (saponin) —»

3/3-OH

-

—

l l a - O K ; 6/3, l l a -d iOH

-

11a-OH; 6/3, l l a -d iOH

l l a - O H ; 6ß, l l a - d i O H

metaboli te - X

R E F .

C-104

1-416; 1-417

1-416; 1-417

C-104

C-104

C-104

1-416; 1-417

D-190

C-104

C-104

C-104

1-416; 1-417

K-478

K-479

1-416; 1-417 1-416; 1-417

D-190

1-416; 1-417

1-416; 1-417

D-190

C-104

301

TABLE I I I


SPECIES

rehmi i *

repens *

r e s t r i c t u s

ruber

1 *

1 *

rugulosus

sai toi

sc le ro t io rum

1 *

1 *

I sojae *

SOURCE

CZAA

IAM

CZAA

MCC

CZAA

IAM

MCC

IAM

MCC

IAM (R-1216) (H-0756)

CZAA

IAM

IAM

IAM mutant

SUBSTRATE









3ß-hydroxy -5-pregnen-20-one







4-andr os tene-3 ,17-d ione






REACTION

Δ5->Δ4; 3j3-OH - 3 - C = 0

metaboli te - X

l i a - O H ; 6/3, l l a - d i O H

metaboli te - X

Δ 5 ^ Δ 4 ; 3/3-OH ^ 3 - C = 0

metaboli te - X

l i a - O H

1 7 - C = 0 ^ 17a-o x a - 1 7 - C = 0

-

17/3-Ac-» 17a-o x a - 1 7 - C = 0

11a-OH; 6/3, l l a - d i O H

11a-OH; 6/3, l l a - d i O H

11a-OH; 6/3, l l a - d i O H

11a-OH

11a-OH

6/3-OH; 11a-OH

1 7 - C = 0 - 17a-o x a - 1 7 - C = 0

Δ 5 - Δ 4 ; 3/3-OH - 3 - C = 0

1 7 ß - A c - 1 7 a -o x a - 1 7 - C = 0

~

6 ß , l l a - d i O H

l i a - O H

R E F .

C-104

C-104

D-190; 1-416; 1-417

C-104

C-104

C-104

D-190

C-104

C-104

C-104

1-416; 1-417

D-190

1-416; 1-417

D-190

1-416; 1-417

1-416; 1-417

C-104

C-104

C-104

1-416; 1-417

1-416; 1-417

1-416; 1-417

302

TABLE I I I


SPECIES

s p a r s u s

species *

sulphureus *

sydowi

*

*

t amar i i

SOURCE

IAM

MCC

NG

Sandoz NG (811,882, 883 ,888 ,895 , 906)

NG

PIRI

IAM

CZAA

IAM

MCC

CZAA

SUBSTRATE

4 - p r e g n e n e - 3 , 20 -dione


1,3,5(10) - e s t r atriene-3/3,17/3-diol (sole carbon source)

3 - h y d r o x y - l , 3 , 5 ( 1 0 ) - e s t r a t r i e n -17-one (sole carbon source)

3/3,6/3,8/3,14/3-tetrahydroxy-4-20,22 -bufatrienolide 6-aceta te 3-glucoside

3/3,14/3-dihydroxy-5ß-20(22)-cardenol ide 3-[glucosyl-digi toxosyl-digi toxosyl-digitoxoside]

3-hydroxy-4-cholenic acid (sole carbon source)

3α,7α, 12a-trihydroxy-5/3-cholanic acid ( sole carbon source)

3/3-chloro-5-cholestene (sole carbon source)

5a, 6/3-dibromocholestan-3/3-ol aceta te ( sole carbon source)



4 - and ros t ene -3 ,17 -d ione




4 -pregnene -3 ,20 -dione


REACTION

-

l l a , 1 7 a - d i O H

—

3/3-[lVgluco-side] -^3/3-OH

glucosyl-digitoxosyl-digitoxosyl-digitoxoside —» digitoxosyl-digitoxosyl-digitoxoside

-

l l a - O H ; l i a , 2 1 -diOH

l l a - O H ; 6/3,11a-diOH

-

Δ ^ Δ 4 ; 3/3-ΟΗ-* 3 - C = 0

l l a - O H ; metaboli te - X

l l a - O H ; 6/3,11a-diOH

l l a - O H

R E F .

1-416; 1-417

D-180

T-1033

T-1033

S-936a

S-936a

T-1033

T-1033

T-1033

T-1033

W-1081

1-416; 1-417

C-104

C-104

C-104

1-416; 1-417

D-190

C-104

TABLE I I I


303

SPECIES

t a m a r i i *

*

*

t e r r e u s

*

1 *

*

t e r r i c o l a

1 *

1 *

1 *

1 * unguis

1 *

SOURCE

CZAA

IAM (mutant)

MCC

NRRL (RBI)

CZAA

IAM (mutant)

MCC

MCC (MF-181)

NRRL

CZAA

IAM

MCC

IAM

MCC

NRRL

SUBSTRATE





Saponins (agave)






Dioscin

Sarsasapogenin

Diosgenin

4 -dehydr otigogenone








Sarsasapogenin

REACTION

Δ5—Δ4; 3/3-OH - > 3 - C = 0

l i a - O H

l i a - O H ; 6/3, l l a - d i O H

l i a - O H

3/3-glycoside (saponin) -* 3/3-OH

1 7 - C = 0 ^ 1 7 a -o x a - 1 7 - C = 0

Δ5-*Δ4; 3/3-OH - 3 - C = 0

17/3-Ac-*17a-o x a - 1 7 - C = 0

l i a - O H ; 6/3, l l a - d i O H

l i a - O H ; 6/3, l l a - d i O H

3/3-glycoside —» 3/3-OH

-

-

—

1 7 - C = 0 - ^ 17a-o x a - 1 7 - C = 0

Δ 5 - Δ 4 ; 3/3-OH - 3 - C = 0

17/3-Ac^l7a-o x a - 1 7 - C = 0

l i a - O H ; 6/3, l l a - d i O H

l i a - O H

-

l i a - O H ; 6/3, l l a - d i O H

—

R E F .

C-104

C-104

1-416; 1-417

D-190

K-479

C-104

C-104

C-104

1-416; 1-417

D-190

R-781

M-587

M-587

M-587

C-104

C-104

C-104

1-416; 1-417

D-190

1-416; 1-417

D-190

M-587

304

TABLE I I I


SPECIES

unguis

usami i

*

*

ustus

*

*

*

var ians *

var iecolor

*

*

vers ico lor

*

*

SOURCE

NRRL

IAM (B-407)

IAM (R-0635)

IAM (mutant)

(59-1)

ATCC-10032

CZAA

IAM

MCC

IAM

CZAA

IAM

MCC

CZAA

IAM

MCC

SUBSTRATE

Diosgenin























REACTION

—

-

l i a - O H

l l a - O H ; 6/3, l l a -d iOH

l i a - O H ; 6/3, l l a - d i O H

l i a - O H

l i a - O H ; 21-OAc ^ 2 1 - O H

-

Δ5-*Δ4; 3/3-ΟΗ - 3 - C = 0

l i a - O H

l l a - O H ; 6/3, l l a - d i O H

l l a - O H

l l a - O H ; 6/3, l l a - d i O H

-

Δ5-*Δ4; 3/3-ΟΗ -» 3 - C = 0

l l a - O H

—

l l a - O H ; 6/3, l l a - d i O H

-

Δ 5 ^ Δ 4 ; 3β-ΟΗ - 3 - C = 0

l l a - O H ; metaboli te - X

l l a - O H ; 6/3, l l a - d i O H

l l a - O H

R E F .

M-587

M-587

1-416; 1-417

1-416; 1-417

1-416; 1-417

M-603

M-603

C-104

C-104

C-104

1-416; 1-417

D-190

1-416; 1-417

C-104

C-104

C-104

1-416; 1-417

D-190

C-104

C-104

C-104

1-416

D-190

305


T r a n s f o r m a t i o n s by Genus: ASPERGILLUS

AZOTOBACTER (Schizo. - Eubacteriales)

SPECIES

vers ico lor

violaceo-fuscus *

wentii

*

*

(in mixed cul ture with Agrobacter ium ethanicus)

AZOTOBACTER

agi l is

chroococcum

indicus

1 oxydans

SOURCE

SSSR(16)

IAM

ATCC-10583

IAM

IAM (mutant)

MCC

NRRL

NG

ATCC-9042

NG

ATCC-9037

ATCC-9540

NG

SUBSTRATE


4 - p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e






Sarsasapogenin

Diosgenin


5-cholesten-3/3-ol

5-cholesten-3/3-ol ace ta te

24 /3-methyl -5 ,7 ,22-choles ta -tr ien-3/3-ol

4 , 4 , 1 4 a - t r i m e t h y l - 5 a , 8 ,24-cholestadien -3/3 -ol

24-e thyl -5 ,22-choles tadien-3/3-ol


5-cholesten-3/3-ol

l l / 3 , 1 7 a , 2 1 - t r i h y d r o x y - 4 - p r e g -nene-3 ,20-d ione

11/3,1 7a, 21 - t r ihydroxy-4 - p r e g -nene -3 ,20-d ione

5-cholesten-3/3-01

REACTION

6/3, l l a - d i O H

-

11a-OH; 6/3, l l a - d i O H

11a-OH

l l a - O H ; 6ß, l l a - d i O H

-

l l a - O H

-

-

-

degradation

degradation

degradation

degradation

degradation

Δ1

degradation

Δ1

Δ1

3/3-OH — 3 - C - O ; Δ5->Δ4; degradat ion

7

Δ

R E F .

T-1010

T-1010

1-416; 1-417

M-603

1-416; 1-417

1-416; 1-417

D-190

M-587

M-587

M-587

T-1015; T-1016

T-1015; T-1016

T-1015; T-1016

T-1015; T-1016

T-1015; T-1016

T-989

M-595

T-989

T-989

H-406; H-407

H-406; H-407 |

306


TABLE I I I

AZOTOBACTER AZOTOMONAS

BACILLUS

TAXONOMY

(Schizo. - Pseudomonadales) (Schizo. - Eubacteriales)

SPECIES

spec ies

vinlandii

AZOTOMONAS

fluorescens

BACILLUS

alvei

b rev is

ce reus

SOURCE

NG

NG

ATCC-13544

IFO(3343)

IFO(333l )

IAM(B-204- l )

IFO

IFO (murao)

IFO (DC-3)

IFO (3001)

IFO (3015)

IFO (3039)

IFO (3131)

SUBSTRATE

5-cholesten-3j3-ol

5-cholesten-3/3-ol

17a, 21-d ihydroxy-4-pregnene-3,2C-dione


1 Ία, 21 -dihydroxy -4 -pr egnene -3,20-dione


17o, 21 -dihydroxy -4 -pregnene-3,20-dione


11/3,21-dihydroxy-4-pregnene -3,20-dione


17a, 21-dihydroxy-4-pr egnene r 3 ,20-dione





REACTION

Δ7; 3 / 3 - O H -3 - C = 0 ; Δ 5 - Δ 4 ;

degradation

degradation

Δ1

1

Δ

11a-OH

-

6/3-OH

11a-OH

6β-ΟΗ;11α-ΟΗ; 14a-OH

14a-OH; 11/3-OH -n-c=o Δ1; 6/3-OH; l l a - O H ; l l / 3 - O H

6/3-OH; l l a - O H

Δ1; 6/3-OH; l l a - O H ; 11/3-OH

l l a - O H

l l a - O H

l l a - O H

— 1

Δ

R E F .

H-406

M-595

T-989

T-989

S-849

S-849

S-944

S-944

S-849

S-849

S-849

S-849

S-849

S-849

S-849

S-849

S-849

S-849

TABLE I I I

307

T r a n s f o r m a t i o n s by Genus: BACILLUS

SPECIES

ce reus

(in mixed cul ture with Myococcus sp. A,)

1 c i rculans

(in mixed cul ture with Myococcus sp. A,)

c los teroides

coagulans

coli (communis)

Taxonomy - now considered in genus -Escher ich ia

fir mus

SOURCE

IFO (3466)

MCC (MB-718)

NRRL B-1666

NG

IFO (3029)

IFO (3329)

IFO(3342)

NG

ATCC-7050

IFO (P-22)

IFO (P-33)

IFO (P-55)

Feces

IFO (3330)

SUBSTRATE

l l ß , 1 7 a , 2 1 - t r i h y d r o x y - 4 - p r e g -nene-3 ,20-d ione




1 l a -hyd roxy -4 -p regnene -3 ,20 -dione


11/3,17«, 21 - t r ihydroxy-4 - p r e g -nene -3 ,20-dione



5-cholesten-3/3-ol (sole carbon source)





3 ,7 ,12- t r iketo-5/3-cholanic acid

3,7-diketo-5j3-cholanic acid

17α, 21 -dihydroxy -4 -pregnene -3 ,20-dione

REACTION

-

1

Δ

11a-OH

11a-OH

14a-OH

6/3-OH; l l a - O H

-

-

-

-

-

-

-

-

-

-

-

7 - C = 0 ^ 7 a - O H

3-C=0->3a-OH; 7 - C = 0 - 7 a - O H

—

R E F .

1-428

1-428

M-568

M-568

F-288

S-859

S-859

S-859

1-428

1-428

S-849

S-849

T-1030

S-849

S-849

S-849

S-849

F-289

S-899

S-849

308

TABLE I I I


SPECIES

lentus

SOURCE

ATCC-13805 (mutant)

SUBSTRATE


3/3-hydroxy - 5 -androsten -17 -one aceta te

4 -andros t ene -3 ,17 -dione

D -homo -17a -oxa-4 -andros tene -3 ,17-dione

17/3-hydroxy-17a-methyl-4-andros ten-3-one

3 ,21-dihydroxy-16a, 17a-oxido-5-pregnen-20-one

17a,21 -d ihydroxy-4-pregnene-3,20-dione

1 la , 21-d ihydroxy-4-pregnene-3 ,11 ,20 - t r ione

6 /3 ,17a ,21- t r ihydroxy-4-preg-nene-3 ,20-d ione

11/3, 17a ,21 - t r i hyd roxy-4 -p reg -nene-3 ,20-dione


14a, 17a ,21 - t r i hyd roxy-4 -p reg -nene-3 ,20-d ione

9a - f luoro- l l /3 ,17a ,21- t r ihydroxy-4-pregnene-3 ,20-d ione

16a -methy l -4 -pr egnene - 3 , 2 0 -dione

17a-hydroxy-16a-methyl -4-pr egnene -3 ,11 ,20 - t r ione

21-hydroxy-16a-methy l -4-p regnene -3 ,11 ,20 - t r i one

17a, 21-dihydroxy-16a-methyl -4 -p regnene -3 ,11 ,20 - t r i one

9 a - f l u o r o - l l ß , 17a ,21- t r ihydroxy-16a -me thy l -4 -p regnene -3 ,20 -dione

l l ß , 17a-dihydroxy-16a-methyl-4-pregnene-3 ,20-d ione

11/3,21 -dihydroxy- 16a -methyl -4-pregnene-3 ,20-d ione

REACTION

Δ1; 3/3-OH -» 3 - C = 0 ; Δ 5 - Δ 4

Δ1; 3ß-OAc -» 3/3-OH; 3 ß - O H ^ 3 - C = 0 ; A 5 - A 4

1

Δ

Δ1

Δ1

3 /3 -OH^3-C=0 ; Δ 5 - Δ 4 ; Δ1

Δ1

Δ1

1

Δ j

Δ1

Δ1

1

Δ

Δ1

1

Δ

Δ1

1

Δ

Δ1

1

Δ

Δ1

Δ1

L

R E F .

R-750

R-750

R-750

R-750

R-750

R-750

R-750

R-750

R-750

R-750

R-750

R-750

R-750

R-750

R-750

R-750

R-750

R-750

R-750

R-750

TABLE I I I

309

Transformat ions by Genus: BACILLUS

SPECIES

lentus

mace rans (Schardinger)

(from leaves of Digitalis purpurea)

mega te r ium

SOURCE

ATCC-13805 (mutant)

NG

IFO(3483)

IFO(3490)

ATCC-13368 (SCH-41) (WC-41)

I F O ( 6 - l )

I F O ( 1 2 - l )

I F O ( 3 7 - l )

IFO(899- l )

IFO(EC-34)

SUBSTRATE

17ö, 21-d ihydroxy-16a-methyl -4 -p regnene-3 ,20-d ione

11/3,17a, 21 - t r ihydroxy-16a -methyl-4 -pregnene - 3 , 2 0 -dione

Digitonin


1 l a , 21 -d ihydroxy-4 -p regnene-3, 20-dione



17«, 21 -dihydroxy -4 -pregnene -3 ,11 ,20 - t r ione

l l a , 1 7 a , 2 1 - t r i h y d r o x y - 4 - p r e g -nene-3 ,20-d ione


17a, 21 -dihydroxy -1 ,4 -pr egna -d i ene -3 ,11 ,20 - t r i one

l l / 3 , 1 7 a , 2 1 - t r i h y d r o x y - l , 4 -pr egnadiene -3 ,20-dione

9a - f luo ro - l l / 3 ,16a ,21- t r ihydroxy-4-pregnene-3 ,20-d ione

9a - f luo ro - l l / 3 ,17a ,21 - t r ihydroxy-4-pregnene-3 ,20-d ione





17a, 21 -dihydr oxy -4 -pregnene -3 ,20-dione

REACTION

Δ1

Δ1

3ß-glycoside (saponin) —» 3j3-OH

—

-

15/3-OH

15/3-OH

15/3-OH

15/3-OH

15j3-OH

Δ χ - Η

Δ1 — H

15β-ΟΗ

15j3-OH

11/3-OH; 2/3-OH

l l a - O H ; 6j3-OH

-

11a-OH

2/3-OH

R E F .

R-750

R-750

S-794

S-849

S-849

H-382

C-126; C-127; H-382

C-126

C-126

C-126; C-127

H-382

H-382

N-669

N-669

S-849

S-849

S-849

S-849

S-849

310

TABLE I I I

T r a n s f o r m a t i o n s by Genus : BACILLUS

SPECIES

megater ium

(in mixed cul ture with Mycobacter ium sp. )

mycoides

SOURCE

NG

NRRL

NRRL B-938

SSSR

NG

SUBSTRATE

5-cholesten-3/3-ol

Sarsasapogenin

Diosgenin


4 - e s t r e n - 3 - o n e

16a-hydroxy-4-es t ren-3 -one

16/3-hydr oxy -4 - e s t r e n - 3 -one

4 - e s t r ene -3 ,16 -dione


21-hydroxy-4 -p regnene-3 ,20-dione ace ta te

17α, 21 -dihydr oxy-4-pregnene -3,20-dione 21-ace ta te

17α,21 -d ihydroxy-4-pregnene-3 ,11 ,20 - t r ione 21-aceta te

17α, 21 -dihydroxy - 1 , 4 -pr egna -d i ene -3 ,11 ,20 - t r i one 21-aceta te

17a, 21 -dihydroxy - 5/3 -pr egnane -3 ,11 ,20 - t r ione 21-aceta te

17α, 20β, 21 - t r ihydroxy-4- p r e g -nene - 3 , 11-dione- 20, 21 -diacetate

16a, 17a-ox ido-4-pregnene-3 , 20-dione


2 4 - m e t h y l - 5 , 7 , 2 2 - c h o l e s t a -trien-3/3-ol

REACTION

—

-

-

-

16a-OH

16/3-OH

1 6 - C = 0 ; (via 16a-OH and 16/3-OH)

16a-OH -1 6 - C = 0

16a-OH -> 16/3-OH (via 16-C=0)

16/3-OH -» 1 6 - C = 0

1 6 - C = 0 -> 16/3-OH

15/3-OH

21-OAc -»21-OH

21-OAc—21-OH

21-OAC-21-OH

21-OAc—21-OH

21-OAC-21-OH

20ß-OAc-*20ß-OH; 21-OAc -» 21-OH; Δ1

2 0 - C = O - » 20a-OH

-

—

R E F .

T-1030

M-587

M-587

M-587

S-793a

S-793a

S-793a

S-793a

S-793a

S-793a

S-793a

D-191; M-568

S-948

S-948

S-948

S-948

S-948

S-917

S-947

T-1018

T-1018

TABLE I I I

311


SPECIES

poly my xa

pro teus (See Genus - Pro teus )

pulvifaciens

SOURCE

IFO-3020

NRRL B-694

IAM (N-19-2)

SUBSTRATE


1 la, 21 -dihydroxy -4 -pr egnene -3,20-dione

3/3-hydroxy-5-androsten-17-one (or acetate)


6 /3-hydroxy-4-andros tene-3 ,17-dione

14ö-hydroxy-4 -andros t ene -3 ,17 -dione


REACTION

-

—

3 ß - O H - 3 - C = 0 ; Δ 5 - Δ 4

Δ1; 3/3-ΟΗ -3 - C = 0 ; Δ 5 - Δ 4

Δ1; 3/3-OAc — 3/3-OH; 3/3-OH-3 - C = 0 ; Δ5->Δ4

3 ß - O H - 3 - C = 0 ; Δ 5 ^ Δ 4 ; 6/3-ΟΗ

14α-OH; 3/3-OH - * 3 - C = 0 ; A 5 - A 4

6/3-OH;X-OH; 3 ß - O H ^ 3 - C = 0 ; Δ5—Δ4

Δ ; Δ 5 - Δ ; 3 j3 -OH^3-C=0; 14α -OH

6-C = 0 ; 3j3-OH ->3-C=0 ; Δ 5 ^ 5ö-H

17/3-OH -> 1 7 - C = 0

17/3-OH -1 7 - C = 0 ; Δ1

Δ 4 - Δ 5 ; ketoniz.

Δ 1

3 j3 -OH^3-C=0; Δ 5 - Δ 4

R E F .

S-849

S-849

1-419; 1-420; T-1027

1-419; 1-420; T-1027

1-419; 1-420

1-419; 1-420; T-1027

1-419; 1-420; S-792; T-1027

S-792; T-1027

1-419; 1-420; S-792

1-419; 1-420; T-1027

1-419; 1-420

1-419; 1-420

1-419; 1-420

1-419; 1-420

1-419; 1-420; T-1027

312

TABLE I I I

T r a n s f o r m a t i o n s by G e n u s : BACILLUS

SPECIES

pulvifaciens

pumilus

putrif icus

pymilus

(in mixed cul ture with Mycococcus sp. AJ

ro seus

species

SOURCE

IAM (N-19-2 )

IAM

NG

IFO(3020)

IFO(3041)

IAM (B-A)

SUBSTRATE


3/3-hydroxy-5-pregnen-20-one acetate




17a, 21-dihydroxy-4-pregnene-3 ,11 ,20 - t r ione



17i3-hydroxy-4-androsten-3-one


11/3,17a, 21- t r ihydroxy-4-pr eg-nene-3 ,20-d ione





17a ,21-d ihydroxy-4-pregnene-3 ,11 ,20 - t r ione


REACTION

3/3-OH—3-C=0; Δ 5 - Δ 4 ; Δ1

3/3-OAc—3-C=0; A 5 A 4

Δ —*Δ

3 / 3 - 0 A c - 3 - C = 0 ; Δ5->Δ4; Δ1

1

Δ

Δ1

Δ 1

1

Δ

-

Δ4 - 5 β - Η

Δ4 -5 /3-Η

Δ4 -5 /3-Η

-

1

Δ

1

Δ

1

Δ

Δ1

Δ1

1

Δ

1

Δ

R E F .

1-419; 1-420; Τ-1027

1-419; 1-420; Τ-1027

1-419; 1-420; Τ-1027

1-419; 1-420 Τ-1027

1-419; 1-420

1-419; 1-420; Τ-1019; Τ-1027

1-419; 1-420

S-849

Μ-545

Μ-545

Μ-545

1-428

1-428

S-849

S-848; S-849

S-848; S-849

S-848; S-849

S-848; S-849

S-848; S-849

TABLE I I I

313


SPECIES

species

sphaer icus

SOURCE

NG

ATCC-245

ATCC-7054

ATCC-7055

SUBSTRATE

3/3-hydroxy - 5 -andros ten -17 -one





12a -ch lo ro -21-hydroxy-4 -p reg-n e n e - 3 , 1 1 , 2 0 - t r i o n e aceta te

17a ,21-d ihydroxy-6a ,16α-d i m e t h y l - 4 - p r e g n e n e - 3 , 1 1 , 20-t r ione

l l / 3 ,17a ,21- t r ihydroxy-16a-methyl-4 -pregnene - 3 , 2 0 -dione

12a- f luoro-21-hydroxy-4-preg-n e n e - 3 , 1 1 , 2 0 - t r i o n e 21-ace ta te

12a - f luo ro - l l ß ,21 -d ihydroxy-4-pregnene-3 ,20-d ione aceta te

5a -andros tane-3 ,17-d ione

5 ö - a n d r o s t a n e - 3 , 1 7 - d i o n e - l a -H3-

5 a - a n d r o s t a n e - 3 , 1 7 - d i o n e - l a -H2

5/3-androstane-3,17-dione

17/3-hydroxy-5a-androstan-3-one

17/3-hydroxy-1/3-methyl-5α-andros tan-3-one

5 a , 10a -es t r ane -3 ,17 -d ione

REACTION

Δ 5 - Δ 4 ; 3/3-ΟΗ— 3 - C = 0 ; 1 7 - C = 0 — 17/3-OH (anaerobic conditions)

17-C=0—17/3-OH (anaerobic conditions)

-

-

1

Δ

20-C=O -> 20/3-OH

Δ1; 21-OAc — 21-OH

Δ1

Δ1

Δ1; 21-OAc -> 21-OH

Δ1; 21-OAc -21-OH

1

Δ

Δ ' - ί Ια -Η 3 )

Δ ' - ί Ια -Η 2 )

-

Δ*; 17/3-OH-» 1 7 - C = 0

Δ1; 17/3-OH -1 7 - C = 0

—

R E F .

S-822

S-822

S-859

S-859

S-859

V-1045

W-1083

A-24; A-25

H-392

W-1083

W-1083

H-373; S-933

B-75a; G-323

R-768; R-769

S-933

H-373

H-373

S-933

314

TABLE I I I


SPECIES

sphaer icus

SOURCE

ATCC-7055

SUBSTRATE

5 a - e s t r a n e - 3 , 17-dione


4 - a n d r o s t e n e - 3 , 1 7 - d i o n e - l a -H3

4 -andros tene -3 17-dione-1/3-H3

4 -andros tene -3 ,17 -dione - l a -H2

4 -andros tene -3 ,17-d ione - l /3 -H2

4 -andros tene -3 ,17 -dione -2 -H2

l a - h y d r o x y - 4 - a n d r o s t e n e - 3 , 1 7 -dione

2 /3-hydroxy-4-andros tene-3 ,17-dione

9a -hydroxy-4 -and ros t ene -3 ,17 -dione

9a, 18-dihydroxy-4-andros tene -3,17-dione

17/3-hydr oxy -4 -androstene -3 -one


2α, 1 Iß -dihydroxy -4 -andr osten -3-one

2a, 17/3-dihydroxy-4-androsten-3-one diaceta te

2/3,17/3 -dihydroxy -4 -andr osten -3-one diaceta te

REACTION

Δ1

Δ1

A' ifrom l a - H 3 , 2/3-H)

Δ 1 ,

Δ 1

1

Δ

Δ1

-

1

Δ


Δ1; r e v e r s e aldol; enol.

Δ1; 1 7 / 3 - O H -1 7 - C = 0

Δ ; enol; 17/3-O H ^ 1 7 - C = 0

Δ 1 ; 17/3-OH — 17-C = 0

2a-OAc-» 2a-OH; 17/3-OAc^ 1 7 - C = 0

Δ1; 2a-OAc-> 2a-OH; 17/3-OAc-17 -C=0

2a-OAc-^2a-OH; 17ß-OAc — 17/3-OH

20-OAc -» 2/3-OH; 17/3-OAc -» 1 7 - C = 0

R E F .

S-933

H-373; H-399; S-933

B-75a; G-323

B-75a

R-469

R-469

R-469

H-373

H-373

K-473

K-473

H-373

G-317; S-933

G-318; H-373

H-399

H-399

H-399

H-399

TABLE I I I

315


SPECIES

sphaer icus

(in mixed cul ture with Curvular ia l una t a - [ l lß-OH])

1 (in mixed cul ture 1 with Curvular ia

l una t a - [ l l ß -OH])

1 (in mixed cul ture 1 with Cunninghamella 1 b lakes leeana-Lend-

ner No. l[llß-OR])

(in mixed cul ture 1 with Cunninghamella

ech inu la t a - [ l l a -OH])

SOURCE

ATCC-7055

SUBSTRATE

2/3,17/3-dihydroxy-4-andr osten -3-one diaceta te

17/3-hydroxy-la -methyl-19 -nor -4 -andros ten-3-one

17ß-hydroxy-2a-methy l -4-andros ten-3-one

17a-ethinyl-9a-f luoro- l l /3 ,17/3-dihydroxy -4 -andr os ten- 3 -one

11/3,17/3-dihydroxy- 17a -methyl -4-andros ten -3-one

17a-ethinyl-17/3-hydroxy-4-andros tene-3 ,11-d ione

17a-ethinyl-11/3,17/3-dihydroxy -4 ,6 -andros tad ien-3 -one

17a-ethinyl-17/3-hydroxy-4,6-andros tad iene-3 ,11-d ione

17 /3-hydroxy-17a-methyl -4 ,9( l l ) -andros tad ien-3 -one


D-nor -4 -p regnene -3 ,20 -d ione

21 -hydroxy-4 -p regnene -3 ,20 -dione aceta te

1 l a , 21 -dihydroxy -4 -pregnene -3 ,20-dione


REACTION

2/3-OAc—2/3-OH; 17/3-OAc— 17ß-OH

Δ \ 17-

Δ \ 21

-

17/3- O H -■c=o

1

Δ

1

Δ

1

Δ

Δ1

1

Δ

Δ 1

Δ1

1

Δ

21-OAc — -OH

1

Δ

1

Δ

Δ1

Δ

1

Δ

R E F .

H-399

H-373

H-373

N-667

G-305

G-304

G-304

G-304

R-775

H-399

R-763

S-933

S-933

H-399; S-942

K-444

K-466

K-466

K-466

316

TABLE I I I



sphaer icus (in mixed cul ture with Stachylidium biocolor - [ l l a - O H , 11/3-OH])

in mixed cul ture with Vert ic i l l ium theobromae - [ l l a -OH, 11/3-OH])

ATCC-7055 17a, 21-dihydroxy-4-pregnene -3,20-dione

15)3 ,17a ,21- t r ihydroxy-4-preg-nene-3 ,20-d ione


l i a , 15/3,17a,21-tetrahydroxy-4-pregnene-3 ,20-d ione

11)3,15/3,17a, 21 - te t rahydroxy-4-pregnene-3 ,20-d ione

17a-hydroxy-16-méthylène-4-pregnene-3 ,20-d ione aceta te

12a- f luoro- l l /3 ,21-dihydroxy-4-pregnene-3 ,20-d ione 2 1 -aceta te

12a - f luoro-21-hydroxy-4-preg-nene -3 , 11 ,20 - t r ione


17a, 21-dihydr oxy-4-pregnene-3 ,11 ,20 - t r ione 21-aceta te

15/3,17a, 21 - t r ihydroxy-4 -p reg -n e n e - 3 , l l , 2 0 - t r i o n e

7a, 17a, 21 - t r ihydroxy-4 -p reg -nene -3 ,11 ,20 - t r i one 2 1 -aceta te

17a, 21 -dihydroxy - 16a - methoxy -4 -p regnene -3 ,11 ,20 - t r i one

17a, 21-dihydr oxy-6a-methyl -4 - p r e g n e n e - 3 , 1 1 , 20- t r ione

17a, 21-dihydr oxy-16-méthylène-4-pregnene-3 ,20-d ione

17a ,21-d ihydroxy-16a-n i t ro-m e t h y l - 4 - p r e g n e n e - 3 , 1 1 , 2 0 -t r ione

K-468

K-468

C-126:

Δ1

Δ1

Δ1

Δ1

Δ1; 21-OAc 21-OH

Δ1

Δ1

Δ1

Δ1; 17a-(20-C=O-- 17-C=

1

Δ

Δ1; 21 -0 21-OH

1

Δ

Δ1

1

Δ

Δ1

OH 21-0

Ac

-

-17/3-OAc)

-

C-127

H-399; S-942

C-126; C-127

C-126; C-127

S-837

W-1083

W-1083

C-127

C-120

C-120

C-126

N-687

S-838

G-300

M-558

R-751

TABLE I I I

317

Transformat ions by Genus: BACILLUS

SPECIES

sphaer icus

SOURCE

ATCC-7055

SUBSTRATE

6a- f luoro-17a ,21-d ihydroxy-6a, 16a -d ime thy l -4 -p reg -n e n e - 3 , l l , 2 0 - t r i o n e 2 1 -aceta te

9a- f luoro-17a ,21-d ihydroxy-6a, 16a -d ime thy l -4 -p reg-n e n e - 3 , l l , 2 0 - t r i o n e 2 1 -aceta te

2a- f luoro-17a ,21-d ihydroxy-4 -pr egnene - 3 , 1 1 , 2 0 - t r ione

11/3,17a, 21- t r ihydroxy-16-methylene -4 -pr egnene -3 ,20 -dione

11/3,17a, 21- t r ihydroxy-16a-me thoxy-4 -p regnene -3 ,20 -dione

11/3,17a, 21 - t r ihydroxy -6a-methyl-4 -pr egnene -3 ,20 -dione

9a- f luoro- l l j3 ,17a ,21- t r ihydroxy-6 a - m e t h y l - 4 - p r e g n e n e - 3 , 2 0 -dione

11/3,17a, 21- t r ihydroxy-16a-nitr omethy 1-4-pr egnene-3,20-dione

9a- f luoro- l l /3 ,17a , 21 - tr ihydroxy-4-pregnene-3 ,20-d ione

12a - f l uo ro - l l / 3 , 17a ,21 - t r i -h y d r o x y - 4 - p r e g n e n e - 3 , 2 0 -dione

9a- f luoro- l l /3 ,15 i3 ,17a ,21-t e t r ahyd roxy -4 -p regnene -3 , 20-dione

9a- f luoro- l l /3 ,15a , 16a, 2 1 -t e t r ahyd roxy -4 -p regnene -3 , 20-dione

9a- f luoro- l l /3 ,16a , 17a, 2 1 -t e t r a h y d r o x y - 4 - p r e g n e n e - 3 , 20-dione

9a- f luoro- l l j3 ,14a , 15j3,170,21-pentahydroxy - 4 - p r e g n e n e - 3 , 20-dione

17/3,20a-oxido -16-ox imino-4-pregnen-3-one

REACTION

Δ1; 21-OAc — 21-OH

Δ1; 21-OAc — 21-OH

1

Δ

1

Δ

1

Δ

Δ1

Δ1

Δ1

Δ1

Δ 1

Δ1

1

Δ

1

Δ

1

Δ

1

Δ

R E F .

A-24

A-25

H-401

T-981

S-838

G-300

G-300

R-751

N-669; S-942

H-380

N-669

N-669

H-399

N-669

N-686

318

TABLE I I I

T ransformat ions by Genus: BACILLUS

SPECIES

sphaer icus

SOURCE

ATCC-7055

ATCC-7063

ATCC-12488

SUBSTRATE

17/3,20a-oxido-16-oximino-5-pregnen -3/3-ol

21-hydroxy-17/3,20a-oxido-16-o x i m i n o - 4 - p r e g n e n e - 3 , 1 1 -dione

17a, 21 -d ihydroxy-4 ,6 -p regna-d i ene -3 ,11 ,20 - t r i one

17a, 21 -dihydroxy-4, 6 -pregna-d i ene -3 ,11 ,20 - t r i one 2 1 -aceta te

11/3,17a, 21 - t r i h y d r o x y - 4 , 6 -pregnadiene-3 ,20-d ione

9a- f luoro- l l /3 ,17a ,21- t r ihydroxy-6a, 16a -dimethyl -4 -pregnene -3,20-dione 21-aceta te

17α-bromethinyl-17/3-methoxy -4 -andr osten - 3 - one

17α - chlor ethiny Ι-Πβ- methoxy -4-andros ten -3-one

17a-bromethinyl-6a-f luoro-17/3-methoxy-4-andros ten-3-one

17a-br omethiny 1 -17/3 - hydr oxy-6a -methy l -4 -andros ten -3 -one

17a -chlor ethiny 1 - 6a -f luor o -1 7/3- methoxy -4 -androsten -3-one

17a -chlor ethiny 1-17/3 -hydroxy -6 a - m e t h y l - 4 - a n d r o s t e n - 3 -one

17a -bromethinyl-6-chloro-17/3-methoxy-4 ,6 -androStadien -3-one

17a-bromethinyl -6- f luoro-17ß-methoxy-4 ,6-andros tad ien-3-one

17a-bromethinyl-17/3-hydroxy -6 -me thy l -4 ,6 -andros t ad ien -3-one

6-chloro-17a-chlor ethinyl-17/3-methoxy - 4 , 6 -andr os tadien-3-one

REACTION

Δ 5 ^Δ 4 ;3 /3 -ΟΗ^ 3 - C = 0 ; Δ 1

Δ1

1

Δ

Δ ; 21 -OAc -» 21-OH

1

Δ

Δ1; 2 1 - O A c -21-OH

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

R E F .

N-686

N-686

G-310

G-310

G-310

A-24; A-25

0-694; 0 -695

0-694; 0 -695

0-694 ; 0 -695

0-694; 0 -695

0-694; 0 -695

0-694; 0 -695

0-694 ; 0 -695

0 -694 ; 0 -695

0-694 ; 0 -695

0 -694 ; 0 -695

TABLE I I I

319


SPECIES

sphaer icus

SOURCE

ATCC-12488

EM

EM(lOOl)

IFO

MCC

SUBSTRATE

17a-chlor ethiny 1-6-flu or o-17/3-methoxy-4 ,6 -andros tad ien-3-one

1 la -chlor ethinyl-17/3 -hydroxy -6 - m e t h y l - 4 , 6 - andros tadi en-s ' one

l l ß , 1 7 a , 2 1 - t r i h y d r o x y - 6 -methy lene -4 -pr egnene - 3 , 2 0 -dione

l l / 3 ,17a ,21- t r ihydroxy-16a-methy l -6 -mé thy lène -4 -pregnene-3 ,20-d ione

1 la, 21 -dihydr oxy -16 - méthylène -4 -p regnene-3 ,20-d ione

11/3,17a,21- t r ihydroxy-16-methy lene -4 - p r e g n e n e - 3 , 2 0 -dione

9a - f luo ro - l l /3 ,17a ,21- t r ihydroxy-16 - méthylène -4 -pregnene -3 ,20-dione

1 la -hydroxy -16 -méthylène - 4 -p regnene-3 ,20-d ione

11/3,1 la -dihydr oxy -16 - méthylène -4 -p regnene-3 ,20-d ione

9a- f luoro- l l /3 ,17a-d ihydroxy-16-methylene -4 -p regnene -3 ,20 -dione

14r*-hydroxy-4-andros tene-3 ,11 , 17-tr ione




11/3-hydr oxy-4-pr egnene -3 ,20 -dione


21 -hyd roxy -4 -p regnene -3 ,11 , 20- t r ione


REACTION

Δ1

1

Δ

Δ1

1

Δ

1

Δ

Δ1

1

Δ

Δ1

Δ1

Δ1

Δ1

—

Δ1

1

Δ 1

Δ

1

Δ

1

Δ

Δ 1

R E F .

0 -694 ; 0 -695

0 -694 ; 0 -695

F-264

F-264

M-558

M-558

M-558

B-68

B-68

B-68

T-955

S-849

S-942

S-942

S-942

S-942

S-942

S-942

320

TABLE I I I


SPECIES

sphaer icus

SOURCE

MCC

MCC MB (431)

NG

SUBSTRATE



9a - f luoro - l l /3 ,17a ,21- t r ihydroxy-4-pregnene-3 ,20-d ione

12a -fluor o -11/3,21 -dihydroxy -4 -pregnene-3 ,20-d ione

12a-f luoro- l l /3 ,21-dihydroxy-4-pregnene-3 ,20-d ione 21-aceta te

1 la, 21 -dihydroxy -16 - méthylène -4 -p regnene -3 ,11 ,20 - t r i one 21-aceta te

l l / 3 ,17a ,21- t r ihydroxy-16-methylene -4 -pr egnene - 3 , 2 0 -dione 21-aceta te

11/3,17a,21-trihydroxy-16/3-me thy l -4 -p regnene -3 ,20 -dione 21-aceta te

9a - f luoro - l l /3 ,17a ,21- t r ihydroxy-16/3-methyl-4-pregnene-3,20-dione 21-aceta te

9a - f luoro- l l /3 ,17a ,21- t r ihydroxy-16 - méthylène -4 -pr egnene -3,20-dione 21-aceta te

12a - f luoro-21-hydroxy-4-preg-nene -3 , 11 ,20 - t r i one aceta te

12a- f luoro- l l /3 ,21-dihydroxy-4-pregnene-3 ,20-d ione 2 1 -aceta te

11/3,1 la, 21 - t r ihydroxy -4 -pr eg-nene -3 ,20-dione

5a-andros tane-3 ,17-d ione

5a - andr o stane - 3 , 1 7 - dione - la - H


4 -andr ostene -3 ,17 -dione - l a -H3

deu te r ioandros tene-3 ,17-d ione

4-androstene-3,17-dione-6/3-H2

REACTION

1

Δ

1

Δ

1

Δ

1

Δ

Δ1; 21-OAc -21-OH

Δ1; 21-OAc -21-OH

Δ1; 21-OAc -> 21-OH

Δ ; 21-OAc -» 21-OH

Δ1; 21-OAc — 21-OH

Δ1; 21-OAc -> 21-OH

Δ1; 21-OAc -» 21-OH

Δ1; 21-OAc — 21-OH

Δ 1 (vitamin K2 (35) identified a s co-factor)

1

Δ

Δ Μ Ι α - Η 3 ) 1

Δ

Δ Μ Ι Γ Ο Π Ι 1α-Η , 2/3-Η)

Δ (cell free)

Δ (cell free)

R E F .

S-942

S-942

S-942

T-984

T-985

W-1083a

W-1083a

T-986; T-987

T-986

W-1083a

W-1083

W-1083

G-291

H-375

G-323

H-375

G-323

M-535

M-535

TABLE I I I

321


SPECIES

sphaer icus

subti l is

SOURCE

NG

IAM (ACTU-B-3-3)

(ACTU-B-3-4)

(ACTU-B-3-5)

(ACTU-B-5-6)

(Hay-1)

(Hay-2)

(Hay-3)

(Hay-4)

(Hay-5)

(Hay-6)

(Hay-8)

IFO(3026)

IFO(3027)

IFO(3033)

IFO(3035)

IFO( 3036 )

SUBSTRATE

4 -p regnene -3 ,20 -d ione -7a -H 3

4 -pr egnene -3 ,20 -dione - 16a -H3

4 - p r e g n e n e - 3 , 2 0 - d i o n e - l l a - H 3 , 12a-H3

4 -p regnene-3 ,20-d ione 20-cycloethyleneketal

11/3,17a,21-trihydroxy-12/3-methyl-4 -pregnene - 3 , 2 0 -dione 21-aceta te

17α, 21 -dihydroxy -4 -pregnene -3,20-dione

17α, 21-d ihydroxy-4-pregnene-3,20-dione










17a, 21 -dihydroxy -4 -pregnene -3, 20-dione





REACTION

Δ1

1

Δ

Δ1

1

Δ

Δ1; 2 1 - O A c ^ 21-OH

2/3-OH

2/3-OH

2/3-OH

2/3-OH

2β-ΟΗ; l i a - O H

2/3-OH

2/3-OH

2/3-OH

2/3-OH

2/3-OH

2/3-OH; l i a - O H

2/3-OH

-

Δ1; l l a - O H

-

2β-ΟΗ; l l a - O H

R E F .

G-323

G-323

G-323

F-251

C-131

S-849

S-849

S-849

S-849

S-849

S-849

S-849

S-849

S-849

S-849

S-849

S-849

S-849

S-849

S-849

S-849

322

TABLE I I I


SPECIES

subti l is

SOURCE

IAM (Natto-1-2)

(Natto-1-3)

(Natto-1-4)

(Natto-1-5)

(Natto-1-6)

(Natto-1-7)

(Natto-1-8)

(Natto-1-9)

(Natto-1-10)

UNTatto-II-l)

NRRL-B-558

(PCI-219)

(PCI-220)

NG

SUBSTRATE


17a, 21 -dihydroxy -4 -pr egnene -3,20-dione

1 la, 21 -dihydroxy - 4 -pregnene -3,20-dione












l l / 3 ,17a ,21 - t r i hyd roxy -4 -p reg -nene-3 ,20-d ione

17a, 21 -dihydroxy -4-pregnene -3 ,11 ,20 - t r ione

REACTION

-

-

2/3-OH

2/3-OH

-

-

2/3-OH

l i a - O H

l l a - O H

-

1

Δ

1

Δ

2ß-OH

1 1

Δ (yield of Δ inc reased if grown in mixed cul ture with Rhizopus nigr icans)

2 0 - C = O -20/3-OH

1

Δ

1

Δ

Δ1; 20-C = O - * 20/3 -OH

R E F .

S-849

S-849

S-849

S-849

S-849

S-849

S-849

S-849

S-849

S-849

S-849

S-849

S-849

L-521; L-522

L-522

L-521; S-801

L-521 ; S-801

L-522

323


TABLE I I I

BACILLUS BACTERIUM

TAXONOMY

(Schizo. - Eubacter ia les)

SPECIES

subti l is

thiaminolyticus

tumescens

BACTERIUM

bifidum (genus and spec ies changed to Lac to-

1 bacil lus parabifidus)

1 cyclo-oxydans

SOURCE

NG

NRRL

IAM

NG

NG

ATCC-12673

SUBSTRATE

3a, 7a, 12a-tr ihydroxy-5/3-cholanic acid (sole carbon source)

5-cholesten-3/3-01 (sole carbon source)

2 4 - m e t h y l - 5 , 7 , 2 2 - c h o l e s t a -trien-3/3-ol (sole carbon source)

Sarsasapogenin

Diosgenin


17α, 21 -dihydroxy -4 -pr egnene -3,20-dione


5-cholesten-3/3-01


A -nor_-17/3 - hydr oxy - 3 - andr os ten-2-one

3/3-hydroxy-9,10-seco-1,3 ,5(10) -andros ta t r i ene -9 ,17-d ione



REACTION

-

—

-

-

-

-

—

—

—

1

Δ

9a-OH

9a-OH (use of inhibi tors for Δ1)

9a-OH; 17/3-O H - 1 7 - C = 0

degradation (product -3aa-H-4a-7a/3-methyl -hexa-h y d r o - 1 , 5 -indane-dione)

Δ1; 20-C = O ^ 20ß-OH

1 Δ

9α-OH

Δ1

REF.

N-675

T-1018; T-1030

T-1018

M-587

M-587

M-587

S-849

T-1030

S-914

S-890

P-740

S-898

S-885

S-985

F-251

S-980; T-1005

S-885

F-251

324

TABLE I I I

T r a n s f o r m a t i o n s by Genus : BACTERIUM


cyclo-oxydans ATCC-12673 1 l a -hyd roxy -4 -p regnene -3 ,20 -dione

16α, 17a-dihydroxy-4-pregnene -3,20-dione


17α, 21 -dihydroxy -4 -pregnene -3 ,11 ,20- t r ione

6a-f luoro-16a, 17a-dihydroxy -4-pregnene-3 ,20-d ione 16, 17-phenylcyclophosphate

16a, 17a-dihydroxy-6/3-methyl -4 -pregnene-3 ,20-d ione 16, 17 -phenylcyclophosphate

16a, 17a-d ihydroxy-4 ,6-pregna-d iene-3 ,20-dione 16 ,17-phenylcyclophosphate

11/3 ,17a ,21- t r ihydroxy-4-preg-nene-3 ,20-d ione (Ref. F-231 r e f e r s to use of dry cel l ma te r i a l r a the r than free growing cells)

ί ϊ /3,17α, 21 - t r ihydroxy-4 -p reg -nene-3 ,20-d ione 21-aceta te

9a- f luoro- l l /3 ,17a ,21- t r ihydroxy 4-pregnene-3 ,20-d ione

1 2 a - c h l o r o - l l j 3 , 1 6 a , 1 7 a , 2 1 -t e t r ahydroxy-4-p regnene-3,20-dione 16, 17-cyclo-sulfate 21-aceta te

9a - f l uo ro - l l j 3 , 16a ,17a ,21 -te t rahydroxy-4-pregnene-3,20-dione

K-480

Δ1; 20-C^ 20j3-OH

Δ1

l

Δ

1

Δ

1

Δ

=o - K-480

F-258; F-259

K-480

K-480

F-259

F-259

F-259

F-231; F-232; K-480; R-779

K-480

K-480

F-262

G-296; G-297; L-505; R-779; S-890; S-908

Δ ; 1 6 a , 1 7 a , 2 1 -t r i O H - 2 0 - C = O -» 16a ,17aa-dihydroxy-17a/3-hydroxymethyl-D -homo-17 -C= O

G-297

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

TABLE I I I

325

T r a n s f o r m a t i o n s by Genus: BACTERIUM

SPECIES

cyclo-oxydans

havaniensis

SOURCE

ATCC-12673

ATCC-4001

SUBSTRATE

9a - f luo ro - l l / 3 ,16α ,17α ,21 -t e t r ahydroxy-4 -p regnene -3,20-dione

6 a - f l u o r o - l l a , 16α, 17α, 2 1 - t e t r a -hydroxy-4 -p regnene -3 ,20 -dione 16,17-acetonide

1 2 a - c h l o r o - l l / 3 , 1 6 a , 1 7 a , 2 1 - t e t r a -hydroxy-4 -p regnene -3 ,20 -dione 16,17-cyclobenzyl-phosphonate 21-aceta te

9a- f luoro- l l /3 ,16a , 17a, 20/3,21 -pentahydroxy-4-pregnen-3-one

9a- f luoro- l l /3 ,16a , H a ^ l - t e t r a -hydroxy -1 ,4 -pr egnadiene -3,20-dione

9 a - f l u o r o - l l ß , 16α, 17α, 20/3,21-pen tahydroxy-1 ,4 -p regna-dien-3-one

5-cholesten-3/3-ol




l l a - h y d r o x y - 1 6 a , 1 7 a - o x i d o -4-pregnene-3 ,20-d ione

21-hydroxy-16a ,17a-ox ido-4-pregnene-3 ,20-d ione ace ta te


17a, 21-dihydr oxy-4 -p regnene-3,20-dione

REACTION

20-C=O-> 2 0/3-OH

Δ1; 20-C = O -20/3-OH

1

Δ

1

Δ

1

Δ

Δ1; 20/3-OH — 20-C=O

Δ ^ Η

20-C=O-> 20/3-OH

Δ ' - Η ; 20-C=O -20/3-OH

Δ ^ Η

20/3-OH -> 20-C=O

Δ 5 - Δ 4 ; 3/3-OH - 3 - C = 0

Δ1

Δ1

Δ1

Δ 1

Δ

Δ1

Δ1

R E F .

G-296

S-908

D-159

F-263

G-294; G-296

G-294; G-296

G-296

G-296; S-908

G-296

G-296

G-294; G-296

T-1005

F-233

F-233

F-233

F-233

F-233

F-233

F-233

326

TABLE I I I

T r a n s f o r m a t i o n s by G e n u s : BACTERIUM

SPECIES

havaniensis

mycoides

SOURCE

ATCC-1004

ATCC-4004

SUBSTRATE



9a- f luoro- l l /3 , 16«, 17a - t r i -hydroxy-4 -p regnene-3 ,20-dione


9a-fluoro-11/3,17ö, 21- t r ihydroxy-4-pregnene-3 ,20-d ione 2 1 -aceta te

3 /3 ,16a,17a,21- te t rahydroxy-9 ( l l ) -5a -p regnen -20 -one 3/3,21-diacetate

11/3,16a, 17a, 21 - te t rahydroxy-4-pregnene-3 ,20-d ione

9 a - f l u o r o - l l j 3 , 1 6 a , 1 7 a , 2 1 -t e t r ahydroxy-4-p regnene-3,20-dione



l l a - h y d r o x y - 16a, 17a-oxido-4-pregnene-3 ,20-d ione



l l / 3 ,17a ,21 - t r ihydroxy-4 -pregnene-3 ,20-d ione

16a ,17a ,21 - t r i hyd roxy-4 -p reg -nene-3 ,20-d ione

9a- f luoro- l l /3 ,16a , 17a - t r i -hydroxy-4 -p regnene -3 ,20 -dione

9a - f l uo ro - l l j 3 , 17a ,21 - t r i -hydroxy-4 -p regnene -3 ,20 -dione

9 a - f l u o r o - l l / 3 , 1 7 a , 2 1 - t r i -hydroxy-4 -p regnene -3 ,20 -dione 21-aceta te

REACTION

Δ1

1

Δ

1

Δ

1

Δ

Δ ; 21-OAc -» 21-OH

1

Δ

3j3-OAc-*3-C = 0 ; Δ 1 ' 4 ; 21-OAc -» 21-OH

1

Δ

1

Δ

1

Δ

Δ1

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

Δ1; 21-OAc -» 21-OH

R E F .

F-233

F-233

F-238

F-233

F-233

F-233

O-705

F-233

F-233

F-240

F-240

F-240

F-240

F-240

F-240

F-240

F-238

F-240

F-240

327

TABLE I I I

T r a n s f o r m a t i o n s by Genus: BACTERIUM BASIDIOBOLUS

BEAUVERIA

TAXONOMY

(Phyco. - Entomophthorales) (Imperf. - Moniliales)

SPECIES

mycoides


species (Schatz) 303

genus incor rec t * (gram posit ive coccus)

s te ro id ic las ium

BASIDIOBOLUS

rana rum (Eidam)

BEAUVERIA

bass iana

spec ies

SOURCE

ATCC-4004

IFO(3040)

LED

NG

NG

NG

CBS

FRI

ATCC-13144

SUBSTRATE

9a - f luo ro - l l /3 ,17a ,21- t r ihydroxy-4-pregnene-3 ,20-d ione 2 1 -aceta te

l l / 3 , 16a ,17a ,21 - t e t r ahyd roxy -4 -pregnene-3 ,20-d ione

9 a - f l u o r o - l l / 3 , 1 6 a , 1 7 a , 2 1 - t e t r a -hydroxy-4 -p regnene -3 ,20 -dione

1 I ß , 17a ,21 - t r i hyd roxy-4 -p reg -nene-3 ,20-d ione

l l / 3 , 17a ,21 - t r i hyd roxy -4 -p reg -nene-3 ,20-d ione

5-cholesten-3j3-ol


SEE UNIDENTIFIED GENUS

1,3,5(10) - e s t r a t r i ene -3,17/3-diol

3/3-hydroxy-5-androstene-17-one


5-cholesten-3/3-ol

17û, 21-dihydr oxy-4-pregnene-3,20-dione


1 Ία, 21 -dihydroxy -4 -pregnene -3 ,20-dione

REACTION

1

Δ

1

Δ

1

Δ

-

1

Δ

1

Δ (dry thalli)

1

Δ

-

util ization

17/3-OH -> 17-C = 0

degradation

degradation

-

6-OH; l i a - O H

11α-OH

11α-OH

R E F .

F-240

F-240

F-240

1-428

1-428

F-231

F-232

T-1030

M-595

E-194

A-23

A-23

A-23

A-23

W-1073

S-849

1-421

328


T r a n s f o r m a t i o n s by Genus: BEAUVERIA

BLAKESLEA BOLETINUS

BOLETUS

(Phyco. - Mucorales) (Basidio. - Agaricales) (Basidio. - Agaricales)

SPECIES

species

BLAKESLEA

t r i s p o r a

BOLETINUS

pictus

BOLETUS

acidus

amer icanus

SOURCE

ATCC-13144

SSSR

AL (F-12)

AL (H-35)

AL (G-119)

SUBSTRATE

16a- t -bu ty l -17a ,21-d ihydroxy-5a-pregnane-3 ,20-d ione

17a ,21-d ihydroxy-16a-methyl -5a-pregnane-3 ,20-d ione

16/3-ethyl-17a, 21-dihydroxy-5a-pregnane-3 ,20-d ione

17a,21-dihydroxy-16/3-methyl-5a-pregnane-3 ,20-d ione

17a ,21-dihydroxy-16a-methyl -4-pregnene-3 ,20-d ione

17a, 21-dihydroxy-16/3-methy 1-4 -pregnene-3 ,20-d ione

17a, 21-dihydroxy-16/3-methyl-4-pregnene-3 ,20-d ione 21-aceta te

17a, 21 -dihydroxy -1 ,4 -pr egna-d i ene -3 , 20-dione

16a - t -bu ty l -17a ,21 -d ihyd roxy - l , 4 -pregnadiene-3 ,20-d ione

17a ,21-d ihydroxy-16a-methy l - l , 4 -pregnadiene-3 ,20-d ione

16/3-ethyl-17a, 21-d ihydroxy-1 ,4 -pregnadiene-3 ,20-d ione




4-pregnene-3 ? 20-d ione

REACTION

11a-OH

11a-OH

11a-OH

11a-OH

11a-OH

11a-OH

l l a - O H ; 2 1 -O A c - 2 1 - O H

l l a - O H

l l a - O H

l l a - O H

l l a - O H

l l a - O H ; 11/3-OH; 6/3-OH

-

-

R E F .

1-421

1-421

1-421

1-421

1-421

1-421

1-421

1-421

1-421

1-421

1-421

E-224

S-825

S-825

S-825

329


BOLETUS BOTRYODIPLODIA

BOTRYTIS (Imperf. - Sphaeropsidales) (Imperf. - Moniliales)

SPECIES

lute us

1 BOTRYODIPLODIA

theobromae

BOTRYTIS

c inerea

SOURCE

AL (H-11)

AMCY

ATCC-12481

ATCC

S

TNAES

SUBSTRATE


16a, 17a-oxido-4-pregnene - 3 , 2 0 -dione

17a, 21 -dihydroxy - 4 - p r e g n e n e - 3 , 20-dione

17a, 21-d ihydroxy-4-pregnene-3 , 20-dione 21-aceta te

4-pr egnene-3 ,20-dione

17a, 21-d ihydroxy-4-pregnene-3 , 20-dione

17a ,21-d ihydroxy-4-p regnene-3 , 20-dione 21-aceta te


2 1 - h y d r o x y - 4 - p r e g n e n e - 3 , 2 0 -dione

1 Iß, 21 -dihydroxy-4 -pregnene - 3 , 20-dione

17 ,21-d ihydroxy-4 -p regnene-3 ,20-dione


REACTION

6/3,1 la -d iOH

l i a - O H

11/3-OH

11/3-OH; 21-OAc —21-OH

l l a - O H

11/3-OH

l l a - O H

Iij3-QH

11/3-OH; 1 1 -C = 0 ( v i a l l ß - O H )

11/3-OH; 11-C = 0(via 11/3-OH); 21 -OAc-21 -OH

11/3-OH; 1 1 - C = 0 (via 11/3-OH)

6/3-OH

6/3-OH

15/3-OH

15/3 -OH

15/3-OH; 11/3-OH—11-C=0

6/3-OH

11/3-OH

6/3-OH

R E F .

S-825

P-746

F-229

F-229

C-98

C-98

C-98

C-98

C-98

C-98

C-98

S-842

S-842

S-842

S-842

S-842

S-842

S-842

S-849


330

TABLE I I I

T r a n s f o r m a t i o n s by G e n u s : BOTRYTIS

SPECIES

cinerea

fabae

paeoniae

reptons

1 species

1 spectabi l is

SOURCE

TNAES

TNAES (CI - 17)

UCT

S

TNAES (PI -1)

ATCC-12482

FRI

NRRL

NRRL

SUBSTRATE


11)3,21 -dihydroxy -4 -pregnene -3,20-dione




1 la, 21 -dihydroxy -4 -pregnene -3,20-dione 21-aceta te








plant saponins

Sarsasapogenin

Diosgenin


REACTION

6/3-OH; 11/3-OH

11/3-OH - » I l - C = 0 ; 1 5 j 3 -OH

2/3-OH; 6/3-OH; 11/3-OH

6/3-OH; 11/3-OH

l i a - O H

11/3-OH

l i a - O H

11/3-OH

11/3-OH; 11-C = 0 (via 11/3-OH)

11/3-OH; 21-OAc - 2 1 - O H

11/3-OH; 1 1 - C = 0 (via l l ß -OH) ;

21-OAc-21-OH

-

-

l i a - O H

11)3-OH

2/3-OH

10/3-OH

11/3-OH

6/3-OH;lla-OH

-

-

-

—

R E F .

S-849

S-849

S-849

S-849

C-98

C-98

C-98

C-98

C-98

C-98

C-98

S-859

S-859

S-859

S-859

S-849

D-150

F-229

S-849

K-478

M-587

M-587

M-587

331


T r a n s f o r m a t i o n s by Genus: BYSSOCHLAMYS CALONECTRIA

^Asco. - Endomycetales) (Asco. - Eypocrea les)

SPECIES

BYSSOCHLAMYS

nivea

CALONECTRIA

decora

(in sequential fermentat ion with one or more of the following cu l tu re s : Curvular ia lunata, Cunninghamella b lakes leeana, Curvular ia brachy-spora and T r i -cothecium roseum)

(in sequential fermentation with one or more of the following cu l tu res : Curvular ia lunata, Cunninghamella b lakes leeana, Curvular ia b rachy-spora and T r i -cothecium roseum)

SOURCE

FRI

C

SUBSTRATE

17a ,21-d ihydroxy-4-pregnene-3 , 20-dione

5o-andros tane-3 ,17-d ione

3ß-hydroxy - 5 -andros ten -17 -one


11/3,17a, 21- t r ihydroxy-5a-pregnane-3 ,20-d ione

17a, 21 - dihy dr oxy - 5a -pr egnane -3 ,11 ,20 - t r ione

17a, 21-dihy dr oxy-5/3-pr egnane -3 ,11 ,20 - t r ione


3/3,21 -dihydroxy-5 -pregnen -20-one


l l / 3 -hydroxy-4 -p regnene-3 ,20-dione

REACTION

-

i , 4

Δ '

-1

Δ ! > 4

Δ

! , 4 Δ

1 . 4

Δ '

-

—

Δ1

Δ1; 17ß-Ac -» 1 7 - C = 0

1

Δ

1

Δ

R E F .

S-849

W-1096

W-1096

W-1096

W-1096

W-1096

W-1096

W-1096

W-1096

W-1096; V-1053

V-1053

W-1107

W-1107

332

TABLE I I I

T r a n s f o r m a t i o n s by Genus: CALONECTRIA


decora

(in sequential fermentation with one or more of the following cu l tu res : Curvular ia lunata, Cunninghamella blakesleeana, Curvular ia b rachy-spora and T r i -cothecium roseum)

CBS


1 l a , 21 -dihydroxy -4 -pregnene -3,20-dione

1 Iß , 21-dihydroxy-4-pregnene -3,20-dione


21 -hydroxy-4 -p regnene -3 ,11 , 20- t r ione

17a, 21-d ihydroxy-4-pregnene-3 ,11 ,20- t r ione

11a, 17a, 21 - t r ihydroxy-4 -p reg -nene-3 ,20-d ione


6a -f luoro-17a-hydroxy-16a -me thy l -4 -p regnene -3 ,20 -dione

l l j3 ,21-d ihydroxy-3 ,20-dike to-4-pregnen-18-a l (18—»11) hemiaceta l

l l ß , 1 7 a , 2 1 - t r i h y d r o x y - 3 , 2 0 -d ike to-4-pregnen-18-a l (18—»11) hemiaceta l

17j3 -hydr oxy - 7a - methyl -thio -4-androsten -3-one aceta te

14/3-hydr oxy-3 -keto-5ß-20(22) -cardenolide

3a, 14/3 -dihydroxy -5/3 -20(22)-cardenolide

7a-SCH3 -» 7a-S(0)CH3; 17ß-OAc -> Πβ-ΟΕ

12/3-OH

3a-OH-»3-C=0

3a-OH—3-C=0; 12/3-OH

V-1053; W-1096

W-1107

W-1096

V-

w V-

w w

V-

w

1053; -1096

1053; -1096

-1096

1053; -1096

W-1096

W-1096

W-1090a

W-1096; W-1104

W-1096

H-405

N

N

N

-677

-681

-681

c

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

TABLE I I I

T r a n s f o r m a t i o n s by Genus : CALONECTRIA

333


decora CBS

OR

VEB

3/3,14/3-dihydroxy-5/3-20(22)-cardenol ide

3/3,14/3-dihydroxy-5/3-20(22)-cardenolide 3-aceta te

3/3,14/3-dihydroxy-5/3,17a-20(22)-cardenolide

3/3,12/3,14/3-trihydroxy-5/3-20(22) cardenol ide

3/3,14/3,16/3-trihydroxy-5/3-20(22) -cardenolide

3/3,14/3,16/3-trihydroxy 5/3-20(22)-cardenolide 3-ace ta te

3/3,14/3,16/3-trihydroxy-5/3-20(22)-cardenolide 16-aceta te

3/3,14/3,16/3-trihydroxy-5/3-20(22) cardenol ide 3 ,16-d iace ta te

1 Ία, 20/3, 21 - tr ihydroxy -4 -p r eg -n e n e - 3 , l l - d i o n e

17a, 21 -dihydroxy -4-pregnene -3 ,11 ,20 - t r i one

17a, 21 -d ihydroxy-1 ,4 -p regna -d i e n e - 3 , 1 1 , 2 0 - t r i o n e

5a -pregnane-3 ,20-d ione

5/3-pregnane-3,20-dione

l l a - h y d r o x y - 5 a - p r e g n a n e - 3 , 2 0 -dione

3/3-OH—3-C=0

12/3-OH

3/3-OH—3-C=0; 12/3-OH

3/3-OAc-+3-C=0 12/3-OH

3 / 3 - O H ^ 3 - 0 0

3 / 3 - O H - > 3 - 0 0

3 /3-OH^3-C=0

3/3-OAc->3-C=0

3ß-OH->3-C=0

3/3-OAc-3|3-OH; 16/3-OAc^l6/3-OH 3/3-OAc->3-C=0; 16/3-OAc—16/3-OH

3/3-OAc-*3-C=0

3j3-OAc-*3/3-OH

20-C=O-20/3-OHJ (limited oxygen)

Δ - 2 0 - C = O -20/3-ΟΗ (normal a e r a -tion)

20-C=O — 20β-ΟΗ

12/3,15a-diOH

12/3,15α-diOH

1 5 Ö - O H

N-677

N-677

N-677

N-677

N-681

N-677

N-677

N-677

N-677

N-677

N-677

N-677

N-677

S-951

S-951

S-951

S-951

S-951

S-816

S-816

S-816

1

Δ

1

Δ

334


T r a n s f o r m a t i o n s by Genus: CALONECTRIA CANDELOSPORA

CANDIDA (Imperf. - Moniliales) (Imperf. - Moniliales)

SPECIES

decora

CANDELOSPORA

penicil loides

CANDIDA

guill iermondii

SOURCE

VEB

FRI

NRRL

SUBSTRATE

l l a -hydroxy-5 /3 -pregnane-3 ,20-dione

3a, 6a -dihydr oxy -5/3 -pr egnan -20-one

3/3-hydroxy -5 -pr egnene - 3 , 2 0 -dione


4 -pregnene-3 ,20-d ione (11α,12α-3Η2)

9ö-hydroxy-4 -p regnene-3 ,20-dione

l l a , - hyd roxy-4 -p regnene -3 ,20 -dione

11/3-hydroxy -4 -pr egnene -3 ,20 -dione

12«-hydroxy-4-pregnene-3 ,20-dione


15/3-hydroxy -4 -pregnene - 3 , 2 0 -dione




Sarsasapogenin

Diosgenin


REACTION

15a -OH

11a-OH

3 ß - O H - 3 - C = 0 ; Δ 5 - Δ 4 ; 12/3,15α-diOH

12/3,15a-diOH

12|3,15a-diOH

(o218)

12/3,15a-diOH

15a-OH

15a-OH

15a-OH

15a-OH; 12a-O H - 1 2 - C = 0

12/3-OH

12/3-OH

15a-OH

15a-OH

11a-OH

-

-

REF.

S-816

S-812

S-816

S-814

K-485

H-370

S-810

S-814

S-817

S-810

S-810

S-814

S-810

S-810

S-849

M-587

M-587

M-587

335


Transformat ions by Genus: CANDIDA

CANTHARELLUS CARPENTELES

CATENABACTERIUM

(Basidio. - Agaricales) (Asco. - Eurotiales) (Schizo. - Eubacteriales)

SPECIES

kruse i

pu lche r r ima

util is

CANTHARELLUS

cibar ius

CARPENTELES

javanicus

CATENABACTERIUM

catenaforme

1 *

1 *

SOURCE

NRRL

IFO(C964)

NRRL

NRRL

FRI

NG

SUBSTRATE

Sarsasapogenin

Diosgenin



17a, 21-dihydr o x y - 1 , 4 - p r e g n a -d iene-3 ,20-d ione

Sarsasapogenin

Diosgenin




5-cholesten-3/3-ol

4-choles ten-3-one


3/3,1 la -dihydroxy -5 -pregnen-20-one


11/3,17a, 21 - t r ihydroxy -4 - p r e g -nene -3 ,20-dione

17a, 21-dihydr oxy-4-pregnene-3 ,11 ,20 - t r ione

17a, 21 -dihydroxy -4 -pregnene -3 ,11 ,20 - t r ione 21-aceta te

REACTION

—

-

-

2 0 - C = O -20/3-OH

2 0 - C = O ^ 20/3-OH

-

-

-

-

11a-OH

— (anaerobic)

— (anaerobic)

— (anaerobic)

— (anaerobic)

— (anaerobic)

3-C=0^3/3-OH; Δ4-+5α-Η

(anaerobic)

3 -C=0-3 /3 -OH; Δ 4 ^ 5 α - Η

(anaerobic)

— (anaerobic)

REF.

M-587

M-587

M-587

T-958

T-958

M-587

M-587

M-587

R-778

S-849

T-973

T-973

T-973

T-973

T-973

P-739 ; T-973

P-739 ; T-973

T-973

336

Transformat ions by Genus:

TABLE I I I

CELLULOMONAS CEPHALOSPORIUM

TAXONOMY

(Schizo. - Eubacter ia les) (Imperf. - Moniliales)

SPECIES SOURCE SUBSTRATE REACTION

CELLULOMONAS

biazotea NRRL

CEPHALOSPORIUM

acremonium NRRL-3092

SarsasapogenH

Diosgenin

4 -dehydrotigogeione

4 - e s t r e n - 3 - o n e


17a-oxa-D-homo - 1 , 4 - a n d r o s t a -d iene-3 ,17-dione

4-pregnene-3 ,20-d ione (with and without 4-C14)

16-C=0; (v ia 16a OH and 16/3-OH)

16a-OH — 16-C=0

16/3-OH -> 16-C = 0

16a-OH

16/3-OH

1 6 - C = 0 -> 16ß-OH

16α-OH -16/3-OH ( via 16-C = 0)

1 7 - C = 0 -13 ,17 - seco -13a-OH-16-COOH

1 7 - C = 0 — 17a-o x a - 1 7 - C = 0

17a-oxa-17-C = 0 - 1 7 , 1 7 a -seco-13q-OH-16-COOH

17ß-Ac-17/3-OH

17j3-Ac—13,17-seco-13q-OH-16-COOH

17|3-Ac->17-c=o

17/3-Ac—17a-oxa-17-C = 0

M-587

M-587

M-587

S-793a

S-793a

S-793a

S-793a

S-793a

S-793a

S-793a

H-398

H-398

H-398

H-398

H-398

H-398

H-398

R E F .

337


T r a n s f o r m a t i o n s by Genus: CEPHALOSPORIUM CEPHALOTHECIUM (Imperf. - Moniliales)

SPECIES

aspe rum

species

subver t ic i l la tum

CEPHALOTHECIUM (See Trichothecium)

1 roseum (Trichothecium

1 ro seum - NRRL-1665)

SOURCE

LED

LED (Z-164)

NRRL-1866

PIRI

ATCC-8685

SUBSTRATE





9a - f luoro - l l /3 -hydroxy-4-p reg-nene-3 ,20-d ione


17a, 21-dihydr oxy-4-pregnene-3,20-dione

17a, 21 -dihydroxy -9/3,11/3-oxido-4-pregnene-3 ,20-d ione

9a -fluor o -11 ß, 21 -dihydr oxy -4 -p regnene-3 ,20-d ione



11/3-hydroxy -4 -pregnene - 3 , 2 0 -dione



11/3,21 -dihydroxy -4 -pregnene -3 ,20-dione

REACTION

7/3-OH

7/3-OH

7/3-OH

7/3-OH

7/3-OH

7/3-OH

7/3-OH

7/3-OH

7/3-OH

1 7 / 3 - A C - 1 7 - 0 0

17/3-Ac— 17a-o x a - 1 7 - C = 0

17a-OH (0218)

17a-OH; 11a, 17a-diOH

17a-OH

6/3,17a-diOH

l l a , 1 7 a - d i O H

6/3,17a-diOH; 21-OAc—21-OH

l l a , 1 7 a - d i O H ; 21-OAc—21-OH

17a-OH;l l /3-OH -+n-c=o

17a-OH

R E F .

B-56

B-55

B-56

B-56

B-56

B-56

B-56

B-56

B-56

B-67

B-67

H-374

M-581; M-600

M-600

M-581

M-581

M-600

M-600

M-581; M-600

M-600

338


TABLE I I I

CEPHALOTHECIUM CERATOSTOMELLA

CERCOSPORA

TAXONOMY

(Asco. - Sphaeriales) (Imperf. - Moniliales)

SPECIES

roseum

CERATOSTOMELLA

fimbriate (fimbriata)

CERCOSPORA (See genus Cercosporina)

apii

baticola

beticola

calotropidis

canescens

chenopodii

c ladosporioides

cru enta

diazu

SOURCE

ATCC-8685

FAHU

IFO (6161)

FAKU

IFO (6162)

KAG (C-32)

KAG (C-33)

CBS

IFO (6163)

CBS

CBS

IFO (6164)

CBS

SUBSTRATE



21 -hydroxy-4 -p regnene -3 ,11 ,20 -tr ione

17ö, 21 -dihydroxy -4 -p regnene-3,20-dione












REACTION

11a-OH

17a-OH

17a-OH

-

oxidation -products not identified

-

-

-

-

oxidation -p roduc t s not identified






R E F .

M-600

M-600

M-581; M-600

S-849

K-472

S-849

K-472

K-472

K-472

K-472

K-472

K-472

K-472

K-472

K-472

TABLE I I I

Transformat ions by Genus: CERCOSPORA

339

SPECIES

fusca

hibsci-cannabini

i tal ica

kaki

kikuchii (see genus Ce rcospo r -

ina)

lagenarium

macrospora

1 malvacearum

medicaginis

melongenae

melonis

SOURCE

CBS

KAG

CBS

CBS

FRI

NARI

TNAES

CBS

CBS

CBS

KAG(C-36)

CBS

SUBSTRATE

17a,21-dihydroxy-4-pregnene-3,20-dione


17«, 21 -d ihydroxy-4-pregnene-3,20-dione

17a,21 -dihydr oxy -4 -pregnene -3,20-dione

17a, 21-dihydr oxy-4-p regnene-3 ,20-d ione

17o,21 -d ihydroxy-4-pregnene-3,20-dione

17a, 21 -dihydr oxy -4 -pregnene -3,20-dione






9a -hyd roxy -4 -and ros t ene -3 ,17 -dione


14a-hydroxy-4-andros tene-3,17-dione

REACTION





-

-

oxidation-products not identified


-

11a-OH

9a,12a-diOH

9a,14a-diOH

9a,15/3-diOH

9a,18-diOH

12a-OH

14a-OH

15/3-OH

18-OH

9a-OH

9a-OH

R E F .

K-472

K-472

K-472

K-472

S-849

S-849

S-849

K-472

K-472

K-472

K-472

K-473

K-473

K-473

K-473

K-473

K-473

K-473

K-473

K-473

K-473

340

TABLE I I I

T r a n s f o r m a t i o n s by G e n u s : CERCOSPORA

SPECIES

melonis

musae

musa rum

nicotianae

oryzae

ros icola

sc i rpicola

s e sami

taiwanensis

vaginae

violae

zebrina

zinniae

SOURCE

CBS

CBS

CBS

CBS

CBS

FRI

NAH

CBS

CBS

IFO(6165)

CBS

CBS

CBS

CBS

KAG

SUBSTRATE

15/3 -hydr oxy -4 -androstene -3,17-dione














17a, 21 -dihydroxy -4 -pregnene-3,20-dione


REACTION

9a-OH

8j3-OH;15j3-OH

-

-


-

l i a - O H

-

-

l i a - O H

X-OH; Δ4 — 5ξ-Η

-



-

-

11a-OH

11/3-OH

R E F .

K-473

K-472; K-473

K-472

K-472

K-472

K-472

S-849

S-849

K-472

K-472

K-472

K-472

K-472

K-472

K-472

K-472

K-472

K-472

341


T r a n s f o r m a t i o n s by Genus: CERCOSPORELLA CERCOSPORINA CHAETOCLADIUM CHAETOMELLA

(Imperf. - Moniliales) (Imperf. - Moniliales) (Phyco. - Mucorales) (Imperf. - Sphaeropsidales)

SPECIES

CERCOSPORELLA herpotr ichoides

CERCOSPORINA

(see genus Cercospora)

CHAETOCLADIUM

1 brefeldii

CHAETOMELLA

1 oblonga

SOURCE

ATCC-12083

FRI

SSSR

ATCC-12718

SUBSTRATE


11/3,12ß-oxido-4-pregnene - 3 , 2 0 -dione

9a - f l uo ro -4 -p regnene -3 ,11 ,20 -t r ione

12a -methyl -4 -pr egnene - 3 , 1 1 , 20- t r ione






20-hydroxy-5a-pregnan-3-one

20-hydroxy-5i3-pregnan-3-one





6ß- f luoro-17a-hydroxy-4-preg-nene-3 ,20-d ione

6a -fluoro -17a, 21 -dihydr oxy -16 -méthylène -4 -pregnene - 3 , 2 0 -dione

REACTION

21-OH

21-OH

21-OH

21-OH

21-OH

-

6/3-OH

l l ß - O H

l l ß - O H

11/3-OH

11/3-OH

11/3-OH

11/3-OH

l l ß - O H

11/3-OH

l l ß - O H

l l ß - O H

R E F .

L-490

L-490

L-490

L-490

L-490

S-849

E-224

S-789

S-789

S-789

S-789

S-789

S-789

S-789

S-789

H-391

A-7

kikuchii

342


Transformat ions by Genus: CHAETOMELLA CHAETOMIUM (Asco. - Sphaeriales)


oblonga

raphigera

ATCC-12718

ATCC-12719

CHAETOMIUM

cochloides NG

funicolum

QM-624

QM-33C

17a, 21 -d ihydroxy-1 ,4 -pregna-diene - 3 , 20-dione





20-hydroxy-5i3-pregnan-3-one




17a, 21-d ihydroxy-1 ,4 -pregna-d iene-3 ,20-d ione

4 ,6 -p regnad iene-3 ,20-d ione


24 -me thy l -5 ,7 ,22 -cho l e s t a t r i en -3/S-ol (sole carbon source)

l l / 3 , 1 7 a , 2 1 - t r i h y d r o x y - l , 4 -pregnadiene-3 ,20-d ione

17a-hydroxy-1 ,4-pregnadiene -20-one

17a, 21-d ihydroxy-1 ,4 -pregna-d iene-3 ,20-d ione

1 1/3 -fluor o- 17α, 21 -dihydroxy -9α- iodo-16α-methy l -1 ,4 -pregnadiene -3 ,20-dione

l l /3- f luoro-17a ,21-dihydroxy-9a-iodo-16/3-methyl - l ,4 -pregna-d iene-3 ,20-d ione

17a, 21-d ihydroxy-1 ,4 -pregna-diene -3 , 11 ,20 - t r iene

17a, 21 -dihydroxy -16a - methyl -1,4 -pregnadiene - 3 , 1 1 , 2 0 -t r ione

11/3-OH

utilization

utilization

3-OH

6/3-OH

3-OH

6/3-OH

6/3-OH

3-OH

6/3-OH

S-789

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

S-789

S-789

S-789

S-789

S-789

S-789

S-789

S-789

S-789

S-789

S-793c

S-793c

C-108

C-108

C-108

N-691

N-691

C-108

N-690; N-692

343



CHAETOMIUM CHALARA

CHLORELLA CHOANEPHORA

CHROMOBACTERIUM

(Imperf. - Maniliales) (Chlorophyta - Chlorococcales) (Phyco. - Mucorales) (Schizo. - Eubacter ia les)

SPECIES

globosum

species

succineum

CHALARA

my coder ma

CHLORELLA (Algae)

1 pyrenoidosa

species

CHOANEPHORA

1 cucurbi ta rum

CHROMOBACTERIUM

1 violaceum

SOURCE

FRI

wise

NRRL

QM(1044)

FRI

UM(C-37-2)

NG

SSSR

NG

SUBSTRATE


3/3,5/3,14/3-trihydroxy-19-oxo-20(22)-cardenolide

plant saponins

17a -hydroxy- l , 4 -p regnad iene -3,20-dione


3/3 -hydroxy - 5 -androsten -17 -one



5-cholesten-3/3-01



5 -cholesten -3/3-ol (sole carbon source)

REACTION

Δ1; l l a - O H

3/3-OH-»3-C=0; 5/3-OH—Δ4

-6/3-OH

-

reduction to 4 products

1 7 - C = 0 -17/3-OH

toxic (but cul ture could be adapted to sub -s t ra te )

-20-C=O -» 20ß-OH

11α-OH; 11/3-OH; 6/3-OH

R E F .

S-849

S-891

K-478

C-108

S-849

G-321

G-321

G-321; G-322

G-321

V-1045

E-224

T-1030

344


T r a n s f o r m a t i o n s by Genus: CIRCINELLA CLADOSARUM

CLADOSPORIUM

(Phyco. - Mucorales) (Imperf. - Moniliales) (Imperf. - Moniliales)

SPECIES

muscae

s implex

spec ies

sydowi

umbel lata

CLADOSARUM

olivaceus (olivaceum)

CLADOSPORIUM

cladospor iodes

fulvam (fulvum)

he rba rum

SOURCE

VEB

SSSR

NRRL

VEB

FRI

NRRL

FRI

NRRL

TNAES (S-10-1)

FRI

SUBSTRATE


9a, 17/3-dihydroxy-4-androsten-3-one


Saponins (sapogenin - glycosides)


dione



Sarsasapogenin

Diosgenin



Saponins (sapogenin - glycosides)



REACTION

9a-OH

9a-OH; 17/3-OH -» 1 7 - C = 0

17/3-OH -1 7 - C = 0

6/3-OH;lla-OH; 11/3-OH

-

9a-OH

14a-OH

9a,14a-diOH

14a-OH

9a-OH

6j3-OH

-

-

-

11a-OH

hydrolysis of glycosides to aglycones

-

REF.

R-748

R-748

R-748

E-224

K-478

S-815

S-815

S-815

S-815

S-815

S-849

M-587

M-587

M-587

S-849

K-478

S-849

S-849

9α-hydroxy-4-pregnene-3,20-

TABLE I I I

Transformat ions by Genus: CLADOSPORIUM

345

SPECIES

he rba rum

res inae

SOURCE

NRRL

CBS

NRRL 2778

SUBSTRATE

Sarsasapogenin

Diosgenin





6a - f luoro-4-pregnene-3 ,20 -dione

6/3-fluoro-4-pr egnene -3 ,20 -dione


l l ß - h y d r o x y - 4 - p r e g n e n e - 3 , 2 0 -dione

6 a - m e t h y l - 4 - p r e g n e n e - 3 , 2 0 -dione

6/3- methyl -4 -pregnene - 3 , 2 0 -dione

6 a - f l u o r o - l i a - h y d r o x y - 4 - p r e g -nene-3 ,20-d ione

6/3-fluoro-1 la -hydroxy -4 - p r e g -nene-3 ,20-d ione

6 a - f l u o r o - l l ß - h y d r o x y - 4 - p r e g -nene-3 ,20-d ione

6/3-fluoro- l l ß -hydroxy -4 - p r e g -nene -3 ,20 -dione

6a -methyl -1 l a -hydroxy -4 - p r e g -nene-3 ,20-d ione

6ß -methyl - l i a -hydroxy -4 - p r e g -nene -3 ,20 -dione

6 a - m e t h y l - l l ß - h y d r o x y - 4 - p r e g -nene-3 ,20-d ione

REACTION

—

-

-

17ß-OH -» 1 7 - C = 0

17ß-Ac — 1 7 - C = 0

17ß-Ac -17ß-OH

17ß-Ac — 17ß-OAc


17ß-Ac -17ß-OAc




17ß-Ac -> 17ß-OAc

17ß-Ac -17ß-OAc


17ß-Ac -17ß-OAc

17ß-Ac -» 17/3-OAc



17ß-Ac -17ß-OAc

17ß-Ac -» 17ß-OAc

R E F .

M-587

M-587

M-587

F-254

F-254

F-254

F-254

F-250

F-250

F-250

F-250

F-250

F-250

F-250

F-250

F-250

F-250

F-250

F-250

F-250

F-250

346


T r a n s f o r m a t i o n s by G e n u s : CLADOSPORIUM

CL AVARIA CLAVICEPS

CLITOCYBE

(Basidio. - Agaricales) (Asco. - Eypocreales) (Basidio. - Agaricales)

SPECIES

res inae

spec ies

CLAVARIA

mucida

CLAVICEPS

purpurea

CLITOCYBE

adirondackensis

ciavipes

odor a

[ species "C"

SOURCE

NRRL-2778

ATCC-13026

MCC(SF-52$

FRI

NG

AL(SS-43)

AL(G-107)

AL(H-21)

AL(G-8)

SUBSTRATE

6/3-methyl-l l /3-hydroxy-4-pregnene-3 ,20-d ione


6ö- f Iuoro -4 -p regnene-3 ,11 ,20-t r ione

6 j3-f luoro-4-pregnene-3 ,11,20-t r ione

6a -methy l -4 -p r e g n e n e - 3 , 1 1 , 20- t r ione

6 ß - m e t h y l - 4 - p r e g n e n e - 3 , 1 1 , 20- t r ione





3/3, 6/3, 8/3,14/3-tetrahydroxy-4,20,22 -bufatrienolide 6-aceta te 3-glucoside

3/3,14/3-dihydroxy-5/3-20(22)-cardenol ide-3- [g lucosyl -digitoxosy 1 -digitoxosy 1 -digitoxoside]





REACTION

17/3-Ac-17/3-OAc

17/3-Ac-17/3-OAc

17/3-Ac-17/3-OAc

17/3-Ac-17/3-OAc

17/3-Ac-17/3-OAc

17/3-Ac 17/3-OAc

1ξ-ΟΗ

7/3-OH

7/3-OK

7/3-OH

6/3-OH;llö-OH

3ß-[l\-gbicosiae] - 3/3-OH

glucosyl-digitoxosyl-digitoxosyl-digitoxoside — digitoxosyl-digitoxosyl-digitoxoside

-

-

-

-

REF.

F-250

F-250

F-250

F-250

F-250

F-250

S-941

S-941

M-570

M-570

S-849

S-936a

S-936a

S-825

S-825

S-825

S-825 J


T r a n s f o r m a t i o n s by G e n u S : CLOSTRIDIUM (Schizo.-Eubacteriales)

347

SPECIES

bifermentans

paraputrificum

1 perfringens

sporogenes

tertium

SOURCE

IMJ

IMJ

NG

IMJ

NG

IMJ

SUBSTRATE


4 -androstene -3,17 -dione

3a-hydroxy-5a-androstan-17-one

3ß-hydroxy-5-androsten-17-one

17/3 -hydr oxy -4 -andr osten - 3 -one

4-androstene-3,17-dione

l,4-androstadiene-3,17-dione

4-pregnene-3,20-dione


21-hydroxy-4-pregnene-3,20-dione acetate

17a, 21 -dihydroxy-4-pregnene-3,11,20-trione

17a, 21 -dihydroxy -4 -pr egnene -3,11,20-trione 21-acetate

3α, 7α, 12a-trihydroxy-5/3-cholanic acid

3/3-hydroxy -4 -andr osten-17-one


5-cholesten-3/3-ol

17/3-hydr oxy-4-andr osten-3-one




REACTION

-

-

-

Δ4-5/3-Η; 3-C=0^3a-OH

Δ^5β-Η; 3-C=0->3a-OH

Δ4^5β-Η

Δ ^ Η ; Δ4 - 5/3-H

l 4

Δ — H; Δ — 5/3-H; 3-C=0 —3a-OH

3-C=0— 3a-OH; Δ4 - 5/3-H

3-C=0-3a-OH; Δ4->5/3-Η

3-C=0-3a-OH; Δ4^5/3-Η

3-C=0^3a-OH; Δ4-5/3-Η

3-C=0->3a-OH; Δ4-5/3-Η

7a-OH—7-C=0

-

-

-

Δ4-5/3; 3-C=0-3a-OH

3-C=0-3a-OH; Δ4-+5/3-Η

3-C=0-3a-OH; Δ4-5/3-Η

3-C=0-»3a-OH; Δ4^5β-Η

REF.

S-822

S-822

S-822

S-822

S-823

S-822

S-824

S-824

S-824

S-823

S-823

S-823

S-823

S-823

N-675

S-822

S-822

S-914

S-823

S-823

S-823

S-823

348

T A B L E I I I TAXONOMY

Transformations by Genus: £ L ° J ™ D I U M

J COCHLIOBOLUS COKEROMYCES

COLLETOTRICHUM

(Asco. - Sphaeriales) (Phyco, - Mucoraies) (Imperf. - Melanconiales)

SPECIES

te r t ium

welchii

COCHLIOBOLUS

miyabeanus

COKEROMYCES

recurva tus

COLLETOTRICHUM

ant i r rh in i

de r r i d i s

gloeosporioides

linde muthianum

SOURCE

IMJ

NG

FAKU

FRI

CBS

Cornell (Plant P a t h -ology Dept0 )

CBS

TNAES

ATCC-12611

SUBSTRATE

1Ία,21 -d ihydroxy-4-pregnene-3 ,11 ,20 - t r ione

17a,21 -d ihydroxy-4-pregnene-3 ,11 ,20- t r ione 21-acetate

5~cholesten-3/3-oi

1Ία,21 -d ihydroxy-4-pregnene-3,20-dione

17a, 21 -dihydroxy -4 -p regnene-3,20-dione

20/3-hydr oxy - A-nor - 5a -p reg -nan-2-one

A-nor -5a -p regnane-2 ,20-d ione

A-nor -3 -p regnene-2 ,20-d ione


17/3-hydr oxy-4 -es t r en-3-one


pregnane-3 ,20-d ione


l l ß , 17a-d ihydroxy-18-nor-4-pregnene-3 ,20-d ione

9a-f luoro- l l /3 ,17a-dihydroxy-16a-methy l -1 ,4 -pregnad iene-3,20-dione

REACTION

3 - C = 0 - 3 a - O H ; Δ4-5/3-Η

3-C = 0 - 3 a - O H ; Δ4-5/3-Η

-

-

6/3-OH;lla-OH

17/3-Ac-17j3-OH; 5a-H -» 5a-OH

5a-H -» 5a-OH

6/3-OH

15a-OH

12/3-OH

12/3-OH; 17/3-OH -*17-C=0

11a-OH

21-OH unspecified products

21-OH unspecified products

21-OH

21-OH

R E F .

S-823

S-823

S-914

S-849

S-849

P-706a

P-706a

L-503a

F-285; F-287; F-288

D-152

D-152

S-849

H-324

H-324

A-12

M-598

TABLE I I I

Transformat ions by Genus: COLLETOTRICHUM

COLLYBIA

TAXONOMY

(Basidio. - Agaricales)

349

SPECIES

lindemothianum

phomoides *

*

pisi

1 species

COLLYBIA

dryophila

SOURCE

ATCC-12611

IAM

ATCC-12521

NARI

NG

OR

ATCC-12520

IAM

AL

SUBSTRATE

17a -hyd roxy - l , 4 -p r egnad i ene -3 ,11 ,20 - t r ione

17a -hydroxy-18-nor -4 -p regnene-3 ,11 ,20 - t r i one

1 la -hydroxy-16a- methyl -18 -nor -4 - p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e




4,9(11) -pregnadiene-3 ,20-d ione


6a-f luoro-16a, 17a, 21 - tr ihydroxy-4-pregnene-3 ,20-d ione 16 ,17 -acetonide

6a-f luoro-16a, 17a, 21- t r ihydroxy-4-pregnene-3 ,20-d ione 16 ,17 -cyclohexanonide

17a-a l ly l -17/3-hydroxy-4-es t ren-3-one

21-hydroxy-4 -p regnene-3 , 20-dione




REACTION

21-OH

21-OH

21-OH

-

11/3-OH

11/3-OH; l i a - O H

6/3,12a-diOH

6/3,X-diOH

9(11)

Δ —9j3,11/3-oxide; 6/3,12a-diOH

l i a - O H

l i a - O H

l l a - O H

16/3-OH

11/3-OH

l l a - O H ; 11^-OH

—

17/3-Ac^l7a-o x a - 1 7 - C = 0

R E F .

H-324

A-10; A-13

A - l l

S-849

T-1003

T-1003

F-277; F-279

F-277; F-279

F-277; F-279; F-280

S-849

D-159

D-159

S-950

T-1004

T-1004

S-849

S-825

350


T r a n s f o r m a t i o n s by Genus: COLLYBIA

CONIDIOBOLUS CONIOTHYRIUM

(Phyco. - Entomophthorales) (Imperf. - Sphaeropsidales)

SPECIES

velutipes

CONIDIOBOLUS

species

CONIOTHYRIUM

hel lebori

helleborine

SOURCE

FRI

NRRL

NRRL-1612

TNAES

SAG (078)

SQ ( mutant)

ATCC-12522

SUBSTRATE


Sarsasapogenin

Diosgenin



1 la, 21 -dihydroxy - 4 -pre gnene -3 ,20-dione




17a-oxa-D-homo-4-andros tene -3,17-dione



REACTION

-

-

-

-

2/3-OH

11α-OH

11α-OH

11/3-OH

12/3-OH

6β-ΟΗ

11/3-OH

12/3-OH

11/3-OH

6/3-OH

7a-OH

l l a - O H

11/3-OH

l l a - O H

l l ß - O H

REF.

S-849

M-587

M-587

M-587

W-1073

W-1073

S-849

R-749

R-749

R-749

R-749

R-749

T-993

F-281 ; F-282; T-994

F-281 ; F-282; T-994

T-1003; T-1004

T-1003; T-1004

T-1003; T-1004

F-288; R-749; T-993; T-1003; T-1004

351


TABLE I I I CONIOTHYRIUM

CONOCYBE COPRINUS

CORDYCEPS CORETHROPSIS

CORIOLUS

TAXONOMY

(Basidio«, - Agaricales) (BasidiOo - Agaricales) (Asco0 - Hypocreales) (Imperfo - Moniliales) (Basidio«, - Agaricales)

SPECIES

helleborine

species

CONOCYBE

sil igenoides

COPRINUS

a t romenta r ius (a t ramentar ius)

sobil iferus

CORDYCEPS

mi l i t a r i s

CORETHROPSIS

hominis

CORIOLUS

1 vers ico lor

SOURCE

ATCC-12522

NRRL-2476

NG

AL(G-75)

AL(G-63)

FRI

FRI

ATCC-13488

SUBSTRATE

1 la, 21 -dihydroxy - 1 , 4 -pr egna -d iene-3 ,20-d ione



17cc-hydroxy-4-pregnene-3,20-dione

11/3,1 la -dihydroxy -4 -pregnene -3,20-dione







REACTION

11/3-OH

21-OH

21-OH

21-OH

21-OH

11«-OH

-

—

6/3-OH; 11a-OH

-

6ß-OH

14a-OH

15/3 -OH

REF.

T-1004

D-186

D-186

D-186

D-186

C-113

S-825

S-825

S-849

S-849

B-63

B-63

B-63

352


T r a n s f o r m a t i o n s by Genus : CORTICIUM (See Rhizoctonia)

(Basidio. - Agaricales)

Other Synonyms - Hypochnus and Pellicularia

SPECIES

centrifugum

centrifugus

graminum

mic rosc le ro t i a

prac t ico la

SOURCE

ATCC-11908

FAHU

FRI

NARI

CMI

NRRL-2727

CMI

SUBSTRATE



17a, 21-dihydroxy-4-pr egnene -3,20-dione





17a, 21 -d ihydroxy- l , 4 -p regna-d iene-3 ,20-d ione





17a, 21-d ihydroxy-4-pregnene-3,20-dione 21-aceta te


17a, 21-d ihydroxy-4-pregnene-3,20-dione 21-aceta te




17a, 21 -d ihydroxy- l , 4 -p regna-d iene-3 ,20-dione

REACTION

1 6 - C = 0 ; 1 7 - C = 0 -17/3-0H

16ß-OH; 1 7 - C = 0 -» 170-OH

-

2/3-OH;6j3-OH; 11a-OH

-

11-OH

11-OH

l l a - O H ; l l / 3 - O H

11-OH

19-OH

19-OH

19-OH

l l ß - O H

l lß-OH;21-OAc - 2 1 - O H

19-OH

19-OH; 21-OAc -»21 -OH

11-OH

11-OH

11a-OH; 11/3-OH

11-OH

R E F .

D-166

D-166

S-849

S-849

S-849

H-349

H-349

H-349

H-349

H-350

H-350

H-350

H-350

H-350

H-350

H-350

H-349

H-349

H-349

H-349

TABLE I I I

353

T r a n s f o r m a t i o n s by G e n u s : CORTICIUM

SPECIES

prac t ico la

roefsi i

sa lmonicolar

sasak i i

SOURCE

NRRL-2724

FAKU

FAKU

ATCC-13269

CMI

IFO

IFO( 5254)

NG

SUBSTRATE





17a, 21 -dihydroxy-4-pr egnene-3,20-dione

17a, 21 -d ihydroxy-1 ,4 -p regna-d iene-3 ,20-d ione




17a, 21 -d ihydroxy-1 ,4 -p regna -d iene-3 ,20-d ione




REACTION

l l ß - O H

-

—

l l ß - O H

l l ß - O H

l l ß - O H

1 1 - C = 0 (via l lß -OH)

11-OH

11-OH

11a-OH; 11/3-OH

11-OH

11a-OH

l l ß - O H

19-OH

6ß-OH

l i a - O H

l l ß - O H

l l ß - O H ; l l - C = 0 (via l l ß -OH)

Δ1; l l ß - O H

19-OH

19-OH

R E F .

H-350

S-849

S-849

H-350

H-350

H-350

H-350

H-349

H-349

H-349

H-349

H-347

H-347

H-347; N-660

H-327

H-325; T-954

H-325; T-954

H-327

H-327

H-325; H-326; T-954

N-672

354


TABLE I I I

CORTICIUM CORTINARIUS

CORTINELLUS CORYNEBACTERIUM

TAXONOMY

(Basidio. - Agaricales) (BasidiOo - Agaricales) (Schizo, - Eubacteriales)

SPECIES

solani (see vagum)

spec ies

vagium

vagum (see solani)

CORTINARIUS

evernius

CORTINELLUS

shiitake

CORYNEBACTERIUM

equi (in mixed cul ture with Tr ichomonas foetus)

(in mixed cul ture with Tr ichomonas foetus)

(in mixed cul ture with Tr ichomonas foetus)

fascians

helvolum (nomen confusum -see mediolanum and Flavobacter ium helvolum)

SOURCE

IFO(6251)

IAM(B-57, B-60 ,B-64)

S

IAM

IFO(6192)

AL(C-351)

FAKU

ATCC-10146

IAM

IAM

NG

SUBSTRATE

1 Ία, 21 -dihydroxy -4 -pregnene -3,20-dione







l l / 3 -hyd roxy -4 -e s t r ene -3 ,17 -dione

4 - e s t r e n e - 3 , 1 1 , 1 7 - t r i o n e





17a-methyl-4-andros tene-3/3 ,17ß-diol

REACTION

Δ1; 6/3-OH

-

11a-OH

11a-OH

11a-OH

11/3-OH

19-OH

Δ4—5a-H

11a-OH

1

Δ ; enol0

1

Δ ; enol.

1

Δ

—

-

3/3-OH->3-C=0; Δ 5 - Δ 4

3/3-OH—3-C=0: Δ —>Δ

R E F .

H-348

S-849

S-849

S-840

H-350

H-350

H-350

S-825

S-849

S-830

S-830

S-830

S-849

S-849

M-546

M-546

TABLE I I I

T ransformat ions by Genus: CORYNEBACTERIUM

355

SPECIES

helvolum

(nomen confusum -see mediolanum and Flavobacter ium helvolum)

hoagii

SOURCE

NG

ATCC-7005

IAM

SUBSTRATE


11/3-hydroxy-19-nor-4-pregnene -3,20-dione

l l ß , 17a-d ihydroxy-19-nor -4-p regnene-3 ,20-d ione

l l ß , 2 1 - d i h y d r o x y - 1 9 - n o r - 4 -pregnene-3 ,20-d ione

1 9 - n o r - 4 - p r e g n e n e - 3 , 1 1 , 2 0 -t r ione

17a-hydroxy-19-nor -4 -p regnene-3 ,11 ,20 - t r ione


9 a - c h l o r o - l l ß - h y d r o x y - 4 -pregnene-3 ,20-d ione

9 a - b r o m o - l l ß , 2 1 - d i h y d r o x y -4-pregnene-3 ,20-d ione 21-acetate

9 a - c h l o r o - l l ß , 17a-dihydroxy-4-pregnene-3 ,20-d ione

9 a - c h l o r o - l l ß , 2 1 - d i h y d r o x y - 4 -pregnene-3 ,20-d ione

11β, 17α, 21 - t r ihydr oxy -4 - p r e g -nene -3 ,20-dione

9 a - f l u o r o - l l ß , 1 7 a , 21- t r ihydroxy-4-pregnene-3 ,20-d ione

9 a - f l u o r o - l l ß , 1 4 a , 1 5 ß , 1 7 a , 2 1 -pentahydroxy-4-pregnene-3,20-dione

4 -pregnene-3 ,20-d ione 20-cycloethyleneketal

9 a - b r o m o - 4 - p r e g n e n e - 3 , 1 1 , 2 0 -t r ione

9a -ch loro-4 -pregnene - 3 , 1 1 , 2 0 -t r ione


REACTION

3 ß - O H ^ 3 - C = 0 ; Δ —»Δ

1

Δ ; enolo

1

Δ ; enol.

1

Δ ; enol.

Δ ; enol.

1

Δ ; enol.

1

Δ 1

Δ

Δ ; 21-OAc -> 21-OH

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

Δ

1

Δ

1

Δ

R E F .

M-546

H-386

H-386

H-386

H-386

H-386

F-251

H-379

N-668

H-379

N-668

N-665; N-670

N-669

N-669

F-251

H-379

H-379

S-849

356

TABLE I I I

Transformat ions by Genus: CORYNEBACTERIUM

SPECIES

mediolanum

(in mixed cul ture with Cunninghamella blakesleeana[Hß-OH])

pseudodiphtheri t icum *

*

*

simplex (see genus -Ar throbacter )

SOURCE

NG

NG

ATCC-6946

SUBSTRATE

3/3-hydroxy -5 -andros ten-17-one


5-androstene-3/3,16a, 17/3-triol

l /3,3/3-dihydroxy-5-pregnen-20-one

3/3,21-dihydroxy-5-pregnen-20-one 21-aceta te

3 /3 ,17a,21- t r ihydroxy-5-pregnen-20-one

3/3 ,17a,21- t r ihydroxy-5-pregnen-

3/3 ,17a,21- t r ihydroxy-5-pregnen-20-one 3 ,21-diace ta te

1 ,3 ,5(10)-es t ra t r iene-3,17/3-diol


5-choiesten-3/3-ol (sole carbon source)

A -nor -17/3-hydroxy -3 -androsten -2-one


17/3-hydroxy-4-estren-3-one aceta te

REACTION

3 /3-OH-3-C=0; Δ 5 - Δ 4

3/3-OH->3-C=0; Δ 5 - Δ 4

3 /3 -OH-3-C=0; Δ5-*Δ4

3 /3 -OH-3-C=0; Δ 5 - Δ 4

3 /3 -OH-3-C=0; Δ 5 ^ Δ 4 ; 21-OAc -»21-OH

Δ5->Δ4 ; 3/3-OH ->3-C=0

Δ5-*Δ4; 3/3 -OH ->3-C=0; 21-OAc-+21-OH

Δ 5 ^ Δ 4 ; 3/3-OAc ->3-C=0; 21 -OAc-*21 -OH

17/3-OH-^17-C=0

Δ 5 - Δ 4 ; 3/3-OH ->3-C=0

Δ 5 ^ Δ 4 ; 3/3-OH ->3-C=0;17/3-OH^17-C = 0

-

9α-ΟΗ; 17/3-OH - 1 7 - C = 0

1

Δ ; enol.

Δ ; enol. 17/3-OH -» 17-C = 0

17/3-OH -» 17-C = 0

Δ*; enol

1ξ-ΟΗ

R E F .

M-591

M-591

A - l

ß - 7 7

M-541; M-544

S-920

S-920

S-920

Z-1133

Z-1133

Z-1133

T-1033

S-885

C-128; K-487; K-488

K-487; K-488

K-487; K-488

G-315; K-487; K-488

G-315; K-487

20-one 21 -acetate

TABLE I I I

T r a n s f o r m a t i o n s by Genus : CORYNEBACTERIUM

357


simplex (see genus -Arthrobacter)

ATCC-6946 10/3,17j3-dihydroxy-4-estren-3-one

9/3, ll/3-oxido-4-estrene-3,17-dione

9a-bromo-4-estrene -3,11,17-trione

4,7-estradiene-3,17-dione

4,6 -estradiene -3,17 -dione

5-androstene-3ß, 17/3-diol

1 la - methyl -16 - méthylène - 5 -androstene-3/3,17/3-diol

3/3 -hydroxy -5 -andr osten -17 -one


17a-bromethinyl-17/3-hydroxy-4-androsten-3-one acetate

1 la -chlor ethinyl-17/3 -hydroxy -4-androsten-3-one acetate

1 la -ethinyl- 17/3-hydroxy -4 -androsten-3-one

17a-ethyl-17/3-hydroxy-4-androsten-3-one

Δ ; enol, D-150

1

Δ ; enol.

1

Δ ; enol.

1

Δ ; enol.

1

Δ ; enol. 1 5 4

Δ ; Δ ->Δ ; 3/3-OH-3-C;

3/3-OH->3-C= Δ 5 - Δ 4 ; 17/3-- 1 7 - C = 0

= 0

= 0 ; OH

Δ ; 3/3-OH -» 3-C = 0 ; 17/3-OH ^ 7 - Ç = 0 ; Δ ^ Δ

1 5 4

Δ ; Δ ->Δ ; 3/3-OH-»3-C=

3ß-OH-»3-C= Δ 5 - Δ 4

Δ1

17/3-OH — 1 7 - C = 0

Δ1; 17/3-OH 1 7 - C = 0

1

Δ

1

Δ

1

Δ

1

Δ

= 0

= 0 ;

R-762

R-762

B-72; Z-1126; Z-1127

Ζ_-Λ127

C-128; N-665; N-670

C-128

C-128; N-665

B-76

C-128; N-665; N-670

C-128; N-665; N-670;

. S-890

C-128

C-128; N-665

0 -694 ; 0 -695

0 -694 ; 0 -695

N-665; N-670

N-677a

358

TABLE I I I


SPECIES

simplex (See genus -Ar throbacter )

SOURCE

ATCC-6946

SUBSTRATE

2/3,17/3-dihydroxy-4-androsten-3-one diacetate

17/3-hy dr oxy -17a - methy I - 4 andros ten-3-one

17a-bromethinyl-6a-chloro-17/3-hydroxy-4-andros ten-3-one aceta te

17a-bromethinyl-6a-f luoro-17/3-hydroxy-4-andros ten-3-one aceta te

6o -chlor o- 17α -chlor ethinyl-17/3-hydr oxy -4 -andr osten -3 - one aceta te

17α-chlor ethiny I-6α-fluor 0-17/3-hydr oxy-4-andr os ten-3-one aceta te

17α-ethyl-11/3,17/3-dihydroxy-4-andros ten-3-one

12a-fluoro-l l /3,17/3-dihydroxy-4-andros ten-3-one

11/3,17/3-dihydroxy-17α-me thy!-4 -andros ten-3-one

17/3-hydroxy-17a-methyl-16-methylene-4-andros ten-3-one

9a, l l /3-dichloro-17/3-hydroxy-17a-methyl -4-andros ten-3-one

9a -b romo-17a-e th iny l - l l /3 , 17/3-dihy dr oxy -16a - me thy 1 - 4 -andr os ten-3-one

9a-chIoro-17a-ethinyl- l l /3 ,17/3-d ihydroxy-16a-methyl -4-andros ten-3-one

17a- ethiny 1- 16a -ethyl -9a -fluor o-11/3,17/3-dihydroxy-4-andro-s ten-3-one

17a - ethiny 1-9a-fluor o -11/3,17/3-dihydroxy -16a-methyl -4 -andros ten-3-one

17a-ethinyl-16a-ethyl-17/3-hydroxy-9/3, l l ß - o x i d o - 4 -andros ten-3-one

REACTION

2/3-OAc-»2/3-OI^ 17/3-OAc — 1 7 - C = 0

1

Δ

1 LA

1

Δ

1

Δ

1

Δ

1

Δ

Δ ; 17/3-OH -» 1 7 - C = 0

1

Δ 1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

R E F .

H-399

N-665; N-667a; N-670

0 -694 ; 0 -695

0 -694 ; 0-695

0-694 ; 0 -695

0-694 ; 0 -695

N-667a

R-772

R-772

N-667a

B-76

G-308

O-701

O-701

O-701

O-701

O-701

TABLE I I I


359

SPECIES

simplex

(in mixed cul ture with Tr ichomonas gallinae)

SOURCE

ATCC-6946

SUBSTRATE

17/3 -hydroxy -16a - methyl -1 7a -(Γ -propiny 1)-9/3,11/3-oxido-4-andros ten-3-one

17/3-hydroxy-17a-methyl-4,9(11)-andr ostadien - 3 - one

17a-bromethinyl-6-chloro-17/3-hydr oxy - 4 , 6 -andr ostadien -3-one ace ta te

17a-bromethinyl-6-f luoro-17/3-hydroxy-4 ,6 -andros tad ien-3-one aceta te

6 -chlor o - l 7α -chlor ethinyl-17/3-hydroxy-4 ,6 -andros tad ien-3-one

17a-chlorethinyl-6-f luoro-17/3-hydr oxy - 4 , 6 -andr ostadien -3-one aceta te

6a -flu oro-17/3 -hydroxy -17a -m e t h y l - 4 , 9 ( l l ) - a n d r o s t a d i e n -3-one

11/3 -hydroxy -4 -andr ostene -3 ,17-dione

9a, l l / 3 -d ich lo ro -4 -andros tene -3,17-dione

1 l a -hydroxy -16a - methyl -4 -andr os tene-3 ,17-d ione

16a -n -butyl -17a - ethinyl -17/3 -h y d r o x y - 4 - a n d r o s t e n e - 3 , 1 1 -dione

16/3-n-butyl-17a-ethinyl-17/3-h y d r o x y - 4 - a n d r o s t e n e - 3 , 1 1 -dione

17/3 -hydroxy -16a - methyl - H a -i l ' -propiny 1) -4 -andros tene -3 ,11-dione

17a - ethinyl - 9a - fluor o -17/3 -hydroxy-16a-methy l -4 -andros tene -3 ,11-d ione

17a-e th inyl -16a-e thyl -9a- f luoro-17/3 -hydroxy -4 -andros tene -3 ,11-dione

REACTION

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

REF.

O-701

G-308

0 - 6 9 4 ; 0 -695

0 -694 ; 0 -695

0 -694 ; 0 -695

0 -694 ; 0 -695

G-308

C-128; N-666; N-667

S-830

G-308

R-752

O-701

O-701

O-701

O-701

O-701

360

TABLE I I I


SPECIES

simplex (in mixed cul ture with Tr ichomonas gallinae)

SOURCE

ATCC-6946

SUBSTRATE

4 -andr ostene -3 ,11 ,17 - t r ione

16/3-methyl -4-andros tene-3 ,11 , 17-tr ione

19-nor -4 -pregnene-3 ,20-d ione

1 9 - n o r - 4 - p r e g n e n e - 3 , 1 1 , 2 0 -t r ione

11/3,21-dihydroxy-19-nor-4-pregnene-3 ,20-d ione

11/3,17q, 21- t r ihydroxy-19-nor -4-pr e gnene-3,20-dione

11/3,1 la, 21 -trihydroxy-19-nor_-4-pregnene-3 ,20-d ione 11 , 21-diacetate

21-hydroxy-19-nor -4 -p regnene-3 ,11 ,20 - t r ione

17a, 21-d ihydroxy-19-nor -4-p r e g n e n e - 3 , 1 1 , 2 0 - t r ione

17a, 21-d ihydroxy-19-nor -4-p regnene -3 ,11 ,20 - t r i one 21-aceta te

3a, 17a, 21- t r ihydroxy-5a-pregnane-11 ,20-d ione

17a, 21-dihydroxy-5a-pr egnane -3 ,11 ,20 - t r ione

17a, 21 -dihydroxy -16/3- methyl -5a -pr egnane - 3 , 1 1 , 2 0 - t r ione

17a, 21 -dihydroxy -16/3 - methyl -5a-pr egnane-3 ,11 ,20- t r ione 21-aceta te

5-pregnene-3 j3,20/3-diol

3/3,17a, 21 - t r ihydroxy-5-p reg-nene-20-one 3 ,21-diace ta te

REACTION

1

Δ

1

Δ

1

Δ ; enol.

1

Δ ; enol.

1

Δ ; enol.

1

Δ ; enol.

1

Δ ; enol.

1

Δ ; enol.

1

Δ ; enol.

1

Δ ; enol.

-

-

1 4

Δ ; Δ 1

Δ

Δ ; 21-OAc -» 21-OH

1 4

Δ ; Δ ; 21-OAc—21-OH

5 4 1

Δ - Δ ; Δ ; 3 /3 -OH-3-C=0; 20/3-OH-* 20-C=O

1 5 4

Δ ; Δ - Δ ; 3 /3 -OAc-3-C=0; 21-OAc — 21-OH

R E F .

S-830

R-752

B-71 ; B-73

B-73

H-386

H-386

H-386

H-386

H-386

H-386

C-128

C-128

K-451

K-451

K-451

K-451

C-128; N-665; N-670

C-115; C-128; N-665; N-670

TABLE I I I

T r a n s f o r m a t i o n s by Genus·. CORYNEBACTERIUM

361


simplex ATCC-6946 3/3,17a, 21 -trihydroxy -5 -preg-nen-20-one 3,21-diacetate



4-pregnene-3,20-dione 20-cycloethyleneketal

lla-hydroxy-4-pregnene-3,20-dione



9α, llß-dibromo-4-pregnene-3, 20-dione

9a-bromo-ll/3-chloro-4-pregnene -3,20-dione

9a-bromo-ll/3-fluoro-4-preg-nene-3,20-dione

9a-bromo-ll/3-hydroxy-4-preg-nene-3,20-dione

9a-chloro-ll/3-fluoro-4-preg-nene-3,20-dione

ll/3-chloro-9a-iodo-4-preg-nene-3,20-dione

3/3-OAc—3-C=0; Δ 5 -Δ 4

3/3-OAc-3-C=0;| Δ5-Δ4; Δ1; 21-OAc-21-OH

3/3-OAc^3-C=0;| Δ5-Δ4; Δ1; 20-C=O^20/3-ΟΗ; 21-OAc -21-OH

Δ1; 3/3-ΟΗ-* 3-C=0

9α-ΟΗ

Δ (ketal pre-vents degrada-tion)

Δ ; 20-C=O 20j3-OH

C-128; N-665

C-115: C-128; N-665

C-115

N-665; N-670

F-251; H-399; T-1005

P-740; S-885

F-251

T-995; T-1001

T-995

N-665; N-670

H-389: N-671

R-754

R-754

R-754

H-379

R-754

R-754 1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

362

TABLE I I I


SPECIES

simplex

SOURCE

ATCC-6946

SUBSTRATE

9a, 11/3-dichloro-4-pregnene -3,20-dione

9a-f luoro -1Iß-hydroxy-4 -p reg -nene-3 ,20-dione

l l /3 - f luoro-9a- iodo-4-pregnene-3,20-dione

11/3,21-dihydroxy-4-pr egnene -3,20-dione



l l /3 -hydroxy-3 ,20-d ike to-4-pregnen-18-oic acid (18 -» 11) lactone

9a -b romo- l l j 3 ,17a -d i ch lo ro -4 -pregnene-3 ,20-d ione

17a-bromo-9a , l l /3 -d ich ioro-4-pregnene-3 ,20-d ione

9 a - b r o m o - 1 7 a - c h l o r o - l l ß - f l u o r o -4-pregnene-3 ,20-dione

9a -b romo- l l j3 -ch lo ro -17a-hydroxy-4-p regnene-3 ,20-dione acetate

9a -b romo -1 1/3 -f luoro- 17a-hydroxy-4-p regnene-3 ,20-dione aceta te

9a -b romo -11/3-f luoro -6a -methyl -4-pregnene-3 ,20-d ione

9a, 17a-d ib romo- l l /3 -ch lo ro -4-p regnene -3 , 20-dione

REACTION

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

2 0 - C = O -20/3-OH

20-C=O -> 20/3-OH; Δ1

1

Δ

1

Δ

1

Δ

X

Δ

1

Δ

1

Δ

1

Δ

1

Δ

R E F .

R-754

H-379

R-754

H-389; N-665; N-670; N-671

H-376

H-389; H-399; L-522; N-665; N-671

L-522

H-389; N-665; N-670; L-522

U-1044

R-761

R-761

R-761

R-761

R-761

R-754

R-761

TABLE I I I


363

SPECIES

simplex

SOURCE

ATCC-6946

SUBSTRATE

9a, l l /3 -d ibromo-17a-hydroxy-4-pregnene-3 ,20-d ione ace ta te

l l / 3 ,17a -d ib romo-9a - iodo-4 -pregnene-3 ,20-d ione

9a, l l / 3 -d ib romo-6a-methy l -4 -pregnene-3 ,20-d ione

9a-ch loro- l l /3 - f luoro-17a-hydroxy-4 -p regnene -3 ,20 -dione ace ta te

9a -ch lo ro - l l /3 - f luoro -6a -methy l -4 -pregnene-3 ,20-d ione

9a-chloro- l l /3-f luoro-6/3-methyl-4 -pregnene-3 ,20-d ione

l l /3 -ch loro-17a-hydroxy-9a-iodo-4-pr egnene-3,20-dione aceta te

l l /3 -ch lo ro -9a - iodo-6a-methy l -4 -p regnene-3 ,20-d ione

11/3 - chlor o-9a-iodo-6/3-methyl-4 -p regnene-3 ,20-d ione

l l j3 -ch loro-9a- iodo-17a-hydroxy-4-pregnene-3 ,20-d ione

9a, 17a-d ich loro- l l /3 - f luoro-4-p regnene-3 ,2 0-dione

9a, l l j3-dich. loro-17a-hydroxy-4-pregnene-3 ,20-d ione

9a, l l /3-d ichloro-17a-hydroxy-4-pregnene-3 ,20-d ione aceta te

9α, l l j3 -d ichloro-17a-hydroxy-4-pregnene-3 ,20-d ione caproate

9a, l l / 3 -d ich lo ro -6a -methy l -4 -pregnene-3 ,20-d ione

9a, 11/3-dichloro-6/3-methyl-4-pregnene-3 ,20-d ione

9a, 11 /3 ,17a- t r ich loro-4-preg-nene-3 ,20-d ione

9a- f luoro- l l /3 ,17a-d ihydroxy-4-pregnene-3 ,20-d ione

9a- f luoro- l l /3 ,21-d ihydroxy-4-pregnene-3 ,20-d ione

REACTION

Δ1

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

Δ1

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

R E F .

R-761

R-761

R-754

R-761

R-754

R-754

R-761

R-754

R-754

R-761

R-761

G-307

R-761

R-761

R-754

R-754

R-761

H-379· N-668

N-668

364

TABLE I I I


SPECIES

simplex

SOURCE

ATCC-6946

SUBSTRATE

1 l a , 21 -dihydroxy -1 7a -methyl -4-pregnene-3 ,20-d ione 21-aceta te


11/3,17a, 21- t r ihydroxy- 4 - p r e g -nene-3 ,20-d ione

(effeat of antibiotics-Ref«, B-37) (use of dr ied thalli-Ref0 F-231)

l l ß , 1 7 a , 2 1 - t r i h y d r o x y - 4 - p r e g -

11β, 17α, 21 - tr ihydroxy -4 -p reg -nene -3 ,20-dione 1 1 , 2 1 -diacetate


21-(N-acetyl amino)-9a- f luoro-11/3,17a-dihydroxy-4-pr eg -nene-3 ,20-d ione

17a-bromo-9a , l l ß - d i c h l o r o -21- f luoro -4 -p regnene-3 ,20-dione

9 a - b r o m o - l l ß - c h l o r o - 2 1 - f l u o r o -17a-hydroxy-4-pregnene-3,20-dione

9a-bromo-11/3-chlor o-21-fluor o-6a -me thy l -4 -p regnene -3 ,20 -dione

9a -b romo-6a , 11/3,21 - t r i f luoro-4-pregnene-3 ,20-d ione

9 a - b r o m o - l l ß , 2 1 - d i f l u o r o - 1 7 a -hydroxy-4-p regnene-3 ,20-dione

9a-bromo-11/3,21-dif luoro-17a-hydroxy-4-p regnene-3 ,20-dione caproate

9a -b romo-1 Iß , 17a, 21- t r ihydroxy-4-pregnene-3 ,20-d ione

REACTION

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

Δ1; 20 -C=O-* 20ß-OH

1

Δ

1

Δ

1

Δ

Δ1

1

Δ

1

Δ

1

Δ

1

Δ

R E F .

H-377

H-384; H-389; N-665; N-671

B-37; F-231; F-232; H-389; H-399; K-467; N-665; N-670; N-671

N-665; N-670

H-389

R-749

R-749

S-911

R-756

R-756

R-755

R-758

R-756

R-756

N-668

nene-3,20-dione 21-acetate

TABLE I I I


365

SPECIES

simplex

SOURCE

ATCC-6946

SUBSTRATE

9a ,17a -d ib romo- l l /3 ,21 -d i f luo ro -4-pregnene-3 ,20-d ione

9a, l l ß - d i b r o m o - 2 1 - f l u o r o - 6 a -me thy l -4 -p r egnene -3 ,20 -dione

9a -ch lo ro- l l /3 ,21-d i f luoro-17a-hydroxy-4 -p regnene -3 ,20 -dione

9a -ch lo ro - l l | 3 ,21 -d i f luo ro -6a -methyl-4 -pr egnene - 3 , 2 0 -dione

1 Iß-ch lor 0-21 -fluor o - l la -hydroxy-9a- iodo-4-pregnene -3,20-dione

l l /3 -ch loro-21- f luoro-9a- iodo-6 a - m e t h y l - 4 - p r e g n e n e - 3 , 2 0 -dione

9a-ch lo ro- l l /3 ,17α , 21 - tr ihydroxy-4-pregnene-3 ,20-d ione

7a -cyano- l l / 3 ,17a ,21 - t r ihydroxy-4-pregnene-3 ,20-d ione

7ß-cyano - l l ß ,17a ,21 - t r i hyd roxy -4-pregnene-3 ,20-d ione

16-chlor méthylène-11/3 ,17a ,21-t r i h y d r o x y - 4 - p r e g n e n e - 3 , 2 0 -dione

9a , l l / 3 -d ich lo ro -6a ,21-d i f luo ro -4-pregnene-3 ,20-d ione

9 a , l l ß - d i c h l o r o - 2 1 - f l u o r o - 1 7 a -hydroxy-4 -p regnene -3 ,20 -dione

9a, l l ß -d i ch lo ro -21 - f luo ro -17a -hydroxy-4-p regnene-3 ,20 -dione ace ta te

9 a , l l ß - d i c h l o r o - 6 a - f l u o r o - 2 1 -iodo-4-pregnene-3 ,20-d ione

9a, l l ß -d i ch lo ro -21 - f l uo ro -6a -me thy l -4 -p r egnene -3 ,20 -dione

9a, l l ß -d i ch lo ro -17a -hyd roxy-21- iodo-4 -p regnene -3 ,20 -dione

REACTION

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

R E F .

R-756

R-755

R-756

R-755

R-756

R-755

N-668

B-75

B-75

W-1084

R-758

R-756

R-756

R-758

R-755

R-756

366

TABLE I I I


SPECIES

simplex

SOURCE

ATCC-6946

SUBSTRATE

9a , l l j3 -d ich loro-21- iodo-6a-methy 1-4-pregnene-3 ,20-dione

9a- f luoro- l l j3 ,17a ,21- t r ihydroxy-4-pregnene-3 ,20-d ione

16- f luormethy lene- l l /3 ,17a ,21-t r ihydroxy-4-p regnene-3 ,20-dione

6a , l l / 3 ,21 - t r i f l uo ro -9a - iodo-4-pregnene-3 ,20-d ione

l l a ,17a ,21 - t r ihydroxy-16 /3 -methyl -4 -pregnene - 3 , 2 0 -dione

l lß ,17a ,21- t r ihydroxy-16 /3 -methoxy-4-p regnene-3 ,20-dione 21-aceta te

11/3,17α, 21 - t r ihy dr oxy -6 -méthyl -ène -4 -pregnene-3 ,20-d ione 21-aceta te

11/3,15/3,17«, 21 - t e t rahydroxy-4-pregnene-3 ,20-d ione

l l j3,16α, 17α, 21 - te t rahydroxy-4-pregnene-3 ,20-d ione

17a-bromo-9a , 11/3-dichloro-21- f luoro-6a-methy l -4-pr e gnene - 3 ,2 0 - dione

9 a - b r o m o - l l j 3 - c h l o r o - 6 a , 2 1 -dif luor o -17a - methyl - 4 -pregnene-3 ,20-d ione

9a-bromo-11/3-chlor o-21-f luoro-17a-hydroxy-6a-methyl -4-pregnene-3 ,20-d ione

9a -b romo- l l /3 -ch lo ro -21- f luoro -17a -hydroxy -6a -methyl -4 -pregnene-3 ,20-d ione aceta te

REACTION

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

y

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

R E F .

R-755

H-389; N-665; N-668; N-669; N-670; N-671

W-1084

R-758

C-109; 1-421

R-760

F-264

C-127

B-54; B-59; B-61

R-759

R-759

R-759

R-759


SPECIES

simplex

SOURCE

ATCC-6946

SUBSTRATE

17a -b romo-9a ,21 -d i ch lo ro -6a , 21-d i f luoro-4-pregnene-3 , 20-dione

9a -b romo- l l /3 ,21-d i f luo ro -17a-hydroxy-6a -me thy l -4 -p reg -nene-3 ,20-d ione

9a -b romo- l l / 3 , 21 -d i f l uo ro -17a -hydroxy-6a -me thy l -4 -p reg -nene-3 ,20-d ione ace ta te

9a -b romo- l l /3 ,21-d i f luoro -17a-hydr oxy - 6a - methyl - 4 -pr e g-nenê-3 ,20-d ione caproa te

9a -b romo-6a , 11/3,21-tr i f luoro-17a-hydroxy-4-p regnene-3 , 20-dione

9 a - b r o m o - 6 a , l l / 3 , 2 1 - t r i f l u o r o -1 l a -hydroxy-4 -p regnene -3 , 20-dione ace ta te

9 a - b r o m o - l l ß , 17a ,21- t r ihydroxy-16a -methyl -4 -pr egnene - 3 , 2 0 -dione

9a, 17a -d ib romo- l l / 3 - ch lo ro -21 -f luoro-6a-methy l -4 -p r egnene-3,20-dione

9a, l l j3-d ibromo-21-f luoro-6a , 17a -dimethy 1-4 -pr egnene -3 ,20-dione

l l /3 -ch loro-6a ,21-d i f luoro-17a-hydroxy-9a- iodo-4-pr egnene-3,20-dione

l l j3 -ch loro-6a ,21-d i f luoro-17a-hydroxy-9a- iodo-4-pr egnene-3,20-dione

9a-ch loro- l l j3 ,21-d i f luoro-6a , 17a-dimethy 1-4-pr egnene-3,20-dione

9a -ch lo ro - l l j 3 - f l uo ro -17a ,21 -d ihydroxy-2a -me thy l -4 -p reg -nene-3 ,20-d ione 21-ace ta te

l l^ -ch loro-21- f luoro-17a-hydroxy-9a - iodo -6a -me thy l -4 -p regnene -3,20-dione

11 ß - chlor o - 21 - fluor o -17a - hydr oxy-9a - iodo-6a -me thy l -4 -p r egnene-3,20-dione aceta te

REACTION

ï 1 Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

REF.

R-759

R-759

R-759

R-759

R-759

R-759

R-752

R-759

R-759

R-759

R-759

R-759

N-691

R-759

R-759

TABLE I I I

CORYNEBACTERIUM

367

368

TABLE I I I


SPECIES

simplex

SOURCE

ATCC-6946

SUBSTRATE

9a-ch lo ro - l l / 3 ,17a ,21 - t r ihydroxy-16a-methyI -4 -p regnene-3 ,20-dione

9a , l l j3 -d ich loro-6a ,21-d i f luoro-17a-hydroxy-4-pregnene-3 , 20-dione

9a , l l /3 -d ich lo ro-6a ,21-d i f luoro-17a-hydroxv-4-pregnene-3 , 20-dione aceta te

9 a , l l ß - d i c h l o r o - 6 a , 2 1 - d i f l u o r o -17α-hydroxy-4-pregnene-3 , 20-dione caproate

9a , l l j3 -d ich loro-6a ,21-d i f luoro-17a-methy l -4 -p regnene-3 , 20-dione

hydroxy-21 -iodo-4 -pregnene -3,20-dione

9a, l l /3-d ichloro-6a-f luoro-17a-hydroxy-21- iodo-4-pregnene -3,20-dione aceta te

9a , l l /3 -d ich loro-21- f luoro-17a-hydroxy-6a -methy l -4 -p reg-nene-3 ,20-d ione

9a, l l /3-dichloro-21-f luoro-17a-hydroxy -6a- methyl-4 -p r eg -nene -3 ,20-dione aceta te

9α, l l /3-dichloro-21-f luoro-17a-hydroxy-6α-methy l -4 -preg-nene-3 ,20-d ione caproate

9a, l l ß - d i c h l o r o - 6 a - f l u o r o - 2 1 -iodo-17a-methy l -4 -pregnene-3,20-dione

9a, l l |3 -d ichloro-21-f luoro-6a , 17a-d imethy l -4 -pregnene-3 , 20-dione

9a, l l j3-dichloro-17a,21-dihydroxy -2a -me thy l -4 -p regnene -3 ,20 -dione 21-aceta te

9α, 11/3-dichlor o - l 7α-hydroxy-21-iodo-6α-methyl -4-pregnene-3,20-dione

9a, 11/3-dichlor o - l 7a -hydroxy -21 -iodo-6a-methyl -4 -pregnene -3,20-dione aceta te

REACTION

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

REF.

R-752

R-759

R-759

R-759

R-759

R-759

R-759

R-759

R-759

R-759

R-759

R-759

N-691

R-759

R-759

9α, l lß-dichloro-6a-fluoro-17a-

TABLE I I I

T r a n s f o r m a t i o n s by G e n u s : CORYNEBACTERIUM

369

SPECIES

simplex

SOURCE

ATCC-6946

SUBSTRATE

9a, l l j3-d ichloro-21- iodo-6a , 17a -dimethyl-4 -pregnene -3 ,20-dione


9a- f luoro- l l j3 ,16a , 1 7 a , 2 1 - t e t r a -hydroxy-4 -p regnene-3 , 20-dione

9 a - f l u o r o - l l ß , 1 6 a , 1 7 a , 2 1 - t e t r a -hydroxy-4 -p regnene -3 ,20 -dione 16 ,21-diace ta te

6 a - f l u o r o - l l ß , 17a ,21- t r ihydroxy-16a -methyl -4 -pregnene - 3 , 20-dione

9a , l l / 3 -d i f l uo ro -17a ,21 -dihydr oxy - 2a - methyl - 4 -p regnene-3 ,20-d ione 2 1 -aceta te

l l j 3 ,17a ,21- t r ihydroxy-6a -methyl-16 -méthylène -4 -p regnene-3 ,20-d ione

l l / 3 ,17a ,21- t r ihydroxy-16a-methy 1 - 6 - méthylène - 4 -p regnene-3 ,20-d ione

9a-ch loro- l l j3 - f luoro-16a , 17a, 21 - t r ihydroxy -2a -methyl -4 -p regnene-3 ,20-d ione 2 1 -aceta te

9a -ch lo ro - l l / 3 - f luo ro -21 -hydr oxy - 2a - methyl -16a, 17a -i sopropyl idenedioxy-4-preg-nene-3 ,20-d ione ace ta te

6a- f luoro- l l /3 ,14a , H a ^ l - t e t r a -hydr oxy -16a - methyl - 4 -pr e g -nene-3 ,20-d ione

17a, 21 -dihydroxy -16/3 - methyl -5a -9(11) -p regnene-3 ,20-dione 21-aceta te

REACTION

1

Δ

1

Δ

Δ1; 2 0 - C = O -20/3-OH

20-C=O-20 /3 -OH

1

Δ

1

Δ

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

9(11)

Δ - 9 a , 11a-oxidejA1; Δ 4 ; 2 1 - O A c -- 2 1 - O H

9 ( H )

Δ - 9 a . 11a-oxide; Δ ; 21-OAc—21-OH

REF.

R-759

B - 6 1 ; G-296; H-399; S-908

S-908

G-296; S-908

B-57; B-59; B-60

U-1042

N-691

B-69

F-264

N-691

N-691

U-1042

C-138

C-138

370

TABLE I I I


SPECIES

simplex

SOURCE

ATCC -6946

SUBSTRATE


21 -hydroxy-4 -p regnene -3 ,11 ,20 -t r ione

9a - f luoro-17a-hydroxy-4-preg-n e n e - 3 , 1 1 , 2 0 - t r ione

9a - f luoro-21-hydroxy-4-pregnene - 3 , 1 1 , 2 0 - t r i o n e

17a, 21-dihydroxy-4-pregnene -3 ,11 ,20- t r ione

17a „21 -dihydroxy -4 -pr egnene -3 ,11 ,20 - t r ione 4-C1 4

17a, 21-dihydroxy-4-pregnene -3 ,11 ,20- t r ione 21-aceta te

9a -b romo-17a ,21-d ihydroxy-4 -p r e g n e n e - 3 , l l , 2 0 - t r i o n e

16a -n -butyl -17a, 21 -dihydroxy -4 - p r e g n e n e - 3 , l l , 2 0 - t r i o n e

16a-n - butyl -17a, 21-dihydroxy-4 -pr egnene - 3 , 1 1 , 2 0 - t r ione 21-aceta te

17α, 21 -dihydroxy -16 - méthylène -4-pr egnene-3 ,11 ,20 - t r ione

9a-ch loro-17a , 21 -dihydroxy- 4 -pr egnene - 3 , 1 1 , 2 0 - t r ione

7a-cyano-17a, 21-dihydroxy-4-p regnene -3 ,11 ,20 - t r i one

2a -fluoro -17a, 21 -dihydroxy -4 -p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e

9a-fluor o -17a, 21-dihydroxy-4-p r egnene -3 ,11 ,20 - t r ione

7/3-cyano-9a-fluoro-17a, 2 1 -d ihydroxy-4 -p regnene -3 ,11 ,20-t r ione

9a- f luoro- l l /3 ,16a , 17a, 20/3,21-pentahydr oxy -1 ,4 -pr egnadien -3-one

REACTION

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

Δ1; 2 0 - C = O ^ 20/3-OH

Δ1

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

20/3-OH -20-C=O

R E F .

H-379

N-665; N-670

H-379

N-668

H-389; N-665; N-670; N-671

H-389

C-120

N-665; N-670

N-668

N-690; N-692

N-690; N-692

M-558

N-668

B-75

H-401

H-379; N-668; N-669

B-75

G-294; G-296

TABLE I I I


371

SPECIES

simplex

SOURCE

ATCC-6946

SUBSTRATE

9a-f luoro- l l /3 ,16α, 17α,20/3,21-pentahydroxy-1 ,4 -pregnadien-3-one

3ß ,21-d ihydroxy-5 ,16-p regna-dien-20-one diaceta te

9a- f luoro- l l /3 , 16α, 170 ,21 - t e t r a -hydroxy -1 ,4 -pr egnadiene -3,20-dione

9a -b romo- l l / 3 ,17a ,21 - t r i hyd roxy - 4 , 6 - p r egnadiene-3 ,20-dione

6a, 9a-d i f luoro- l l /3 ,17a , 21 - t r i -hydr oxy -4 ,6 -pr egnadiene -3,20-dione

4,9(11)-pr egnadiene-3 ,20-dione

17a-bromo-4 ,9(11)-pregnadiene -3,20-dione

1 7 a - c h l o r o - 4 , 9 ( l l ) - p r e g n a d i e n e -3,20-dione

6ß- f luo ro -4 ,9 ( l l ) - p r egnad i ene -3,20-dione

21-f luoro-4,9(11)-pregnadiene -3,20-dione

17a -hydroxy-4 ,9 ( l l ) -p regnad iene -3 ,20-dione

17a-hydroxy-4,9(11)-pr egnadiene - 3 , 2 0 - dione capr oate

21 -hydroxy-4,9(11) -pregnadiene -3,20-dione

6a-methyl-4 ,9(11) -pregnadiene -3 ,20-dione

6/3-methyI-4,9( l l ) -pregnadiene -3 ,20-dione

17a-methy l -4 ,9 (11)-pregnadiene-3,20-dione

1 7 a - b r o m o - 6 a - f l u o r o - 4 , 9 ( l l ) -p regnad iene-3 ,20-d ione

1 7 a - b r o m o - 6 a - m e t h y l - 4 , 9 ( l l ) -pr egnadiene-3 ,20-dione

REACTION

Δ1 — H

1 5 4

Δ ; Δ ^ Δ ; 3 j3-OAc-3 - C = 0 ; 21-OAc ^ 2 1 - O H

Δ 1 - * H

Δ

Δ

Δ

Δ

Δ1

Δ

Δ

Δ1

Δ

Δ

Δ

Δ

Δ

Δ

Δ

R E F .

G-296

H-388; O-700

G-296

A-7

A-7

R-754; R-773

R-761

R-761

R-757

R-773

R-773

R-761

R-755

R-754; R-755

R-754

R-761

R-759

R-759

372

TABLE I I I


SPECIES

simplex

SOURCE

ATCC-6946

SUBSTRATE

6a - f luo ro -17a -hydroxy-4 ,9 ( l l ) -pregnadiene-3 ,20-d ione

6a - f l uo ro -21 - iodo -4 ,9 ( l l ) -p r egnadiene -3 ,20 -dione

2 1 - f l u o r o - 6 a - m e t h y l - 4 , 9 ( l l ) -pregnadiene-3 ,20-d ione

6a, 21-dif luoro-4,9(11)-pr egna-diene-3 ,20-dione

17a-hydroxy-4,9(11)-pregna-diene-3 ,20-dione cyclo-pentylpropionate

17a -hydroxy-21- iodo-4 ,9 ( l l ) -pr egnadiene -3 ,20-dione

17a -hydroxy-21- iodo-4 ,9 ( l l ) -pregnadiene-3 ,20-d ione aceta te

21 -hydroxy-16a -mercap to -4 ,9 ( l l ) -pr egnadiene-3,20-dione 16,21-diaceta te

2 1 - i o d o - 6 a - m e t h y l - 4 , 9 ( l l ) -pr egnadiene-3,20-dione

6 a , 1 7 a - d i m e t h y l - 4 , 9 ( l l ) -pregnadiene -3 ,20-dione

17a-bromo-6a , 21 -dif luoro-4, 9(11) -pr egnadiene - 3 , 2 0 -dione

17a-bromo-6a-f luoro-21- iodo -4,9(11) -pregnadiene - 3 , 2 0 -dione

17a -bromo-21-f luoro -6a -methyl -4,9(11) -p regnad iene -3 ,20-dione

17a-bromo-21- iodo-6a-methy l -4 , 9 ( l l ) - p r e g n a d i e n e - 3 , 2 0 -dione

9a, l l j3-dichloro-17a-hydroxy-4 ,9(11) -pregnadiene-3 ,20-dione cyclopentylpropionate

6a-f luoro-17a-hydroxy-21- iodo-4,9(11) -p regnad iene -3 ,20-dione

6a-f luoro-17a-hydroxy-21- iodo-4,9(11) -p regnad iene-3 ,20-dione aceta te

REACTION

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

R E F .

H-391

R-758

R-755

R-758

R-761

R-756

R-756

R-764

R-755

R-759

R-759

R-759

R-759

R-759

R-761

R-759

R-759

TABLE I I I


373

SPECIES

simplex

SOURCE

ATCC - 6946

SUBSTRATE

21 -fluor o -17a -hydroxy - 6a - methyl -4 ,9 (11) -p regnad iene-3 ,20-dione

21 -fluoro - 17a -hydroxy-6a -methyl - 4 , 9 ( l l ) - p r e g n a d i e n e - 3 , 2 0 -dione caproate

6a- f luoro-21- iodo-17a-methyl -4,9(11) -p regnad iene -3 ,20 -dione

21- f luoro-6a ,17a-d imethy l -4 , 9(11) -pregnadiene -3 ,20-dione

6a ,21-d i f luoro-17a-hydroxy-4 , 9 ( l l ) -p regnad iene -3 ,20 -d ione

6a ,21-d i f luoro-17a-hydroxy-4 , 9(11)-pregnadiene-3,20-dione aceta te

6a ,21-d i f luoro-17a-hydroxy-4 , 9(11)-pregnadiene-3 ,20-dione caproate

6a ,21-d i f luo ro -17a-methy l -4 ,9 ( l I -pregnadiene-3 ,20-d ione

17a - hy dr oxy - 21 - iodo - 6a - methy 1 -4 ,9 (11) -p regnad iene-3 ,20-dione

21 - iodo -6a ,17a -d ime thy l -4 ,9 ( l l ) -p regnadiene-3 ,20-d ione

17a,21-dihydroxy-6/3,16a-di-methyl -4 ,9(11) -pregnadiene-3,20-dione 21-ace ta te

17a,21-dihydroxy-6/3,16/3-di-methyl-4,9(11) -pregnadiene -3,20-dione 21-ace ta te

16 - f luo rme thy l - l l / 3 ,17a ,21 - t r i -hydroxy-4 ,15-pregnadiene -3,20-dione

l l ß , 1 7 a , 2 1 - t r i h y d r o x y - 1 6 - m e t h y l -4 ,15-p regnad iene -3 ,20-d ione

l l / 3 , 1 7 a , 2 1 - t r i h y d r o x y - 6 a , 1 6 - d i -methy l -4 ,15-pregnad iene -3,20-dione


17a-hydroxy-9/3,1 l ß - o x i d o - l , 4 , 6 -p regna t r i ene-3 ,20-d ione

REACTION

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

20-C=O — 20j3-OH

R E F .

R-759

R-759

R-759

R-759

R-759

R-759

R-759

R-759

R-756

R-759

N-691

N-691

W-1084

W-1084

B-69

H-388; O-700

G-303

374

TABLE I I I

T r a n s f o r m a t i o n s by Genus : TAXONOMY

CORYNEBACTERIUM CORYNESPORA (Imperfc - Moniliales)

CORYNEUM (Imperf. - Melanconiales)

SPECIES

simplex

species

xe rose

CORYNESPORA

casai icol i

CORYNEUM

cardinale

SOURCE

ATCC-6946

IFO(3530)

soil

NG

CMI(6302)

ATCC-13063t

SUBSTRATE

17a,21-dihydroxy-9j3, 11/3-oxido-1,4,6 -pregnat r iene - 3 , 2 0 -dione

5 -choles ten- 3/3-ol

Diosgenin

3a, 7a, 12a-tr ihydroxy-5/3-cholanic acid

3α, 7α, 12a-tr ihydroxy-5/3-cholanic acid

3 ,7 ,12- t r ike to -5ß-cho lan ic acid

5 -cholesten -3/3-ol

5 - choles ten- 3 j3-ol

Saponins (agave)


REACTION

2 0 - C = O -2 0/3 -OH

3/3-OH->3-C=0; Δ 5 - Δ 4

3/3-OH->3-C=0; Δ 5 - Δ 4

3/3-OH->3-C=0; Δ 5 - Δ 4 ; Δ1

3a-OH—3-C=p; 7a-OH— H: Δ : Δ4

3a-OH-3-C = 0 ; 7a-OH - Δ6; Δ4

3 a - O H - 3 - C = 0 ; 7 a - O H - H ; Δ4

3a-OH->3-C=0; Δ4

3a-OH—3-C=0

3 a - O H - 3 - C = 0 ; 7 α - Ο Η - Δ 6 ; Δ4

3a-OH—3-C=0; Δ4

7 - C = 0 - 7 a - O H ; Δ4

3/3-OH—3-C=0; Δ5->Δ4

-

3/3-glycoside (saponin) — 3/3-OH

11a-OH

R E F .

G-303

T-1005

N-665; N-670

N-665; N-670

H-358; H-367

H-367

H-367

H-367

H-367

T-974

T-974

T-975

T-975

C-136

T-1030

H-351

T-991

7 - C = 0 ->Δ 6

375


TABLE I I I

CORYNEUM CRINSPORIUM

CUCURBITARIA CUNNINGHAMELLA

TAXONOMY

(Imperf. - Moniliales) (Asco„ - Sphaeriales) (Phyco. - Mucorales)

SPECIES

cardinale

CRINSPORIUM

panorum

CUCURBITARIA

laburni

CUNNINGHAMELLA

africana

albida

bainier i

blakesleeana

SOURCE

ATCC-13063t

NAGAS

C

SSSR

SSSR

ATCC-9244

ATCC-8688a (Up John

H-334)

SUBSTRATE

17a, 21 -d ihydroxy-4-pregnene-3,20-dione 21-ace ta te


not given



6a -ch lo ro -17a ,21-d ihydroxy-4 -pregnene-3 ,20-d ione 2 1 -ace ta te

6 a - c h l o r o - 1 7 a , 2 1 - d i h y d r o x y - l , 4 -pregnadiene-3 ,20-d ione

6a-f luoro-16a, 17a, 21 - t r ihydroxy-1,4 -p regnad iene-3 ,20 -dione

6a-f luoro-21-hydroxy-16a, 17a-isopropyl idenedioxy-4-preg-nene-3 ,20-d ione

3a, 11/3,17a-tr ihydroxy-pregnan-20-one

3/3, 11/3,17a-tr ihydroxy-pregnan-20-one

11/3-hydroxy -pr egnane -3 ,20 -dione

11/3,17a-dihydroxy-5a-pregnane-3,20-dione

l l /3 ,21-d ihydroxy-5a-pregnane-3,20-dione

3a, 11/3 ,21- t r ihydroxy-5a-preg-nane-3 ,20-d ione

11/3,17a, 21 - t r ihydroxy-5a-pr eg -nane-3 ,20-d ione


REACTION

l l a - O H - 2 1 - O A c —21-OH

15/3-OH

17a-OH

l l a - O H ; 11/3-OH; l l - C = 0 ( v i a l l / 3 -OH) 6/3-OH; 11/3-OH; l l -C-=0(v ia 11/3-OH) l l /3-OH;21-OAc ^ 2 1 -OH

11/3-OH

11/3-OH

11/3-OH

9α-ΟΗ; 11/3-OH - 1 1 - C = 0

9α-ΟΗ; 11/3-OH - i i -c=o

9α-ΟΗ; 11/3-OH -»ii-c=o

9a-OH; 11/3-OH '■-* n-c=o

9a-OH; 11/3-OH ^n -c=o

9a-OH; 11/3-OH ->n-c=o

9a-OH; 11/3-OH - 1 1 - C = 0

l l / 3 - O H ; l l - C = 0 (via 11/3-OH)

R E F .

T-991

K-486

W-1106; W-1107

E-224

E-224

R-770

R-770

R-771

R-771

H-342

H-342

H-342

H-342

H-342

H-342

H-342

0-696

376

TABLE I I I

Transformat ions by Genus: CUNNINGHAMELLA

SPECIES

blakesleeana

(in mixed cul ture with Baci l lus sphaer icus -ATCC-7055[A1])

SOURCE

ATCC-8688a (Upjohn-H-334)

SUBSTRATE



11/3,17a -dihydr oxy -4 -pregnene -3,20-dione


(effect of nutr ients - Ref. 0 -696 and S-919)

(use of vitamin K to inhibit by -products - Ref. S-920)

(effect of ethanol and phenols -Ref. M-556)

(effect of enzyme inhibi tors -Ref. M-555)

(effect of ethanol and phenols -Ref. M-556)

(effect of environment and nutr ients)

19,21-dihydr oxy-4-pregnene-3,20-dione


11a,21-dihydroxy-4,17(20)-pregnadien-3-one

11/3,21-dihydroxy-4,17(20)-pregnadien-3-one

11α, 22 -dihydroxy -bisnor -4 -cholen-3-one

REACTION

9 a - O H ; l l a - O H -n-c=o 11/3-OH

14a-OH

ll/3-OH(0218)

9a-OH; 11/3-OH -n-c=o 6/3-OH

11/3-OH

11/3-OH; 11 - C = 0 (via 11/3-OH)

1 1 - C = 0 (via 11/3-OH); 6/3-OH; 14a-OH

—

11/3-OH

9a-OH

l lß -OH—11-C=0

9a-OH; 11/3-OH

^n-c=o 9a-OH

9a-OH; 11/3-OH -n-c=o 6/3-OH

R E F .

H-342

M-555

M-555

H-3 74

H-342

H-339; S-919

M-556; N-659; 0 -696 ; S-919; S-920

H-339; M-555; M-556; S-919

S-919

K-466

B-40

H-344

H-344

H-342

H-342

H-342; H-344

M-578

TABLE I I I


377

SPECIES

blakesleeana

(ATCC number 1 repor ted a s elegans 1 in catalog)

SOURCE

ATCC-8688b

ATCC-9245

SUBSTRATE

6a, 16a -d ime thy l -4 -p regnene-3 , 20-dione

16a, 17a-methy lene-4-pregnene-3,20-dione

6a-ch loro-16a , 17a-methylene-4-pregnene-3 ,20-d ione

6a-f luoro-16a, 17a-méthylène-4-pregnene-3 ,20-d ione

6ß-f luoro-16a, 17a-méthylène -4 -p regnene-3 ,20-d ione

6a-methyl -16a , 17a-méthylène -4 -pregnene-3 ,20-d ione

16a, 17a -mé thy lène -1 ,4 -p re gna-d iene-3 ,20-d ione

6a-f luoro-16a, 17a-méthylène -1 ,4-pregnadiene-3 ,20-d ione

6/3-fluoro-16a, 17a-méthylène-1,4 -pregnadiene -3 ,20-d ione

6a-methyl -16a , 17a-methylene-1 ,4-pregnadiene-3 ,20-d ione

16α, 17α-mé thy lène -4 ,6 -p regna-d iene-3 ,20-d ione

6-chloro-16a , 17a-méthylène-4 ,6 -pregnadiene -3 ,20-dione

6-f luoro-16a, 17a -mé thy lène -4 ,6 -pregnadiene-3 ,20-d ione

6-methyl-16a, 17a-méthylène-4 , 6 -pregnadiene -3 ,20-dione

1 6 a , 1 7 a - m e t h y l e n e - l , 4 , 6 - p r e g n a -t r i ene -3 ,20-d ione

6-f luoro-16a, 17a -me thy lene - l , 4 , 6 -p regna t r i ene -3 ,20 -d ione

6-methyl-16a, 17a -me thy lene - l , 4 , 6 -p r egna t r i ene -3 ,20 -d ione


17a, 21 -dihydroxy - 7 - methyl -4 -pregnene-3 ,20-d ione 21-ace ta te

REACTION

11/3-OH

llj3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

R E F .

S-923

C-92

C-92

C-92

C-92

C-92

C-92

C-92

C-92

C-92

C-92

C-92

C-92

C-92

C-92

C-92

C-92

M-641; M-645

B-33

378

TABLE I I I

T ransformat ions by Genus: CUNNINGHAMELLA

SPECIES

b lakes leeana (ATCC number repor ted as elegans in catalog)

(in sequential fermentation with Ophiobolus he rpo t r i -chus [21-OH] and Tr icothecium roseum [17a-OH])

(in sequential fermentation with

[17α -OH])

(in sequential fermentation with Tr icothecium r o s e u m [17Ö-OH] and Calonectr ia decora [A1])

(in sequential fermentation with Tr icothecium r o s e u m [17a-OH] )

(in sequential fermentation with Ophiobolus he r po t r i -c h u s [ 2 1 - O H ] a n d Tr icothecium r o s e u m [17a-OH])

* *

*

*

1 *

SOURCE

ATCC-9245

C

CBS

SUBSTRATE

17a ,21-d ihydroxy-4 ,14-pregna-d iene-3 ,20-d ione

17a ,21 -d ihyd roxy-4 ,9 ( l l ) -p r egna -d iene-3 ,20-d ione




d, 1-21-hydroxy-4-pregnene-3,20-dione

18 ,21-d ihydroxy-4-pregnene-3,20-dione

21-hydroxy-3 ,20-d ike to -4 -p reg-nen-18-a l

21 -hydroxy -3 ,20-d ike to-4 -p reg -nene-18-a l aceta te

1,4 -pr egnadiene -3 ,20-dione



REACTION

14

Δ —>14a,15a-oxide

11/3-OH; Δ " - » 14a,15a-oxide

9 (11)

Δ 7—9/3,11/3-oxide

11/3-OH; 11/3-OH

-n-c=o

11/3-OH; 11/3-OH - 1 1 - C = 0

11/3-OH; 11/3-OH

^n-c=o

d , l - d - l l / 3 - O H ; l l - C = 0 ( v i a 11/3-OH) + 1

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11a-OH

11/3-OH

l l / 3 - O H ; l l - C = 0 (via 11/3-OH)

6/3-OH

11/3-OH

R E F .

ß - 6 6 ; S-865

S-865

ß - 6 6

W-1106

W-1106

W-1107

W-1102

W-1100

W-1100

W-1100

W-1106

C-98

C-98

C-98

C-98

C-98 1

Tricothecium roseum

TABLE I I I

T r a n s f o r m a t i o n s by Genus : CUNNINGHAMELLA

379

SPECIES

blakesleeana

(Lendner)

(in sequential fermentation with Tr ichoderma glaucum [17a-OH] and Wojnowicia graminis - NRRL-2472 [21-OH])

1 *

1 *

1 *

1 *

1 * 1 * 1 * 1 *

1 * 1 *

SOURCE

CZAS

IFO

MCC

NG

OIAB(l)

OIAB(2)

PEU

QM-631

SUBSTRATE


3j3,14/3-dihydroxy-5/3-20(22)-cardenolide



(mechanism of hydroxylation)




4-pregnene -3 ,20-dione





4 -p regnene-3 ,20-d ione (method to obtain higher y i e ld s -dilution cul ture)

REACTION

11/3-OH

16/3-OH

11/3-OH

14a -OH

11/3-OH

11a-OH; 14a-OH; 6 ß , l l a - d i O H

l l a - O H

7/3-OH

lß,7/3-diOH; 5/3,7/3-diOH

3/3-OH^3-C=0

l l a - O H ; 14a-OH; 6/3,11a-diOH

6/3-OH

7/3-OH

1/3,7/3-diOH; 50,7/3-diOH

3 /3 -OH-3-C=0

l l a - O H

11/3-OH

l l / 3 - O H ; l l - C = 0 (via 11/3-OH)

6/3-OH

11/3-OH

11-OH

R E F .

T-1028

N-651

M-566

N-661

B-64

N-682

N-682

N-682

N-682

N-682

N-682

N-682

N-682

N-682

N-682

C-98

C-98

C-98

C-98

C-98

W-1066

380

TABLE I I I


SPECIES

blakesleeana

echinulata

*

*

*

*

*

(Thaxter - 7)

(In mixed cul ture with Bacil lus sphaer icus - ATCC-7055 [ Δ1])

1 1

SOURCE

SSSR

UC

VEB

SSSR

ATCC-1387

FRI

IPB

NG

NRRL

SUBSTRATE

1 7a, 21 -dihydroxy -4 -pregnene -3,20-dione


l l cz -hydroxy-4-pregnene-3 ,20-dione

6/3-methyI-4-pregnene-3,20-dione



3,20-dione


1 l a -hydroxy-4 -p regnene -3 ,20 -dione


17a, 21-dihydroxy-4-pre gnene-3,20-dione

17a, 21 - d ihydroxy-4-pregnene-3,20-dione




Sarsasapogenin

Diosgenin

4-dehy dr otigogenone

REACTION

l l / 3 -OH; l l -C = 0 (via 11/3-OH

11/3-OH

6/3-OH

l l ß - O H

11/3-OH

l l / 3 - O H ; l l - C = 0 (via 11/3-OH)

6/3,14a-diOH

l i a - O H

l i a - O H

l l a - O H

l l a - O H

l l a - O H

6/3-OH; l l a - O H

l l a - O H

11/3-OH

l l / 3 - O H ; l l - C = 0 (via l lß -OH)

6/3-OH

11/3-OH

l l a - O H

-

-

—

R E F .

E-224

E-202

E-202

L-520

M-601

M-601; M-636; M-641

S-811

E-224

Z-1125

Z-1125

Z-1125

Z-1125

S-849

C-98

C-98

C-98

C-98

C-98

K-466

M-587

M-587

M-587

echinata 17a,21-dihydroxy-4-pregnene-

TABLE I I I

T r a n s f o r m a t i o n s by Genus : CUNNINGHAMELLA

381

SPECIES

elegans (Lendner)

* * *

* *

1 *

homothallica

r a m o s a

SOURCE

C

CZAS

OIAB

SSSR

VEB

SSSR

CZAS

SUBSTRATE

15a-hydroxy-4-andros tene-3,17-dione

6a-f luoro-14a, 17α, 21-tr ihydroxy -16a- methyl -4 -p regnene-3,20-dione





14/3-hydroxy -3 -keto-5/3-20(22) -cardenolide



l i a , 17a ,21 - t r i hyd roxy-4 -p reg -nene-3 ,20-d ione


l l / 3 , 17a ,21 - t r i hyd roxy -4 -p reg -nene-3 ,20-d ione 21-aceta te

11/3,17α, 21 - t r i hyd roxy -1 ,4 -pr e gnadiene - 3,2 0 - dione




REACTION

11/3-OH

l l a - O H

11/3-OH

l l a - O H

11/3-OH

l l / 3 - O H ; l l - C = 0 (via 11/3-OH)

6/3-OH

11/3-OH

l l a - O H ; 14a-OH; 6/3, l la-diOH

6/3-OH; l l a - O H

7/3-OH

7/3-OH

l l a - O H ; 11/3-OH; 11-C^O (via l l ß -OH)

-

1 1 - C = 0 (via 11/3-OH)

2 1 - O A c -21-OH

11/3-OH-> l l - C = 0 ; 2 1 - O A c -»21 -OH

-

6ß,14a-diOH

6/3-OH; 11/3-OH; 1 1 - C = 0 (via 11/3-OH)

6/3-OH; l l a - O H ; 11/3-OH; 1 1 - C = 0 (via 11/3-OH)

R E F .

U-1043

U-1042

U-1042

C-98

C-98

C-98

C-98

C-98

N-682

N-682

N-682

N-682

E-224; E-225

E-225

E-225

E-225

E-225

E-225

S-811

E-224

C-98

382

TABLE I I I

T r a n s f o r m a t i o n s by Genus : CUNNINGHAMELLA CURVULARIA

TAXONOMY

(Imperf0 - Moniliales)

SPECIES

r a m o s a

species

ver t ic i l la ta

CURVULARIA

brachyspora (in sequential fermentat ion with Ophiobolus he rpo t r i -chus[21-OH])

(in mixed cul ture with Mycobacterium)

falcata *

(in sequential fermentation with Mycobacterium sp.

f al lax *

geniculata

SOURCE

SSSR

NRRL

P a r k e - Davis (M-2047)

SSSR

C

P F

C

QM-102H

VEB

C

VEB

IFO(6284)

SUBSTRATE


plant saponins

16α, 17α, 21 - [ 3 , 1 , 1 -2 -pyrazolino] 4 -p regnene-3 ,2 0-dione

17a,21 -dihydroxy -4-pregnene -3,20-dione


18-0X0-4-pregnene 3 ,20-dione


17a ,21 -d ihyd roxy -4 ,9 ( l l ) -pregnadiene-3 ,20-d ione

21-hydroxy-4-pregnene-3 ,20 -dione


17a, 21 -dihydroxy -4 -pregnene -3,20 dione



21-hydroxy-4-pregnene-3 ,20-dione



REACTION

6ß-OH; l l ß - O H ; l l - C = 0 ( v i a l lß -OH)

-l l ß - O H

l l a - O H ; l l ß - O H

l l ß - O H

l l ß - O H

l l ß - O H

9(H) Δ '-.9/3,11/3-oxide

7a-OH

l l ß - O H

l l ß - O H

l l ß - O H

l l ß - O H ; 14a-OH; 7 a , l l ß - d i O H ; 7a,14a-diOH; l l ß , 14a -d iOH; 6ß,14a-diOH

7a-OH

l l ß - O H ; 14a-OH; 7a, 14a-d i O H ; l l ß , 1 4 a -diOH

6ß-OH; l l ß - O H ; 14a-OH

R E F .

E-224

K-478

M-593

E-224

W-1106; W-1107

W-1107

S-868

S-865

M-585

S-878

S-878

S-868

Z-1132

M-585

Z-1132

K-469

1

Δ

TABLE I I I

T ransformat ions by Genus: CURVULARIA

383

SPECIES

geniculata

inaequalis

lunata

(in mixed cul ture with one or more of the following: Al te rnar ia pass i f lorae [Δ 1 1 λ

Calonectr ia decora[A Didymella lycopers ic i [ Δ 1 ] , Leptosphaer ia maculans [ l7a-OH ] , Ophiobolus he rpo t r i -c h u s [ 2 1 - O H ] , Tr icothecium r o s e u m [ l7o-OH|)

*

(in mixed cul ture with Leptosphaer ia maculans [17«-OH ] )

SOURCE

VEB (C)

VEB(XCI)

VEB-(XCXXXIII)

V E ß -(XCIV)

ATCC

ATCC-12017

C

SUBSTRATE







6/3-hydroxy-3a,5a-cyclopregnan-20-one

17a, 21 -dihydroxy -6a , 16a -d i -methyl - 4 - p r e g n e n e - 3 , 2 0 -dione 21-aceta te





6/3,21-dihydroxy-4-pregnene -3 ,20-dione

d, 1-17a, 21 -dihydroxy -4 -pregnene -3,20-dione

REACTION

11/3-OH; 14a-OH; 7a,14a-diOH; 6/3,14a-diOH; l l ß , 1 4 a - d i O H

11/3-OH; l l /3 ,14a-diOH

14a-OH; 6/3,14a-diOH; 7a,14a-diOH

11/3-OH; l l /3,14a-diOH

11/3-OH

11/3-OH

l l / 3 - O H ; l l - C = 0 (via 11/3-OH)

l l a - O H : metaboli te - X

l l ß - O H

l l ß - O H ; 21-OAc - 21-OH

l l ß - O H

7α-ΟΗ

11/3-OH

d , l - d - l l ß - O H + 1

l l ß - O H

d , l — d-l l /3-OH + 1

R E F .

Z-1132

Z-1132

Z-1132

Z-1132

C-98

C-98

C-98

C-98

W-1070

S-805

W-1106; W-1107

M-585

W-1106

W-1106

N-654

W-1102

384

TABLE I I I

Transformat ions by Genus: CURVULARIA

SPECIES

lunata

*

*

*

*

(in sequential ferment-ation with Actinoplanes missour i ens i s -Α Τ Ο Ο - Ι δ β δ ΐ Δ 1 ] )

SOURCE

C

EM

IFO (6286)

KAG(49)

LRL

MCC

NRRL-2380

SUBSTRATE

19 ,21-d ihydroxy-4-pregnene-3,20-dione

6a- f luoro-17a ,21-dihydroxy-16a-methyl -4 -pr egnene - 3,20 -dione

2 1 - h y d r o x y - l , 4 - p r e g n a d i e n e -3,20-dione

1 la -hydroxy -16 -méthylène -4 -p regnene-3 ,20-d ione

1 la, 21 -dihydr oxy -16 - méthylène -4-pregnene-3 ,20-d ione



14a ,17a ,21 - t r ihydroxy-4 -p reg -nene-3 ,20-d ione


6a- f luoro-17a ,21-d ihydroxy-16a-me thy l -4 -p regnene -3 ,20 -dione

17a, 21-dihydroxy-4-pregnene -3,20-dione (effect of nutr ients - t r a ce elements)


REACTION

11/3-OH

11/3-OH

14α-OH

11/3-OH

11/3-OH

11/3-OH

9α-ΟΗ

Πα-ΟΗ

11/3-OH

14α-ΟΗ

6/3-OH

11α-ΟΗ; 14α-ΟΗ

6/3,14a-diOH

7a,14a-diOH

7α-OH

6/3-OH

11/3-OH

11/3-OH

l l ß - O H

10/3-OH

l l ß - O H

14α-ΟΗ

10/3,11/3-diOH

R E F .

N-654

U-1042

U-1042

W-1106

B-68

M-558

K-469

K-469

K-469

K-469

K-469

K-469

K-469

K-469

K-469

K-469

M-536

M-536

D-192

D-150

D-150

D-150

D-150

TABLE I I I

T ransformat ions by Genus: CURVULARIA

385


lunata NRRL-2380 17a-ethyl-17/3-hydroxy-1,4-andros tad ien-3-one

17a -hyd roxy - l -5a -p regnene -3,20-dione ace ta te

1 7 a - m e t h y l - l - 5 a - p r e g n e n e - 3 , 20-dione

21 - f luo ro -19-nor -4 -p regnene -3,20-dione

17a-hydr oxy -19 -nor_-4 -pr egnene -3,20-dione


17a-bromo-4-pregnene - 3 , 2 0 -dione

1 la -chloro -4-pregnene - 3 , 2 0 -dione



6 /3-methyl -4-pregnene-3 ,20-dione

17a -b romo-6a - f l uo ro -4 -p reg -nene-3 ,20-d ione

1 la -bromo -6a -methyl -4 -pr eg -nene-3 ,20-d ione

6a - f luo ro -17a -me thy l -4 -p reg -nene-3 ,20-d ione

17a, 21-dihydroxy-4-pregnene -3,20-dione (compare reac t ion with C. lunata - IFO-6286-Ref. K-469)

(effect of ant ibiot ics - Ref. B-37o In mixed cul ture with Baci l lus sphaer icus - ATCC-7055 - Ref. K-444)

11/3-OH

11/3-OH

11/3-OH

N-677a

11/3-OH

11/3-OH

11]3-ΟΗ

11/3-OH

14α-ΟΗ

7a,14a-diOH

11/3-OH

11/3,14a-

11/3-OH

diOH

R-761 ; R-773

R-761

R-755

R-761 ; R-773

D-187

D-187

S-871

D-187

R-756; R-773

R-761

11/3-OH

l l /3,14a-diOH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

l l a - O H

S-871

S-876

S-871; S-875

R-754; R-757; R-773

R-759

R-756; R-759

R-759

K-443; K-469

B-37; K-443; K-444

386

TABLE I I I


SPECIES

lunata

SOURCE

NRRL-2380

SUBSTRATE

17a, 21 -dihydr oxy -4 -pr egnene -3,20-dione (compare reac t ion with C0 lunata - IFO-6286-Ref. K-469)

(in mixed cul ture with M. phlei - Ref. S-868)

(with cel l free enzyme)

(compare reac t ion with IFO-6286 - Ref. K-469)

(compare react ion with IFO-6286 - Ref0 K-469)

(effect of t r a c e e lements -solvents)

(compare react ion with IFO-6286 - Ref. K-469)

(effect of t r a c e e lements -so lven ts ; compare react ion with IFO-6286 - Ref0 -K-469)

(enzyme prepara t ion)

17a-hydroxy-21-methyl -4-pregnene-3 ,20-d ione

21-hydroxy-17a-methy l -4 -p reg-nene-3 ,20-d ione aceta te

1 la -hydroxy -16 -méthylène -4 -pregnene-3 ,20-d ione

6a, 17a-dimethyl -4-pregnene -3,20-dione

6/3-fluoro-17a-hydroxy-21-methyl-4-pregnene-3 ,20-d ione


REACTION

11/3-OH

11/3-OH

11/3-OH

14a-OH

6j3,14a-diOH

7a, l l j3-diOH

7a,14a-diOH

11/3,14a-diOH

20-C=O — 20/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH; 21-OAc — 21-OH

14a-OH;21-OAc — 21-OH

ll j6-OH;14a-OH; 21-OAc^21-OH

l l /3,14a-diOH; 21-OAc-»21-OH

R E F .

K-466; K-469

S-868; S-871; S-875; S-879

Z-1134

K-443; K-469; Z-1134

K-469

K-443

K-469; S-879

Δζ2; K-443; K-469; S-879; S-877

T-1017; Z-1134

H-391

H-377

B-68

R-759

H-391

A-3

A-3

A-4; A-5

A-3

TABLE I I I


387

SPECIES

lunata

SOURCE

NRRL-2380

SUBSTRATE

17a ,21-d ihydroxy-16a-methyl -4 -pregnene-3 ,20-d ione

17a ,21-dihydroxy-16-methyIene-4-pregnene-3 ,20-d ione

15/3,17a, 21 - t r i hyd roxy -4 -p reg -nene-3 ,20-d ione

1 6 a , 1 7 a , 2 1 - [ 3 , l , l - 2 - p y r a z o l i n o ] 4 -p regnene-3 ,20-d ione

16-chlor méthylène-17 a , 21 -d i -hydroxy-4 - p r e g n e n e - 3 , 2 0 -dione

6a - f luoro-17a ,21-d ihydroxy-21-methyl-4 -pregnene - 3 , 2 0 -dione 21-ace ta te

6a- f luoro-17a ,21-d ihydroxy-16-methylene -4 - p r e g n e n e - 3 , 2 0 -dione

16 -fluor o méthylène-17 a, 21 -d i -hydroxy-4 - p r e g n e n e - 3 , 2 0 -dione

17a, 21-dihy dr oxy - 6a - methyl -16 -méthylène -4 -pregnene - 3 , 2 0 -dione 21-aceta te

17α-hydroxy-16-mé thy lène-1 ,4-pregnadiene-3 ,20-d ione

17a, 21-d ihydroxy-4 ,9(11)-pregna-d iene-3 ,20-d ione

17a, 21-d ihydroxy-4 ,9(11) -pregna-d iene-3 ,20-d ione [11,12a-H3] 21-ace ta te


REACTION

l l ß - O H

15a-OH

ll /3,14a-diOH

l l ß - O H

l l ß - O H

l l ß - O H

l l ß - O H

l l ß - O H ; 21-OAc - 21-OH

11/3-OH

11/3-OH

l l ß - O H ; 21-OAc — 21-OH

l l ß - O H

9(11) Δ - 9/3,11/3-oxide

14a-OH 9(11)

14a-OH; Δ — 9ß ,1Iß-ox ide

9(11)

Δ —9/3, U ß " oxide; 21-OAc —21 -OH

21-OAc—21-OH

Δ *—11/3,12/3-oxide

R E F .

C-96

C-96

C-96

T-981

C-126

W-1113

W-1084

H-390

A-7

W-1084

B-69

B-68

B-65; B-66; S-865

B-65

B-65

K-484

K-484

K-484

388

TABLE I I I


SPECIES

lunata

SOURCE

NRRL-2380

NRRL-2434

OR

SAG

SY(192)

SY(961-29E)

Takeda

UC

SUBSTRATE

17a, 21-d ihydroxy-4 ,14-pregna-diene-3 ,20-dione

17a, 21-dihydroxy-16-methyl-4 ,15-pregnadiene-3 ,20-d ione

16-fluor methyl-17a, 21-dihydroxy-4 ,15-pregnadiene-3 ,20-d ione 21-aceta te

17α, 21-dihydroxy-6α, 16-dimethyl -4 ,15 -p regnad iene -3 ,20 -dione

17a ,21-d ihydroxy-4 ,6 -pregna-diene - 3 , 1 1 , 2 0 - t r ione

1 ,4 ,16 -p regna t r i ene -3 ,20 -dione

9 a - b r o m o - l l ß , 1 7 a , 2 1 - t r i h y d r o x y -1 , 4 , 6 - p r e g n a t r i e n e - 3 , 2 0 -dione

9a -ch lo ro -17a ,21 -d ihydroxy- l , 4 , 6 - p r e g n a t r i e n e - 3 , 1 1 , 2 0 -t r ione

9a -f luoro- 17a, 21 -d ihydroxy-1 , 4 , 6 -pregnat r iene - 3 , 1 1 , 2 0 -t r ione

17a, 21 -dihydroxy -6a, 16a -di -me thy l -4 -p regnene -3 ,20 -dione

17a, 21 -dihydroxy-16a-methyl -l , 4 -p regnad iene -3 ,20 -d ione 21-aceta te

17ß-hydroxy-17a-methyl -4-andros tene-3-one

17α, 21-d ihydroxy- la -methy l -4 -pregnene-3 ,20-d ione

19-nor -4-pregnene-3 ,20-d ione



17a, 21-dihydroxy-7-methyl-4 -pregnene-3 ,20-d ione 2 1 -aceta te

REACTION

14

Δ —» 14a, 15a-oxide

11/3-OH; Δ 1 4 -14a,15a-oxide

l l ß - O H

ll /3-OH;21-OAc -> 21-OH

11/3-OH

2 0 - C = O -20/3-OH

l l ß - O H

14a-OH

14a-OH

14a-OH

l l ß - O H

11/3-OH

16ß-OH

16ß-OH; 16ß-OH -^16 -C=0

l l ß - O H

l l ß - O H

11/3,21-diOH

14a-OH

l l ß - O H ; 21-OAc - 21-OH

R E F .

B-66; S-865

S-865

W-1084

W-1084

ß-69

G-306

H-388; O-700

G-301; G-302

G-301; G-302

G-301; G-302

S-903

S-904

S-950

S-950

W-1112

B - 7 1 ; B-73

R-783

N-661

B-33

TABLE I I I


389

SPECIES

lunata

*

*

*

*

*

maculans

oryzae

pa l lescens *

SOURCE

VEB

VEB (XCIII)

VEB(XCV)

VEß (CII)

VEB CIII

IFO (6292)

VEB(CXXXI)

C

SUBSTRATE

4-pregnene-3 ,20-d ione (effect of inhibi tors and Fe -Ref. Z-1130)

17α, 21 -dihydroxy -4 -pregnene -3,20-dione 21-aceta te

4 -pregnene-3 ,20-d ione (comparison of different spec ies and s t ra ins-ef fec t of nu t r i en t s - t r ace e lements -p H-inhibitor s - cofactor s -subs t ra te specificity-Ref. Z-1132)




(plus other s u b s t r a t e s -products of which a r e un-known or questionable s t ruc tu re -See page 262 of Ref. Z-1132)

17a, 21-dihydroxy-4-pregnene -3,20-dione (comparison of different s t r a ins - Ref. K-469)



12a-f luoro- l l /3-hydroxy-4-pregnene-3 ,20-d ione

9a- f luoro- l l /3 ,17a ,21- t r ihydroxy-4-pregnene-3 ,20-d ione

11/3,21 -dihydroxy -3 ,20-dike to -4 -pregnen-18-a l

REACTION

11/3-OH

6j3,14a-diOH

7a,14a-diOH

ll /3,14a-diOH

11/3-OH; 21-OAc - 21-OH

11/3-OH; 14a-OH

7a,14a-diOH

6/3,14a-diOH

l l ß , 14a -d iOH

7a,14a-diOH

ll /3,14a-diOH

7a,14a-diOH

ll /3,14a-diOH

7a,14a-diOH

ll /3,14a-diOH

6j3-OH;l la-OH; 14a-OH; 6/3, 14a-diOH; 7a, 14a-diOH

11/3-OH; 11)3, 14a-diOH

7a-OH

14a-OH

14a-OH

14a-OH

R E F .

Z-1130

S-811

Z-1130

Z-1130

Z-1131

Z-1132

Z-1132

Z-1132

Z-1132

Z-1132

Z-1132

Z-1132

Z-1132

Z-1132

Z-1132

K-469

Z-1132

M-585

W-1103

W-1108a

W-1108

390

TABLE I I I

T r a n s f o r m a t i o n s by G e n u s : CURVULARIA

SPECIES

pal lescens

(in mixed cul ture with Mycobacterium sp. -

M) *

*

*

*

species

*

*

t e t r a m e r a

* *

*

*

t r ifoli i *

*

*

uncinata *

* *

*

SOURCE

NRRL-2381 (QM-371-D)

P F

VES(XCVI)

CI

P F

VEB

FRI

VEB (CO)

IFO(6241)

VEB( CXXXIV)

SUBSTRATE





17a ,21 -d ihydroxy-4 ,9 ( l l ) -pregnadiene -3 ,20-dione [11,12a-H3] 21-aceta te





17a, 21-dihydr oxy-4-pregnene-3,20-dione (compare with other spec i e s -Ref. K-469)


REACTION

11/3-OH

11/3-OH

11/3-OH

14a-OH

6ß,14a-diOH

7a,14a-diOH

ll /3,14a-diOH

14a-OH

7a,14a-diOH 9 ( l l )

Δ - 9 ß , l l / 3 -oxide; 21-OAc -» 21-OH

7a,14a-diOH

7a-OH

-

11/3-OH

14a-OH

6ß,14a-diOH

7a,14a-diOH

11/3,14a-diOH

6/3-OH

11a-OH

14a-OH

6/3,14a-diOH

7a,14a-diOH

11/3-OH

14a-OH

6/3,14a-diOH 7a,14a-diOH ll /3,14a-diOH

R E F .

S-875

S-868

Z-1132

Z-1132

Z-1132

Z-1132

Z-1132

Z-1132

Z-1132

K-484

S-813

S-813

S-849

Z-1132

Z-1132

Z-1132

Z-1132

Z-1132

K-469

K-469

K-469

K-469

K-469

Z-1132

Z-1132 Z-1132 Z-1132 Z-1132

391


T r a n s f o r m a t i o n s by Genus : CYLINDROCARPON (imperf» - Monmaies)


radic icola ATCC-11011 17/3-hydroxy-4-androsten-3-one

(with cel l free enzyme)

4 -andros tene-3 ,17-d ione (with KCN to inhibit Δ Ref. S-898)

D-homo-17a -oxa -4 -andros t ene -3,17-dione


17ß-hydroxy- l , 4 -andros t ad ien -3-one

5a-pregnane-3 ,20-d ione (with cel l free enzymes)

5j3-pregnane-3,20-dione (with cell free enzymes)

19 -nor -4 -p regnene-3 ,20-d ione

4 -pregnene-3 ,20-d ione (with cell free enzymes -see Ref0 S-890)



Δ ; 17/3-OH -» 17a -oxa -17 -C=0

9a-OH

Δ ; 1 7 - C = 0 -17a -oxa -17 -C=0

F-269; F-274; F-284

S-890

P-740 ; S-898

H-398

H-398

1 7 - C = 0 - > 17a-o x a - 1 7 - C = 0

17/3-OH -> 1 7 - C = 0

17/3-OH-* 17a-o x a - 1 7 - C = 0

J j 4

Δ

4 1 4

Δ ; Δ '

9a-OH

1

Δ

Δ1; 17i3-Ac— 17a -oxa -17 -C=0

Δ ; 17/3-Ac -» 17/3-OH

Δ ; 17/3-Ac -> 1 7 - C = 0

1

Δ

1

Δ

1

Δ ; 17a-OH-17j3-(20-C=O-21-OH) -*17a-oxa-17-c=o

P-733

P-733

P-733

S-890

S-890

P-740; S-898

P - 7 3 3 ; S-890

F - 2 5 1 ; F-269; F-274; F-284; H-398; P-733

P-733

P-733

F-251

F-275

F-269; F-275; F-284

1

Δ

1

Δ

392

TABLE I I I

T r a n s f o r m a t i o n s by Genus: TAXONOMY

CYLINDROCARPON A

CYLINDROCEPHALUM (Imperf0 - Moniliales)

SPECIES

radicicola

CYLINDROCEPHALUM

aureum

SOURCE

ATCC-11011

ATCC-12720 (QM-610)

SUBSTRATE

17a, 21 -dihydroxy-4-pregnene -3,20-dione 21-aceta te

16α, 17a-ox ido-4-pregnene-3 ,20-dione

9a -b romo- l l / 3 -hydroxy-4 -p reg -nene-3 ,20-dione

9a -ch lo ro - l l /3 -hydroxy-4-p reg-nene-3 ,20-dione

9 a - f l u o r o - l l ß - h y d r o x y - 4 - p r e g -nene-3 ,20-dione

9a- f luoro- l l /3 ,16a-d ihydroxy-4-pregnene-3 ,20-d ione (use of cel l free enzyme)

6a ,9a -d i f luoro- l l /3 ,16a-d i -hydroxy-4-p regnene-3 ,20-dione (with cell free enzymes)

4 -p regnene -3 ,11 ,20 - t r ione

9 a - b r o m o - 4 - p r e g n e n e - 3 , 1 1 , 2 0 -t r ione

9o -ch lo ro -4 -p regnene -3 ,11 ,20 -t r ione

9a - f luo ro -4 -p regnene -3 ,11 ,20 -t r ione

5-choles ten-3ß-ol



REACTION

Δ1; 21-OAc — 21-OH

16a,17a-oxido-17/3-Ac -16a-OH-17a-o x a - 1 7 - C = 0

17/3-Ac—17-C=0

17/3-Ac->17-C=0

17/3-Ac->17-C = 0

1

Δ

1

Δ

Δ ; 17/3-Ac — 17a-oxa -17-C=0

9 a - B r - H ; Δ ; 17ß-Ac - 17a-o x a - 1 7 - C = 0

17/3-Ac-*17-C=0

Δ1; 1 7 / 3 - A c -17a -oxa -17 -C=0

Δ ; 17/3-Ac — 17a-oxa -17-C=0

-

17j3-Ac-»17-C=0

17j3-Ac^l7ß-OH

17ß-(20-C=O-21-OH)->17-C=0

17ß-(20-C=O-21-OH)->17ß-OH

R E F .

F-275

E-195

T-996

T-996

T-996

S-890

S-890

L-492

L-492

T-996

T-996

L-492; T-996

T-1005

S-880

S-880

S-880

S-880

TABLE I I I

T r a n s f o r m a t i o n s by G e n u s : CYLINDROCEPHALUM DACTYLIUM

DALDINIA DEBARYOMYCES

TAXONOMY

(Imperfo - Moniliales) (AscOo - Sphaeriales) (AscOo - Endomycetales)

SPECIES

aureum

DACTYLRJM

dendroides

DALDINIA

concentr ia (concentrica)

DEBARYOMYCES

hansenii

SOURCE

ATCC-12720 (QM-610)

NRRL-2574 (QM-508)

NRRL-2575 (QM-513)

QM

FRI

NRRL

SUBSTRATE

21-hydroxy-4 -p regnene-3 ,20-dione propionate



16a-methyl -4-pr egnene - 3 , 2 0 -dione



l i a - h y d r o x y - 4 - p r e g n e n e - 3 , 2 0 -dione

17a -hydraxy-4 -p regnene -3 ,20 -dione




Sarsasapogenin

Diosgenin


REACTION

17/3-(20-C=O-2 1 - O P r ) -» 1 7 - C = 0

17/3-(20-C=O-21-OPr) -» 17/3-OH

l l a , 1 7 a - d i O H

l l a , 1 7 a - d i O H

l l a , 1 7 a - d i O H

l l a , 1 7 a - d i O H

l l a - O H

17a-OH

l l a , 1 7 a - d i O H

17a-OH

l l a - O H

l l a - O H

l l a , 1 7 a - d i O H

l l a - O H

6j3-OH; l l a - O H

—

-

R E F .

S-880

S-880

D-188

D-188

M-571

D-188

D-189

D-189

D-189

D-189

D-189

D-189

D-189

D-189

S-849

M-587

M-587

M-587

393

394


T r a n s f o r m a t i o n s by G e n u s : DEMATIACEAE (Family) (Imperf0 - Moniliales)

DEMATIUM (Imperfo - Moniliales) DERMOLOMA (Basidio. - Agaricales)

DIAPORTHE (Asco„ - Sphaeriales) DIDYMELLA (Asco0 - Sphaeriales)

SPECIES

species

DEMATIUM

puliulans

DERMOLOMA

species

DIAPORTHE

numurai

DIDYMELLA

lycopersici

SOURCE

NG

NRRL

AL(F-27)

FRI

IAM

(A-47)

AMCY

ATCC-11847

C

SUBSTRATE

17«, 21 -dihydroxy-4-pregnene -3,20-dione

Sarsasapogenin

Diosgenin




17o, 21 -dihydroxy-4-pregnene -3,20-dione

11β, 17α, 21 - t r ihydroxy-4 -p reg -nene-3 ,20-d ione (use of dr ied thalli)


(use of spo res - Ref. S-835, S-836)

2a-f luoro- 17a, 21 -dihydroxy -4 -p regnene -3 ,11 ,20 - t r i one

17/3-hydroxy -4 -andros ten-3 -one

17a-ethinyl-17jS-hydroxy-4-andros ten-3-one

REACTION

20-C=O -> 20/3-OH

—

-

-

6/3,l la-diOH

-

-

2/3-OH

1

Δ

17a-OH-17j3-(20-C=O-21-OH) — 1 7 - C = 0

11a-OH

20-C=O-+ 20j3-OH

1

Δ

1

Δ 1

Δ

R E F .

V-1045

M-587

M-587

M-587

S-825

S-849

S-849

S-849

F-231

V-1048

S-835; S-836; V-1048

S-835; S-836; V-1048

H-401

W-1105

V-1052; W-1096; W-1104

TABLE I I I

Transformat ions by Genus: D I D Y M E L L A

395

SPECIES

lycopers ic i

SOURCE

C

SUBSTRATE

17ß-hydroxy-17ö-methyl -4-andr ei-s ten-3-one

17/3-hydroxy-17a-vinyl-4-andro-s ten-3-one

l - and ros t ene -3 ,17 -d ione


p regnane-3 ,20-d ione

17a, 21-dihydr.oxy-5a-pregnane-3 ,11 ,20 - t r ione

5α -1 -pregnene-3 ,20-d ione





d , l - l l ß , 1 7 a , 2 1 - t r i h y d r o x y - 4 -pregnene-3 ,20-d ione

9a - f luo ro - l l /3 ,17a ,21- t r ihydroxy-4-pregnene-3 ,20-d ione

9a - f luoro- l l j3 ,17a ,21- t r ihydroxy-4-pregnene-3 ,20-d ione 2 1 -aceta te

17a,21-dihydroxy-9/3,11/3-oxido-4-pregnene-3 ,20-d ione 2 1 -aceta te

d, 1-11/3,17a, 21- t r ihydroxy-4-pregnene-3 ,20-d ione 2 1 -t r imethylace ta te

d, 1-11/3,21-dihydroxy-3, 20-d i -ke to -4 -p regnen-18-a i (18 -» 11) hemiace ta i


17a,21 -dihydroxy-4 -pregnene -3 ,11 ,20 - t r ione

d , l - 1 7 a , 2 1 - d i h y d r o x y - 4 - p r e g -n e n e - 3 , 1 1 , 2 0 - t r i o n e

REACTION

Δ1

1

Δ

4

Δ 1

Δ

Δ 1 ' 4

* V

4

Δ

Δ1

1

Δ

1

Δ

1

Δ

d,l—d-Δ + 1

1

Δ

Δ ; 2 1 - O A c -21-OH

Δ1; 2 1 - O A c -21-OH

d , l ->d-A X + 1

afl^d-Al + 1

1

Δ

1

Δ

d , l ^ d-Δ 1 + 1

R E F .

V-1052; 1 W-1096; W-1104

W-1109

W-1096

W-1096

W-1096

W-1096

W-1096

W-1096

W-1096

V-1052; W-1096

V-1052: W-1096

W-1102

W-1096

V-1052

W-1096

W-1102

V-1055; W-1102

W-1096

V-1052; W-1096

V-1055> W-1102

396

TABLE I I I

T r a n s f o r m a t i o n s by Genus: DIDYMELLA DIDYMOCLADIUM

DIPLODIA

TAXONOMY

(Imperf. (Imperf.

Moniliales) Sphaeropsidales)

SPECIES

lycopers ic i

vodakii

DIDYMOCLADIUM

te rna tum

DIPLODIA

nata lens is

SOURCE

C

CBS

C

AMCY

ATCC-9055

SUBSTRATE

17a-methy l -21-hydroxy-4-preg-n e n e - 3 , l l , 2 0 - t r i o n e 2 1 -aceta te

21-hydroxy-4 ,6 -pregnad iene-3,20-dione 21-aceta te

4, l l - p r egnad iene -3 ,20 -d ione

17a,21 -dihydroxy -4 -pregnene -3,20-dione

3/3, 1 Iß -dihydroxy -5α -pregnan-20-one

3ß-hydroxy -19 -nor-4 -pr egnen -20-one

16a ,17a-ox ido-4-pregnene-3 , 20-dione


A-nor -3 -p regnene-2 ,20-d ione




l l / 3 ,17a ,21 - t r i hyd roxy-4 -p reg -nene-3 ,20-dione


17a, 21-dihydroxy-4-pregnene-3 ,11 ,20- t r ione

17a, 21-d ihydroxy-1 ,4 -p regna-diene-3 ,20-dione

l l j 3 , 1 7 a , 2 1 - t r i h y d r o x y - l , 4 -pregnadiene-3 ,20-d ione

REACTION

1

Δ

Δ1; 21-OAc-> 21-OH

1

Δ

2 0 - C - O - * 20/3-OH

16a-OH

16a-OH

l l a - O H

7a-OH

7a-OH

7a-OH

7a-OH

7a-OH

7a-OH

7a-OH

7a-OH

7a-OH

7a-OH

R E F .

V-1052; W-1096

V-1052; W-1096

V-1052; W-1096

S-836

W-1092

W-1093

P-746

T-997

L-502; L-506; >V-1078

T-997

T-997

T-997; T-998; T-999

T-997

T-997

T-997

T-997

T-997

TABLE I I I

397

T r a n s f o r m a t i o n s by G e n u s : DIPLODIA DIPLODASCUS DOTHICHIZA

TAXONOMY

(Asco. - Endomycetales) (Imperf. - Sphaeropsidales)

SPECIES

nata lensis

tuber icola

DIPLODASCUS

albidus

DOTHICHIZA

ferruginosa

SOURCE

FRI

IAM

FRI

ATCC-11918

SUBSTRATE




7/3-hydroxy-4-pregnene - 3 , 2 0 -dione

17o,21-d ihydroxy-4-pregnene-3,20-dione


3 - h y d r o x y - l , 3 , 5 (10) -es t ra t r i en-17-one







REACTION

l l ö - O H

Δ ->Δ ; 3/3-OH - 3 - C = 0 ; 7/3-OH

Δ —Δ ; 3ß-OH - 3 - C = 0 ; 7j3,15/3-diOH

7/3-OH

7/3,15j3-diOH

15j3-OH

7o-OH

20-C=O -> 20/3-OH

-

11/3-OH

llj3-OH

l l ß - O H

l l ß - O H

l l ß - O H

l l ß - O H

11/3-OH

R E F .

S-849

A-28; T-1025

A-28; T-1025

A-28; T-1023; T-1025

A-28; T-1025

A-28; T-1025

A-28; T-1023

A-28

S-849

K-449

K-449

K-449

K-449

K-449

K-449

K-449

398


ECHINODONTIUM (Basidio. - Agaricales) ELSINOE (Asco. - Myriangiales)

T r a n s f o r m a t i o n s by Genus : ENDOMYCES (Asco. - Endomycetaies) ENDOTINIA (Taxonomy Unclear - Prob. ENDOTHIA)

(Asco. -Sphaeriales) ENTOMOPHTHORA (Phyco. - Entomophthorales)

SPECIES

tsugicola

ELSINOE

ampelina

fawcetti

ENDOMYCES

lindneri

ENDOTINIA (probably ENDOTHIA)

pa ra s i t i ca

ENTOMOPHTHORA

coronata

EPICOCCUM

humicola

SOURCE

IAM (2-2)

IAM (2-3)

FRI

TNAES

TNAES

FRI

TNAES

ATCC-10151

ATCC-12722 (QM-1049)

SUBSTRATE












20-hydroxy-5/3-pregnan-3-one

2 0 - hy dr oxy - 5a -pr egnan - 3 - one


REACTION

-

-

~

-

-

-

-


6-OH; 11α-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

R E F .

S-849

S-849

S-849

S-849

S-849

S-849

S-849

W-1073

W-1073

R-782

R-782

R-782

R-782

R-782

E P I C O C C U M (Imberf. - Moniliales)

TABLE I I 1

Transformat ions by Genus: EPICOCCUM

399

SPECIES

humicola

*

*

neglectum

*

oryzae

1 *

SOURCE

ATCC-12722 (QM-1049)

ATCC-12723 (QM-1070)

ATCC-12724 (QM-1053)

SUBSTRATE



17a, 21 -dihydr oxy -4 -pr e gnene -3 ,20-dione

17a, 21-dihydr o x y - 1 , 4 - p r e gna-d iene-3 ,20-d ione

4 ,6 -p regnad iene -3 ,20-d ione









17a, 21-dihydroxy - 1 , 4 - p r egna-d iene-3 ,20-d ione

4 ,6 -pregnadiene -3 ,20-d ione








17a, 21 -dihydroxy-4-pregnene -3 ,20-dione

6/3 -fluoro -17a -hydroxy - 21 - methyl -4 -p regnene-3 ,20-d ione

REACTION

11/3-OH

11/3-OH

11/3-OH

20-C = O ^ 20/3 -OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

R E F .

R-782

R-782

R-782

R-782

R-782

R-782

R-782

R-782

R-782

R-782

R-782

R-782

R-782

R-782

R-782

R-782

R-782

R-782

R-782

R-782

R-782

R-782

R-782

R-782

H-391

TABLE I I I

Transformations by Genus: EPICOCCUM

SPECIES

oryzae

purpurascens

species

yuccae

SOURCE

ATCC-12724 (QM-1053)

FRI

QM-649

ATCC-12725 (QM-284e)

SUBSTRATE

6a -f luor o -1 la, 21 -dihydr oxy -16-mé thy lène -4 -p regnene-3 ,20-dione

17a, 21 -dihydroxy -1 ,4 -pr egna -d iene-3 ,20-d ione



17/3-hydroxy -4 -andros ten-3 -one



20-hydroxy-5j3-pregnan-3-one



17a, 21 -dihydroxy -4-pregnene -3,20-dione

17a, 21-d ihydroxy-1 ,4 -pregna-diene-3 ,20-dione




2 0 - hy dr oxy - 5a-pr e gnan - 3 - one






17a, 21-d ihydroxy-1 ,4-pr egna- J d iene-3 ,20-dione

4 ,6 -pregnad iene-3 ,20-d ione

REACTION

11/3-OH

11/3-OH

11/3-OH

-

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3 -OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

R E F .

A-7

R-782

R-782

S-849

R-782

R-782

R-782

R-782

R-782

R-782

R-782

R-782

R-782

R-782

R-782

R-782

R-782

R-782

R-782

R-782

R-782

R-782

R-782

R-782

400


401


T r a n s f o r m a t i o n s by Genus: EPIDERMOPHYTON

EREMASCUS EREMOTHECIUM

ERWINIA ESCHERICHIA

(Imperf. - Moniliales) (Asco. - Endomycetales) (Asco. - Endomycetales) (Schizo. - Eubacteriales) (Schizo. - Eubacteriales)

SPECIES

floccasum

EREMASCUS

albus

EREMOTHECIUM

ashbyii

ERWINIA

aroideae

carotovora

(in mixed cul ture with Mycococcus sp. Ax)

ESCHERICHIA

coli

1 (in mixed cul ture 1 with Mycococcus

sp. Ax)

SOURCE

FRI

NRRL

SQ

FAKU

IFO (3380)

LAM (s t ra in 2 , 6 -Bordet ,Naj iar ATCC-3635)

(s t ra in 7)

(s t ra in 8)

(ML-3)

IFO (3043)

SUBSTRATE

17ö, 21 -dihydroxy-4 -pregnene-3,20-dione

Sarsasapogenin

Diosgenin


• 3ß-hydroxy-5-pregnen-20-one

17ö, 21 -dihydroxy -4 -pregnene -3,20-dione

l l j 3 ,17a ,21 - t r i hyd roxy-4 -p reg -nene-3 ,20-d ione

17ö, 21-dihydroxy-4-pregnene -3,20-dione

17ö, 21-dihydroxy-4-pregnene -3,20-dione

1 la, 21 -dihydroxy-4 -pregnene -3,20-dione

1 7 Ö , 21-d ihydroxy-4-pregnene-3,20-dione

l l /3 ,17o ,21-d ihydroxy-4-pregnene-3 ,20-di one

REACTION

-

-

-

-

Δ -»Δ ; 3/3-OH - 3 - C = 0

—

1

Δ

-

2/3-OH

11α-ΟΗ;11β-ΟΗ

2/3-OH

—

1

Δ

R E F .

S-849

M-587

M-587

M-587

P-710

S-849

1-428

1-428

S-849

S-849

S-849

S-849

1-428

1-428

402


TABLE I I I

ESCHERICHIA EUGLENA

FLAVOBACTERIUM

TAXONOMY

(Phytomastigina - Euglenoidina) (Schizo. - Eubacter ia les)

SPECIES

coli

freundii

EUGLENA (Protozoa)

grac i l i s va r . bac i l la r i s

FLAVOBACTERIUM

androstenedionicum

SOURCE

IMJ

NG

NIH

NG

NG

SUBSTRATE


3α, 7a-dihydroxy-5/3-cholanic acid


5 -cholesten -3/3 -ol (sole carbon source)

24/3-methyl -5 ,7 ,22-choles ta-triene-3/3-01

3a-hydroxy-5/3-cholanic acid (preparat ion of 3-hydroxy bile acid dehydrogenase -grown in p re sence of cholic acid»)



3/3-hydroxy-5-androsten -17-one

REACTION

5 4

Δ -»Δ ; 3]3-OH - 3 - C = 0

7a-OH-»7-C = 0

3a-OH->3-C = 0 ; 7a-OH-+7-C=0; 12a-OH -> 1 2 - C = 0

7 a - O H ^ 7 - C = 0

utilization

utilization

3 a - O H - > 3 - C = 0

6 - C = 0

1 7 - C = 0 -17/3-OH

Δ 4 - 5 α - Η ; 3-C=0— 3a-OH

Δ 4 - 5 α - Η ; 3-C=0—3a-OH; 17-C=0-*17/3-OH

Δ*—Δ*; 3/3-OH - 3 - C = 0 ; 17/3-OH -* 1 7 - C = 0

Δ 5 - Δ 4 ; 3/3-OH - 3 - C = 0

R E F .

S-822

N-675

S-799

N-675

S-914; T-1030

C-140; M-595; S-793c

S-793c

H-352; H-353

G-322

G-322

G-322

G-322

E-219

E-219

TABLE I I I

Transformat ions by Genus: F L A V O B A C T E R I U M

403

SPECIES

androstenedionicum

(variant i)

aquatile

aurant iacum

buccalis

carbonil icum

dehydrogenans var . hydrolyticum

SOURCE

NG

RIND (36-1)

NRRL

RIND (38-3)

NG

ATCC-13930 (WC-130)

SUBSTRATE

3/3,17a-dihydroxy-5-pregnen-20-one

5-andros tene-3ß , 17/3-diol

3 /3 ,17a ,21- t r ihydroxy-5-pregnen-20-one

3 /3 ,17a ,21- t r ihydroxy-5-pregnen-20-one 21-aceta te

3 /3 ,17a ,21- t r ihydroxy-5-pregnen-20-one 3 ,21-d iace ta te

3 /3 ,17a ,21- t r ihydroxy-5-pregnen-20-one 3-formate 21-aceta te

Sarsasapogenin

Diosgenin



3/3,17a, 21 - t r ihydroxy -5 -pr egnen -20-one 21-ace ta te


3 /3 ,17a ,21- t r ihydroxy-5-pregnen-20-one 3-formate 21-ace ta te

5/3-androstene-3/3,17/3-dioI

5 ,9-cyclo - l -androstene-11/3,17/3-diol -3-one 11-aceta te 17-propionate

16 ,16-di f luoro-5-andros ten-3/3-ol-17-one

1 6 , 1 6 - d i f l u o r o - 3 - h y d r o x y - l , 3 , 5 (10) -es t ra t r ien-17-one 3-methyl ether

REACTION

Δ —Δ ; 3/3-OH — 3 - C = 0

Δ5->Δ4; 3/3-OH -» 3-C = 0 ; 1 7 / 3 - O H -1 7 - C = 0

-

21-OAc-*21-OH

-

3-formate —» 3j3-OH

-

-

-5 4

Δ ->Δ ; 3/3-OH ->3-C=0

Δ -*Δ ; 3/3-OH ->3-C=0; 2 1 -O A c - 2 1 - O H

Δ -»Δ ; 3/3-OAc ^ 3 - C = 0

-

Δ5->Δ4; 3/3-OH —3-C=0;17/3-OH—17-C = 0

Δ5->Δ4; 3/3-OH -» 3-C = 0

Δ -11/3-OAc — 1/3,11/3-oxide

1 7 - C = 0 ^ 17a -OH; 3/3-OH ^ 3 - C = 0 ; Δ 5 - Δ 4

1*7-C=0 -17a-OH

R E F .

E-222

E-220

P-744

P-744

P-744

P-744

M-587

M-587

M-587

P-744

P-744

P-744

P-744

M-592

M-592

R-777

R-774

R-774

404

TABLE I I I

Transformat ions by Genus: FLAVOBACTERIUM

SPECIES

dehydrogenans var . hydrolyticum

SOURCE

ATCC-13930 (WC-130)

SUBSTRATE

16-diazo-3ß-hydroxy-5-andros ten -17-one

17a-ethinyl-l l /3,17/3-dihydroxy-4 ,6 -andros tad ien-3 -one diacetate

1 la - ethiny 1 -11 j3,1 7/3 -dihydroxy -l , 4 , 6 - a n d r o s t a t r i e n - 3 - o n e diacetate

11/3, 17/3-dihydroxy-17a-methyl-1,4,6 -andr os ta t r ien - 3 -one diacetate

3/3-hydroxy -16 -méthylène - 5 -andros ten-17-one

5-pregnene-3/3,20a-diol

5-pregnene-3/3, 20/3-diol

7a-methyl-5-pregnene-3/3 , 7/3, 20/3-triol

3/3-hydroxy -D-nor -5 -pregnen -20-one

1 la - ch loro- 3/3-hydroxy -5 -pregnen -20-one aceta te

1 ß , 3 /3-dihydr oxy -5 -pregnen -20-one

3 j3 ,17o,21- t r ihydroxy-5-pregnen-20-one 21-aceta te


3/3-hydroxy-16,16-dimethyl-5-pregnen-20-one

3/3-hydroxy-16/3-methyl-16a, 17a-oxido-5-pregnen-20-one

3/3 ,17a,21- t r ihydroxy-16a-methyl -5-pregnen-20-one 21-aceta te

3β, 17α, 21 - t r ihydroxy-16ß- methyl -5-pregnen-20-one 3 , 2 1 -diacetate

REACTION

3 ß - O H ^ 3 - C = 0 ; Δ3-+Δ4

11/3,17/3-diOAc ->ll/3,17/3-diOH

11/3-OAc -» ll/3-OH;17/3-OAc->17/3-OH

11/3-OAc—11/3-OH; 17/3-OAc -> 17/3-OH

3j3-OH-+3-C = 0 : Δ —*Δ

Δ —Δ ; 3/3-OH ->3-C = 0

Δ ' - Δ 4 ; 3/3-OH ->3-C = Oj 20/3-O H ^ 2 0 - C = O

Δ —Δ; 3/3-OH^ 3-C = O;20/3-OH - 2 0 - C = O

Δ -»Δ ; 3/3-OH ^ 3 - C = 0

5 4 Δ -»Δ ; 3/3-OAc - 3 - C = 0

Δ —Δ ; 3/3-OH - 3 - C = : 0

3ß-OH-»3-C = 0 ; A5->A4;21-OAc —21-OH

3 ß - O A c - 3 - C = 0 ; Δ -*Δ4; 21-OAc ->21-OH

3/3-OH-»3-C=0; Δ5->Δ4

3ß-OH-»3-C=0: Α^ Λ 4

Δ —»Δ 3/3-OH-3-C = 0 ; Δ5-»Δ4; 21-OAc -»21-OH

3/3-OAc-^3-C = 0 ; Δ5-+Δ4; 21-OAc -»21 -OH

R E F .

R-763

G-304

G-304

G-305

B-76

N-693

N-693

R-776

R-763

R-761

N-688; N-689

H-378

H-378

S-837

S-837

C-109; 1-421; 1-422

C-109; 1-421; 1-422

TABLE I I I


405

SPECIES

dehydrogenans

SOURCE

ATCC-13930 (WC-130)

SUBSTRATE

3/3 ,17a,21- t r ihydroxy-16-methylene-5-pregnen-20-one 3 ,21-d iace ta te

1/3,3/3,17a, 21 - t e t r ahydroxy-5 -pregnen-20-one 1 , 3 , 2 1 -t r i ace t a t e

l l / 3 , 1 7 a , 2 1 - t r i h y d r o x y - 5 , 9 -cyc lo - l -p regnene -3 ,20 -d ione 11/3,21-diacetate

l l / 3 , 17a ,21 - t r i hyd roxy -4 -p reg -nene-3 ,20-d ione 11/3,21-diacetate

21-hydroxy-17j3,20a-oxido-16-ox imino -4 -p regnene -3 ,11 -dione aceta te

9 a - b r o m o - l l / 3 - c h l o r o - 1 7 a , 2 1 -d ihydroxy-5-p regnene-3 ,20-dione 21-aceta te

9 a - b r o m o - l l / 3 - f l u o r o - 1 7 a , 2 1 -d ihydroxy-5-p regnene-3 ,20-dione 21-aceta te

l l / 3 -b romo-9a - f l uo ro -17a ,21 -d ihydroxy-5 -p regnene-3 ,20-dione 21-aceta te

l l / 3 - ch lo ro -9a - f luo ro -17a ,21 -d ihydroxy-5-p regnene-3 ,20-dione 21-ace ta te

9a , l l /3 -d ich loro-17a ,21-d ihydroxy -5 -p regnene -3 ,20 -d i one 21-aceta te

9a , l l /3-d i f luoro-17a ,21-dihydroxy -5 -pregnene-3 ,20-d ione 21-aceta te

9a - ch lo ro - l l / 3 - f l uo ro -17a ,21 -dihydroxy-2o-iïB t h y l - 5 -p regnene-3 ,20-d ione 2 1 -aceta te

9a, l l /3 -d ich loro-16a-e thyl -17a , 21 -dihydroxy - 5 -pregnene -3,20-dione 21-ace ta te

9a , l l /3 -d ich loro-17a ,21-d ihydroxy -6 -methy l -5 -pregnene - 3 , 2 0 -dione 21-aceta te

REACTION

5 4

Δ —Δ ; 3/3-OAc - 3 - C = 0 ; 2 1 -OAc—21-OH

l/3-OAc-l/3-OH; 21-OAc—21-OH; 3 /3 -OAc-3-C=0; Δ 5 - Δ 4

11/3,21-diOAc— 11/3,21-diOH; Δ ^ Ι Ι β - Ο Η - * 1/3,11/3-oxide

l l / 3 - O A c - l l / 3 -OH; 21-OAc -21-OH

21-OAc -21-OH

21-OAc—21-OH

21-OAc—21-OH

21-OAc—21-OH

21-OAc—21-OH

21 -OAc-21 -OH

21-OAc-21 -OH

21 -OAc-21 -OH

21-OAc—21-OH

2 1 - O A c - 2 1 - O H

R E F .

T-981

N-689

G-292; R-777

C-129

N-686

N-691

N-691

N-691

N-691

N-691

N-691

N-691

N-691

N-691

406

TABLE I I I


SPECIES

dehydrogenans

SOURCE

ATCC-13930 (WC-130)

SUBSTRATE

9a, l l /3-dichloro-17a, 21-dihydroxy -2a -me thy l -5 -p regnene -3 ,20 -dione 21-aceta te

9a, l l ß - d i c h l o r o - 1 6 a , 17<*,21-t r i hyd roxy-5 -p regnene -3 ,20 -dione 21-aceta te

9a, l l /3-dichloro-21-hydroxy-16a, 17a-isopropylidenedioxy-5-pregnene-3 ,20-d ione aceta te

9a, l l /3-dif luoro-17a, 21-dihydroxy -2a -me thy l -5 -p r egnene -3 ,20 -dione 21-aceta te

9a-chloro- l l /3- f luoro-21-hydroxy -2a-methyl -16a , 17a- i so -propyl idenedioxy-5-pregnene-3,20-dione aceta te

9a-chloro- l l i3- f Iuoro-16a , 17a, 21 - t r ihydroxy-2a -me thy l -5 -pregnene-3 ,20-d ione 2 1 -aceta te

3ß, 16a-dihydroxy-17/3-methyl-18 -no r -5 ,13 -17a -p regna -dien-20-one

3/3,16/3-dihydroxy-17/3-methyl-18-nor_-5,13-17a-pregna-dien-20-one

21-hydroxy-17a-methy l -1 ,4 -pregnadiene -3 ,20 -dione aceta te

11/3,17a-dihydroxy-21-mercapto-l a 4 -p regnad iene -3 ,20 -d ione 21 -aceta te

11/3,21-dihydroxy-17a-methyl-1,4 -pregnadiene -3 ,20-dione 21-aceta te

9a - f luoro- l l /3 ,17a-d ihydroxy-21-mer cap to-1 ,4-pregnadiene -3,20-dione 21-aceta te

6 /3-bromo-l l /3 ,17a,21- t r ihydroxy -1 ,4 -pregnadiene -3 ,20-dione t r i ace ta t e

REACTION

21-OAc-+21-OH

21-OAc^21-OH

21-OAc—21-OH

21-OAc-^21-OH

21-OAc—21-OH

21-OAc—21-OH

3/3-OH^3-C=0; Δ5->Δ4

3/3-OH-»3-C=0; Δ5-*5ξ-Η

3 / 3 - 0 H ^ 3 - C = 0 : Λ 5 A 4

Δ—* Δ 3/3-OH-+3-C = 0 ; Δ 5 - 54-H

21-OAc-^21-OH

21-SAc-»21-SH

21-OAc^21-OH

21-SAc^21-SH

l l / 3 , 1 7 a , 2 1 -triOAc—11/3, 17a ,21- t r iOH

R E F .

N-691

N-691

N-691

N-691

N-691

N-691

S-839

S-839

S-839

S-839

H-377

N-685

H-377

N-685

N-690

TABLE I I I

T ransformat ions by Genus: F L A V O B A C T E R I U M

407

SPECIES

dehydrogenans

SOURCE

ATCC-13930 (WC-130)

SUBSTRATE

9a-fluoro-6£, 11/3,17a, 21 -tetra-hydroxy -1,4 -pregnadiene -3,20-dione tetraacetate

17a-hydr oxy-21-mer capto-1,4-pregnadiene-3,11,20-trione 21-acetate

9a-fluoro-17a-hydroxy-21-mer capto -1,4 -pr egnadiene -3,11,20-trione 21-acetate

9a-fluoro-6£,17a,21-trihydroxy-1,4-pregnadiene-3,11,20-trione 6,21-diacetate

ll/3,17a,21-trihydroxy-l,5-pregnadiene-3,20-dione 21-acetate

11β, 17α, 21 -trihydroxy-1,5-pregnadiene-3,20-dione triacetate

9a-bromo-ll/3-chloro- 17a, 21-dihydroxy -1,5 -pr egnadiene -3,20-dione 21-acetate

ll/3-bromo-9a-chloro-17a,21-dihydr oxy -1,5 -pr e gnadiene -3,20-dione 21-acetate

9a-bromo-llj3-fluoro-17a, 21-dihydroxy -1,5 -pre gnadiene -3,20-dione 21-acetate

ll/3-bromo-9a-fluoro-17a, 21-dihydroxy-1,5-pr egnadiene-3,20-dione 21-acetate

9a, 11/3-dibromo- 17a, 21-dihydroxy -1,5 -pregnadiene -3,20-dione 21-acetate

9a-chloro-ll/3-fluoro-17a, 21-dihydroxy - 1 , 5-pregnadiene -3,20-dione 21-acetate

llj3-chloro-9a-fluoro-17a,21-dihy dr oxy -1,5 -pre gnadiene -3,20-dione 21-acetate

ll/3-chloro-9a-iodo-17a, 21-dihydroxy-1,5-pre gnadiene-3,20-dione 21-acetate

REACTION

6ξ,11/3,17α,21-tetraOAc^ 6ξ, 11/3,17α, 21-tetraOH

21-SAc-*21-SH

21-SAc^21-SH

6£-OAc-6£-OH; 21-OAc^21-OH

21-OAc->21-OH

11/3,17a,21-triOAc^ll/3,17a, 21-triOH

21-OAc^21-OH

21-OAc—21-OH

21-OAc->21-OH

21-OAc-*21-OH

21-OAc^21-OH

21-OAc^21-OH

21-OAc—21-OH

21-OAc->21-OH

REF.

G-309

N-685

N-685

G-309

N-690

N-690

N-691

N-691

N-691

N-691

N-691

N-691

N-691

N-691

408

TABLE I I I


SPECIES

dehydrogenans

SOURCE

ATCC-13930 (WC-130)

SUBSTRATE

9a , l l / 3 -d i ch lo ro -17a ,21 -d i -vydroxy -1 ,5 -pregnadiene -3,20-dione 21-aceta te

16a-e thyl - l l /3 ,17a ,21- t r ihydroxy -1 ,5 -pregnadiene - 3 , 2 0 -dione 21-aceta te

l l /3- f luoro-17a ,21-dihydroxy-9a-iodo-1 ,5 -p regnad iene-3 ,20-dione 21-aceta te

9a- f luoro- l l /3 ,17a ,21- t r ihydroxy - 1 , 5 -pregnadiene -3 ,20-dione t r i ace ta te

9ö, l l /3-dif luoro-17ö,21-dihydroxy -1 ,5 -p regnad iene-3 ,20-d ione 21-aceta te

11/3,17o,21-tr ihydroxy-16û-methyl -1 ,5 -pregnadiene - 3 , 2 0 -dione 21-aceta te

11/3,17α, 21-trihydroxy-16/3-methy l -1 ,5 -pregnadiene - 3 , 2 0 -dione 21-aceta te

9o-bromo-11/3-chlor o - l 6α-ethyl-17α, 21-d ihydroxy-1 ,5 -pregna-d iene-3 ,20-d ione 21-aceta te

9a-bromo- l l /3 -ch loro-21-hydroxy -16α, 17a-isopropylidenedioxy-1,5 -pregnadiene -3 ,2 0-dione 21-aceta te

9a -b romo-16a-e thy l - l l / 3 ,17a , 21 -t r ihydroxy-1 ,5 -p regnad iene -3,20-dione 21-aceta te

9a -b romo- l l / 3 - f l uo ro -17a ,21 -dihydroxy-1 ,5-pregnadiene -3,20-dione 21-aceta te

9a-bromo- l l /3 - f luoro-21-hydroxy-16a, 17a-isopropylidenedioxy-1,5 -pregnadiene -3 ,20-dione 21-aceta te

9α-bromo-11/3 ,17a ,21- t r ihydroxy-16a-methy l -1 ,5 -p regnad iene-3,20-dione 21-aceta te

9a -b romo- l l / 3 ,17a ,21 - t r i hyd roxy-16β -methyl -1 ,5 -pregnadiene -3,20-dione 21-aceta te

6 , 9 a - d i b r o m o - l l ß - f l u o r o - 1 7 a , 21 -d ihydroxy-1 ,5 -pregnadiene -3 ,20-dione 21-aceta te

REACTION

21-OAc->21-OH

21-OAc->21-OH

21-OAc-+21-OH

l l / 3 , 1 7 a , 2 1 - t r i -OAc-*ll/3,17a, 21-tr iOH

21-OAc^21-OH

21-OAc-21-OH

21-OAc^21-OH

21-OAc—21-OH

21-OAc-*21-OH

21-OAc-21-OH

21-OAc-*21-OH

21-OAc-21-OH

21-OAc-*21-OH

21-OAc-*21-OH

21-OAc-21-OH

R E F .

N-691

N-690; N-692

N-691

N-690

N-691

N-690; N-692

N-690; N-692

N-691

N-691

N-690; N-692

N-691

N-691

N-690; N-692

N-690; N-692

N-691

TABLE I I I

Transformat ions by Genus: FLAVOSACTERIUM

409

SPECIES

dehydrogenans

SOURCE

ATCC-13930 (WC-130)

SUBSTRATE

9 a , l l / 3 - d i b r o m o - 1 7 a , 2 1 - d i -hydroxy-6-methy 1-i, 5 -pregna-d iene-3 ,20-d ione 21-aceta te

9 a , l l / 3 - d i b r o m o - 1 7 a , 2 1 - d i -hydroxy-16/3-methyl- l , 5-pregnadiene-3 ,20-d ione 21-aceta te

9α, l l ß - d i b r o m o - 1 7 a , 21 -d i -hydroxy-16α-methy 1-1, 5-pregnadiene-3 ,20-d ione 21 -aceta te

9a-chloro- l l j3- f luoro-16a , 17a, 21 - t r i hyd roxy-1 ,5 -p regna -d iene-3 ,20-d ione 21-aceta te

9a -ch lo ro - l l / 3 - f l uo ro -17a ,21 -d ihydroxy-16/3-methyl - l ,5 -pregnadiene-3 ,20-d ione 21-ace ta te

9 a - c h l o r o - l l ß - f l u o r o - 1 7 a , 2 1 -dihydr oxy - 6 - methy 1-1,5-pregnadiene -3 ,20-dione 21-aceta te

9a-chloro- l l /3- f luoro-21-hydroxy-16a, 17a-isopropylidenedioxy-1,5 -pregnadiene -3 ,20-dione aceta te

9a -ch loro- l l j3 ,17a ,21- t r ihydroxy-1 6 a - m e t h y l - l , 5-pregnadiene -3,20-dione 21-aceta te

9a -ch lo ro - l l j3 ,17a , 21- t r ihydroxy-16j3 - methyl - 1 , 5 -pre gnadiene -3,20-dione 21-ace ta te

9 a , l l j 3 - d i c h l o r o - 1 6 a , 1 7 a , 2 1 - t r i -hydroxy-1 ,5-pregnadiene -3,20-dione 21-ace ta te

9a , l l /3 -d ich loro-17a ,21-d ihydroxy - 1 6 a - m e t h y l - l , 5-pregnadiene -3,20-dione 21-ace ta te

9a , l l /3 -d ich lo ro-21-hydroxy-16a , 17a - isopr opylidenedioxy - 1 , 5 -p r e gnadiene -3 ,20 - dione ace ta te

9a , l l /3 -d ich loro-17a ,21-d ihydroxy -16j3-methyl- l , 5-pregnadiene -3 ,20-dione 21-aceta te

REACTION

21-OAc—21-OH

21-OAc^21-OH

21-OAC-21-OH

21-OAc—21-OH

21-OAC-21-OH

21-OAc-21-OH

21-OAc^21-OH

21-OAc—21-OH

21-OAc->21-OH

21 -OAc-21 -OH

21-OAc—21-OH

21-OAc-*21-OH

21-OAC-21-OH

R E F .

N-691

N-691

N-691

N-691

N-691

N-691

N-691

N-690; N-692

N-690; N-692

N-691

N-691

N-691

N-691

410

TABLE I I I

Transformations by Genus: FLAVOBACTERIUM

SPECIES

dehydrogenans

SOURCE

ATCC-13930 (WC-130)

SUBSTRATE

9a , l l /3-d ichloro-17a ,21-dihydroxy -6-methy 1-1,5-pregnadiene-3,20-dione 21-aceta te

16a -e thy l -9a - f luo ro - l l / 3 ,17a ,21 -t r ihydroxy - 1 , 5 -pr egnadiene -3,20-dione 21-aceta te

11/3- fluor o - 21 - hy dr oxy - 9a - iodo -16a, 17a-isopropylidenedioxy-1,5 -pr egnadiene -3 ,20-dione 21-aceta te

l l /3- f luoro-17a,21-dihydroxy-9a-iodo-6 -me thy l -1 , 5-pregna-diene-3 ,20-dione 21 -ace t a t e

l l /3- f luoro-17a ,21-dihydroxy-9a-iodo-16a-methy l -1 , 5-pregna-diene-3 ,20-dione 21-aceta te

l l /3- f luoro-17a ,21-dihydroxy-9a-iodo-16/3-methy l - l ,5 -pregna-diene-3 ,20-dione 21-aceta te

9a-fluoro-11/3,17a, 21- t r ihydroxy-16a-methy 1-1, 5-pr egnadiene -3,20-dione 21-aceta te

9a- f luoro- l l /3 ,17a , 21- t r ihydroxy-16/3-methyl - 1 , 5 -pr egnadiene -3,20-dione 21-aceta te

9a, 11 ß -dif luor o -17a, 21 -dihydr oxy-16a - methyl -1 ,5 -pregnadiene -3,20-dione 21-aceta te

9a , l lß -d i f luoro-17a ,21-d ihydroxy-16/3-methy 1-1, 5-pregnadiene 3,20-dione 21-aceta te

9a-bromo- l l /3 - f luoro-17a , 21 -d i -hydr oxy-6 ,16a -d ime thy l -1 , 5-pregnadiene-3 ,20-d ione 2 1 -aceta te

9a-bromo- l l /3 - f luoro-17a , 21 - d i -hydr oxy-6,16/3-dimethyl- l , 5-pregnadiene-3 ,20-d ione 2 1 -aceta te

9a , l l /3 -d ibromo-17a ,21-d ihydroxy-6 ,16a -d ime thy l -1 ,5 -p r egna-d iene-3 ,20-dione 21-aceta te

9a , l l /3 -d ibromo-17a ,21-d ihydroxy-6,16/3-dimethyl- l , 5 -pregna-diene-3 ,20-dione 21-aceta te

REACTION

21-OAc^21-OH

21-OAc—21-OH

21-OAc->21-OH

21-OAc^21-OH

21-OAc^21-OH

21-OAc-21-OH

21-OAc—21-OH

21-OAc—21-OH

21-OAc—21-OH

21-OAc-»21-OH

21-OAc^21-OH

21-OAc—21-OH

21-OAc-*21-OH

21-OAc^21-OH

R E F .

N-691

N- 690; N-692

N-691

N-691

N-691

N-691

N-690; N-692

N-690; N-692

N-691

N-691

N-691

N-691

N-691

N-691

TABLE I I I


411

SPECIES

dehydrogenans

SOURCE

ATCC-13930 (WC-130)

SUBSTRATE

9a,ll/3-dichloro-16a,17a,21-tri-hydroxy-6-methyl-l, 5-pregna-diene-3,20-dione 21-acetate

9a,ll/3-dichloro-17a,21-di-hydroxy-6,16a-dimethyl-l,5-pr egnadiene-3, 20-dione 21-acetate

9a,ll/3-dichloro-17a,21-dihydroxy -6,16/3-dimethyl-l,5-pregna-diene-3,20-dione 21-acetate

9a-chloro-ll/3-fluoro-16a, 17α , 21-trihydroxy-6-methyl-l,5-pr egnadiene -3,20-dione 21-acetate

9o-chloro-llß-fluor 0-21-hydroxy-16a, 17a-isopropylidenedioxy-6-methyl-l, 5-pregnadiene -3,20-dione acetate

9a,ll/3-difluoro-17a,21-dihydroxy -6,16a-dimethyl-l,5-pregna-diene-3,20-dione 21-acetate

9a, 11/3 -dif luoro -17a, 21 -dihydr oxy -6,16/3-dimethyl-l, 5-pr egna-diene-3,20-dione 21-acetate

17a,21-dihydroxy-l, 5-pregna-diene-3,11,20-trione 21-acetate

17a,21-dihydroxy-l, 5-pregna-diene-3,ll,20-trione 21-isobutyrate

9a-bromo-17a,21-dihydroxy-l,5-pr egnadiene-3,11,20-trione 21-acetate

16a-n-butyl-17a,21-dihydroxy-1,5 -pr egnadiene -3,11,20-trione 21-acetate

16/3-n-butyl-17a, 21-dihydroxy-1, 5-pregnadiene-3,11,20-trione 21-acetate

9a-chloro-17a, 21-dihydroxy-1,5-pre gnadiene -3,11,20-tr ione 21-acetate

16a-ethyl-17a,21-dihydroxy-l,5-pregnadiene-3,ll,20-trione 21-acetate

REACTION

21-OAC-21-OH

21-OAc^21-OH

21-OAc^21-OH

21-OAc-21-OH

21-OAc->21-OH

21-OAc^21-OH

21-OAc^21-OH

21-OAc—21-OH

21-O-i-Bu — 21-OH

21-OAc—21-OH

21-OAc-»21-OH

21-OAc-21-OH

21-OAc—21-OH

21-OAc^21-OH

REF.

N-691

N-691

N-691

N-691

N-691

N-691

N-691

N-690

N-690

N-690

N-690; N-692

N-690; N-692

N-690

N-690; N-692

412

TABLE I I I


SPECIES

dehydrogenans

L

SOURCE

ATCC-13930 (WC-130)

EM

SUBSTRATE

9a-f luoro-17a, 21-dihydr o x y - 1 , 5 -p regnad iene -3 ,11 ,20 - t r ione 21-aceta te

1 7α, 21 -dihydroxy -16a - methyl -1,5 -pregnadiene - 3 , 1 1 , 2 0 -t r ione 21-aceta te

17α, 21 -dihydroxy-16/3- methyl -1,5 -pregnadiene - 3 , 1 1 , 2 0 -t r ione 21-aceta te

9 a - b r o m o - 1 6 a - e t h y l - 1 7 a , 2 1 -dihydr oxy - 1 , 5 -pregnadiene -3 ,11 ,20- t r ione 21-aceta te

9a -bromo-17a ,21-d ihydroxy-1 6 a - m e t h y l - l , 5-pregnadiene -3 ,11 ,20 - t r ione 21-aceta te

9a -bromo-17a ,21-d ihydroxy-16j3-methyl-l , 5 -pregnadiene -3 ,11 ,20- t r ione 21-aceta te

16a -e thy l -9a - f luoro -17a ,21-dihydr oxy-1 ,5-pregnadiene -3 ,11 ,20- t r ione 21-aceta te

9α-fluor o -17α, 21-dihydr oxy -16α-methy l -1 ,5 -pregnadiene -3 ,11 ,20- t r ione 21-aceta te

9a-f luoro-17a, 21 -dihydroxy-16ß-methyl -1 ,5 -pregnadiene -3 ,11 ,20- t r ione 21-ace ta te

9 a - f l u o r o - l l / 3 , 1 6 a , 1 7 a , 2 1 - t e t r a -h y d r o x y - l , 4 , 6 - p r e g n a t r i e n e -3,20-dione 16,21-diace ta te

l l j 3 , 1 7 a , 2 1 - t r i h y d r o x y - l , 4 , 6 -p regna t r i ene -3 ,20-d ione 11-formate 21-aceta te

3/3-hydroxy-16-méthylène-5-androsten -17-one

3/3,17/3-dihydr oxy-17α-methyl-16-méthylène-5-andros tene

3/3-hydroxy-pyrazolo-[4 . 3 : 16 .17]-5-andros tene

1

3/3, l ] j3- dihydr oxy -Δ 2 - isoxazol ino-[4 .5 1 :16„17]-5-andros tene

3/3,17a, 21 - t r ihydroxy -16-méthylène-5-pregnen-20-one 3 ,21-diaceta te

REACTION

21-OAc—21-OH

21-OAC-21-OH

21-OAc-21-OH

21-OAc-21-OH

21-OAc-*21-OH

21-OAc—21-OH

21-OAc-21-OH

21-OAc-21 -OH

21-OAc->21-OH

16a-OAc -» 16a-OH; 2 1 -O A c - 2 1 - O H

11-formate —» l l /3-OH;21-OAc - 2 1 -OH

3/3-OH->3-C=0; Δ 5 - Δ 4

3 /3 -OH-3-C=0; Δ5—Δ4

3 /3 -OH-3-C=0; Δ 5 - Δ 4

3 /3 -OH-3-C=0: Α ^ Λ 4

Δ —*Δ 3/3-OAc—3-C=0; 21-OAc-*21-OH: Δ —»Δ

R E F .

N-690

N-690; N-692

N-690; N-692

N-690; N-692

N-690; N-692

N-690; N-692

N-690; N-692

N-690; N-692

N-690; N-692

G-299

G-302

B-76

B-76

B-76

B-76

M-558


SPECIES

dehydrogenans

f lavescens

1 (in mixed cul ture with Mycococcus sp. Ax)

flavotennae

1 fulvum

SOURCE

NG (see genus Micrococcus)

IFO (3085)

RIND (37-3)

NG

RIND (39-2)

SUBSTRATE

l ,3 ,5 (10) -es t r a t r i ene -3 ,17 /3 -d io l



1 la -ethinyl - 5 -andr ostene - 3/3, 17/3-diol

3ß-hydroxy - 5 -andr osten -17 -one


5-cholesten-3/3-ol

3/3-hydroxy-27-nor-5-choles ten-25-one

11/3,17α, 21 - t r i hyd roxy-4 -p reg -nene -3 ,20-dione


3 /3 ,17a ,21- t r ihydroxy-5-pregnen-20-one 21-ace ta te

3 /3 ,17a ,21- t r ihydroxy-5-pregnen-20-one 3-formate 21-ace ta te

3/3, 17α,21 - t r ihydroxy-5-p regnen-20-one 3 ,21-d iace ta te

5-cholesten-3/3-01 (effect of nutr ients)

3/3,17a, 21- t r ihydr oxy-5-pr egnen-20-one

3/3,17a, 21- t r ihydr oxy-5-pr egnen-20-one 21-ace ta te

REACTION

17/3-OH -> 1 7 - C = 0

3 /3-OH^3-C=0; 17/3-OH — 1 7 - C = 0

3/3-OH—3-C=0; Δ 5 - Δ 4

3/3-OH—3-C = 0 ; Δ5->Δ4

3 ß - O H - 3 - C = 0 ; Δ 5 - Δ 4

3/3-ΟΗ—3-C=0; Α^ A 4

Δ —>Δ

utilization

3 /3 -OH-3-C=0; A 5 A 4

Δ —*Δ

-

1

Δ

-

21-OAc->21-OH

3-OFo->3-OH

-

degradation

Δ ^ Δ 4 ; 3/3-OH-> 3 - C = 0

Δ -»Δ ; 3/3-ΟΗ— 3 - C = 0

R E F .

A-15; A-16; E-216

A-15; A-16

A-15; A-16; E-217

A-15; A-16; E-215

A-15; A-16; A-17; E-214

A-15; A-16; E-214

E-214

M-595

A-15; A-16; E-214

1-428

1-428

P-744

P-744

P-744

P-744

A-19

P-744

P-744

TABLE I I I

FLAVOBACTERIUM

413

414

TABLE I I I


SPECIES

fulvum

helvoium ( Nomen confusum -see Corynebacter ium helvoium and C. mediolanum)

mar i s

sewanense *

species

SOURCE

RIND (39-2)

SCH

NG

NG

ATCC-13552

NG (AC-5)

RIND (35-1)

SUBSTRATE

3/3 ,17a,21- t r ihydroxy-5-pregnen-20-one 3-formate 21-aceta te

3 /3 ,17a,21- t r ihydroxy-5-pregnen-20-one 3 ,21-d iace ta te


5-cholesten-3j3-ol

Digitonin

17j3-hydroxy-17a-methyl-4-andros ten-3-one

4 -p regnene-3 ,20 -dione


17o^21-dihydroxy-4-pregnene-3,20-aione

l l ß , 1 7 a , 2 1 - t r i h y d r o x y - 4 - p r e g -nene-3 ,20-dione

9ö-f luoro- l l /3 , 17a ,21- t r ihydroxy-4-pregnene-3 ,20-d ione

17a, 21 -dihydroxy-4-pregnene -3 ,11 ,20- t r ione

5-cholesten-3j3-ol (sole carbon source - effect of nutr ients)

3 /3 ,17a ,21- t r ihydroxy-5-preg-nen-20-one

3/3, 17a ,21- t r ihydroxy-5 -p reg-nen-20-one 21-ace ta te

3 /3 ,17a ,21- t r ihydroxy-5-preg-nen-20-one 3-formate 21-aceta te

REACTION

Δ —Δ ;3-OFo— 3-C=0 ; 21-OAc -»21 -OH

-

5 4

Δ —Δ ; 21-OAc —21 -OH; 3/3-OH—3-C=0

3 /3 -OH-3-C=0; Δ 5 - Δ 4

3/3-glycoside (saponin) —* 3/3-OH

1

Δ

1

Δ 1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

(with asparagine - no react ion)

(without a s p a r a -g i n e - d e g r a d a -tion)

utilization

Δ —Δ ; 3/3-OH— 3 - C = 0

Δ5-*Δ4; 3/3-OH-3 - C = 0 ; 21-OAc —21-OH

Δ —Δ ;3j3-OFo - 3 - C = 0 ; 21-OAc —21-OH

R E F .

P-744

P-744

M-544

A-19; A-21 ; A-22; B-50

S-795

1-430

1-430

1-430

1-430

1-430

1-430

1-430

A-19

M-595

P-744

P-744

P-744

415



FLAVOBACTERIUM FOMES

FRAMETES FUMAGO

FUSARIUM

(Basidio. - Agaricales) (Taxonomy Unclear - Probably TRAMETEÉ (Imperf. - Moniliales) (Imperf. - Moniliales)

SPECIES

species

FOMES

pinicola

robs lus

1 spec ies

FRAMETES (see TRAMETES)

1 Pi n i

FUMAGO

species

FUSARIUM

aquaeductum

(var. d imerum)

SOURCE

RIND (35-1)

RIND (38-3) (39-2)

FRI

IAM

IAM

IAM

FRI

CZAS

CZAS

SUBSTRATE

3/3,17a, 21 - tr ihydroxy -5 - p r eg -nen-20-one 3 ,21-d iace ta te

3/3,21-dihydroxy-5-pregnen-20-one


3/3,17a, 21- t r ihydroxy-5-pr eg-nen-20-one

3/3,17a, 21- t r ihydroxy-5-pregnen-20-one 21-aceta te

3ß, 21-dihydroxy-16a, 17a-oxido-5-pregnen-20-one 21-aceta te










REACTION

-

3/3-OH->3-C=0; Δ5->Δ4

3 /3 -OH^3-C=0:

3/3-OvH^3-C=0; Δ 5 - Δ 4

3 /3 -OH^3-C=0: Δ 5 - Δ 4

3/3-OH->3-C=0: Δ ^ Δ 4

-

-

—

—

-

6/3-ΟΗ;15α-ΟΗ

-

6/3-ΟΗ;15α-ΟΗ

R E F .

Ρ-744

Ρ-742

Ρ-742

Ρ-742

Ρ-742

Ρ-742

S-849

S-849

S-849

S-849

S-849

C-97

C-97

C-97

C-97

416

TABLE I I I

T r a n s f o r m a t i o n s by G e n u s : FUSARIUM

SPECIES

a r thoce ra s

aspidioti

avenaceum

(var. herbarum)

1 batatat is

bulbigenum

(var. plum)

buxicola

caucas icum (poss. synonym for

solani)

SOURCE

OIAß (F-75)

OIAB (F-61)

CZAS

CZAS

OIAB (F-68)

ATCC-7618

OIAß (F-59)

OIAB (F-76)

CZAS

C

SUBSTRATE


17o, 21-dihydroxy-4-pregnej ie-3,20-dione












3/3 - hydroxy - 5 -andr osten -17 -one



3/3-hydroxy-5a-pregnan-20-one aceta te


REACTION

-


6/3-OH;15a-OH

-

6/3-OH;15a-OH

-


1

Δ


-

6j3-OH;15a-OH

-

Δ 1 ' 4

Δ1; 3 / 3 - O H -3 - C = 0 ; Δ 5 - Δ 4

1

Δ

Δ1; 17-C = 0 -17a -oxa -17-C=0

1 7 - C = 0 - 17a-o x a - 1 7 - C = 0

A 1 . 4.

Δ ' ; 3/3-OAc->3-C=0; 17/3-OAc -> 1 7 - C = 0

17/3-Ac-+17-C=0 3 ß - O A c - 3 - C = 0

Δ 1 ' 4 ; 17/3-Ac — 1 7 - C = 0

17ß-Ac— 17-C=0

R E F .

K-462

K-462

C-97

C-97

1 C-97

C-97

K-462

C-125

K-462

K-462

C-97

C-97

V-1056

V-1056

V-1056; W-1095

W-1095

W-1095

V-1056

V-1056

V-1056

V-1056

1

TABLE I I I

417


SPECIES

caucasicum

(For Ref. W-1116, 1117 and 1118 -interact ion of un-sa tura ted and sa tura ted s t e ro ids . )

SOURCE

C

CBS

SUBSTRATE




andros tane-3 ,17-d ione




3/3-hydroxy-5o-pregnan-20-one

3ß-hydroxy-5a-pregnan-20-one ace ta te


5/3-pregnane-3, 20-dione

5a -16-pregnene-3 ,20-d ione



REACTION

1 5 4 Δ ; Δ - Δ ; 17j3-Ac->17-C=0 3/3-OH-3-C = 0

17/3-Ac — 1 7 - C - O

17ß-Ac 3-» 17-C = 0 ; Δ

Δ1; 17/3-(20-C = 0-21-OH) -» 1 7 - C = 0

Δ 1 , 4

Δ ^ β - Ο Η -» 3-C = 0 ; Δ5->Δ4

Δ ' ; 1 7 / 3 - Ο Η -> 1 7 - C = 0

1

Δ

Δ > ; 3 /3-OH^3-C=0; 17)3-Ac-»17-C=0

1

Δ ; 3ß-OAc-3 -C = 0 ; 17j3-Ac-17-C=0

A 1 ' 4 ; 17/3-Ac^l7-C=0

Λ 1 4

Δ > ; 17/3-Ac -»17a-o x a - 1 7 - C = 0

17/3-Ac — 1J-C=0; Δ

-1 4

Δ - 1 7 - A c - » 1 7 - C = 0

1 5 4 Δ ; Δ —Δ ; 17/3-A c - 1 7 - C = 0 ; 3 /3-OH^3-C=0

Δ1; 17]3-Ac—17a - o x a - 1 7 - C = 0

Δ1;17β-Αο — 1 7 - C = 0

R E F .

V-1056; W-1095

V-1056

V-1056; W-1095

V-1056; W-1095

W-1116

W-1118

W-1118

W-1116; W-1117; W-1118

W-1118

V-1056

W-1116; W-1118

W-1116

W-1116

W-1116

W-1118

W-1118

W-1116

W-1116; W-1117; W-1116;

418

TABLE I I I

Transformat ions by Genus: FUSARIUM

SPECIES

caucasicum

SOURCE

CBS

CZAS

SUBSTRATE



16a, 17ö-ox ido-4-pregnene-3 ,20-dione

3/3-hydroxy-5,16-pregnadien-20-one


17/3-hydroxy-4-androsten-3-one ace ta te

17/3-hydroxy-4-androsten-3-one benzoate

17/3-hydroxy-4-androsten-3-one isobutyrate

17/3-hydroxy-4-androsten-3-one formate

17/3 -hyd roxy-4 -and ros t en -3 -one propionate


REACTION

17/3-Ac-1 7 - C = 0

A1;17/3-(20-C= O-21-OH) -1 7 - C = 0

Δ1; 16α, 17a-oxido-17/3-Ac— 1 7 - C = 0

1 5 4 16

Δ ; Δ —Δ ; Δ -1 7 - A c - 1 7 - C = 0 ; 3 /3-OH-3-C=0

1 16

Δ ; Δ -17-Ac ->17-C = 0

Δ1; 17j6-OAc-1 7 - C = 0

Δ ;17/3-OAc— 17a-oxa-17-C=0

-

-

Δ ;17/3-OFo-> 17a-oxa-17-c=o ^-,ΙΊβ-ΟΈΌ-* 1 7 - C = 0

A1;17i3-OPr — 17a-oxa-17-C=0

Δ1; 17j3-OPr -+ 1 7 - C = 0

6/3-OH

15a-OH 1

Δ

Δ 1 ; 1 7 - 0 = 0 - > 17/3-OH

1 7 - C = 0 - * 1 7 a -o x a - 1 7 - C = 0

R E F .

W-1116

W-1118

W-1118

W-1118

W-1118

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97; H-399

C-97

C-97

TABLE I I I

419

T r a n s f o r m a t i o n s by Genus: FUSARIUM

SPECIES

caucas icum

cocophilum

coeruieum

concolor

cu lmorum

d imerum

1 d ive r s i sporum

SOURCE

CZAS

PIRI

CZAS

OIAB (F-83)

ces CZAS

EM (2092)

VEB

OIAB (F-39)

OIAB (F-43)

SUBSTRATE








4 - p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e



17α, 21 -dihydroxy -4-pregnene -3,20-dione


17a, 21 -dihydroxy -4-pregnene -3 ,20-dione


REACTION

A 1 ;17-C = 0 -17a-oxa-17-

c=o 1

Δ

17j3-OH — 17-C=0

17/3-OH-17a-oxa-17-C = 0

Δ ;17/3-OH — 1 7 - C = 0

Δ ;17/3-OH-+17a o x a - 1 7 - C = 0

A^HjS-Ac — 1 7 - C = 0

Δ ; 17/3-Ac -17/3-OH

17/3 -Ac— 17-C = 0

Δ ; 17/3-Ac -> 17a-oxa-17-C=0

Δ ; 17/3-Ac—17a-oxa-17-C = 0

6β-ΟΗ;15α-ΟΗ

--

15α-OH

6β-ΟΗ;15α-ΟΗ

-l i a - O H

15α-OH

6/3-OH

11α-OH


R E F .

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

M-588

C-97

C-97

K-462

M-599

C-97

C-97

M-557

K-452

K-462

K-462

K-462

420

TABLE I I I


SPECIES

equiseti

expansum

gibosum

(var. acuminatum)

gigas

g raminearum

herberum

heterosporum

javanicum

SOURCE

EM{2083)

CZAS

CZAS

CZAS

CZAS

OIAB (F-55)

CZAS

ATCC-12575

SUBSTRATE

lia, 21 -dihydroxy -4 -pregnene -3,20-dione 21-aceta te

17α, 21-d ihydroxy-1 ,4 -pregna-diene-3 ,20-dione

17a, 21-d ihydroxy-4 ,6 -pregna-d iene-3 ,20-dione

1 7 a , 2 1 - d i h y d r o x y - l , 4 , 6 - p r e g n a -t r iene -3 ,20 -dione















4-pregnene-3 ,20-d ione 20-cyclo-ethyleneketal


REACTION

l i a - O H

l i a - O H ; 21-OAc ^ 2 1 - O H

l l a - O H

l i a - O H

l l a - O H

6/3-OH; 15a-OH

—

6/3-OH; 15a-OH

-

6j3-OH; 15a-OH

-

6/3-OH; 15a-OH

—

6/3-OH; 15a-OH

-


6/3-OH; 15α-ΟΗ

-

17/3-Ac->17-C=0 Δ1; l l a - O H

Δ1; 17/3-Ac-» 17a-oxa-17-C=0

1

Δ ; 17/3-Ac -» 17/3-OH; l l a - O H

Δ1; 17/3-Ac — 17a-oxa-17-C=0

1

Δ

Δ1; 17/3-Ac-» 17a-oxa-17-C=0

R E F .

M-557

M-577

M-557

M-557

M-557

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

K-462

C-97

C-97

F-274

F-274

F-274

F-274

F-251

F-274


TABLE I I I

421

T r a n s f o r m a t i o n s by Genus : FUSARIUM

SPECIES

javanicum

la ter i t ium

SOURCE

CZAS

QM-524

CZAS

SUBSTRATE



4 - p r e g n e n e - 3 , 20-dione



17/3-hydroxy -4 - andros ten-3 -one aceta te

17/3-hydroxy -4 - andros ten-3 -one benzoate

17/3-hydroxy-4-androsten-3-one isobutyrate

17/3-hydroxy-4-androsten-3-one for mate

17/3-hydroxy -4 - andros ten-3 -one propionate

4 - andr osten e- 3 ,17-dione

REACTION

6/3-OH;15a-OH

Δ ;17ß-Ac-> 17a-oxa-17-C=0

A 1 ; l l a -OH;17 j3 -A c - 1 7 - C = 0

Δ ; 17/3-Ac-> 17a-oxa-17-C = 0

Δ*; 17/3-Ac-17/3-O H ; l l o - O H

Δ1; 17/3-Ac — 1 7 - C = 0

1

Δ

Δ1; 20-C = O -20/3-OH

Δ ; 17/3-OAc-17-C = 0

Δ ;17/3-OAc— 17a - o x a - 1 7 - C = 0

-

-

1

Δ ; 17ß-OFo— 17a-oxa-17-C=0

Δ ; 17/3-OFo-17-C = 0

Δ1; 17 /3 -OPr -1 7 a - o x a - 1 7 - C = 0

Δ1; 17 /3 -OPr -1 7 - C = 0

6/3-OH

15α -OH

Δ 1 ; 1 7 - C = 0 -17/3-OH

1 7 - C = 0 - 1 7 a -o x a - 1 7 - C = 0

1 7 a - o x a - 1 7 - C = 0

R E F .

C-97

C-97

F-274; F-278

F-278

F-287

F-287

F-276

F-275

F-275

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

422

TABLE I I I


SPECIES

la ter i t ium

(var. fructigenum)

lini

SOURCE

CZAS

OIAB (F-52)

OIAB ( F - l )

ATCC-9593

CBS

SUBSTRATE

17j3 -hydroxy -4 - androsten -3 -one








(6/3,15a-diOH - co r r ec t ed to 12/3,15a-diOH; Dodson, R. M. , Helv. 48; 1933, 1965)

21 -hydroxy-4 -p regnene-3 ,20-dione


17a ,21-d ihydroxy-4-pregnene-3 ,20- dione 21 - ace täte

REACTION

1

Δ

17ß-OH -1 7 - C = 0

17/3-OH-»17a-o x a - 1 7 - C = 0

Δ1; 17β-ΟΗ -1 7 - C = 0

Δ ; 17/3-OH — 17a - oxa - 17 - C= 0

Δ ; 17/3-Ac — 1 7 - C = 0

Δ1; 17/3-Ac-» 17/3-OH

17/3-Ac-* 17-C=0

1

Δ ; 17/3-Ac^l7a-o x a - 1 7 - C = 0



15a-OH

15a-OH

15a-OH

15a-OH

6/3,15a-diOH

15a-OH; Δ*-» 5 | - H

15a-OH

15a-OH

15a-OH; 21-OAc — 21-OH

R E F .

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

K-462

K-462

M-599

T-980

T-980

T-980

T-980

T-980

T-980; W-1074

T-980

T-980

TABLE I I I

T ransformat ions by Genus: FUSARIUM

423


uni CBS

FAHU

NARI

OIAB (F-85 )

Uß








[ 6/3,15a-OH - co r r ec t ed to 12/3,15a-diOH - Dodson, K .M. Helv. 48; 1933 (1965)]



12/3-OH


3/3,14/3-dihydroxy -5/3-20(22)-cardenolide 3-aceta te

3/3,14/3-dihydroxy-5/3-20(22)-cardenolide -3 - (L - rhamnoside 2 1 ,3 1 ,4 1 - t r i ace ta t e )

3/3,14/3-dihydroxy-5/3-20(22)-ca rdeno l ide -3- (D-cymaros ide 4 -acetate)

Πα-ΟΗ

oxidation products not identified

15a-OH

15a-OH; 17/3-OH - 1 7 - C = 0

15a-OH

15a-OH

6/3, 15a-diOH

15a-OH; Δ 5ξ-Η

15a-OH

12/3-OH

3 - C = 0 - 3 a - O H

3 - C = 0 - 3 a - O H ; 12/3-OH

12/3-OH

12/3-OH; 3/3-OAc ->3/3-OH

2 1 - O A c - 2 i - O H ; S ' - O A c - ^ - O H ; 4 1 -OAc^4 1 -OH

4 1 -OAc-4 1 -OH

W-1074

S-849

S-849

K-462

G-319

G-319

G-319

G-319

G-319

G-319

G-319

C-320; T-978

G-320; T-978

G-320; T-978

G-320; T-978

G-320; T-978

T-978

T-978

424

TABLE I I I


SPECIES

Uni

SOURCE

UB

SUBSTRATE

3/3,14/3-dihydroxy-5/3-20(22)-cardenolide 3-[D-glucosyi-D-g lucosy l -D-cymaros ide j

3/3,14/3-dihydroxy-5/3-20(22)-cardenolide 3-[digitoxosyl-digitoxosyl -digitoxoside -t e t raace ta te ]

3/3,14/3-dihydroxy-5/3-20(22)-cardenolide 3-[digitoxosyl-digitoxosyl-digitoxoside ]

3/3,14/3-dihydroxy-5/3-20(22)-

3/3,14/3-dihydroxy-5/3-20(22)-cardenolide 3-[D-rhamnoside]

3 - O a c e t y l - 1 4 - a n h y d r o -digitoxigenin

3/3, 5/3,14/3-trihydroxy-19-oxo-20(22)-cardenolide 3/3-D-glucoside

3/3,5/3,14/3-trihydroxy-19-oxo-20(22)-cardenolide 3/3-D-glucoside t e t raace ta te

3/3,5/3,14/3-trihydroxy-19-oxo-20(22)-cardenolide 3-[D-glucosyl -D-glucosyl -D-cymaros ide heptaacetate |

3/3, 5/3,14/3-trihydroxy-19-oxo-20(22)-cardenolide 3-[D-glucosyl -D-cymaros ide t e t raace ta te ]

3β, 5/3,14/3,19-tetrahydroxy-20(22) -cardenolide

14/3,16/3-dihydroxy-3-keto-5/3-20(22)-cardenolide

REACTION

digi toxigenin-3-[D-glucosyl-D-glucosyl-D-cymaros ide |—> digi toxigenin-3-[D-cymaros ide j

digi toxosyl-digitoxosyl-digitoxoside -t e t raace ta te —» digitoxosyl-digitoxosyl-digitoxoside

—

—

-

—

3j3-D-glucoside - 3/3-OH

3/3-D-glucoside t e t raace ta te -* 3/3-OH

strophanthidin-3-[D-hepta-ace ty l -D-g luco-sy l -D-g lucosy l -D-cymaros ide] -* s t rophanthidin-3 - [D-cymaro-side]

D-glucosyl -D-c y m a r o s i d e -te t raace ta te —> D-glucosyl -D-cymaros ide

-

3-C=0-^3ff-OH

R E F .

T-978

G-320; T-978

G-320; T-978

G-320; T-978

G-320; T-978

T-978

T-978

T-978

T-978

T-978

T-978

T-977

cardenolide 3-[D-cymaroside |

TABLE I I I

425


SPECIES

lini

lycopers ic i

SOURCE

UB

NRRL

S

TNAES

SUBSTRATE

3/3,14/3,16/3-trihydroxy-5j3-20(22) -cardenol ide

3ß, 14/3,16/3~trihydroxy-5/3-20(22) -cardenoiide 3 -D-cymaros ide 4 1 ,16-d iace ta te

3/3,14/3,16/3-trihydroxy-5/3-20(22) -cardenoiide 3 -D-cymaros ide 4 1 ,16-d iace ta te

3/3,14j3,19-trihydroxy-5a-20(22)-cardenolide

3/3, 11α, 14/3-trihydroxy-5/3-20(22) -cardenoi ide

3 - k e t o - l l a , 14/3-dihydroxy-5/3-20(22)-cardenoiide

3,11 - diketo -1 Aß - hydr oxy - 5/3 -20(22)-cardenoiide

3-keto-14/3,19-dihydroxy-4,20 (22) -cardadienol ide

3/3,14/3-dihydroxy-5/3 -16,20(22) -cardadienolide

14ß-hydroxy-3-keto-5/3-20,22-bufadienolide

3/3,14/3-dihydroxy-5/3-20, 22-bufadienolide

Sarsasapogenin

Diosgenin





17o, 21 -dihydroxy -4 -pregnene -3 ,20-dione


1 7a, 21 -dihydroxy -4 -pregnene -3 ,20-dione

REACTION

12/3-OH

41-OAc—4X-OH

4 1 - O A C - 4 1 - O H ; 1 6 - O A C - » 16-OH

-

-

-

-

-

-

12/3-OH

12/3-OH

-

-

-

15a-OH

6/3-OH

15a-OH

6ß-OH

X-OH; 15a-OH

—

R E F .

T-977

T-978

T-978

T-978

T-978

T-978

T-978

T-978

T-978

T-979

T-979

M-587

M-587

M-587

S-849; S-858; S-859

S-849; S-858

S-849; S-858

S-849; S-858

S-849; S-858

S-849

426

TABLE I I I


SPECIES

lycopers ic i

m a c r o c e r a s

mer i smoides

mic roc rea

moniliforme (imperfect s tage of Gibberelia fujikuroi)

(var. lactis)

(var. subglutinans)

(var. majus)

nivale

niveum

niveus

SOURCE

VEB

CZAS

CZAS

CZAS

ATCC-10052

CZAS

OIAB (F-7)

(F-5)

SY

CZAS

OIAB

S

SUBSTRATE






4 -androstene -3 ,17-dione


1 I ß , 21 -dihydroxy -4 -pregnene -3,20-dione








17o, 21 -dihydroxy -4 -pregnene -3,20-dione

l ,3 ,5 (10) -es t ra t r i ene-3 ,17 j3-d io l

l , 3 ,5 (10) -es t ra t r i ene-3 ,17 /3 -d io l 3-methylether

l , 3 , 5 ( 1 0 ) - e s t r a t r i e n - 3 - o l - 1 7 - o n e





1 l a -hyd roxy-4 -p regnene -3 ,20 -dione


REACTION

15a-OH

6j3-OH;15a-OH

-

6/3-OH;15a-OH

-

6/3-OH; 15a-OH

-

15a-OH

6/3-OH; 15a-OH

-

Öß-OH;15a-OH

-

6/3-OH; 15a-OH

-



15a-OH

6ß-OH

15a-OH

6/3-OH; 15a-OH

oxidation -produc ts not identified

-

—

11a-OH

R E F .

K-452

C-97

C-97

C-97

C-97

C-97

C-97

M-599

C-97

C-97

C-97

C-97

C-97

C-97

K-462

K-462

C-139

C-139

C-139

C-97

C-97

K-462

S-859

S-859

S-859

TABLE I I I

427

T r a n s f o r m a t i o n s by Genus : FUSARIUM

SPECIES

niveus

o r thoceras

oxysporum

(var. o r thoceras )

1 (var. aurant iacum)

poae

pruni

redolens

ro seum

SOURCE

TNAES

ATCC-10082

CBS

ATCC-7601

ATCC-9991

CZAS

FRI

OIAB (F-3)

OIAB (F-4)

OIAB (F-40)

OIAB (F-69)

EM(2087)

VEB

SUBSTRATE



17j3-hydroxy-4-estren-3-one

17a,21 -dihydr oxy -4 -pregnene -S j l l ^ O - t r i o n e


21 -hydroxy - 5/3 -pr egnane - 3 , 2 0 -dione aceta te



17a, 21 -d ihydroxy-4-pregnene-3 ,11 ,20- t r ione 21-aceta te













REACTION

6/3-OH

15a-OH

15a-OH

15a-OH; 17/3-OH - 1 7 - C = 0

1

Δ

15a-OH

15a-OH;21-OAc - 2 1 - O H

15a-OH

15a-OH

15a-OH;21-OAc - 2 1 - O H

6/3-OH;15a-OH

-

6/3-OH; 15a-OH

-

-

-

-



11a-OH

6/3-OH

15a-OH

6/3,15a-diOH

R E F .

S-849

M-599

D-151

D-151

C-125

M-599

M-599

M-599

M-599

M-599

C-97

C-97

C-97

C-97

S-849

K-462

K-462

K-462

K-462

M-557

R-747

R-747

R-747

428

TABLE I I I


SPECIES

roseum

sambucinum

sa rcochroum

semi tec tum

solani

SOURCE

VEB

CZAS

CZAS

CZAS

OIAß (F-42)

AMCY

ATCC-12823

AY

C

SUBSTRATE

1 7a, 21 -dihydroxy -4 -pr egnene -3,20-dione








3/3-hydroxy-16a, 17a-oxido-5-pregnen-20-one

2a-f luoro-17a, 21 -dihydroxy - 4 -pregnene - 3 , 1 1 , 2 0 - t r ione

4 -pregnene-3 ,20-d ionê (use of spores)

1 7 G , 21 -dihydroxy -4 -pregnene -3,20-dione (use of spores)

l i a , 17a, 21 - t r ihydroxy-4 -p reg -nene-3 ,20-d ione (use of spores)



3ß -hydr oxy - 5 -andr osten -17 -one



5α-pregnan-3 ,20-dione

REACTION

6/3-OH

15a-OH

6/3-OH; 15a-OH

-

6/3-OH; 15a-OH

-

6/3-OH; 15a-OH

-


11α-ΟΗ

1

Δ

1

Δ

Δ1

1

Δ

Δ 1 ' 4

1

Δ

Δ5—Δ4;3β-ΟΗ-> 3 - C = 0 ; Δ 1

-1 4

Δ 1 ' ; 3ß-OAc-*3-C = 0 ; 17/3-Ac-*17-C=0

17/3-Ac-17-C=0; 3ß-OAc-^3-C=0

17/3-Ac-»17-C=0

17/3-Ac-17-C=0

R E F .

R-747

R-747

C-97

C-97

C-97

C-97

C-97

C-97

K-462

P-746

H-401

S-835

S-835; V-1048

S-835; V-1048

V-1056·, 'vV-1095

V-1056; W-1095

V-1056

V-1056

V-1056; W-1095

V-1056

V-1056; W-1095

V-1056; W-1095

TABLE I I I

429


SPECIES

solani

*

SOURCE

C

CZAS

SUBSTRATE



17α,21 -dihydroxy -4 -pr egnene -3,20-dione


17a, 21-dihydroxy-4-pregnene -3 ,11 ,20 - t r i one

l l /3 -hydroxy-3 ,20-d ike to -4-pregnen-18-o ic acid (18—*11) lactone

l l / 3 - h y d r o x y - 3 , 2 0 - d i k e t o - l , 4 -pregnadien-18-o ic acid (18 -* 11) lactone

1 Ίβ -hydroxy -4 -andros ten - 3 -one aceta te

17/3-hydr oxy-4-andros ten-3 -one benzoate

17/3-hydroxy-4 -androsten -3 -one isobutyrate

17/3-hydroxy-4-androsten-3-one formate

17/3-hydroxy-4-androsten-3-one propionate

REACTION

17/3-Ac->17-C=0

1 5 4

Δ ; Δ —Δ ;17/3-A c ^ l 7 - C = 0 ; 3 /3 -OH-3-C=0

1 7 - C = 0

(weitere Substanz)

1

Δ

A i ;17ß- (20-C = 0-21-OH) — 17-C = 0

(weitere Substanz)

1

Δ

17/3-Ac-*17-C=0

17/3-Ac-*17-C=0; 13/3-COOH -» 13/3-H; Δ1

17j8-Ac-17-C=0; 13/3-COOH -» 13α-Η; Δ1

Δ1; 17/3-Ac — 17ß-OH

17/3-Ac - x 1 7 - C = 0 ; Δ

17ß-Ac^l7/3-OH

Δ ; 17/3-OAc -» 1 7 - C = 0

ΔΧ;17β-ΟΑο — 17a-oxa-17-C=0

-

-

Δ ; 17/3-OFo— l i a - o x a - 1 7 - C = 0

Δ1;17β-ΟΡΓ-> 1 7 - C = 0

R E F .

V-1056; W-1095

V-1056; W-1095

V-1056; W-1095

V-1056

V-1053

V-1056; W-1095

V-1056

V-1053

U-1044

U-1044

U-1044

U-1044

U-1044

U-1044

C-97

C-97

C-97

C-97

C-97

C-97

A i ;17ß- (20-C

430

TABLE I I I


SPECIES

solani

(var. aduncisporum)

(var. argi laceum)

(var. coeruleum)

(var„ redolens)

SOURCE

CZAS

IFO

SUBSTRATE

17/3-hydroxy-4-androsten-3-one propionate













REACTION

Δ1; 17 /3-OPr-17a-oxa-17-C=0

6/3-OH

15a-OH

A 1 ;17-C = 0 -17/3-OH

1 7 - C = 0 — 1 7 a -oxa-17-C = 0

A 1 ; 1 7 - C = 0 - 1 7 a -oxa-17-C = 0

1

Δ

17/3-OH-17-C=0

17/3-OH-17a-o x a - 1 7 - C = 0

Δ1; 17/3-OH-1 7 - C = 0

A1;17/3-OH->17a-o x a - 1 7 - C = 0

A1;17/3-Ac -1 7 - C = 0

A1;17/3-Ac-> 17/3-OH

17/3-Ac-17-C=0 1

Δ ; 17/3-Ac— 17a-o x a - 1 7 - C = 0

6/3-OH;15a-OH

-

6/3-OH;15a-OH

-

6ß-OH;15o-OH

-

6/3-ΟΗ;15α-ΟΗ

-1

Δ

AX;17ß-Ac — 17/3-OH

R E F .

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

C-97

N-663; N-664

N-663; N-664

TABLE I I I

431


SPECIES

solani

(var. eumart i i )

species

SOURCE

IFO

(K-101)

(K-102)

OR

uc

VEB

EM (2070)

EM (2083)

SUBSTRATE







17a, 21-dihydroxy-4-pregnene -3 ,11 ,20 - t r ione

17a ,21-d ihydroxy-4-pregnene-3, 20-dione


17a ,20/3 ,21- t r ihydroxy-4-preg-nene-3 ,11-d ione

1 7a, 21 -dihydroxy -4 -pregnene -3 ,11 ,20 - t r ione

17a -hydroxy-4 -p regnene-3 ,20-dione aceta te

3 -ketobisnor -4 - cholen -22 -al


17a, 21 -dihydroxy-4 -pregnene -3 ,20-dione

17a-hydroxy-16-méthylène-4-pregnene-3 ,20-d ione

17a, 21 -d ihydroxy-16-méthylène-4-pregnene-3 ,20-d ione

REACTION

Δ1; 17/3-Ac -> 1 7 - C = 0

Δ ; 17/3-Ac->17a-o x a - 1 7 - C = 0

5 4 1

Δ ->Δ ; Δ ; 3/3-O H - 3 - C = 0 ; 17/3-(20-C=O-21-OAc)->17a-oxa-17-C = 0

Δ1; 17/3-Ac-17a-o x a - 1 7 - C = 0

Δ1; 17/3-(20-C=O -21-OH) - 17a-o x a - 1 7 - C = 0

1.

Δ

-

1

Δ

1

Δ

Δ ;17 /3 -Ac^ l7a -o x a - 1 7 - C = 0

17 /3 -Ac-17-C=0

Δ ; 17/3-Ac -> 1 7 - C = 0

1

Δ

20-C=O—20/3-OH

1

Δ

15a-OH

15a-OH

11a-OH

11a-OH

11a-OH

R E F .

N-663; N-664

N-663; N-664

K-462

K-462

K-462

K-462

K-462

K-462

K-462

S-949

S-949

S-949

S-949

S-949

B-36

M-599

K-452

M-557

B-68

M-558

432


TABLE I I I

FUSARIUM FUSICLADIUM

TAXONOMY

(Imperf. - Moniliales)

SPECIES

species

sphaer iae

sporot r ichel la

(var. poae)

sporotr ichioides

sulphureum

udum

vasinfectum

FUSICLADUM

diospir i

SOURCE

NRRL

OIAB ( F - 8 , 3 2 , 3 4 )

OIAB (36)

OR

Takeda

CZAS

CZAS

OIAB (F-41)

ATCC-7642

ATCC-10084

ATCC-7808

TNAES (B- l )

SUBSTRATE



17û!, 21 -dihydroxy -4 -pr egnene -3,20-dione

17a,21 -dihydroxy -4 -pregnene -3 ,11 ,20 - t r ione

(virtually anaerobic)

17a,20/3 ,21- t r ihydroxy-4-pr egnene -3 ,11 -dione

17a,21 -d ihydroxy-1 ,4 -pregna-diene -3 ,11 ,20 - t r i one

3/3,14/3,16/3-trihydroxy-5j3-20(22)-cardenolide





4 -androstene -3 ,17-dione





5/3-pregnane -3 ,11 ,20 - t r i one


REACTION

hydrolysis of glycosides to aglycones (sapogenins)


-

2 0 - C = O -20/3-OH

A 1 ; 2 0 - C = O -20/3-OH

1

Δ

20-C=O -20/3-OH

3/3-OH-^3-C=0

12/3-OH

6/3-OH; 15a-OH

-

6/3-OH; 15a-OH

-

6/3-OH; 15a-OH

-


15a-OH

15a-OH

15a-OH

R E F .

K-478

K-462

K-462

S-951

S-951

S-951

S-951

K-434

K-434

C-97

C-97

C-97

C-97

C-97

C-97

K-462

M-599

M-599

M-599

S-849

433


TABLE I I I FUSIDIUM

GANODERMA GELASINOSPORA

GEOTRICHUM GIBBERELLA

TAXONOMY

(Imperf. - Moniliales) (Basidio. - Agaricales) (Asco. - Sphaeriales) (Imperf. - Moniliales) (Asco. - Hypocreales)

SPECIES

species

GANODERMA

applam (applanatum)

GELASINOSPORA

t e t r a s p o r a

GEOTRICHUM

lact is

GIBBERELLA

baccata

1 cyanea

1 fujikuroi

SOURCE

Sear le (M-61-1)

FRI

ATCC-14512

FRI

C

CBS

CBS

CBS

FAKU

IFO

Takeda

SUBSTRATE

3/3-hydr oxy - 5-andr osten -17-one


17û-(21-carboxyethyl)-17/3-hydroxy-4-andros ten-3-one gamma lactone







24-ethyl-5 ,22-choles tadien-3/3-ol




3/3,14/3,16/3-trihydroxy-5/3-20(22)-cardenol ide

REACTION

7a-OH

1 7 - C = 0 -17/3-OH

l i a - O H

7a-OH

-

15a-OH

15a-OH

15a-OH

15-OH

d, l->d-15a-OH + 1

15-OH

15a-OH

-

12/3-OH

3/3-OH-3-C = 0

3/3-OH^3-C = 0 ; 16/3-OH -1 6 - C = 0

R E F .

D-175

D-175

S-849

T-1035

S-849

U-1043

M-585; U-1043

U-1043

M-599

W-1102

M-599

M-599

S-849

N-651

K-434

K-434

434

TABLE I I I

T r a n s f o r m a t i o n s by G e n u s : GIBBERELLA


saubinetti

CBS

FRI

TBRI

17/3 - hydr oxy -1 la - methy 1 -4 -andros ten-3-one


11/3-hydroxy-4-androstene -3,17-dione



4,9(11) -pregnadiene-3 ,20-d ione





11/3,21 -d ihydroxy-4-pregnene-3,20-dione


14ß-hydroxy-3-keto-5/3-20(22)-cardenolide

3/3,14/3-dihydroxy -5/3-20(22)-cardenolide

6j3-OH

6ß-OH

15α-OH

6/3-ΟΗ

15α-OH

l l - O O (via l lß -OH) 6/3 -OH

15α-OH

6/3-OH

15α-ΟΗ

15α-ΟΗ

6/3-OH; l i a - O H

15a-OH

X-OH; 15a-

15a-OH

6β-ΟΗ

15a-OH

12/3-OH

3 - C = 0 ^ 3 a

3-C=0->3a-12/3-OH

12/3 -OH

OH

OH

OH:

U-1043

U-1043

U-1043

U-1043

U-1043

U-1043

U-1043

U-1043

U-1043

U-1043

M-599

S-849

S-849; S-858; S-859

S-849; S-858

S-859

S-849; S-858

S-858

S-849

S-849; S-858

S-858

S-859

0-699

0 -699

0-699

0 -699

C

S 15α-OH

6β-ΟΗ

TABLE I I I

TAXONOMY

435

Transformat ions by Genus: GIBBERELLA GLIOCLADIUM (Imperf. - Moniliales)

SPECIES

saubinett i

zeae

GLIOCLADIUM

catenulatum

SOURCE

TBRI

ATCC-10910

ATCC-10523

SUBSTRATE

3/3,14/3,16/3-trihydroxy-5/3-20(22)-cardenolide

3/3,14/3, 16ß-trihydroxy-5/3-20(22)-cardenolide 16 -aceta te



5a -p regnane -3 ,11 ,20 - t r i one


5 /3-pregnane-3 ,6 ,20- t r ione

3/3-hydroxy-21-ethyl-5-pregnen-20-one


4 -pregnene-3 ,20-d ione 20-cyc io-ethyleneketal

6ß -hydroxy-4 -p regnene -3 ,20 -dione


2 1 - m e t h y l - 4 - p r e g n e n e - 3 , 2 0 -dione

17a, 21 -dihy d roxy-4 -p regnene -3,20-dione

REACTION

12/3-OH

12/3-OH

16/3-OAc — 16/3-OH

12/3-OH; 16/3-OAc — 16/3-OH

15a-OH

15a-OH

17/3-Ac^l7-C=0

17/3-Ac—17-C=0

17/3-Ac^l7-C=0

17j3-Bu—17-C = 0

17/3-Ac— 17-C=0

17/3-Ac -> 17-C = 0 ;6ß -OH

6/3-OH

17/3-Ac^l7-C=0

17/3-(20-C=O-21-OH) -> 1 7 - C = 0

17/3-(20-C=O-2 1 - O H ) -1 7 - C = 0 ; 6/3-OH

17/3-Pr-*17-C=0

17a-OH-17/3-(20-C=O-21-OH) —17-C=0

17a-OH-17/3-(20-C=O-21-OH) — 17-C = 0;6/3-OH

R E F .

Q-699

0-699

0-699

Q-699

M-599

M-599

M-633

M-633

M-633

M-633

M-633; P-726

M-633; P-726

F-251

M-633

M-633

M-633

M-633

M-633

M-633

436

TABLE I I I

Transformat ions by Genus: GL IOCLADIUM

SPECIES

catenulatum

del iquescens

luteolum

roseum

SOURCE

ATCC-10523

NRRL

CBS

CBS

ATCC-10521

FRI

S

SUBSTRATE

l i a , 17a, 21 - tr ihydroxy - 4 - p r e g -nene -3 ,20-d ione

4 -pr egnene - 3 , 1 1 , 2 0 - t r ione


17a, 21-dihydroxy-4-pregnene -3 ,11 ,20- t r ione 21-aceta te

3 -ketobisnor -4 -cholen-22 -al

Diosgenin



21 -hydroxy-4 -p regnene-3 ,20-dione aceta te

3 /3 ,17a ,20a- t r ihydroxy-5a-pregnane


17α, 21-dihydroxy-4-pregnene -3,20-dione


1 I ß , 21 -dihydroxy -4-pregnene -3,20-dione

REACTION

17α-ΟΗ-17β-(20-C=0-21-OH) — 17-C = 0

17 j3 -Ac^ l7 -C=0

17a-OH-17/3-(20-C=0-21-OH) -1 7 - C = 0

17a-OH-17/3-(20-C = 0 - 2 1 - O A c H 1 7 - C = 0

20a-HC=O — 20/3-HC=O

2 2 - C = 0 - 2 2 - O H

-

~

-

17/3-(20-C=O-21-O A c H 1 7 - C = 0

17/3-(20-C=O-2 1 - O A c H 1 7 - C = 0 ; 6/3-OH

17/3-(20-C=O-21-OAc)->17-C=0

17/3-(20-C=O-21-OAc)->17-C=0; 60-OH

11α-ΟΉ-1Ίβ-(20α -OH-21-H) -> 1 7 - C = 0

17/3-(20-C=O-21-O A c H l 7 - C = 0

17/3-(20-C=O-21-OAc)-»17-C=0; 6/3-OH

-

1

Δ

1

Δ

R E F .

M-633; M-637

M-633

M-633

M-633

W-1068

W-1068

M-587

M-587

M-587

M-633

M-633

M-633

M-633

M-633

M-633

M-633

S-859

S-857; S-859

S-857; S-859

Sarsasapogenin

437


T r a n s f o r m a t i o n s by G e n u s : GLIOCLADIUM GLOEOSPORIUM (Imperf0 - Moniliales)


species

GLOEOSPORIUM

cyclaminis

foliicolum

kaki

laeticola

NG

NRRL

OR

KAG

FAKU (438)

KAG

TNAES


11/3,17a, 21 - tr ihydroxy -4 -p reg -nene -3 ,20-dione



24/3-methyl -5 ,7 ,22-choles ta -trien-3j3-ol (sole carbon source)

plant saponins

3j3-(N, N-dimethylamino) -5 -conenine




|4 -pregnene -3 ,20 -dione


|21-hydroxy-4-pregnene-3 , 20-dione




|l 7a, 21-d ihydroxy-4-pregnene-3,20-dione

uti l ization

util ization

3/3-N-(CH3)2-> 3-C = 0 ; Δ5->Δ4

6/3-OH

l l a - O H

11a-OH

6 ß , l l a - d i O H

l l a - O H

l l a - O H

l l a - O H

l l a - O H

l l a - O H

s roseum

R E F .

S-857; S-859

S-857; S-859

S-857; S-859

S-793c

S-793c

K-478

D-148

K-464

K-464

S-849

K-464

S-849; S-855

S-849; S-855

S-849; S-855

S-849; S-855

S-849; S-855

S-849; S-855; S-859

S-849

S-849

S

S

1

Δ

1

Δ

438

TABLE I I I

T r a n s f o r m a t i o n s by Genus: GLOEOSPORIUM GLOMERELLA

TAXONOMY

(Asco. - Sphaeriales)

SPECIES

laeticola

ol ivarum (taxonomically -perfect s tage of Glomerel la cingulata)

GLOMERELLA

cingulata

*

1 *

SOURCE

TNAES

KAG

NI

TNAES

ATCC-10529

ATCC-10530

ATCC-10531

ATCC-10532

ATCC-10533

ATCC-10534

SUBSTRATE






17a, 21-d ihydroxy-4-pregnene-3 ,11 ,20- t r ione


17a, 21-dihydroxy-16a-methyl-5a-pregnane-3 ,20-d ione

17a, 21-d ihydroxy-1 ,4 -p regna-d iene-3 ,20-dione



16/3-ethyl-17a,21-dihydroxy-l , 4 -pregnadiene-3 ,20-d ione


17a, 21-dihydroxy-16a-me thy 1-1 ,4-pregnadiene-3 ,20-dione

16a- te r t -bu ty l -17a , 21 -dihydroxy -5a-pregnane-3 ,20-d ione

16ß-ethyl-17a, 21-dihydroxy -5a-pregnane-3 ,20-d ione

REACTION

l l a - O H

1

Δ

2 0 - C = O -20/3-OH

Δ 1

Δ

1

Δ

1

Δ

20-C = O-> 20/3-OH

Δ1; 20-C=O -20/3-OH

l l a - O H

l l a - O H

l l a - O H

l l a - O H

l l a - O H

l l a - O H

l l a - O H

l l a - O H

l l a - O H

l l a - O H

R E F .

S-849

K-464

K-464

K-465

K-465

K-465

K-465

K-465

K-465

S-859

C-109

C-109

C-109

C-109

C-109

C-109

C-109

C-109

C-109

TABLE I I I

439

T r a n s f o r m a t i o n s by G e n u s : GLOMERELLA


cingulata ATCC-10534

fluctigena

ATCC-12097

FRI

KAG

QM-1407

TNAES

1 la, 21 -dihydr oxy -16a - methy 1 -5a -pregnane-3 ,20-d ione

17a,21-dihydroxy-16/3-methyl-5a -pregnane-3 ,20-d ione

17α, 21-dihydroxy-4-pregnene -3 ,20-dione

1 la, 21 -dihydroxy -16a - methy 1 -4 -p regnene-3 ,20-d ione

1 la, 21 - dihydr oxy -16/3 - methy 1 -4 -pregnene-3 ,20-d ione

17a,21-dihydroxy-16/3-methyl-4 -pregnene-3 ,20-d ione 2 1 -aceta te

D -nor -1 ,4 -pregnadiene - 3 , 2 0 -dione

1 la, 21 -dihydroxy - 1 , 4 -pr egnadiene-3 ,20-dione

17a, 21-dihydr o x y - 1 , 4 -pregnadiene-3 ,20-d ione 2 1 -aceta te

16j3-ethyl- 17a, 21 -dihydroxy -1,4 -pregnadiene -3 ,20-d ione

17a, 21-dihydroxy-16a-methyl -1,4 -pregnadiene -3 ,20 -dione

17a, 21 -dihydr oxy-16/3- methy 1-1 ,4-pregnadiene -3 ,20-d ione

| 3 - h y d r o x y - l , 3 , 5 ( 1 0 ) - e s t r a t r i e n -17-one


17a, 21-dihydroxy-4-pr egnene -3 ,20-dione

17a, 21 -dihydr oxy-16/3-methyl -4-pregnene -3 ,20-dione 2 1 -ace ta te


11a-OH

11a-OH

l l a - O H

l l a - O H

l l a - O H

l l a - O H ; 21-OAc-> 21-OH

l l a - O H

l l a - O H

l l a - O H ; 2 1 - O A c ^ 21-OH

l l a - O H

l l a - O H

l l a - O H

7a-OH

15a-OH

l l a - O H

6/3-OH

l l a - O H

l l a - O H ; 2 1 - O A c -21-OH

l l a - O H

C-109

C-109

C-109

C-109

C-109

C-109

R-763

C-109

C-109

C-109

C-109

C-109

L-494

L-494

S-849

K-464

K-464

C-109

S-849

440

TABLE I I I

T r a n s f o r m a t i o n s by Genus: GLOMERELLA

SPECIES

fusaroides

*

*

glycines

SOURCE

ATCC-9552

ATCC-3422

SUBSTRATE

l ,3 ,5 (10) -es t ra t r i en -3 ,17 /3 -d io l

3 - h y d r o x y - l , 3 , 5 ( 1 0 ) - e s t r a t r i e n -17-one

17a ,21-dihydroxy-16ß-methyl -5a-pregnane-3 ,20-d ione

17α, 21 -dihydroxy-4-pregnene -3,20-dione

l ,3 ,5 (10) -es t ra t r i ene-3 ,17 j3 -d io l

3-hydroxy - 1 , 3 , 5 ( 1 0 ) - e s t r a t r ien-17-one

REACTION

7a-OH

15a-OH

7a-OH; 17/3-OH -» 1 7 - C = 0

15a-OH; 17j3-OH — 1 7 - C = 0

7a-OH

15a-OH

7a-OH; 1 7 - C = 0 -17/3 -OH

15a-OH; 1 7 - C = 0 -Πβ-ΟΕ

l l a - O H

l i a - O H

7a-OH

15a-OH

7a-OH; 1 7 / 3 - O H -1 7 - C = 0

7a-OH

15a-OH

7a-OH; 1 7 - C = 0 - + 17β-ΟΗ

15a-OH; 1 7 - C = 0 — 17β-ΟΗ

R E F .

L-495; L-497

L-495; L-497

L-497

L-497

L-494; L-495; L-497

L-494; L-495; L-497

L-497

L-494; L-497

C-109

C-109

L-495; L-497

L-495; L-497

L-497

L-495; L-497

L-495; L-497

L-497

L-497

TABLE I I I

441

T r a n s f o r m a t i o n s by G e n u s : GLOMERELLA

SPECIES

glycines

gosypii (gossypii)

lagenar ium *

1 *

major *

1 *

I mume *

SOURCE

ATCC-11871

CBS

IAM

CBS

S

TNAES

CBS

KAG

SUBSTRATE

3-hydroxy- l , 3 ,5 (10 ) -e s t r a t r i en -17-one

16a- t e r t -butyl -17a, 21-dihydroxy -5a-pregnane-3 ,20-d ione


16/3-ethyl-17a, 21 -dihydroxy -5a-pregnane-3 ,20-d ione


1 7 a , 2 1 - d i h y d r o x y - l , 4 -pregnad iene- 3 ,20-dione

17a, 21-d ihydroxy-1 ,4 -pregnadiene-3 ,20-d ione 2 1 -aceta te

16a - ter t - butyl -17a ,21 -dihydroxy -1,4 -pregnadiene -3 ,20-dione



21-hydroxy-4-pr egnene-3,20-dione




17a, 21-dihydroxy-16/3-methyl -1 ,4-pregnadiene-3 ,20-d ione


REACTION

7a-OH

15a-OH

15a-OH; 1 7 - C = 0 ^ 17/3-OH

11a-OH

—

l l a - O H

11a-OH

l l a - O H

l l a - O H ; 2 1 - O A c -21-OH

l l a - O H

l l a - O H

6/3, l la-diOH

l l a - O H

l l a - O H

l l a - O H

l l a - O H

l l a - O H

l l a - O H

l l a - O H

R E F .

L-494

L-494

L-494

C-109

S-849

C-109

C-109

C-109

C-109

C-109

S-849; S-855

S-849; S-855

S-849; S-855

S-849; S-855

S-849; S-855

S-849

C-109

C-109

K-464

442

TABLE I I I

T r a n s f o r m a t i o n s by Genus: GIOMERELLA GNOMONIA

TAXONOMY


SPECIES

phacidiomorpha *

rubicola *

GNOMONIA

cingulata

e r rabunda

e ry thros toma

fimicola

f ragar iae

SOURCE

CBS

CBS

SQ

SQ

SQ

SQ

ATCC-11430

SUBSTRATE

17a, 21-dihydroxy-4-pregnene -ίΓ, 20-dione

16a - t e r t -bu ty l -17a ,21-dihydroxy -1 ,4 -pr egnadiene -3,20-dione



17a, 21-dihydroxy-16a-methyl -4-pr e gnene - 3,2 0 - dione


17a, 21-dihydroxy-16a-methyl -4 -pregnene-3 ,20-d ione


17a, 21-dihydroxy-16a-methyl -4-pregnene -3,20-dione


17a, 21-dihydroxy-16-methyl -4 -pregnene-3 ,20-d ione

17/3 - hy dr oxy - A - nor - 3 -andros ten-2-one



17a -oxa -D-homo-4-andros t ene -3,17-dione




9a- f luoro- l l j3-hydroxy-4-pregnene-3 ,20-d ione


REACTION

l i a - O H

l i a - O H

l l a - O H

2/3-OH

2/3-OH

2/3-OH

2/3-OH

2/3-OH

2/3-OH

2/3-OH

2ß-OH

1/3-OH

2/3-OH

2/3-OH

2/3-OH

2/3-OH; 16a-OH

2/3-OH

2/3-OH

2/3-OH

2/3-OH

R E F .

C-109

C-109

C-109

L-496

L-496

L-496

L-496

L-496

L-496

L-496

L-496

L-496

L-496

L-496

L-496

L-499

L-496; L-499

L-496

L-496

L-496

443

TABLE I I I

T r a n s f o r m a t i o n s by G e n u s : GNOMONIA GRAPHIOLA GUIGNARDIA GYMNOPILUS HANSENULA

TAXONOMY

(ßasidiOo - Ustilaginales) (Asco. - Sphaeriales) (Basidio. - Agaricales) iAsco. - Endomvcetales)

SPECIES

f ragar iae

GRAPHIOLA

cyl indrica

GUIGNARDIA

1 camel l iae

GYMNOPILUS

junenius

1 spec ies

HANSENULA

1 anomala

SOURCE

ATCC-11430

NI

FRI

AL (C-142)

AL (2-6-69)

NRRL

SUBSTRATE

6a-f luoro-17a, 21-dihydroxy 4 -pregnene-3 ,20-d ione

21-hydroxy-16a ,17a-oxido-4-pregnene-3 ,20-d ione

17a, 21-dihydroxy-16a-methyl -4 -pregnene-3 ,20-d ione

6 a - f l u o r o - 1 6 a , 1 7 a , 2 1 -t r i hydroxy-4 -p regnene -3 ,20 -dione 16,17-acetonide



l l j 3 ,17a ,21- t r ihydroxy-4 -pregnene-3 ,20-d ione

17a, 21 -dihydroxy-4 -pregnene -3 ,11 , 20- t r ione




Sarsasapogenin

Diosgenin


REACTION

2/3-OH

2/3-OH

2/3-OH

2/3-OH

Δ1

Δ1

Δ1

Δ1

l l a - O H

R E F .

L-496

L-496

L-496

L-496

K-465

K-465

K-465

K-465

S-849

S-825

S-825

M-587

M-587

M-587

444


TABLE I I I

HAPLOSPORELLA HEBELOMA

HELICOBASIDIUM HELICOCERAS

HELICOSTYLUM

TAXONOMY

(Imperf. - Sphaeropsidales) (Basidio. - Agaricales) (Basidio. - T re me Hales) (Imperf. - Moniliales) (Phyco. - Mucorales)


HAPLOSPORELLA

spec ies Sear le (M-1086)

HEBELOMA

s map lz ans

HELICOBASIDIUM

mompa

HELICOCERAS

WURB (M-84)

FAKU

NARI

oryzae

HELICOSTYLUM

FRI

p i r i forme ATCC

ATCC 8992




17a, 21 -dihydroxy -4-pr egnene -3,20-dione



17a ,21-dihydroxy-4 ,14 -pregnadiene-3 ,20-d ione

11/3,17a-dihydroxy-5a-pregnane-3 ,20-d ione

11/3,21 -dihydroxy-5a-pregnane-3 ,20-d ione

3a, 11/3,21-tr ihydroxy-5a-pregnane-3 ,20-d ione

l l / 3 ,17a ,21- t r ihydroxy-5a -pregnane-3 ,20-d ione

3a, 11/3,17a-trihydroxy-5/3-pregnan-20-one

1/3-OH

6/3-OH

7/3-OH

reac t ion not identified

D-165

D-165

D-165

R-778

S-849

S-849

S-849

8-OH(later shown M - 6 4 0 to be 9a-OH)

Δ14 -> 14a, 15a-oxide

9a-OH;ll /3-OH-> n-c=o 9a-OH; 11/3-CH—I n-c=o 9a-OH; 11/3-OH-n-c=o 9a-OH; llß-OH-^1 n-c=o |9a-OH; 11/3-OH— n-c=o

B - 66

H-342

H-342

H-342

H-342

H-342

TABLE I I I

T r a n s f o r m a t i o n s by G e n u s : HELICOSTYLUM

445


p i r i forme ATCC-8992 3/3,11/3,17a-trihydroxy-5/3-pregnan-20-one

l l /3-hydroxy-5/3-pregnane-3,20-dione

19 -nor -4 -p regnene -3 ,20 -d ione





11/3,17o-dihydroxy-4-pregnene-3,20-dione

11/3,21 -dihydr oxy -4 -pregnene -3 ,20-dione 21-aceta te

17α, 21 -dihydr oxy -4 -pregnene -3 ,20-dione

11/3,17a, 21- t r ihydr o x y - 4 - p r e g -nene-3 ,20-d ione 21-ace ta te

9α-OH; 11/3-OH -n-c=o 9a-OH;i l /3-OH —n-c=o 14a-OH


14α-OH

14-OH

9α-OH

8-OH (later shown to be 9a-OH)

14a-OH; 21-OAcl - 2 1 -OH

9a-OH; 21-OAc - 2 1 - O H

9a-OH;l l /3-OH - 1 1 - C = 0

9a-OH;l l /3-OH — 1 1 - C = 0 ; 2 1 -O A c - 2 1 -OH

6/3-OH

H-342

H-342

B-73

M-636

E-204; M-614

M-636

H-342

M-640

E-204

E-204

H-342

H-342

E-204: M-601;

9a-OH

11a-OH

14a-OH

M-636

E-204 M-601 M-609

9a-OH; 11/3-OH - 1 1 - C = 0 ; 21-OAc—21-OH

M-632 M-636

E-204; M-601; M-636

E-204; M-601; M-617; M-636

H-342

446

TABLE I I I

Transformat ions by Genus: HELICOSTYLUM

SPECIES

pi r i forme

species

SOURCE

ATCC-8992

IFO

NRRL

SUBSTRATE

9a- f luoro- l l /3 ,15^ , 17ö J 21 - t e t r a -hydroxy-4-pregnene-3 , 20-dione

9a - f luor o -11 ß, 1 la, 21 - t r ihy dr oxy-l , 4 -p regnad iene -3 ,20 -d ione

9a -f luor o -17a, 21 -dihydr oxy - 1 , 4 -p regnad iene -3 ,11 ,20 - t r i one

l i a , 21 -dihydroxy-4,17(20)-pregnadien-3-one

11/3,21-dihydroxy-4,17(20)-pregnadien-3 -one

17a, 21-d ihydroxy-4 ,14-pregna-d iene-3 ,20-d ione

11/3,17a, 21 - t r i hyd roxy - l , 4 , 6 -

17a, 21 -d ihyd roxy-1 ,4 ,6 -p regna -t r i e n e - 3 , 1 1 , 2 0 - t r i o n e

Diosgenin

Solasodine

Tomatidine

3ß, 14/3-dihydroxy-5ß-20(22)-cardenolide


REACTION

14a-OH

14a-OH

14a-OH

9a-OH; l l a - O H - 11-C = 0

9a-OH; 11/3-OH -» n-c=o

14

Δ -*14a,15a-oxide

9a-OH

14a-OH

9a-OH

14a-OH

7/3, l la-diOH

Ίβ,ΙΙα-άίΟΉ; 7/3-OH->7-C = 0

7β-ΟΗ

9a-OH

l l a - O H

7a-OH

9a-OH

7 a , l l a - d i O H

12/3-OH

16/3-OH

R E F .

N-669

N-669

N-669

H-342

H-342; H-344

ß - 6 6 ; S-865

G-301; G-302

G-301; G-302

G-301; G-302

G-301; G-302

H-368

H-368; H-369

S-791

S-791

S-791

S-791

S-791

S-791

N-651

N-651

K-478

pregnatr iene -3,20-dione


T r a n s f o r m a t i o n s by Genus : HELMINTHOSPORIUM (imperf. - Monmaies)

447

SPECIES

avenae

br izae

buchloes

coices (coicis)

gramineum

1 *

i r r e g u l ä r e

kusanoi

l e e r s i i

SOURCE

FRI

NI

NIHJ

OIAB (H-9)

NI

OIAB (H-10)

CBS

NI

NI

NARI

CBS

NI

OIAB

NI

OIAB (H-20)

SUBSTRATE


17«, 21 -dihydroxy-4 -pregnene -3,20-dione

1 7a, 21 -dihydroxy-4 -pregnene -3,20-dione








11)3,17a, 21 - tr ihydroxy -4 -p reg -nene -3 ,20 -dione








REACTION

—

-

-

14a-OH

-


10/3 -OH

14a-OH

6/3-OH; l l a - O H

possible side chain degrada-tion

-

1

Δ

1

Δ

-

6/3-OH

6/3-OH


6/3-OH; l l a - O H

6/3-OH

R E F .

S-849

S-849

S-849

K-460

S-849

K-460

D-153

D-153

S-849

K-465

S-849

K-460; K-465

K-465

K-465

S-849

D-153

S-849

K-460

S-849

K-460

448

TABLE I I I

T ransformat ions by Genus: HELMINTHOSPORIUM

SPECIES

lepochloae

maydis

nodulosum

oryzae

panici-meliacei (panici-mil iacei)

sat ivum

SOURCE

NI

OIAB(H-5)

OIAB1H-6)

OIAB(H-19)

NI

OIAB(H-18)

S

NI

OIAB(H-2)

OIAB(H-3)

IAM

NIHJ ( F - l - 4 0 )

OIAB(H-15)

SUBSTRATE


1 Ta, 21 -dihydr oxy -4 -pregnene -3,20-dione



17a, 21-dihydr oxy-4-pr egnene -3,20-dione










REACTION

l i a - O H



11a-OH

-


-

-

6ß-OH

-

15α-OH

15/3-OH

7a,15j3-diOH

7/3,15/3-diOH

14a,15/3-diOH

15a-OH

-


R E F .

S-849

K-460

K-460

K-460

S-849

K-460

S-849

S-849

K-460

K-460

T-1022

T-1022

T-1022

T-1022

T-1022

T-1024

S-849

K-460

TABLE I I I

T r a n s f o r m a t i o n s by Genus : HELMINTHOSPORIUM

449

SPECIES

se t a r i ae

s igmoideum

spec ies

SOURCE

NI

OIAB(H-8)

NIHJ(B-15)

NARI

OIAB1H-37)

OIAB(H-39)

OIAB(H-40)

OIAB(H-42)

MCC (1-39)

NIHJ(B-8)

NIHJ(B-36)

NIHJIB-37)

NIHJ(B-66)

NIHJ(B-69)

NIHJ(B-70)

NIHJ(B-74)

OIABÎH-12)

OIAB(H-13)

SUBSTRATE




17a, 21 -dihydroxy-4 -pregnene-3,20-dione















17a, 21 -dihydroxy -4 -p regnene -3,20-dione

REACTION

l i a - O H

l i a - O H

-

-

l i a - O H

l i a - O H

6j3-OH; l i a - O H

11/3-OH

6ß-OH; l l a - O H

7a-OH

7a-OH

-

1

Δ

1

Δ

l l a - O H

-

• -

l l a - O H

-

R E F .

S-849

K-460

S-849

S-849

K-460

K-460

K-460

K-460

K-460

M-570

M-570

S-849

S-849

S-849

S-849

S-849

S-849

S-849

K-460

K-460

450

TABLE I I I

T r a n s f o r m a t i o n s by Genus : HELMINTHOSPORIUM


species

t e r e s

t r i t i c i -vulgar is

tu rc icum

velur inum (velutinum)

zonatum

OIAß (H-16)

OIAB ^H-27)

S

OIAB (H-43)

NI

OIAB(H-25)

NIHJ

NIHJ(B-34)

NIHJ(B-51)

NIHJ(F-1-73) |

OIAB ÎH-11)

S (4068)

S

OIAB (H-30)

NARI

NIHJ

















17a, 21 -dihydroxy-4-pregnene -3 ,11 ,20- t r ione




K-460

6/3, l la-diOH

1

Δ

6/3-OH; 14a-OH

6/3-OH

2ß-OH

Δ ->5/3-H

_

K-460

S-857

K-460

S-849

K-4j60

K-460

S-849

14a-OH

S-849

S-849

S-849

K-460

S-849

S-849; S-857

S-849; S-857

S-849; S-857

S-849; S-857

S-849; S-857

K-460

S-849

S-849

1

Δ

1

Δ

1

Δ

1

Δ

451

TABLE I I I

T r a n s f o r m a t i o n s by Genus: HELMINTHOSPORIUM HEMISPORA

HENDERSONIA

TAXONOMY

(Imperf. - Moniliales) (Imperf. - Sphaeropsidales)

SPECIES

zizaniae

HEMISPORA

rogosa

HENDERSONIA

a b e r r a n s

acicola

(in mixed culture with Aspergi l lus niger [ l i a -OH])

(in mixed cul ture with Tr ichoderma album [17a-OH])

herpotr icha

1 phragmi t i s

rubi

(in mixed cul ture with Tr ichoderma nigrovi rens [17a-OH])

(in mixed cul ture 1 with Stigmina

platani [11/3-OH])

SOURCE

NI

OIABÎH-4)

FRI

MCC

ATCC-2585

NRRL-2595

NRRL-2594

MCC

NRRL-2593

SUBSTRATE


17a, 21 -dihydr oxy -4 -pre gnene -3,20-dione

l l / 3 , 17a ,21 - t r i hyd r oxy - 4 - p r eg -nene-3 ,20-d ione

17a, 21 -dihydroxy -4 -pregnene -3 ,11 ,20 - t r i one





11/3 -hydroxy-4 -p regnene -3 ,20 -dione

11/3,17a-dihydroxy-4-pregnene-3,20-dione



REACTION

oxidation -products not ideatified

1

Δ

-

1

Δ

Δ1

-

21-OH

21-OH

21-ΟΗ

21-OH

21-OH

21-OH

21-OH

21-OH

21-OH

21-OH

R E F .

K-465

K-465

K-465

K-465

K-460

S-849

D-183

M-566

M-566

M-566

D-183

D-183

D-183

D-183; M-566

M-566

M-566

452


TABLE I I I HISTOPLASMA

HORMODENDRUM HUMICOLA

HURODAKE HYALOPUS

HYDROGENOMONAS

TAXONOMY

(Asco. - Endomycetales) (Imperf. - Moniliales) (Imperf. - Moniliales) (Taxonomy Unclear) (Imperf. - Moniliales) (Schizo. - Pseudomonadales)

SPECIES

HISTOPLASMA

capsulatum

HORMODENDRUM

olivaceum

pedrosoi

vir ide

HUMICOLA

gr i sea (grisae)

HURODAKE

(Taxonomy Unclear)

HYALOPUS

nopporoensis

HYDROGENOMONAS

facilis

SOURCE

FRI

ATCC-13596

FRI

LED(Z-IO)

FRI

S (15)

FRI

ATCC-11228

SUBSTRATE








4 -andros tene-3 ,17-d ione (autotrophic)


(autotrophic and heterotrophic)


17a, 21 -dihydroxy -4-pregnene -3 ,11 ,20- t r ione

(heterotrophic)

REACTION

-

15a-OH

-

15a-OH

-

6/3-OH; l l a - O H

6/3 -OH; l l a - O H

1 7 - C = 0 - » 17/3-OH

2 0 - C = O ^ 20/3-OH

2 0 - C = O -20/3-OH

2 0 - C = O -20/3-OH

R E F .

S-849

A-9; B-58

S-849

B-56

S-849

S-849

S-849

F-228

F-228

F-228

F-228

453

T r a n s f o r m a t i o n s by Genus·.

TABLE I I I

HYGROPHORUS HYPHOLOMA HYPOCHNUS HYPOMYCES

TAXONOMY

(ßas id io . - Agar icales) (Basidio. - Agar icales) (ßas idio . - Agar icales) (Asco. - Hypocreales)


HYGROPHORUS

conicus

HYPHOLOMA

species

HYPOCHNUS

centrifugum

centrifugus

sasaki i

HYPOMYCES

aurant ius

haematococcus (var. cancr i - Ref. M-574)

AL(C-219)

NRRL-2471

S

TNAES

CBS

FAHU

IAM

CBS

OR

UC





3£-hydroxy-4-andros ten-17-one

17a -ethyl -17/3 -hydr oxy -4 -andros ten-3-one

17/3-hydr oxy-17a-propy 1-4-andros ten-3-one


11/3,17a, 21 - t r ihydroxy -4 - p r eg -nene -3 ,20-d ione




3/3-(N,N-dimethylamino)-5-conenine

5 a - p r e g n a n e - 3 , l l , 2 0 - t r i o n e


6 ß , l l a - d i O H

15a-OH

11a-OH

19-OH

19-OH

19-OH

19-OH

19-OH

11a-OH

16a-OH

3/3-N(CH3)2 -3-C = 0 : Λ 5 - Δ 4

17/3-Ac^ 17/3-OH

Δ

R E F .

S-825

D-191; M-568

S-849

S-849

S-869

S-869

S-869

S-869

S-870

S-849

S-849

D-149

D-148

M-574

F-251

454

TABLE I I I

TAXONOMY

(Schizo.

SPECIES

solani

INTESTINAL MICROORGANISMS

unidentified

IRPEX

consors

lacteus

ISARIA

farinosa

SOURCE

NG

human feces

r a t feces

IAM

FRI

IAM

FRI

IRPEX ISARIA

SUBSTRATE


17/3-hydroxy- 17a -methyl -4 -andros ten-3-one


17a, 21 -d ihydroxy-4-pregnene-3 ,11 ,20 - t r ione

5-cholesten-3j3-ol (anaerobic)

5-cholesten-3/3-ol

7-cholestenol

5,7-choiestadien-3/3-ol

5 -st igmasten-3/3-ol

17α,21 -dihydroxy -4 -pregnene -3,20-dione




(ßas id io . - Agaricales) Imperf. - Moniliales)

REACTION

Δ1; 17/3-OH — 17a-oxa-17-

c=o 1

Δ

1

Δ

1

Δ

Δ ^ δ β - Η

Δ ^ δ β - Η

Δ5— 5/3-H

Δ ^ δ β - Η

-

11α-ΟΗ

6j3-OH;l la-OH

6/3-ΟΗ; l l a - O H ; 11/3-ΟΗ

R E F .

L-525

L-525

L-525

L-525

S-914

C-133

C-133

C-133

C-133

S-849

S-849

S-849

S-849

T r a n s f o r m a t i o n s by Genus: HYPOMYCES INTESTINAL MICROORGANISMS -

(Genera not Identified)

455


TABLE I I I

KABATIELLA KAIGARADAKE KAWARADAKE

KLOECKERA LACTOBACILLUS

TAXONOMY

(Imperf. - Moniliales) (Taxonomy Unclear) (Taxonomy Unclear) (Imperf. - Moniliales) (Schizo. - Eubacter ia les)

SPECIES

KABATIELLA

phoradendr i

KAIGARADAKE

(taxonomy unclear)

KAWARADAKE

(taxonomy unclear)

KLOECKERA

apiculata

LACTARIUS

chysor rheus

vole mus

LACTOBACILLUS

brevis

(in mixed cul ture with Mycococcus sp. Δ1)

SOURCE

ATCC-11129

S(27)

S (16)

NRRL

AL(F-31)

AL(SS-15)

IFO(3345)

SUBSTRATE


12a -me thy i -4 -p regnene -3 ,11 ,20 -t r ione




Sarsasapogenin

Diosgenin




l l j 3 ,17a ,21 - t r i hyd roxy-4 -p reg -nene-3 ,20-d ione

REACTION

21-OH

21-OH

21-OH

6/3-OH; 11a-OH

6/3-OH

-

-

-



-

1

Δ

R E F .

L-498

L-498

L-498

S-849

S-849

M-587

M-587

M-587

S-825

S-825

1-428

1-428

456

TABLE I I I

T r a n s f o r m a t i o n s by Genus.· LACTOBACILLUS LENITZITES

LENTINUS LENTODIUM

LENZITES

TAXONOMY

(Taxonomy Unclear) (Basidio. - Agaricales) (Basidio. - Agaricales) (ffasidip. - Agarir.alfifi)

SPECIES

buchnen


bulgaricus


LENITZITES

betulina

sep ia r ia

s tyrac ina

tennis

LENTINUS

vulpinus

LENTODIUM

squamosum

LENZITES

abietina

SOURCE

IFO(3230)

IFO(3492)

IAM

IAM

IAM

IAM

AL (C-137)

AL (G-17)

C

SUBSTRATE

l l j 3 ,17a ,21 - t r ihydroxy-4 -p reg -nene-3 ,20-d ione

l l / 3 ,17a ,21 - t r i hyd roxy-4 -p reg -nene-3 ,20-dione









REACTION

-

1

Δ

-

—

6/3-OH; 11a-OH

-

-

-



d,l-*d-15j3-OH + 1

6j3-OH

15/3-OH

R E F .

1-428

1-428

1-428

1-428

S-849

S-849

S-849

S-849

S-825

S-825

W-1102

M-585

M-585

457


TABLE I I I

LENZITES LEPIOTA

LEPTOSPHAERIA LEUCOPAXILLUS

TAXONOMY

(Basidio. - Agaricales) (Asco. - Sphaeriales) (ßasidio. - Agaricales)

SPECIES

bebulina (betulina)

s tyrac ina

LEPIOTA

molybdites

p r o c e r a

rachodes

LEPTOSPHAERIA

1 maculans


lunata -[11/3-OH])


lunata -[llj3-OH -l l / 3 - O H - > l l - C = 0 ] )

LEUCOPAXILLUS

1paradoxus

SOURCE

S

FRI

AL(G-19)

ALIG-59)

NRRL-2368

FRI

WURB(M-44)

WURBIM-76)

C

AL(F-55)

SUBSTRATE













21 -hyd roxy - l , 4 -p r egnad i ene -3,20-dione


REACTION

-

6/3-OH

-







17a -OH

17a-OH

17a-OH

6j3, l la-diOH

R E F .

S-859

S-859

S-859

S-849

S-825

S-825

R-778

S-849

R-778

R-778

W-1107

W-1106

W-1106

S-825

i i a u c i na

458


TABLE I I I LICHTHEIMIA

LOPHOTRIChUS LYCOPERDON LYOPHYLLUM

MACROSPORIUM MARASMIUS

MARGARINOMYCES

TAXONOMY

iPhyco0 - Mucorales) (Asco. - Sphaeriales) (Basidio. - Lycoperdales) (Basidio. - Agaricales) (Imperfo - Moniliales) (Basidio. - Agaricales) (Imperf. - Moniliales)

SPECIES

LICHTHEIMIA

corymbifera

r amosa

LOPHOTRICHUS

mart in i (used in mixed culture)

LYCOPERDON

umbrinum

LYOPHYLLUM

aggregatum

MACROSPORIUM

bataticoia

MARASMIUS

s iccus

MARGARINOMYCES

species

SOURCE

SSSR

SSSR

c

NRRL-2372

AL(SS-60)

FRI

AL(SS-21)

FRI

SUBSTRATE



not given



17a, 21 -dihy droxy -4 -pregnene -3,20-dione



REACTION

l l a - O H ; 11/3-OH

11a-OH; 11/3-OH

17a-OH



2/3-OH


R E F .

E-224

E-224

W-1106; W-1107

R-778

S-825

S-849

S-825

S-849

459


T r a n s f o r m a t i o n s by Genus: MEDICAGO

MELANCONIALES MELANOSPORA METARRHIZIUM

MICROCOCCUS

(Spermatophyta - Rosales) (Imperf. - Melanconiales) (Asco. - Hypocreales) (Imperf. - Moniliales) (Schizo. - Eubacter ia les)

SPECIES

MEDICAGO (Plant-Alfalfa)

sat iva

TAXONOMIC ORDER MELANCONIALES

(genus not given)

MELANOSPORA

pa ras i t i ca (used in mixed culture)

METARRHIZIUM

anisopliae

spec ies

MICROCOCCUS

candidus

1 c i t reus


1 congloneratus

SOURCE

-

Lepetit (L-952)

C

NI

PD (M-2313)

IAM

IFO (3332)

IAM

SUBSTRATE

1 la, 21 -dihydr oxy -1 ,4 -pregna -d i e n e - 3 , 1 1 , 20-tr ione

17«, 21-dihydroxy-1 ,4 -p regna-d iene-3 ,20-dione

not given

6/3-hydroxy-3a, 5a-cvclopregnan-20-one


1 6 α , 1 7 α , 2 1 - [ 3 , 1 , 1 - 2-pyrazolino] -4 -p regnene-3 ,20-d ione



11/3,17a, 21 - t r i hyd roxy-4 -p reg -n e n e - 3 , 20-dione



REACTION

20-C=O -20a-OH

11a-OH

17a-OH

11a-OH

11a-OH

11a-OH

oxidation

-

-

-

oxidation

R E F .

L-526

T-990

W-1106; W-1107

K-483

K-483

M-593

1-414; 1-415

1-414; 1-415

1-428

1-428

1-414; 1-415 1-414; 1-415

460

TABLE I I I

Transformat ions by Genus: MICROCOCCUS

SPECIES

dehydrogenans (see a lso under genus - Flavo-bacter ium)

fiava

f la vu s

(in mixed cul ture with Mycococcus sp. A,)

lute us

lysodeikticus

pi l tonensis

pyogenus aureus

1 (in mixed cul ture with Mycococcus sp. A,)

SOURCE

NG

IAM

IFO (3242)

IAM

U9-2)

IAM

NG

IFO (3061)

SUBSTRATE

l , 3 ,5 (10 ) - e s t r a t r i ene -3 ,17 /3 -diol

5 -andros tene-3ß , 17/3-dioi

17a-ethinyl-5-androstene-3/3, 17/3-diol



3/3-hydroxy -27 -nor - 5 -choles ten-25-one










REACTION

17/3-OH — 1 7 - C = 0

Δ5->Δ4; 3/3-OH ^ 3 - C = 0

Δ5 Δ4; 3/3-OH ^ 3 - C = 0 ; 17/3-OH — 1 7 - C = 0

3/3-OI}-3-C = 0 ; Δ 5 ^ Δ

Δ 5 - Δ 4 ; 3/3-OH - 3-C = 0

3/3-OH-*3-C=0; A 5 A 4

Δ ^ Δ

Δ 5 - Δ 4 ; 3/3-OH -> 3 - C = 0

-

-

-

-

oxidation

—

oxidation

-

-

R E F .

M-546

E-212; E-217

E-217

C-84

A-14; E-213; E-214

E-214

E-214

1-414; 1-415

1-414; 1-415

1-428

1-428

1-414; 1-415

1-414; 1-415; S-849

1-414; 1-415

1-414; 1-415; S-849

T-1030

1-428

1-428

461


Transformat ions by Genus: MICROCOCCUS MICROMONOSPORA (Schizo. - Actinomycetales)

SPECIES

roseus

species

subflavus

(in mixed cul ture with Mycococcus sp. - AJ

ureae

var ians

MICROMONOSPORA

1 chalcea

SOURCE

Takeda

ATCC-13553 (IFO-3769)

ATCC-13554

ATCC-13555

IAM

IFO(3062)

IAM

(S-4)

IAM

(P-93)

ATCC-10026

SUBSTRATE

l l / 3 ,17a ,21 - t r i hyd roxy-4 -pregnene-3 ,20-d ione



l l / 3 , 17a ,21 - t r i hyd roxy -4 -p reg -nene-3 ,20-dione

17o ,21-d ihydroxy-4-pregnene-3,20-dione






e s t r an -3 -one

5a -andros tan-3-one

17a-hydroxy-5a-andros tan-3-one


l l j3 -hydroxy-4-es t ren-3-one


4 ,6 -andros t ad iene -3 ,17 -d ione

5a-pregnan-3-one



REACTION

1

Δ

1

Δ

1

Δ

1

Δ

-

-

1

Δ

-

—

oxidation

x,4 A ', enol.

1 4

Δ ' 1 4

Δ '

Λ 1 ' 1

Δ1; enol. 1

Δ X

Δ

Δ 1 ' 4

1 4

Δ '

Δ 1 ' 4

R E F .

1-431

1-431

1-431

1-431

S-849

1-428

1-428

1-414; 1-415

1-414; 1-415; S-849

1-414; 1-415

1-414; 1-415; S-849

S-867

S-867

S-867

S-867

S-864

S-864

S-864

S-867

S-867

S-867

462

TABLE I I I

Transformat ions by Genus: MICROMONOSPORA

SPECIES

chalcea

SOURCE

ATCC-10026

SUBSTRATE

5a -p regnane -3 , 11 ,20- t r ione

5/3-pregnan-3-one

l l /3-hydroxy-5/3-pregnan-3-one






l l /3-hydroxy-5/3-pregnane-3,20-dione

14a -hydr oxy -5/3-pregnane -3,20-dione

17a-hydroxy-5/3-pregnane-3,20-dione

21-hydroxy-5/3-pregnane-3,20-dione

11/3,21 -dihydr oxy -5/3-pregnane -3,20-dione

11/3,14a, 17a ,21- te t rahydroxy-5/3-pregnane -3 ,20-dione

5/3-pregnane - 3 , 1 1 , 2 0 - t r ione



11/3,21-dihydr oxy-4-pregnene-3,20-dione




11/3,14a, 17a, 21 - tetrahydroxy -4 -pregnene-3 ,20-d ione

17a, 21-dihydr oxy-14α, 15α-oxido-4-pregnene-3 ,20-d ione

REACTION

1 4

Δ ' 1 4

Δ '

A1 '* 1 4

Δ ' 1 4

Δ 1 4

Δ '

Λ 1 ' 4

A ' ' 4

1 , 4

Δ

A 1 '*

1 4

Δ

Δ4; Δ 1 ' 4

Δ 1 ' 4

Δ 1 ' 4

Δ ν

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

REF.

S-867

S-867

S-867

S-867

S-867

S-867

S-867

S-867

S-867

S-867

S-867

S-867

S-867

S-867

S-867

S-864

S-867

S-867

S-864

S-864; S-867

S-864

S-864

S-864

T A B L E I I I


463

SPECIES

chalcea

SOURCE

ATCC-10026

ATCC-12452

SUBSTRATE

11/3,17a,21-tr ihydroxy-14a, 15α-oxido-4-pregnene-3 ,20-d ione

4 - p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e

17a, 21 -dihydroxy -4 -p regnene -3 ,11 ,20- t r ione

14a, 17a ,21 - t r i hyd roxy-4 -p reg -n e n e - 3 , 1 1 , 2 0 - t r i o n e

17a, 21-dihydroxy-4,9(11)-p regnad iene -3 , 20-dione


4 ,16-p regnad iene -3 ,20-d ione

5/3-bisnor-cholan-3-one

e s t r an -3 -one

5a-andros tan-3-one

17a -hy dr oxy - 5a -andr ostan -3 -one

5a -andros tan-3 ,17-d ione

17/3-hydroxy-4-est ren-3-one



5a-pr e gnan-3 -one

5a -pregnan-3 ,11-d ione



5/3-pregnan-3-one

11/3-hydroxy -5/3-pregnan-3 -one

14a - hy dr oxy - 5/3-pr e gnan - 3 - one


20-hydr oxy-5/3-pre gnan-3-one


5/3-pr egnane-3 ,20-dione

11 ß - hy dr oxy - 5/3 -pr e gnane -3,20-dione

REACTION

1

Δ

1

Δ 1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

A*'4

1 4 .

Δ ' ; enoi.

A ' ' 4

1 , 4

Δ

Λ 1 ' 4

Δ ; enol. 1

Δ 1

Δ

A 1 ' 4

Δ 1 ' 4

Λ 1 ' 4

1 4

Δ

Λ 1 ' 4

1 , 4

Δ

Λ 1 ' 4

A 1 ' 4

1 4

Δ ' 1 4

Δ ' 1 4

Δ ' 1 , 4

Δ

R E F .

S-864

S-864

S-864; S-867

S-864

S-864

S-864

S-864

S-867

S-867

S-867

S-867

S-867

S-864

S-864

S-864

S-867

S-867

S-867

S-867

S-867

S-867

S-867

S-867

S-867

S-867

S-867

S-867

464

TABLE I I I


SPECIES

chalcea

SOURCE

ATCC-12452

SUBSTRATE

14a -hydr oxy -5/3 -pregnane -3,20-dione

1 la -hydr oxy -5/3 -pregnane -3,20-dione


11/3,21 -dihydroxy - 5/3 -pregnane -3,20-dione

l l /3 ,17a ,21- t r ihydroxy-5/3-pregnane-3 ,20-d ione

11/3,14α,17α,21 - tetrahydroxy -5/3-pregnane-3,20-dione

5/3-pregnane-3,11,20- t r ione

17a, 21 -dihydr oxy -5/3 -pregnane -3 ,11 ,20- t r ione




9a-f Iuoro- l l /3 ,17a , 21-tr ihydroxy -4-pregnene-3 ,20-d ione

11/3,14a, 17a, 21-tetrahydroxy -4-pregnene-3 ,20-d ione

17a, 21-dihydroxy-14α, 15α-oxido-4-pregnene-3 ,20-d ione

11/3,17a, 21- t r ihydroxy-14a , 15a-oxido-4 -pregnene -3 ,20-dione


17a, 21-dihydroxy-4-pregnene -3 ,11 ,20 - t r ione

14a, 17a, 21 - t r ihydroxy-4 -p reg -n e n e - 3 , 11 ,20- t r ione

17a, 21-dihydroxy-4 ,9(11)-pregna-d iene-3 ,20-d ione

17a ,21-d ihydroxy-4 ,14-pregna-d iene-3 ,20-d ione

REACTION

1>4

Δ

1 4

Δ '

4 1 , 4

Δ ; Δ

A*'4

1 , 4

Δ

1 , 4

Δ

1 4

Δ

1 4

Δ '

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ 1

Δ

1

Δ

1

Δ

1

Δ

R E F .

S-867

S-867

S-867

S-867

S-867

S-867

S-867

S-867

S-864

S-864

S-864; S-867

S-864

S-864

S-864

S-864

S-864

S-864; S-867

S-864

S-864

S-864

•



MICROMONOSPORA MILAN YEAST

MONILIA MONILIALES

MONOSPORIUM MORCHELLA MORTIELLA

(Imperf. - Moniliales) (imperf. - Moniliales) (Imperfo - Moniliales) (Asco. - Pez iza les ) (Taxonomy Unclear)

SPECIES

chalcea

spec ies

MILAN YEAST (See under genus Saccharomyces)

MONILIA

spec ies

TAXONOMIC ORDER MONILIALES

(genus not given)

MONOSPORIUM

apiospermum

MORCHELLA

c r a s s i p e s

MORTIELLA 1 (Taxonomy Unclear)

pusi l la

SOURCE

ATCC-12452

NG

NG

NRRL

Lepetit (L-1465)

FRI

NRRL-2369

FRI

SUBSTRATE


5 ß -b isnor - cholan - 3 - one


24 /3-methyl -5 ,7 ,22-choles ta t r ien-3/3-01 (sole carbon source)


plant saponins

17a, 21 -d ihydroxy-1 ,4 -p regna -diene - 3 ,2 0 -dione

1 la, 21 -dihydr oxy -4 -pr egnene -3 ,20-dione



REACTION

Δ1

Δ 1 ' 4

uti l ization

util ization

3/3-OH-»3-C=0: A 5 A 4

Δ —>Δ

-

11α-OH; 14α-OH

-


6/3-OH

R E F .

S-864

S-867

S-793c

S-793c

M-552

K-478

T-990

S-849

R-778

S-849

465

466


T r a n s f o r m a t i o n s by Genus : MORTIERELLA (Phyco. - Mucoraies)

SPECIES

MORTIERELLA

alpina

bainier i

*

candelabrum *

isabell ina

marburgens i s

*

oligospora

polycephala *

*

pusi l ia

*

tuberosa

*

SOURCE

ATCC-8979

CBS

CBS

CBS

NRRL

CBS

NRRL

CBS

CBS

CBS

SUBSTRATE

1,3, 5(10)-estratr iene-3,17/3-01





9a- f luoro- l l /3 ,17o ,21 -trihydroxy-4-pregnene-3 ,20-d ione

9a- f luoro- l l /3 , 17a,21-tr ihydroxy-4-pregnene-3 ,20-d ione

Sarsasapogenin

Diosgenin



9a- f iuoro- l l /3 ,17a ,21- t r ihydroxy-4-pregnene-3 ,20-d ione

Sarsasapogenin

Diosgenin

4-dehydr otigogenone




1 lö -hyd roxy-4 -p regnene -3 ,20 -dione

9a- f luoro- l l /3 ,17a , 21- t r ihydroxy-4-pregnene-3 ,20-d ione


9a- f Iuoro- l l /3 ,17a ,21- t r ihydroxy-4-pregnene-3 ,20-d ione

REACTION

6/3-OH

6/3-OH; 1 7 - C = 0 -»17/3-OH

6/3-OH

6/3-OH

14-OH

6β-ΟΗ

1ξ-ΟΗ

1ξ-ΟΗ

---

6/3-ΟΗ

Ιξ-ΟΗ

---

6/3-ΟΗ

Ιξ-ΟΗ

6/3-ΟΗ

6/3-ΟΗ

Ιξ-ΟΗ

6/3-ΟΗ

Ιξ-ΟΗ

R E F .

L-493; L-497

L-493

L-495

F-239

F-237

F-239

F-237

F-237

M-587

M-587

M-587

F-239

F-237

M-587

M-587

M-587

F-239

F-237

F-239

F-239

F-237

F-239

F-237

TABLE I I I

467

T r a n s f o r m a t i o n s by G e n u s : MORTIERELLA MUCOR

TAXONOMY

(Phyco. - Mucorales)

SPECIES

zonata

*

*

MUCOR

adr ia t icus

adventit ius

angulisporus

berol inensis

buntingii

chr i s t i anens i s

c i rc inel lo ides

1 corymbifer

SOURCE

ATCC-13309

SSSR

UC

SSSR

SSSR

SSSR

UC

SSSR

FAR MIT

SUBSTRATE





9a - f luoro- l l j3 ,17a ,21- t r ihydroxy-4-pregnene-3 ,20-d ione

9a- f luoro- l l /3 ,16a , 17a, 2 1 - t e t r a -hydroxy-4 -p regnene -3 ,20 -dione



17a-hydroxy-4-pregnene-3 ,20 -dione

21-hydroxy -4 -p regnene-3 ,20-dione








REACTION

6/3-OH

6/3-OH

6j3-OH

6/3-OH

1ξ-ΟΗ

1ξ-ΟΗ

6/3-OH; l l a - O H

11-OH

11-OH

11-OH

11-OH

6j3-OH;l la-OH

6/3-OH

6/3-OH

(8-OH) rev i sed 9a-OH

6/3-OH

6/3,14a-diOH

products of un-known or questionable s t ruc tu re

unknown

R E F .

F-239

F-239

F-239

F-239

F-237

F-237

E-224

M-601; M-636

M-601; M-636

M-601; M-636

M-601; M-636

E-224

E-224

E-224

M-640

E-224

C-82

C-82

C-82

468

TABLE I I I

T r a n s f o r m a t i o n s by Genus: MUCOR

SPECIES

dimorphosporus

d i spe r sus

dubius

e rec tus

geaevensis

globosus

glomerula

g r i seo cyanus

gr iseo cyanus (+)

SOURCE

SSSR

UC

UC

SSSR

SSSR

UC

SSSR

UC

ATCC-1027

ATCC-1207a

SUBSTRATE

1 7a, 21 -dihydr oxy -4 -pregnene -3,20-dione



17ö-hydroxy-4-pregnene-3 ,20-dione




17«, 21-dihydr oxy-4-pregnene-3,20-dione









21-hydroxy-4 -p regnene-3 ,20-dione acetate

17/3-hydroxy - 4 - e s t r e n - 3 -one


REACTION

6j3-OH

(8-OH) rev i sed 9α-OH

oxidation

oxidation

oxidation

oxidation

6β-ΟΗ;11α-ΟΗ

6/3-ΟΗ;11α-ΟΗ; l l ß - O H

11-OH

11-OH

11-OH


11-OH

6/3-OH; l l a - O H ; 11/3-OH

(8-OH) r ev i s ed 9a-OH

14a-OH

14a-OH

14a-OH; 21-OAc -»21 -OH

21 -OAc-21 -OH

14a-OH

14a-OH

R E F .

E-224

M-640

M-601; M-636 M-601; M-636

M-601; M-636

M-601; M-636

E-224

E-224

M-601; M-636

M-601; M-636

M-601; M-636

M-640

M-601; M-636

E-224

M-640

E-204

E-204

E-204

E-204

M-610; M-634

M-610; M-634

TABLE I I I

T r a n s f o r m a t i o n s by Genus : MUCOR

SPECIES

griseo-cyanus (+)

g r i seo-cyanus (-)

1 guil l iermondii

1 h iemal is

1 (var. albus)

SOURCE

ATCC-1207a

ATCC-1207b

AY

SSSR

ATCC-8690

ATCC-6800

NRRL-2684

SSSR

SUBSTRATE

19-nor -4 -p regnene -3 ,20 -d ione



21 -hydroxy-4 -ü regnene -3 ,20 -dione ace ta te

17a ,21-d ihydroxy-4 ,14-p regna-d iene-3 ,20-d ione

3j3-hydroxy-14a-5,20(22)-cardadienolide ace ta te



4 -p regnene-3 ,20-d ione (using spores)

6a- f luoro-17a ,21-d ihydroxy-16a-methyl -4 -pregnene -3 ,20 -dione





17a, 21 -dihydr oxy-4-p regnene-3,20-dione

REACTION

oxidation

11-OH

14a-OH

11-OH

(8-OH) r ev i sed 9a-OH

7a-OH

7a,14a-diOH

14a-OH

14a-OH;21-OAc - 2 1 - O H

14 Δ —14a, 15a-oxide

7a-OH; 3j3-OAc —3/3-OH

11-OH

11-OH

14a-OH

llj3-OH

6/3-OH

11-OH

11-OH

6/3,14a-diOH

7a,14a-diOH

6/3-OH

R E F .

M-601; M-636

M-601; M-636

M-601; M-636; M-614

M-601; M-636

M-640

C-94

C-94

M-601; M-635; M-636

M-635

B-66; S-865

C-95

M-601; M-636

M-601; M-636

S-835; V-1048

V-1042a

E-224

M-601; M-636

M-601; M-636

D-177

D-177

E-224

469

470

TABLE I I I

Transformat ions by Genus: MUCOR

SPECIES

hie m a u s

humicoia (humicolus)

humilis

hypochninus

javanicus

mandshur icus

mic rosporus

mucedo

SOURCE

uc

SSSR

SSSR

SSSR

NI

SSSR

UC

SSSR

UC

ATCC-7941

ATCC-9635

ATCC-9836

FRI

NI

SUBSTRATE



1 7a, 21 -dihydroxy -4-pregnene -3,20-dione

1 7Ö , 21 -dihydroxy -4 -pregnene -3,20-dione



3/3,14/3-dihydroxy-5/3-20(22)-cardenoiide

14/3-hydroxy-3-keto-5/3-20(22)-cardenoiide













REACTION

(8-OH) rev ised 9a-OH

6/3-OH

6/3-OH

6/3-OH

6/3, l la-diOH

6/3-OH; 11a-OH; 14a-OH

3/3-OH->3-C = 0 ; l/3-OH;7/3-OH; 1/3,7/3-diOH; 5j3,7/3-diOH

7/3-OH

6/3-OH

(8-OH) rev ised 9a-OH

6/3-OH; 11a-OH

oxidation

oxidation

oxidation

oxidation

11-OH

11-OH

11-OH

6/3-OH;lla-OH

6/3,1 l a -diOH

R E F .

Μ-640

E-224

E-224

E-224

N-682

N-682

N-682

N-682

E-224

Μ-640

E-224

M-601; M-636

M-601; M-636

M-601; M-636

M-601; M-636

M-601; M-636

M-601; M-636

M-601; M-636

S-849

N-682

TABLE I I I

471

T r a n s f o r m a t i o n s by Genus : MUCOR

SPECIES

mucedo

murorum

pa ras i t i cus

1 *

SOURCE

NI

SSSR

UC

VEB

SSSR

ATCC-6476

SUBSTRATE


3/3,14/3-dihydroxy-5ß-20(22)-cardenoiide

14/3-hydroxy-3 -keto-5/3-20(22) -cardenolide




1 7a, 21 -dihydr oxy -4 -pregnene -3 ,20-dione


19-nor -4 -p regnene-3 ,20-d ione





17a ,21-d ihydroxy-4 ,14-p regna-d iene-3 ,20-d ione

REACTION

6j3-OH;l la-OH

7j3-OH

7/3-OH

6/3-OH;l la-OH

(8-OH) r ev i sed 9α -OH

6ß,14a-diOH

6ß-OH

11α-OH

14α-OH

oxidation

11-OH

11-OH

unknown

9a-OH;21-OAc - 2 1 - O H

14a-OH

products of unknown or questionable s t ruc tu re

unknown

6j3-OH

11a-OH

14a-OH 14

Δ — 14a, 15a-oxide

R E F .

N-682

N-682

N-682

E-224

M-640

S-811

E-224

M-601

E-204; 1-424; M-601; M-614; N-682

M-636

M-601

M-601

T-980

M-640

T-980

T-980

T-980

N-682

M-601; N-682

N-682

B-66; S-865

472

TABLE I I I

T r a n s f o r m a t i o n s by G e n u s : MUCOR

SPECIES

pa ras i t i cus

*

* * *

*

*

pi r i fo rmis

plumbeus

SOURCE

ATCC-6476

SSSR

NRRL

SSSR

UC

SUBSTRATE


3a, 14/3-dihydroxy -5/3-20(22)-cardenolide

3j3,14j3-dihydroxy-5/3-20(22)-cardenolide

(Ref. N-683-acce le ra t ion of hydroxylation by pre incuba-tion with 4 - p r e g n e n e - 3 , 2 0 -dione)

3ß, 14/3-dihydroxy-17a-20(22)-cardenolide



Sarsasapogenin

Diosgenin




REACTION

3 -C=0-* 3a-OH

3 - C = 0 -3/3-OH

5/3-Η-Δ4

(via 5/3-OH)

3 α - Ο Η -3 - C = 0

1/3-OH

5/3-OH

7/3-OH

1/3,7/3-diOH

5/3,7ß-diOH

3 /3 -OH-3 - C = 0

3/3-OH— 3 - C = 0 ; 5/3-Η-Δ4

5/3-OH

3/3-OH-> 3 - C = 0


6/3-OH; l l a - O H

6/3-OH

oxidation

R E F .

N-682 N-678

N-678

N-682

N-681

N-682

1-423; N-678; N-682; N-683

N-678; N-682; N-683

N-682

N-682

N-678; N-682

N-678

N-681

N-681

M-640

E-224

M-587

M-587

M-587

E-224

M-601; M-636

TABLE I I I

T r a n s f o r m a t i o n s by Genus: MUCOR

SPECIES

plumbeus

pusi l ius

r a c e m o s u s

1 ramannianus

rouxii

1 rouxianus

SOURCE

UC

SSSR

NI

SSSR

UC

SSSR

UC

ATCC-4857

SSSR

SUBSTRATE








3/3,14/3-dihydroxy-5/3-20(22)-cardenol ide


4-pr e gnene - 3,2 0 - dione









REACTION

oxidation

oxidation

oxidation

6/3-OH; l i a - O H

l i a - O H ; 14α-ΟΗ; 6 ß , l l a - d i O H

6/3-OH; 11α-OH; 14α-OH

7/3-OH

7/3-OH; 1/3,7/3-diOH; 5/3,7/3-diOH; 3/3-OH-+3-C=0

6/3-OH

oxidation

oxidation

oxidation

(8-OH) rev i sed 9α-ΟΗ

oxidation

6/3-OH; l i a - O H


11-OH

11-OH

11a-OH

R E F .

M-601; M-636

M-601; M-636

M-601; M-636

E-224

N-682

N-682

N-682

N-682

E-224

M-601; M-636

M-601; M-636

M-601; M-636

M-640

M-601; M-636

E-224

M-640

M-601; M-636

M-601; M-636 1

E-224

473

474


Transformat ions by Genus.· MUCOR MYCENA

MYCOBACTERIUM (Basidio. - Agaricales) (Schizo. - Actinomycetales)

SPECIES

rouxianus

simplex

solani

spec ies

sphaerosporoa

spinosus

stolonifer

va r ians

vuillemini

MYCENA

strobi l inoides

MYCOBACTERIUM

album

berol inense

SOURCE

uc

uc

uc

NRRL

UC

UC

UC

SSSR

SSSR

AL (SS-75)

NG

NG

P F

SUBSTRATE




17a, 21 -dihydroxy - 4 -pregnene -3 ,20-dione



plant saponins




1 7a, 21 -dihydroxy -4 -pregnene -3 ,20-dione



5-choIesten-3/3-oI

5-cholesten-3/3-01

17ß-hydroxy-4-es t ren-3-one


4 ,6 -androstadiene -3 ,17 -dione


REACTION

oxidation

oxidation

oxidation

oxidation






6/3-OH


util ization

utilization

degradation

Δ 1

Δ 1

Δ 1

Δ1

R E F .

M-601; M-636

M-601; M-636

M-601; M-636

M-601; M-636

M-640

M-640

K-478

M-640

M-640

M-640

E-224

E-224

S-825

S-916

M-594; M-595

T-952

S-873

S-873

S-873

S-873

TABLE I I I

Transformations by Genus: MYCOBACTERIUM

SPECIES

berol inense

(In sequential fermen-tation with Cur vu 1-a r i a sp . -[11/3-OH])

1 butyricum

SOURCE

PF

PF

SUBSTRATE


17ö, 21 -dihydr oxy -4 -pre gnene -3,20-dione

9 a - f l u o r o - l l ß , 1 7 a , 2 1 - t r i -hydroxy-4 -p regnene -3 ,20 -dione

11/3,14a, 17a, 21 - te t rahydroxy-4-pregnene-3 ,20-d ione

17a, 21-dihydr oxy-14α, 15α-oxido-4-pregnene-3 ,20-d ione

l l ß , 17a ,21- t r ihydroxy-14a , 15a-oxido -4 -pregnene -3 ,20-d ione

4 ,6 -pr egnadiene -3 ,20-d ione

1 7 a , 2 1 - d i h y d r o x y - 4 , 9 ( l l ) -pregnadiene -3 ,20-dione

4 -pregnene - 3 , 1 1 , 2 0 - t r ione

14a, 17a ,21 - t r ihydroxy-4 -p r e g n e n e - 3 , 1 1 , 2 0- t r ione

17a, 21 -dihydr oxy -4 -pregnene 3,20-dione



4, 6 -andros tad iene-3 ,17-d ione


11/3,17a-dihydr oxy-4-pregnene-3,20-dione


9a- f luoro- l l j3 ,17a , 21 - t r i -hydroxy-4 -p regnene -3 ,20 -dione

l l ß , 14a, 17a, 21 - te t rahydroxy-4-pregnene-3 ,20-d ione

17a ,21-d ihydroxy-14a ,15a-ox ido-4-pregnene-3 ,20-d ione

REACTION

Δ1

Δ1

Δ1

Δ1

Δ 1

Δ1

Δ1

Δ1

Δ1

Δ1

Δ1

Δ1; enol.

Δ1

Δ1

Δ 1

Δ1

Δ1

Δ1

Δ 1

Δ 1

R E F .

S-873

S-873

S-873

S-874

S-873

S-873

S-873

S-873

S-873

S-874

S-868

• S-873

S-873

S-873

S-873

S-873

S-873

S-873

S-874

S-873

475

476

TABLE I I I

Transformat ions by Genus: MYCOBACTERIUM

SPECIES

butyricum

(in mixed cul ture with Curvular ia sp . -[11/3-OH])

cheionei

cholesterol icum

flavum

SOURCE

P F

U

NG

NG

IPB-390

SUBSTRATE

11/3,17ö, 21- t r ihydroxy-14a, 15α-oxido-4-pregnene-3 ,20-dione

4 ,6 -pregnad iene-3 ,20-d ione

17α, 21 -dihydroxy-4,9(11) -pregna-diene-3 ,20-dione

4 -pr egnene -3 ,11 ,20 - t r ione

14α, 17α, 21 - t r ihydroxy-4 -p reg -nene - 3 , 1 1 , 2 0 - t r ione


4-pregnene-3 ,20-d ione 20-cycloethyleneketal

5-choiesten-3/3-oi (sole carbon source)

5-cholesten-3j3-ol (sole carbon source)







REACTION

Δ1

1

Δ 1

Δ

1

Δ 1

Δ

1

Δ

1

Δ

utilization

utilization

Δ1; 17/3-OH-» 1 7 - C = 0

1

Δ

Δ1; 1 7 - C = 0 - > 17/3-ΟΗ

Δ1; 17β-(20β-OH-21-H)-» 1 7 - C = 0

Δ;Πβ-(20β-O H - 2 1 - H ) -17/3-ΟΗ

Δ1; 1 7 / 3 - A c ^ 1 7 - C = 0

Δ1; 17/3-Ac — 17/3-ΟΗ

Δ1; 17/3-(20-C= Ο-21-ΟΗ) -* 1 7 - C = 0

1

Δ

Δ1; 2 0 - C = O -20/3-OH

R E F .

S-873

S-873

S-873

S-873

S-874

S-868

F-251

M-594

M-594; M-595; T-952

C-100

C-100

C-100

C-100

C-100

C-100

C-100

C-100

C-100

C-100

1

TABLE I I I

T ransformat ions by Genus: M Y C O B A C T E R I U M

477

SPECIES

flavum

fortuitum

1 friedmannii

SOURCE

IPB (390)

IMJ(SG-988)

P F

SUBSTRATE

17a,21-dihydroxy-4-pregnene-3,11,20-trione

17a, 21-dihydroxy -1,4-pregna-diene-3,11,20-trione

3a-hydroxy - 5a-andr ostan-17-one

3a-hydroxy-5/3-androstan-17-one




4,6-androstadiene-3,17-dione


11β, 17α-dihydroxy-4-pregnene-3,20-dione


REACTION

Δ1

Δ*;20-Ο=Ο-> 20/3-OH

20-C=O-20/3-OH

3a-OH—3-C=0, Δ4

3a-OH->3-C=Q Δ1'4

3a-OH-3-C=0; Δ Ι Μ .

9a-OH; rev. aldol. ; enol. ; 9-C=0-9^-OH

3a-OH^3-C=0; Δ4

3a-OH-3-C=0; Δ1 '4

3a-OH-^3-C=0; Δ1'4; 9a-OH; rev. aldol. ; enol. ; 9-C=0^9£-OH

Δ1; Δ 5 - Δ 4 ; 3/3-OH — 3-C=0

Δ 5 - Δ 4 ; 3/3-OH ^ 3 - C = 0

A 1. A 5 A 4·

Δ ; Δ - Δ ; 3/3-OH-»3-C=0; 9a-OH; rev. aldol. ; enol. ; 9-C=0-9£-OH Δ1; enol.

Δ1

1

A

A1

Δ 1

1

Δ

REF.

C-100; C-101

C-100; C-101

C-100

S-818

S-818

S-818

S-818

S-818

S-818

S-818

S-818

S-818

S-873

S-873

S-873

S-873

S-873

S-873

478

TABLE I I I


SPECIES

friedmannii

(in mixed cul ture with Curvular ia sp . -[11/3-OH])

hyalinum

lacticola

SOURCE

P F

NG

ATCC-9626

ATCC-12297

NG

P F

SUBSTRATE



17a ,21-dihydroxy-14a ,15a-oxido-4-pregnene-3 ,20-d ione

l l /3 ,17a ,21- t r ihydroxy-14a ,15a-oxido-4-pregnene-3 ,20-d ione


17a, 21 -dihydroxy -4 ,9 ( l l ) -p regna-d iene-3 ,20-d ione

4 - p r e g n e n e - 3 , l l , 2 0 - t r i o n e

14a, 17a, 21 - tr ihydroxy -4 -pr egnene -3 ,11 ,20 - tr ione

17a, 21-dihydroxy-4-pr egnene -3, 20-dione

5-cholesten-3/3-ol

17a, 21-dihydroxy-4-pr egnene -3, 20-dione


17a ,21-d ihydroxy-6a ,16a-d i -me thy l -4 -p regnene -3 ,11 ,20 -t r ione

5-cholesten-3/3-01 (Ref. T-952, T-1030 -sole carbon source)



4 ,6 -andros tad iene-3 ,17-d ione


11/3,17a-dihydroxy-4-pregnene -3,20-dione

17a, 21-d ihydroxy-4-pregnene-3, 20-dione

REACTION

Δ

Δ

Δ

Δ

Δ

Δ

Δ

Δ1

Δ

utilization

Δ1; 2 0 - C = O -20/3-OH

1

Δ

1

Δ

utilization

Δ ; enol. 1

Δ 1

Δ 1

Δ

1

Δ

1

Δ

R E F .

S-873

S-874

S-873

S-873

S-873

S-873

S-873

S-874

S-868

S-916

S-945

T-1005

A-24; A-25

M-595; S-916; T-952; T-1030

S-873

S-873

S-873

S-873

S-873

S-873

TABLE I I I

T ransformat ions by Genus: MYCOBACTERIUM

479

SPECIES

lacticola

1 (in mixed cul ture with Curvular ia sp . -[11/3-OH])

1 luteum

phlei

1 (in mixed cul ture 1 with Curvular ia lunata

-NRRL-2380-[l l /3-OH

SOURCE

P F

NG

AMCY

ATCC-354

ATCC-10142

SUBSTRATE



17a, 21 -dihydroxy-14a, 15a-oxido-4-pregnene-3 ,20-d ione

11β, 17α, 21- t r ihydroxy-14a , 15α-oxido-4-pregnene-3 ,20-d ione


17a ,21-d ihydroxy-4 ,9 ( l l ) -p regna-d iene-3 ,20-d ione

4 -pr egnene - 3 , 1 1 , 2 0 - t r ione

14a, 17a, 21 - tr ihydroxy -4 -pr eg -nene - 3 , 1 1 , 2 0 - t r ione


5-cholesten-3/3-ol

11 /3 ,17a ,21- t r ihydroxy-4-preg-nene-3 ,20-d ione

11/3,21 -dihydroxy -4 -p regnene -3,20-dione

6a, 9a -d ib romo- l l /3 ,17a , 21 - t r i -hy dr oxy -16 - me thy lene - 4 -p regnene-3 ,20-d ione

6a, 9a -d i f luoro- l l /3 ,17a , 2 1 - t r i -hydroxy -16 - mé thy lène-4-pregnene-3 ,20-d ione 2 1 -propionate

6a-fluoro -17a-hydroxy-21 -methyl-4 , 9 ( l l ) - p r e g n a d i e n e - 3 , 2 0 -dione

2a- f luoro-17a ,21-d ihydroxy-4-pregnene - 3 , 1 1 , 2 0 - t r ione




4 ,6 -androstadiene -3 ,17 -dione

REACTION

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ 1

Δ

1

Δ 1

Δ

1

Δ

utilization 1

Δ

1

Δ

1

Δ

Δ1; 21-OPr-> 21-OH

1

Δ

1

Δ

Δ1; 14α-ΟΗ

1

Δ ; enol. 1

Δ 1

Δ

R E F .

S-873

S-874

S-873

S-873

S-873

S-873

S-873

S-874

S-868

S-916

F-231

S-873

A-7

A-7

H-391

H-401

S-868

S-873

S-873

S-873

TABLE I I I

Transformat ions by Genus.· MYCOBACTERIUM

SPECIES

phlei

ranae

SOURCE

ATCC-10142

ATCC-12298

NG

P F

ATCC-110

SUBSTRATE

1 la -hydroxy-4-pr egnene-3 ,20-dione



9a- f luoro- l l /3 ,17o,21- t r ihydroxy-4-pregnene-3 ,20-d ione

17a, 21-dihydroxy-14o, 15a-oxido-4-pregnene-3 ,20-d ione

11/3, 17a, 21 - t r ihydroxy-14a ,15a-oxido - 4 -pr e gnene - 3 , 2 0 - dione

4 ,6 -p regnad iene-3 ,20-d ione

d iene-3 ,20-dione


l l ß , 1 7 a , 2 1 - t r i h y d r o x y - 6 a , 1 6 a -dimethyl-4 -pregnene - 3 , 2 0 -dione

5-cholesten-3/3-ol (Ref. T-952 ,T-1030 -sole carbon source)

11/3,14α, 17a ,21- te t rahydroxy-4-pregnene-3 ,20-d ione

14a ,17a ,21 - t r i hyd roxy-4 -p reg -nene -3 ,11 ,20 - t r i one



4 ,6 -andros tad iene-3 ,17-d ione



17a, 21-dihydroxy-4-pregnene-3 ,20-dione

9a-f luoro- l l j3 ,17a , 21- t r ihydroxy-4-pregnene-3 ,20-d ione

REACTION

Δ

Δ

Δ

Δ

Δ

Δ

Δ

Δ

Δ

Δ

utilization

1

Δ

1

Δ

Δ ; enol. 1

Δ 1

Δ 1

Δ

1

Δ

1

Δ

1

Δ

R E F .

S-873

S-873

S-873

S-873

S-873

S-873

S-873

S-873

S-873

A-24; A-25

M-594; M-595; S-916; T-952; T-1030

S-874

S-874

S-873

S-873

S-873

S-873

S-873

S-873

S-873

480

17ö,21-dihydroxy-4,9(ll)-pregna-^

TABLE I I I


481

SPECIES

ranae

(in mixed cul ture with Curvular ia sp. -[Πβ-ΟΗ|)

rhodochrous

SOURCE

ATCC-110

NC

P F

ATCC-12674

SQ(SC-2318)

SUBSTRATE

11/3, 14α, 17a ,21- te t rahydroxy-4-pregnene-3 ,20-d ione

17a,21-dihydroxy-14a,15a-oxido-4-pregnene-3 ,20-d ione

11/3,17a, 21 - t r ihydroxy-14a , 15a-oxido-4-pregnene-3 ,20-d ione


17a ,21-d ihydroxy-4 ,9 ( l l ) -p regna-d iene-3 ,20-d ione

4 -p r egnene -3 ,11 ,20 - t r i one

5-cholesten-3/3-ol

14a, 17a ,21 - t r i hyd roxy-4 -p reg -nene - 3 , 1 1 , 2 0 - t r ione








9a- f luoro- l l /3 ,16a , 17a, 2 1 - t e t r a -hydroxy - 4 - p r e g n e n e - 3 , 2 0 -dione

6a, 9a-d i f luoro- l l /3 ,16a , 17a, 2 1 -t e t r ahydroxy-4 -p regnene-3,20-dione

9a- f luoro- l l /3 ,16a , 17a, 2 1 - t e t r a -hydroxy-1 , 4 -pr egnadiene -3,20-dione

9a- f luoro- l l /3 ,17a ,20 /3 ,21- te t ra -hydroxy-1 ,4 -p r egnadiene -3 ,20-dione

REACTION

1

Δ

1

Δ

1

Δ

1

Δ 1

Δ

1

Δ

utilization 1

Δ

1

Δ

1

Δ

1

Δ 1 4

Δ ' 4 1 4

Δ ; Δ 1

Δ 1

Δ

1

Δ

20-C=O-20 /3 -OH

1

Δ

20-C=O-20 /3 -OH

A ^ H ; 2 0 - C = O -+20/3-OH

20/3-OH-20-C=O

R E F .

S-874

S-873

S-873

S-873

S-873

S-873

M-594

S-874

S-868

F-232

S-890

S-890

S-890

S-890

T-1002

G-296; S-890; T-1002

G-296

S-890

G-296

G-296

G-294

482

TABLE I I I


SPECIES

rhodochrous

rubroper t inc tum [rhodochrous - J„ ßac t .

7 3 : , 15 (1957)]

salmonicolor

smegmat i s

SOURCE

SQ(SC-2318)

SQ(SC-2921)

WISC

SQ(SC-2753)

NG

NG

ATCC-278

ATCC-361

ATCC-12051

ATCC-12549

SUBSTRATE

9a-f luoro- l l /3 ,16α, 17α, 20/3,21-pen tahydroxy-1 ,4 -p regna-d iene-3 ,20-dione

5-choiesten-3/3-ol


9a- f luoro- l l /3 ,17a , 21 -trihydroxy-4-pregnene-3 ,20-d ione

17/3-hydroxy-A-nor-3-androsten-2-one


9a- f iuoro- l l /3 ,17a ,21- t r ihydroxy-4-pregnene-3 ,20-d ione

(Ref. T-952 - sole carbon source)

5-cholesten-3/3-01 (sole carbon s o u r c e )




11/3,14a, 17a, 21- te t rahydroxy-4-pregnene-3 ,20-d ione

17a ,21-d ihydroxy-4-pregnene-3 ,11 ,20- t r ione

14a, 17a, 21 - t r ihydroxy-4 -p reg -nene - 3 , 1 1 , 2 0 - t r ione



17α, 21 -dihydroxy- 4 -pregnene -3,20-dione 21-aceta te

REACTION

20/3-OH -» 20-C=O

Δ 5 ^ Δ 4 ; 3 β - Ο Η ^ 3 - C = 0

1

Δ 1

Δ

9a-OH;17/3-OH - 1 7 - C = 0

9a-OH 1

Δ

utilization

utilization

i Δ

1

Δ

1

Δ

2 0 - C = O -20/3 -OH

1

Δ

1

Δ

1

Δ

ι Δ

Δ ; 2 1 - O A c -21-OH

14α-OH; 21-OAc - 2 1 - O H

Δ ; 21-OAc — 21-OH

14α-OH; 21-OAc -> 21-OH

R E F .

G-294; G-296

T-1005

T-1005

T-1005

S-885

S-885

T-1005

S-916; T-952

T-952

S-873

S-872; S-873

S-873

S-873

S-873; S-874

S-873

S-873; S-874

S-873

S-873

S-873

S-873

S-873

r u b r um 5-cholesten-3i3-ol

TABLE I I I


483


smegmat i s IMJ(SC-98) 3a-hydroxy-5a-andros tan-17-one

3α -hydr oxy - 5/3 -andros tan -17 -one



3 a - O H - 3 - C = 0 ; Δ 4

3a-OH->3-C = 0 ; A l » *

9a-OH; 3a-OH - 3 - C = 0 ; Δ 1 ' 4 ; r ev . aidol. ; enol.

3 a - O H - 3 - C = 0 : Δ Ι Μ ; 9α-OH; r ev . aldoL ; enol . ; 9 - C = 0 - 9 4 - O H

3 a - O H - 3 - C = 0 ; Δ 4

3a-OH 3-C=0;

9a-OH; 3a-OH - 3 - C = 0 ; Δ 1 ' 4 ; r ev . a l do l . , enol.

3a-OH 1>4 .

3-C=0 ; Δ ; " 9α-ΟΗ; r ev . aldol. ; enol. ; 9 - C = 0 ^ 9 £ - O H

Δ5— Δ4; 3/3-OH ^ 3 - C = 0

Δ - Δ -3j3-OH +3-C=0

9α-ΟΗ; Δ1; Δ 5 - Δ 4 ; 3/3-OH ^ 3 - C = 0 ; r ev . aldol. ; enol.

Δ1; Δ 5 - Δ 4 ; 3 j 3 - O H - 3 - C = 0 ; 9a-OH; r ev . aldol . ; enol. ; 9 _ 0 = θ - 9 ξ - Ο Η

Δ4->5α-Η

3 - C = 0 ^ 3 a - O H ; Δ 4 - 5 α - Η

Δ1; 9α-ΟΗ; rev . aldol . : enol.

S-818

S-818

S-818

S-818

S-818

S-818

S-818

S-818

S-818

S-818

S-818

S-818

S-820

S-820

S-820

S-820

1

Δ

484

TABLE I I I


SPECIES

smegmat i s

(in mixed cul ture with Curvular ia sp . - [ l lß-OHp

SOURCE

IMJ (SG-98)

NG

NRRL-B-ieo1?

P F

SUBSTRATE




3a, 12a-dihydroxy-5ß-cholanic acid


5-cholesten-3/3-ol (Ref. S-793C sole carbon source)

5-cholesten-3/3-01 succinate

24/3-methyl-5, 7 ,22-cho les ta -tr iene-3j3-ol

9a - f luoro - l l /3 ,17a ,21- t r ihydroxy-6α, 16α-dimethyl-4-pre gnene-3,20-dione


REACTION

Δ1; 9a-OH; r ev . a idol. ; eno l . ; 9-C=0 - 9 ξ - 0 Η

Ä;17j3-Ac-»17-c=o 9α-ΟΗ; Δ1; r ev , aldol. ; eno l . ; 17/3-Ac ->17-C=0

17/3-Ac-»17-C = 0 ; Δ1; 9α-OH; r ev . aldoL; eno l . ; 9 - C = 0 ^ 9 ξ - Ο Η

degradation [ A , B ] t o C 1 3 H20Û3

degradation [ A , B j t o C 1 5 H2204

degradation [ A , B l t o C 1 5 Η « 0 3

utilization

pa r t i a l u t i l iza-tion

utilization

Δ 1

Δ1

R E F .

S-820

S-820

S-820

S-820

S-821

S-819

S-821

S-915

S-915

S-915

S-915

S-793c; S-915

S-915

S-793c

A- 24; A- 25

S-868

TABLE I I I


485

SPECIES

smegmat i s

spec ies

Baci l lus megather ium ΜΑΊ)

*

thamnopheos

SOURCE

SQ(SC-1684)

NG

SSSR (193)

SSSR(B-5)

NG

P F

SUBSTRATE

9 a - f l u o r o - l l / 3 , 1 7 a , 2 1 - t r i -hydroxy-4 -p regnene -3 ,20 -dione

5-cholesten-3/3-ol


17a,21 -d ihydroxy-4-pregnene-3 ,11 ,20 - t r ione

17a, 20/3,21 - t r ihydroxy-4-pregnene-3 ,11-d ione 20/3,21-diacetate


5-choiesten-3/3-ol






1 la. 21 -dihydroxy -4 -pregnene -3,20-dione

9 a - f l u o r o - l l / 3 , 1 7 a , 2 1 - t r i -hyd roxy-4 -p regnene -3 ,20 -dione

11/3,14a, 17a ,21- te t rahydroxy-4-p regnene-3 ,20-d ione

17a, 21-dihydroxy-14a, 15a-oxido-4-p regnene-3 ,20-d ione

11/3 ,17a ,21- t r ihydroxy-14a ,15a-oxido - 4 -pr e gnene - 3 ,2 0 - dione

4 , 6 - p r egnadiene-3 ,20-dione

I

REACTION

Δ1

3 / 3 - O H - 3 - C = 0 : Δ 5 - Δ 4

3 / 3 - O H - 3 - C = 0 ; Δ5->Δ4; 6-C = 0

cholesterol—* r ing A cleavage to C26H4403

1

Δ

Δ1

20/3-OAc^20/3-OH; 21-OAc-> 21-OH

2 0 - C = O - 2 0 / 3 -OH

util ization

Δ ; enol.

Δ1

Δ1

Δ1

Δ1

Δ1

Δ1

Δ1

Δ 1

Δ 1

Δ1

R E F .

T-1005

S-930; L-524

S-930

S-930

K-476

K-477

S-917

S-917

M-594

S-873

S-873

S-873

S-873

S-873

S-873

S-873

S-874

S-873

S-873

S-873

(in mixed culture with

486

TABLE I I I


SPECIES

thamnopheos

(in sequential fe rmenta-tion with Curvular ia sp. [11/3-OHD tuberculos is (3CG-st ra in)

SOURCE

P F

IMJ

PF

SUBSTRATE



14a ,17a ,21 - t r i hydroxy-4 -p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e




3ß-hydroxy-5-andros ten -17 -one



4 ,6 -andros tad iene -3 ,17-d ione




REACTION

Δ1

1

Δ

Δ1

Δ1

3 a - O H ^ 3 - C = 0 : Δ4

3 a - O H ^ 3 - C = 0 ; Δ 1 ' 4

3 a - O H ^ 3 - C = 0 : Δ 1 ' 4 ; 9a-OH; rev . aldol . ; enoliz. ; 9 - C = 0 - * 9 | - O H

3 a - O H - 3 - C = 0 ; Δ4

3 a - O H - » 3 - C = 0 : Δ 1 ' 4

3 a - O H - 3 - C = 0 ; Δ 1 ' 4 ; 9a-OH; rev . aldol. ; enol. ; 9 -C=0-*9£-OH

Δ1; Δ5->Δ4; 3/3-OH^3-C=0

Δ5-*Δ4; 3/3-OH ^ 3 - C = 0

Δ1; Δ 5 - Δ 4 ; 3/3-OH-+3-C=0; 9α-OH; rev . aldol. ; enol.; 9 - C = 0 - 9 | - O H

Δ ; enol.

Δ 1

Δ1

Δ1

Δ 1

Δ1

REF.

S-873

S-873

S-874

S-868

S-818

S-818

S-818

S-818

S-818

S-818

S-818

S-818

S-818

S-873

S-873

S-873

S-873

S-873

S-873

TABLE I I I

487

Transformat ions by Genus·. MYCOBACTERIUM MYCOCLADUS MYCOCOCCUS

TAXONOMY

(Phyco. - Mucorales) iSchizo. - Actinomycetales)

SPECIES

tuberculos is

(in sequential f e rmenta -tion with Curvular ia sp. [11/3-OH])

MYCOCLADUS

1 hyalinus

MYCOCOCCUS

1 species

SOURCE

P F

SSSR

ATCC-13556 (IFO-3574)

SUBSTRATE


l l / 3 ,14a ,17a ,21 - t e t r ahydroxy-4-pregnene-3 ,20-d ione

17a, 21-dihydroxy - 14o, 15a-ox ido-4 -p regnene -3 ,20 -dione

l l j 3 ,17a ,21- t r ihydroxy-14a ,15a -oxido-4-pregnene-3 ,20-d ione

4 ,6 -pr egnadiene -3 ,20-dione

1 7 a , 2 1 - d i h y d r o x y - 4 , 9 ( l l ) -pr egnadiene-3 ,20-dione

4 -p r egnene -3 ,11 ,20 - t r i one

14a, 17a ,21- t r ihydroxy-4 -p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e







9a- f luoro- l l /3 ,17a , 21 - t r i -hydroxy-4 -p regnene -3 ,20 -dione


REACTION

Δ1

1

Δ

1

Δ

Δ1

1

Δ 1

Δ

1

Δ 1

Δ

1

Δ

l l a - O H

Δ1

1

Δ

Δ1

l

Δ

Δ1

1

Δ

R E F .

S-873

S-874

S-873

S-873

S-873

S-873

S-873

S-874

S-868

E-224

1-429

1-429

1-429

1-429

1-429

1-429

TABLE I I I

Transformat ions by Genus: MYCOCOCCUS

SPECIES

spec ies

(in mixed cul ture with: Acetobacter acet i

IFO-3169

Acetobacter xylinum IFO-3174

Achromobacter liquidum IFO-3084

Aerobacter arogenus IFO-3321

Agrobacter ium tumefaciens IFO-3058

Baci l lus ce reus IFO-3466

Bacil lus c i rcu lans IFO-3029

Bacil lus pymilus IFO-3020

Bac te r ium mycoides IFO-3040

Erwinia carotovora IFO-3380

Escher ichia coli IFO-3043

Flavobacter ium flavescens IFO-3058

Lactobacil lus b rev is IFO-3345

Lactobacil lus buchneri IFO-3230

Lactobacil lus bulgaricus IFO-3492

Micrococcus c i t r eus IFO-3332 )

SOURCE

ATCC-13557 (IFO-3588)

IFO (AJ

SUBSTRATE


REACTION

Δ1

1

Δ

Δ 1

Δ 1

Δ1

Δ 1

Δ1

Δ 1

Δ1

Δ1

Δ1

1

Δ

R E F .

1-429

1-428

1-428

1-428

1-428

1-428

1-428

1-428

1-428

1-428

1-428

1-428

1-428

1-428

1-428

1-428

1-428

488

TABLE I I I

T ransformat ions by Genus: MYCOCOCCUS

SPECIES

species (in mixed cul ture with Micrococcus flavus -IFO-3242

Micrococcus pyogenus - IFO-3061

Micrococcus sub-flavus- IFO-3062

Pseudomonas aeruglnosa-IFO-3505

Pseudomonas fragi -IFO-3458

Pseudomonas f luor-escens - IFO-3459

Pseudomonas g rav -eolens - IFO-3460

Pseudomonas sp. -TAKEDA - B - l , B - 6 , ß - 7 , ß - 9 , 3 - 2 4 , B - 2 9 , B - 3 4 , 3 - 3 6 , 3 - 3 8 , B - 3 9 , B - 4 4 , B - 4 9

1 Pseudomonas s t r i a -faciens - IFO-3309

Sarcina albida -IFO-3063

Sarcina lute a -IFO-3232

Ser ra t i a m a r c e s c e n s -IFO-3046

1 Vibrio pe rco lans -IFO-3348

Xanthomonas malvacerum - IFO-3383)

SOURCE

IFO

SUBSTRATE

l l / 3 ,17ö ,21 - t r i hyd roxy-4 -p reg -nene-3 ,20-d ione

REACTION

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

R E F .

1-428

1-428

1-428

1-428

1-428

1-428

1-428

1-428

1-428

1-428

1-428

1-428

1-428

1-428

489

490


MYCOGONE T r a n s f o r m a t i o n s by Genus: ^ ^ £ * L L A

MYROTHECIUM NADSONL\

(Imperf. - Moniliales) (Schizo. - Pseudomonadales) (Asco. - Sphaericales) (Imperf. - Moniliales) (Asco. - Endomycetales)

SPECIES

MYCOGONE

jaepii

MYCOPLANA

bullata

dimorpha

MYCOSPHAERELLA

hori i

la tebrosa

MYROTHECIUM

ror idum

species

NADSONIA

fulvescens

SOURCE

FRI

NG

NRRL

TNAES

CBS

OR

AMCY

NRRL

NRRL

SUBSTRATE



Sarsasapogenin

Diosgenin


1 7 a , 2 1 - d ihydroxy-4-pregnene-3,20-dione



17a-ethyl-17/3-hydroxy-4-e s t r en -3 -one

3ß-hydroxy-16a ,17a-ox ido-5-pregnen-20-one

plant saponins

Sarsasapogenin

Diosgenin


REACTION

l i a - O H

16/3 -OH

1 6 - C = 0 (via-16/3-OH)

16j3-OH

16/3-OH

l i a - O H

R E F .

S-849

T-1030

M-587

M-587

M-587

S-849

D-149

D-149

S-950

S-950

P-746

K-478

M-587

M-587

M-587

491


T r a n s f o r m a t i o n s by Genus: NAEMATOLOMA NAUCORIA

NEOCOSMOSPORA NEUROSPORA

(ßas id io . - Agaricales) (Basidio. - Agaricales) (AscOo - Hypocreales) (Asco. - Sphaeriales)

SPECIES

NAEMATOLOMA

subla tera t ium

NAUCORIA

confragosa

NEOCOSMOSPORA

1 vas infecta

NEUROSPORA

c r a s s a

SOURCE

AL(H-6)

VEB

A U C - 1 7 2 )

ATCC-12717

ATCC-10336

NG

WFEB(74)

SUBSTRATE



14o-hydroxy-4-p regnene-3 ,20-dione


5ß-pregnane-3 ,20-d ione



21-hydroxy-4-pr egnene-3 ,20-dione

21 -hydroxy-4 -p regnene -3 ,20 -dione acetate

4 -pregnene - 3 , 1 1 , 2 0 - t r ione


5-choles ten-3ß-ol (sole carbon source)

24/3-methyl -5 ,7 ,22-nholes ta-tr iene-3/3-ol (sole carbon source)


REACTION


6/3,14a-diOH

6/3-OH

6/3,17a-diOH

17/3-Ac^ 17/3-OH

17/3-Ac-> 17β-ΟΗ

17/3-Ac — 17/3-OH

17j3-(20-C=O-21-OH)-17 j3-OH

nß-(2o-c=o-21-OAc) ^17 /3 -OH

1 7 / 3 - A c -17j3-OH

X-OH

util ization

uti l ization

9a-OH

R E F .

S-825

S-811

S-811

S-825

S-881

S-881

S-881

S-881

S-881

S-881

M-601; M-624; M-636

S-793c

S-793c

S-937

492

TABLE I I I

Transformat ions by Genus: NEUROSPORA NIGROSPORA

TAXONOMY


SPECIES

sitophila

species

NIGROSPORA

oryzae

spec ies

SOURCE

ATCC-9278

FRI

Sear le (M-714J

ATCC-8667

ATCC-12771

FRI

ATCC-12773

SUBSTRATE

5ß-pregnane-3 ,20-d ione

4 -p regnene -3 ,20 -d ione







17ß-hydr oxy-4-andros ten-3-one





16a ,17a -ox ido-4 -p regnene -3 ,20 -dione





REACTION

X-OH

X-OH

X-OH

X-OH

X-OH

X-OH

7a-OH

X-OH

X-OH

15a-OH

12|3,15a-diOH

X-OH

X-OH

X-OH

15/3-OH

15a-OH; 2 1 -OAc-*21-OH

6/3-OH; l i a - O H

X-OH

R E F .

M-601; M-624

M-601; M-624

M-601; M-624

M-601; M-624

M-601; M-624

M-601; M-624

S-849

T-1037

M-596

M-596

M-596

M-596

M-596

M-596

M-596

M-596

M-596

S-849

M-596

TABLE I I I

493

Transformat ions by Genus: NIGROSPORA J NOCARDIA

TAXONOMY

(SchizOo - Actinomycetales)

SPECIES

spec ies

sphaer ica

NOCARDIA (synonym - proac t ino-mycetes)

a s t é ro ïdes 1 (synonym for spec ies

blackwellii)

1 *

SOURCE

ATCC-12774

ATCC-12772

NI

ATCC-3308

ATCC-9970

SUBSTRATE



3a, 14/3-dihydroxy-5/3-20(22)-cardenolide

3/3,14/3-dihydroxy-5/3-17a-20(22)-cardenolide



3/3,14/3,16/3-trihydroxy-5ß-20(22)-cardenolide 3-aceta te

3/3,14/3,16/3-trihydroxy-5/3-20(22)-cardenolide 16-acetate

3/3,14/3,16/3-trihydroxy-5/3-20(22)-cardenolide 3 , 1 6 -diacetate

2a-f luoro-17a, 21-dihydroxy-4-p regnene -3 ,11 -20 - t r i one

11/3,17a, 21-tr ihydroxy-5/3-pregnane-3 ,20-d ione

11/3,17a, 21 - t r ihydroxy-4 -p regnene-3 ,20-d ione

REACTION

15a-OH

X-OH

3a-OH-»3-C=0

3 a - O H ^ 3 - C = 0 ; 12ß-OH

3 /3-OH-3-C = 0

12/3-OH; 3/3-O H - 3 - C = 0

12/3-OH

3/3-OH -+3-C=0

3/3-OAc — 3/3-OH

3 / 3 - O H - 3 - C = 0

3/3-OAc^ 3 - C = 0 ; 16ß-OAc-> 16/3-OH

3/3-OAc — 3/3-OH; 16/3-OAc-> 16ß-OH

3/3 -OAC-+ 3-C = 0

3/3-OAc-* 3/3-OH

1

Δ

4

Δ

Δ 1

R E F .

M-596

M-596

N-681

N-681

N-6 81

N-677

N-677

N-677

N-677

N-677

N-677

N-677

N-677

N-677

H-401

S-939

S-939

494

TABLE I I I

T r a n s f o r m a t i o n s by Genus: NOCARDIA

SPECIES

as té ro ïdes (synonum for spec ies blackwellii)

*

aurant ia

*"

SOURCE

ATCC-9970

ATCC-10904

LED

SÇKSC-2626)

AMCY

ATCC-12674

SQ

SUBSTRATE

11/3,17a, 21 - t r ihydroxy- 16a -methyl -4 -pregnene-3 ,20-d ione

l l ß , 17a, 21- t r ihydroxy-6a , 16a-dimethy 1-4-pregnene - 3 , 2 0 -dione

11/3, 17a, 21 - tr ihydroxy -4 - p r e g -nene-3 ,20-d ione

5 - choie sten-3/3-01

9a - f iuoro- l l /3 ,17a ,21- t r ihydroxy-4-pregnene-3 ,20-d ione

11/3,17a, 21- t r ihydroxy-4-pr eg -n e n e - 3 , 20-dione

(use of dr ied thalli)

17α, 21-d ihydroxy-4-pregnene-3, 20-dione

6a-fluor 0-11/3,16a, 17a, 21 - t e t r a -hydroxy - 9 a - m e t h y l - 4 - p r e g -nene-3 ,20-dione

9a- f luoro- l l /3 ,17a , 21 - tr ihydroxy -4 -pregnene-3 ,20-d ione

6a, 9a-di f luoro- l l /3 ,16a , 17a, 21 -te trahydroxy - 12a -methyl -4 -p regnene-3 ,20-d ione

6a, 12a-dif luoro- l l /3 ,16a, 17a, 21 -t e t r ahydroxy-4 -p regnene-3,20-dione

5-cholesten-3/3-ol

4 -choles ten-3 -one (use of cell free enzymes)

6a-chloro-12a- f Iuoro- l l /3 ,16α, 17α, 21 - tetrahydroxy -4 -pregnene -3,20-dione

6a-chloro-12a-f luor o - l 1/3,16a, 17a, 21- te t rahydroxy-4-pregnene -3,20-dione 16,17-acetonide

12a-chloro-6a- f luoro-16a , 17a, 21 -t r i h y d r o x y - 4 - p r e g n e n e - 3 , 1 1 , 20-tr ione

REACTION

1

Δ

1

Δ

1

Δ

utilization

Δ1

1

Δ

1

Δ

9α-OH

1

Δ

1

Δ

1

Δ

1

Δ

Δ5—Δ4; 3/3-OH ->3-C=0

1

Δ

1

Δ

1

Δ

1

Δ

R E F .

H-392

A-24; A-25

S-939

M-D95

T-1005

F-231

S-890; T-1005

P-740; S-898

F-260

T-1005

F-260

F-261

T-1005

S-890

F-261

F-261

F-261


TABLE I I I

Transformat ions by Genus: NOCARDIA

495

SPECIES

aurant ia

*

*

*

*

blackwellii (see a s t é r o ï d e s )

SOURCE

SQ(SC-2316)

SQ(SC-2317)

ATCC-6846 (Squibb-SC-1584)

UC

SUBSTRATE



5-cholesten-3/3-01


9o -fluoro-11/3,17a, 21 - t r i -hydroxy-4 -p regnene -3 ,20 -dione

5-cholesten-3/3-ol

17a, 21-d ihydroxy-5a-pregnane-3,20-dione

17a, 21 -dihydroxy -5a -pregnane -3 ,11 ,20 - t r ione

3a, 11/3,17a, 21- te t rahydroxy-5/3-pregnan-20-one

17a,21-dihydroxy-5/3-pregnane-3,20-dione

11/3,17a, 21 -tr ihydroxy-5/3-pregnane-3 ,20-d ione

3a ,17a ,21- t r ihydroxy-5 /3-pregnane-11 ,20-d ione

3a ,17a ,21- t r ihydroxy-5 /3-pregnane-11 ,20-d ione 2 1 -aceta te

3a ,17a ,21 - t r i hyd roxy-16a -methy 1-5/3-pregnane-11,20-dione 21-aceta te

3a ,17a ,21- t r ihydroxy-16/3-methyl-5 /3-pregnane-11,20-dione 21-aceta te

17α, 21-dihydroxy-5/3-pregnane-3 ,11 ,20 - t r ione 21-ace ta te

9 a - f l u o r o - l l / 3 , 1 7 a , 2 1 - t r i -hyd roxy-4 -p regnene -3 ,20 -dione

2a - f luoro- 17a, 21 -dihydroxy -4 -pregnene - 3 , 1 1 , 2 0 - t r i o n e


REACTION

Δ1

1

Δ

3/3-OH^3-C = 0

Δ1

1

Δ

Δ 5 - Δ 4 : 3 /3 -OH^3-C=0

Δ 1 ' 4

Δ 1 ' 4

Δ 1 ' 4 ; 3α -ΟΗ—3-C=0

Δ 1 ' 4

Δ 1 ' 4

Δ1'4; 3a -OH—3-C=0

Δ , 3a -OH—3-C=0 2 1 - O A c ^ 2 1 - O H

Δ 1 ' 4 ; 3a -OH->3-C=0

1>4

Δ ; 3a-OH — 3 - C = 0

Δ 1 ' 4 ; 21 -OAC-21-OH

Δ1

Δ1

Δ1

R E F .

T-1005

T-1005

T-1005

T-1005

T-1005

T-1005

S-939; S-943

S-943

S-943

S-939; S-943

S-939; S-943

S-943

S-939

S-902

S-905

S-939; S-943

T-1005

H-401

F-251

496

TABLE I I I


SPECIES

braz i l i ens i s *

coeliaca *

convoluta *

coral l ina

1

SOURCE

SQ(SC-2627)

SQ(SC-2751) (WC-704)

ATCC-4275

ATCC-999

SUBSTRATE

9a - f luo ro - l l / 3 ,17û ,21- t r ihy -d r o x y - 4 - p r e g n e n e - 3 , 2 0 -dione

9ö - f luo ro - l l / 3 ,17a ,21 - t r ihy -d r o x y - 4 - p r e g n e n e - 3 , 2 0 -dione


17/3-hydroxy-4-estren-3-one (possible synonym -Myco-bac te r ium rhodochrous -Ref0 F-231 - use of dr ied thalii) (Ref., F-232 and H-399 -use of inhibitors)

4 - e s t r ene -3 ,16 -d ione

16a-hydroxy-4-es t ren-3 -one

16/3-hydroxy-4- e s t r en -3 -one


2a, 17/3-dihydroxy-4-androsten-3-one

2a, 17/3-dihydroxy-4-androsten-3-one diacetate

2/3, 17/3-dihydroxy-4-andr os ten-3-one diacetate

REACTION

Δ1

1

Δ

Δ1

Δ1; enoL ; 17j3-OH-> 1 7 - C = 0

Δ1; enoL

Δ1; enoL ; 16a-OH-+ 1 6 - C = 0

Δ ; enoL , 1 6 / 3 - 0 H -1 6 - C = 0

1

Δ

17/3-OH — 1 7 - C = 0

Δ1; 17/3-OH — 1 7 - C = 0

Δ1; 17/3-OH -1 7 - C = 0

Δ1; 2a-OAc-+ 2a-OH; 17/3-OAc->17-C=0

2a-OAc —2a-OH; 1 7 ß - O A c -1 7 - C = 0

Δ1; 2/3-OAc — 2/3-OH; 17/3-OAc->17-C=0

2/3-OAc — 2/3-OH; 17/3-OAc-*17-C=0

R E F .

T-1005

T-1005

S-939

F-231 H-399

S-793a

S-793a

S-793a

F-231 ; H-399"

F-231 ; H-399

F-231 ; H-399

H-399

F-231 ; H-399

H-399

H-399

H-399

TABLE I I I


497


coral l ina ATCC-999 4 -andros tene-3 ,17-d ione

9a-fluoro-11/3,16a, 1 7 a a - t r i -hydroxy -17a/3-hydroxy methyl -D -homo-4 -andros tene - 3 , 1 7 -dione


l l /3 ,21-d ihydroxy-4-pregnene-3,20-dione


9a -ch lo ro - l l /3 ,21 -d ihydroxy-4 -pregnene-3 ,20-d ione

9a- f luoro-7a , l l /3-dihydroxy-4-pregnene-3 ,20-d ione

9a -fluor o-11/3,21 -dihydroxy -4 -pregnene-3 ,20-d ione

7a, 11/3,21-tr ihydroxy-4-pregnene-3,20-dione

11/3,17a, 21 - t r ihydroxy -4 - p r e g -nene -3 ,20-dione

la -fluoro-11/3,17a, 21 - t r ihydroxy -4-pregnene-3 ,20-d ione

9a-f luoro-7a , 11/3,21-trihydroxy-4-pregnene-3 ,20-d ione

9a-fluoro-11/3,16a, 21- t r ihydroxy -4-pregnene-3 ,20-d ione

9a-fluoro-11/3,17a, 21 - t r ihydroxy-4-pregnene-3 ,20-d ione

l l /3 ,17a ,21- t r ihydroxy-2a-methy l -4 -pregnene-3 ,20-d ione 2 1 -aceta te

11/3 ,16a ,17a ,21- te t rahydroxy-4-pregnene-3 ,20-d ione

21 -OAc-21-OH

21-OAc^21-OH 1

Δ

F-231 ; F-232; H-399

S-910

F -231 ; F-232; H-399

F - 2 3 1 ; H-399

F -231 ; F-232; H-399

H-399

B-56

F - 2 3 1 ; H-399

B-56

F-230; F -231 ; F-232; H-399

F - 2 3 1 ; H-401

3-56

H-403

F - 2 3 1 ; K-399; H-403

F -231 ; H-399

H-399

B - 6 1 ; F - 2 3 1 ; H-399

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

498

TABLE I I I


SPECIES

coral l ina

*

*

*

NOTE: For source ATCC-4273 above - possibly Mycobacterium ag res t e and Mycobacterium rhodochrous - J . Gen. Microbio l . , 21 : 139

[(1959)

SOURCE

ATCC-999

ATCC-4273

ATCC-4275

ATCC-13258

SUBSTRATE

9 a - c h l o r o - l l / 3 , 1 6 a , 1 7 a , 2 1 - t e t r a -hydroxy-4-pregnene-3 ,20-d ione

9 a - f l u o r o - l 4 , l l / 3 , 1 7 ö , 2 1 - t e t r a -hydroxy-4 -p regnene -3 ,20 -dione

9a-f luoro-6/3,11/3,170,21-tetra-hydroxy -4 -pregnene-3 ,20-d ione

9a- f luoro- l l /3 ,16a , 1 7 a , 2 1 - t e t r a -hydroxy-4 -p regnene-3 ,20-dione

9a-fluoro-11/3,16a, 1 7 a , 2 l - t e t r a -hydroxy-4 -p regnene-3 ,20-dione 16 ,21-diace ta te

9 a - f l u o r o - l l / 3 , 1 6 a , 1 7 a , 2 1 - t e t r a -hydroxy-4-pregnene-3 ,20-d ione 16,17-acetonide

2 a , 9 a - d i f l u o r o - l l / 3 , 1 6 a , 1 7 a , 2 1 -t e t r ahyd roxy -4 -p regnene -3 ,20 -dione 16,17-acetonide

9a-fluoro-6/3,11/3,16a, 17a, 21 -pen tahydroxy-4-pregnene-3 ,20-dione 16,17-acetonide


2a-f luoro-17a, 21-dihydroxy-4-pr egnene - 3 , 1 1 , 2 0 - t r ione



9a- f luoro- l l /3 ,17a , 21 - t r ihydroxy -4 -pregnene-3 ,20-d ione

5-choIesten-3/3-ol


19-hydroxy-4 -andros tene -3 ,17-dione

REACTION

1

Δ

—

1

Δ

1

Δ

1

Δ ; 1 6 a - O A c ^ 16a-OH;21-OAc - 21-OH

1

Δ

Δ1

1

Δ

1

Δ

Δ1

1

Δ

1

Δ 1

Δ

Δ5-*Δ4; 3/3-OH ^ 3 - C = 0

9a-OH; Δ1; r ev . aldol. ; enol.

1

Δ ; r e v e r s e aldol;

(Formaldehyde î ) enol.

R E F .

H-399

H-399

F-231

B - 6 1 ; F -231 ; H-399; O-704

B - 6 1 ; F-255; O-704

F-231 ; H-399

H-401

H-400

F -231 ; H-399

H-401; H-402

S-939

T-1005

T-1005

T-1005

M-597

M-597

TABLE I I I

499


SPECIES

coral i ina

*

erythropol is 1 (Mycobacterium 1 rhodochrous , J .

Bact. 73: 23,1957)

SOURCE

ATCC-13258

ATCC-13259

NG

ATCC-4277 (Squibb SC-

2820)

NCTC-2569

NG

SUBSTRATE



19 -hydroxy-4 -and ros t ene -3 ,17 -dione



24/3 - methyl - 5 , 7 , 2 2 - cholesta -trien-3/3-ol (sole carbon source)

l l / 3 , 17a ,21 - t r i hyd r oxy - 4 - p r eg -nene-3 ,20-d ione


1 ,3 ,5(10)-es t ra t r ien-3 ,17/3-dio l

l , 3 , 5 ( 1 0 ) - e s t r a t r i e n - 3 , 1 6 a , 1 7 / 3 -t r io l


3 -hydr oxy - 5 -andr osten -17 -one



3α, 7α-dihydroxy-5/3-cholanic acid

3α, 12α -dihydroxy -5/3-cholanic acid

3α, 7α, 12α-trihydroxy-5/3-cholanic acid

5 -cholesten -3/3-ol ace ta te

5-cholesten-3/3-ol pa imi ta te

24/3-methyl-5, 7 ,22 -cho les t a t r i en -3/3-01 (sole carbon source)

REACTION

9a-OH

9a-OH; Δ ; r e v . aidol. ; enoL

9a-OH

1

Δ ; r ev . aldol; (Formaldehyde f )

enol.

9a-OH

9a-OH; 17/3 -Ac -»17/3-OH

utilization

util ization

1 Δ

utilization

-

-

util ization

utilization

util ization

-

-

util ization

util ization

-

util ization

util ization

R E F .

D-173

D-172; M-597

D-172; M-597

M-597

D-173

D-172

S-793c

S-793c

T-1005

M-595; S-793c

S-793c

S-793c

S-793c

S-793c

S-793c

S-793c

S-793c

S-793c

S-793c

S-793c

S-793c

S-793c

500

TABLE I I I


SPECIES

farcinica

formica

*

gardner i * (see as téro ïdes)

globerula (Mycobacterium rhodo-c h r o u s - J . ßac t . 73: 24, 1957) *

*

i talica n. s.

leishmanii

*

SOURCE

NG (No. 1, 2)

NRRL-2470

ATCC-9604 (Squibb-SC-

1940) NCTC-6531

(Squibb - SC-6531)

NG

ATCC-9356

FAR MIT

ATCC-6855

SUBSTRATE


24/3-methyl -5 ,7 ,22-choles ta-trien-3/3-ol (sole carbon source)

l l /3 ,17a ,21- t r ihydroxy-5/3-pregnane-3 ,20-d ione


9a- f luoro- l l /3 ,17a ,21- t r ihydroxy-6a, 16a-dimethyl -4-pregnene -3,20-dione

9a-f luoro- l l /3 ,17α, 21 -trihydroxy-4-pregnene-3 ,20-d ione

9a- f luoro- l l i3 ,17a ,21- t r ihydroxy-4-pregnene-3 ,20-d ione


24j3-methyl-5 ,7 ,22-choles ta-t r i en -3ß -o l (sole carbon source)

l l j3 ,17a,21- t r ihydroxy-5j3-pregnane-3 ,20-d ione

11)3,17a, 21 - t r ihydroxy-4-pregnene-3 ,20-d ione (Ref. B-37 - use of antibiotics^



l l j3 ,17a ,21- t r ihydroxy-4-pregnene-3 ,20-d ione

9a - f iuoro- l l /3 ,17a ,21- t r ihydroxy-4-pregnene-3 ,20-d ione

9a - f luoro- l l /3 ,17a ,21- t r ihydroxy-1,4 -pregnadiene -3 ,20-dione

11/3,17a, 21-trihydroxy-5/3-pregnane-3 ,20-d ione


9a-f luoro-17a, 21-dihydroxy-6a, 16a -dimethy 1-4 -pregnene -3 ,11 ,20- t r ione

REACTION

utilization

utilization

Δ4

1

Δ

1

Δ

1

Δ

1

Δ

utilization

utilization

Δ4

1

Δ

Δ1

16α-ΟΗ

16α-ΟΗ

16α-ΟΗ

16α-ΟΗ

Δ4

Δ1

Δ 1

R E F .

S-793c

S-793c

S-939

S-939

Α - 2 4 ; Α-25

Τ-1005

Τ-1005

S-793C

S-793C

S-939

β-37 S-939

Τ-1005

S-918

S-918

S-918

S-918

S-939

S-939

• Α-24; Α-25

501

TABLE I I I


SPECIES

maculata

madurae *

mexicanus

minima

*

opaca

SOURCE

NG

SQ(SC-2628)

NG

ATCC-8674

ATCC-4276

SUBSTRATE


24 /3-methyl -5 ,7 ,22-choles ta t r ien-3/3-01 (sole carbon source)

9a -fluoro-11/3,1 la, 21 -tr ihydroxy-4-pregnene-3 ,20-d ione


24j3-methyl-5 ,7 ,22-choles ta t r ien-3/3-01 (sole carbon source)

l l j3 ,17a ,21- t r ihydroxy-5ß-p regnane -3 ,20 -d ione






11/3,1 la- dihydroxy- 4 -pregnene -3,20-dione


9a-f luoro-17a, 21-dihydroxy-4-pregnene-3 ,20-d ione

11/3 ,17a,21- t r ihydroxy-4- p r e g -nene-3 ,20-d ione (use of antibiotics)

17α, 21-dihydroxy-14α, 15α-oxido-4-pregnene-3 ,20-d ione

11/3,17α, 21- t r ihydroxy-14a , 15α-oxido-4-pregnene-3 ,20-d ione

l l ß , 1 4 a , 1 7 a , 2 1 - t e t r a h y d r o x y - 4 -pregnene-3 ,20-d ione

6 a , 9 a - d i f l u o r o - l l / 3 , 1 7 a , 2 1 - t r i -hydroxy -16-méthy lène-4-pregnene-3 ,20-d ione

4 - p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e

2a- f luoro- l 7a, 21-dihydroxy-4-pregnene-3 ,20-d ione

REACTION

utilization

util ization

1

Δ

utilization

util ization

Δ4

1

Δ

1

Δ ; enol. 1

Δ

Δ 1

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

Δ 1

1

Δ

1

Δ

1

Δ

1

Δ 1

Δ

R E F .

S-793c

S-793c

T-1005

S-793c

S-793c

S-939

S-939

3-37

ß - 3 7

ß - 3 7

ß - 3 7

B-37

ß - 3 7

ß - 3 7

ß - 3 7

B-37

ß - 3 7

ß - 3 7

A-7

ß - 3 7

H-401

502

TABLE I I I

Transformat ions by Genus: NÛCARDIA

SPECIES

opaca

paraffinae

polychromogenes

r e s t r i c t u s

SOURCE

ATCC-4276

SQ (SC-2812) (WC-560)

NG

NG

AY

NCTC-6846

Sp-WISC

SUBSTRATE

14a, 17a, 21 - t r ihydroxy-4 -p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e


17a,21 -dihydroxy-4,9(11) -pr egnadiene-3 ,20- t r ione

17a ,21-d ihydroxy-4 ,14-pr egnadiene -3 ,20 -dione

17a -hydroxy-21-me thy l -4 ,9 ( l l ) -pr egnadiene -3 ,20 -dione

9a - f luo ro - l l / 3 ,17a ,21 - t r i hy -droxy-4-pregnene-3 ,20-d ione


24j3-methyl-5 ,7-22-choles ta-trien-3/3-ol (sole carbon source)


24i3-methyl-5 ,7-22-choles ta-t r i e n - 3/3-ol (sole carbon source)

19-hydroxy-4, 7 -andros tad iene-3,17-dione

19-methoxy-4, 7 -andros tad iene-3,17-dione

5-cholesten-3j3-ol

1 7j3 -hy dr oxy - A -_nor - 3 -andr osten -2-one

9a -hyd roxy-4 -and ros t ene -3 ,17 -dione (enzyme preparat ion)

17/3-hydroxy-5-androsten-3-one cycloethyleneketal

3 ,4-dihydroxy - 9 ,10 ^s_eço-1,3, 5(10)-andros tene-9 ,17-dione (cell free extract)


REACTION

Δ1

Δ1

Δ 1

Δ1

Δ1

Δ1

utilization

utilization

utilization

utilization

Δ1; r ev . aldol; enol.


util ization

9a-OH·, 17/3-OH-» 1 7 - C = 0


1 7 β - Ο Η -1 7 - C = 0

degradation [A,B1

Δ 1

9a-OH

R E F .

B-37

B-37

B-37

B-37

H-391

T-1005

S-793c

S-793c

S-793c

S-793c

B-38

B-38

M-595

S-885

S-885

S-885

S-896

S-885

S-885

TABLE I I I

503


SPECIES

restrictus

1 *

1 *

SOURCE

Sp-WISC

SQ

SQ(SC-2914 SC-2915 SC-2917 SC-2919)

WC(545)

SUBSTRATE

4-pregnene-3 ,20-d ione (with KCN)

9 a - f l u o r o - l l ß , 17α, 2 1 - t r i -hydroxy-4 -p regnene -3 ,20 -dione

3/3, 5/3,14j3-trihydroxy-19-oxo-20(22)-cardenolide

14/3-hydroxy-3,19-dioxo-4,20 (22) -cardadienolide

14/3-hydroxy -3 -keto-19 -nor -4 ,20(22)-cardadienol ide




l l j 3 ,17a ,21 - t r ihydroxy-4 -pregnene-3 ,20-d ione


9a- f luoro- l l /3 ,17o ,21- t r ihydroxy 4 -pregnene-3 ,20-d ione

5-cholesten-3/3-ol

17j3-hydroxy-A-nor-3-androsten-2-one

17j3-hydroxy-17a-methyl-A-nor-3 -andros ten-2 -one

A, 19 -b i sno r -3 -and ros t ene -2 .17 -dione

REACTION

9a -OH; 17j3-Ac-+ 1 7 - C = 0

Δ1

3 /3 -OH-3 - C = 0 ; 50-ΟΗ-+Δ4

3/3-OH -3 - C - O ; δ β - Ο Η - Δ ^ Δ 1 ; 1 0 ß - H C = O ^ 10/3-H; enol.

Δ1; 10/3-HC-O -» 10/3-H; enol.

Δ1; enol.

Δ1; enol.

Δ 1

Δ1

Δ1

Δ1

Δ1

Δ 5 - Δ 4 ; 3 j3-OH^ 3 - C = 0

9a-OH; 17 /3-OH-1 7 - C = 0

9a-OH

9a-OH

R E F .

S-885

S-885

K-481

K-481

K-481

K-481

S-889

S-889

S-889

S-889

T-1005

T-1005

T-1005

W-1080

W-1080

W-1080

504

TABLE I I I


SPECIES

r e s t r ictus

SOURCE

WC(545)

SUBSTRATE


4 -andros tene-3 ,17-d ione (cell free extract-Ref . S-883)

9a -hydroxy-4 -and ros t ene -3 ,17 -dione (cel l -free extract)

19 -hydroxy-4 -andros tene -3 ,17-dione


A - n o r - 3 - pr egnene -2 ,20 -dione

4 -pregnene-3 ,20-d ione (cell free ex t rac t - Ref. S-883)

REACTION

Δ 1

9α-ΟΗ; Δ1; rev . aldol; eno l . ; 17ß-OH - 1 7 - C = 0

9α-ΟΗ; Δ1; r ev . aldol; eno l . ; 9 - C = 0 -9/3-OH 17/3-OH-1 7 - C = 0

9α-ΟΗ; Δ 1

r ev . aldol; eno l . ; 9 - C = 0 - 9 a - O H 17/3-OH-1 7 - C = 0

1 7 - C = 0 -17/3-OH; 9a-OH; Δ1; r ev . aldol; enol. ; 9 - C = 0 - 9 / 3 - O H

17/3-OH-1 7 - C = 0 degradation; [A ,ß ]

Δ 1

9α-OH

9α-OH; Δ1; r ev . aldol; enol.


Δ ; r ev . aldol; enol.

degradation; [A,B]

9a-OH

Δ1

R E F .

S-883

W-1063

W-1063

W-1063

W-1063

W-1063

S-883; S-884; S-894

S-884; S-894

S-884; S-894; S-895

S-884; S-894

S-884; S-894

S-895

W-1079

S-883; T-1005

TABLE I I I

505

T r a n s f o r m a t i o n s by G e n u s : NOCARDIA

SPECIES

r e s t r i c t u s

*

1 *

r u b r a * (Mycobacterium rhodo-ch rous - J . ßac t . 73 :15 , 1957) ~~ salmonicolor

1 *

1 spec ies

SOURCE

WC(545)

SQ(SC-2823) (vVC-546)

NG

NG

SQ(SC-2750) (WC-647)

ATCC-13259

ATCC-13934

SUBSTRATE

4-pregnene-3 ,20-d ione (use of inhibitor s-Ref. S-898)

17α, 21 -dihydroxy -4 -pr egnene -3,20-dione (cel l -free extract)

l l / 3 ,17a ,21 - t r i hyd roxy-4 -pregnene-3 ,20-d ione (cel i -free extract)

9a - f luo ro - l l / 3 ,17a ,21 - t r i hy -d roxy-4-p regnene-3 ,20-d ione (cel l -free extract -Ref . S-883)

9a - f l uo ro - l l / 3 ,16α ,17α ,21 -t e t r ahydroxy-4 -p regnene -3,20-dione (cel l - f ree extract)

17a ,21-d ihydroxy-4-pregnene-3 ,11 ,20 - t r ione (cel l - f ree extract)

5-cholesten-3j3-ol



24/3-methyl -5 ,7 ,22-choles ta -tr ien-3/3-ol (sole carbon source)

9a - f l uo ro - l l j 3 , 17a ,21 - t r i -hydroxy-4 -p regnene -3 ,20 -dione


4 , 9 ( l l ) - a n d r o s t a d i e n e - 3 , 1 7 - d i o n e

17a-(21-carboxyethyl)-17ß-hydroxy-4-andros ten-3-one spirolactone

REACTION

9a-OH

17/3-Ac-> 1 7 - C = 0

Δ1

9a-OH

Δ 1

1

Δ

Δ 1

1

Δ

Δ5->Δ4; 3/3-OH->3-C=0

Δ 1

util ization

utilization

Δ 1

9α-ΟΗ; Δ1; r ev . aldol; enolo

9α, 11α-oxide

9α-OH

R E F .

P -740 ; S-897; S-898

S-898

S-883

P-740

S-883

S-883; S-884; S-894; T-1005

S-883; T-1005

S-883

T-1005

T-1005

S-793c

S-793c

T-1005

D-171

S-886

D-173

506

TABLE I I I

T ransformat ions by Genus: NOCARDIA


species ATCC-13934

ATCC-14558

ATCC-14559

Searle (A-20-10)

NG





12a-aza - 3/3 - hydr oxy - C - homo-5a-pregnane-12 ,20-d ione

12a-aza-3/3 ,17a-dihydroxy-C-homo_-5a-pr e gnane -12,2 0-dione



3a, 7a, 12a-tr ihydroxy-5/3-choianic acid

5-cholesten-3/3-ol (sole carbon source - Ref. S-793c)

9a-OH;17ß-Ac - 1 7 - C = 0

9a-OH

D-172

D-172

9a-OH; 17/3-Ac -*17.β-ΟΗ

17/3-Ac-17-c=o 9a-OH

9a-OH

o ( l l )

Δ v - 9 a , 11a-oxide

3/3-OH-*3-C=0; Δ1»4 (5a-H)

3 /3 -OAc-3 - C = 0 ; Δ 1 ' 4

9a-OH

9a-OH; Δ*; r ev . aldol; enol.

9a-OH

degradation

Δ 5 -Δ 4 ;3 /3-ΟΗ - 3 - C = 0

3/3-OH->3-C=0; Δ 5

Γ Δ 4 ; 17/3-(2 -isooctyl) —► 17-C = 0

5 4 !

Δ 5 - Δ 4 ; Δ ;

D-172

D-172

D-173

D-173

S-886

M-563

M-563

D-170

S-796

H-330

L-501 ; S-793c

W - l l l l

W - l l l l 3/3-OH->3-C=0; 17/3-(21-isoocty0| - 1 7 - C = 0

3/3-OH—3-C-0; Δ 5 -Δ 4 ;17 /3 - (2 χ -isooctyl)-»17/3-(2 -propionic acid)

W - l l l l

507


TABLE I I I

NOCARDIA OÏDIUM

OMPHALIA OOSPORA

TAXONOMY

(Imperf. - Moniliales) (ßas id io . - Agar icales) (Imperf. - Moniliales)


species

OÏDIUM

species

OMPHALIA

t ra lucida (in mixed cul ture with| T r i choderma v i r i d e -NRRL-2473[17a-OH] and Wojnowicia graminis - NRRL-2472 [21-OH])

OOSPORA

aurant i i

lact is

NG

SQ

NRRL

MCC

TNAES

UC


24/3-methyl-5,7,22-cholesta-trien-3ß-ol (sole carbon source)

plant saponins



not given

3j3-OH->3-C = 0 ; Δ 5 - Δ 4 ; Δ^,ΙΊβ-(2x-isooctyI)-> 17/3-(21-prop-ionic acid)

utilization

decomposit ion

A 1>4

9a -OH

11/3-OH

oxidation

REF.

W - l l l l

S-793c

S-794

S-887; S-888

S-887; S-888

S-887; S-888; S-897

S-897

K-478

M-566

S-849

M-601; M-636

digitonin

5a-pregnane-3,20-dione

5/3-pr egnane -3,20 -dione


(use of inhibitors)

1

Δ

1

Δ

508

TABLE I I I

T r a n s f o r m a t i o n s by Genus : OPHIOBOLUS

TAXONOMY



graminis

herpotr ichus

( in mixed cul ture with one of the following: Curvular ia b lakes -leanna [110-OH; 1 1 -C=0] - Curvular ia brachyospora [11/3-OH] - Curvular ia l u n a t a [ l l ß - O H ] -Rhizopus n igr icans [11a-OH])

NARI

C


d, l - 1 9 - n o r - 4 - p r e g n e n e - 3 , 20-dione

4 -p regnene-3 , 20-dione

d , l - 4 - p r e g n e n e - 3 , 20-dione


d , l -9a - f luo ro - l l / 3 -hydroxy-4 -pregnene-3 ,20-d ione

d, 1-11/3, 18/3-dihydroxy-4-preg-nene-3 ,20-d ione


d , l - i l / 3 -hydroxy-3 ,20 -d ike to -4 -p regnen-18-o ic acid (18-11) lactone

11/3,16a -dihydroxy -3 ,20 -diketo-4-pregnen-18-o ic acid (18-11) lactone

d , l - l l / 3 -hydroxy-3 ,20 -d ike to -4-pregnen-18-a l (18— 11) hemiaceta l

1,4 -pregnadiene -3 ,20-dione

11 /3 ,17a-d ihydroxy- l ,4 -preg-nadiene -3 ,20-dione

17a-hydroxy-1 ,4-pregnadiene -3 ,11 ,20 - t r ione


11a-OH

d , l -> d-21-OH

S-849

W-1102 + 1

21-OH

d , l - d-21-OH + 1

21-OH

d , l - d - 2 1 - O H + 1

d , l - d - 2 1 - O H + 1

21-OH

M-584; W-1101

W-1102

M-584; W-1101

W-1102

W-1102

M-584; W-1101

d , l - d -+ 1

d , l -

21

d-21-OH +

21-OH

d , l - d + 1

21-OH

21-OH

21-OH

21-OH

-21

OH

1

-OH

W-1101; W-1102

V-1055

W-1091

W-1102

W-1101

W-1101

W-1101

W-1106

TABLE I I I

509

T r a n s f o r m a t i o n s by Genus : OPHIOBOLUS

SPECIES

herpotr ichus (in mixed cul ture with

Trichothecium roseum |17a-OH|)

(in mixed cul ture with one of the following: Calonectr ia decora lA^-Curvu la r i a brachyspora [11/3-OH | -Tr ichothecium roseum [17a-OH])

(in mixed cul ture with Trichothecium ro seum 117a-OH]

Calonectr ia decora ΙΑΊ)

(in mixed cul ture with 1 Calonectr ia decora

lA^-Tr ico thec ium roseum [17a-OH])

(in mixed cul ture with Cunninghamella blakesleeana [11/3-OH] -Tr ichothecium roseum 117a-OH])

(in mixed cul ture with Trichothecium ro seum [17a-OH])

(in mixed cul ture with Trichothecium ro seum [17a-OH])

(in mixed cul ture with Curvular ia b rachy-spora [11/3-OH])

SOURCE

C

PIRI .

SCH

SUBSTRATE


11/3 -hydroxy -4 - pr egnene - 3 , 2 0 -dione

4 - p r e g n e n e - 3 , 1 1 , 20- t r ione

1,4 -pr egnadiene -3 ,20-d ione

11/3-hydroxy-1,4-pregnadiene -3,20-dione

1,4 -pregnadiene - 3 , 1 1 , 2 0 - t r i o n e

4 - p r e g n e n e - 3 , 1 8 , 20- t r ione


3/3-hydroxy-5,16-pregnadien-20-one

11/3,17a -dihydr oxy -1 ,4 -pr egna -d iene-3 ,20-d ione

17a-hydroxy-1 ,4-pregnadiene -3 , 1 1 , 20- t r ione

11a -hyd roxy-1 ,4 ,16 -p regna -t r i ene -3 ,20 -d ione

l l / 3 - h y d r o x y - l , 4 , 1 6 - p r e g n a -t r i e n e - 3 , 20-dione

REACTION

21-OH

21-OH

21-OH

21-OH

21-OH

21-OH

21-OH

21-OH

21-OH

21-OH

Δ 4 - 5 α - Η

21-OH

21-OH

21-OH

21-OH

21-OH

R E F .

W-1106

W-1107

W-1106; W-1107

W-1107

W-1106; W-1107

W-1106

W-1106

W-1106

W-1106

W-1081

W-1081

H-388; O-700

H-388; O-700

H-388; O-700

H-388; O-700

H-388; O-700

510

TABLE I I I

Transformat ions by Genus: OPHIOBOLUS

SPECIES

herpotr ichus

he teros t rophus

SOURCE

uc

WFEB

C

NIHJ

S

SUBSTRATE








l i a , 21-dihydroxy-4-pregnene -3,20-dione



1 l a , 1 la, 21 - t r ihydr oxy -4 -p regnene-3 ,20-d ione

11/3,17a, 21 - t r ihydr oxy - 4 -pregnene-3 ,20-d ione


17a-hydroxy-3 ,20-d ike to -4-p regnen-18-a i

l l ß , 21 -dihydroxy -3 ,20-d ike to -4 -p regnen-18-a l (18-+11) hemiaceta l






REACTION

21-OH

21-OH (0218)

Δ1

Δ 1

Δ1

Δ1

Δ1

Δ1

Δ1

Δ1

1

Δ

Δ1

Δ1

Δ 1

Δ1

1

Δ

1

Δ

Δ1

Δ1

R E F .

M-576; M-577

H-374

W-1105

W-1105

W-1105

W-1105

W-1105

W-1105

W-1105

W-1105

W-1105

W-1105

W-1105

W-1105

W-1105

S-849

S-849; S-857

S-849; S-857

S-849; S-857

S-849; S-857

TABLE I I I

T ransformat ions by Genus: OPHIOBOLUS

SPECIES

heteros t rophus

miyabeanus

sat ivus

SOURCE

S

c

FRI

S

NARI

SUBSTRATE


3ß-hydroxy-5-andros ten -17-one



3/3 ,21-dihydroxy-5-pregnen-20-one



1 l ö , 21 -dihydroxy -4 -pregnene -3,20-dione



1 l a , 1 la, 21 - t r ihydr oxy -4 -p regnene-3 ,20-d ione

l l / 3 , 17a ,21 - t r i hyd roxy -4 -pregnene-3 ,20-d ione


17a-hydroxy-3 ,20-d ike to -4-p regnen-18-a l

l l /3 ,21-d ihydroxy-3 ,20-d ike to -4 -p regnen-18-a l (18-^11) hemiaceta l



17a-hydroxy-4-pr e g n e n e - 3 , 2 0 -dione


17a, 21 -d ihydroxy-4-pregnene-3, 20-dione

REACTION

Δ 1

Δ1

1

Δ

Δ1

Δ1

Δ1

Δ1

Δ1

Δ1

Δ1

Δ1

Δ1

Δ1

Δ1

Δ 1

l i a - O H

Δ1

6ß-OH

R E F .

S-849; S-857

W-1105

W-1105

W-1105

W-1105

W-1105

W-1105

W-1105

W-1105

W-1105

W-1105

W-1105

W-1105

W-1105

W-1105

S-849

S-859

S-859

S-849; S-859

S-849

511

512


TABLE I I I

OPKIOBOLUS OPHIOSTOMA

PAECILOMYCES PANAEOLUS

TAXONOMY

(Asco. -Sphaeriales) (Imperf. - Moniliales) (Basidio0 - Agaricales)

! ! SPECIES

species

OPHIOSTOMA

catanianum

PAECILOMYCES

species

vari toi

PANAEOLUS

papilionaceus

SOURCE

C

NG

NG (Sandoz-

904)

NRRL

FRI

AL (G-60)

SUBSTRATE



1 Iß , 21 -dihydr oxy -4 -pregnene -3,20-dione

17flf, 21-d ihydroxy-4-pregnene-3,20-dione




3/3, 6/3, 8/3,14/3-tetrahydroxy-4, 20,22 -bufatrienolide 6-acetate 3-glucoside

3/3,14/3-dihydroxy-5/3-20(22)-cardenol ide-3- |g lucosy l -digitoxosyl-digitoxosyl-digitoxosidel

Digilanid A

plant saponins



REACTION

Δ ^ Π β - Α ΰ -17-C = 0

1

Δ

1

Δ

Δ1

1

Δ

utilization

utilization

3/3|lVgluco-s ide | -3/3-OH

glucosyl-digitoxosyl-digitoxosyl —» digitoxosyl-digitoxosyl-digitoxoside

select ive cleav-age of glucose from sugar chain

-

—


R E F .

V-1053

V-1053

V-1053

V-1053

V-1053

S-793c

S-793c

S-936a

S-936a

S-936a

K-478

S-849

S-825

513


TABLE I I I

PANELLUS PARASITELLA

PARENDOMYCES PAXILLUS

PELLICULARIA

TAXONOMY

(ßasidiOo - Agaricales) (Phyco. - Mucorales) (Imperf. - Moniliales) (Basidio. - Agaricales) (3as id io . - Agaricales)

SPECIES

PANELLUS

stypticus (stipticus)

PARASITELLA

simplex

PARENDOMYCES

as té ro ïdes

PAXILLUS

involutus

vernal is

PELLICULARIA (see Corticium)

filamentosa f. s. t ims i i

f. s. sasaki i

f. s. solani

f. s. mic rosc le ro t i a

NOTE: f. s. = forma 1 sec iaus

SOURCE

AL (C-224)

FRI

FRI

AL (H-19)

AL (H-25)

IFO (6259)

IFO(6298)

SUBSTRATE



17a, 21-dihydroxy-4-pregnene -3, 20-dione



17a, 21 -dihydroxy -4-pregnene -3, 20-dione

9a -hyd roxy -4 -and ros t ene -3 ,17 -dione

1Iß - hyd roxy-4 -and ros t ene -3 ,17 -dione

14a -hydroxy-4 -andros t ene -3 ,17 -dione

REACTION




6/i-OH; l l a - O H

6/J-OH; l l a - O H ; 11/i-OH; 19-OK

Δ1; 6/3-OH; l l a - O H

6/i-OH; 14a-OH

l l j 3 - O H - l l - C = O; 14a-OH

l l a - O H ; 11/3-OH

R E F .

S-825

S-849

S-849

S-825

S-825

T-957

T-957

T-957

T-955

T-955

T-955

514

TABLE I I I

Transformat ions by Genus: PELLICULARIA PENICILLIUM

TAXONOMY


SPECIES

filamentosa f. s. mic rosc le ro t i a

PENICILLIUM

aculeatum

adametzi

*

NOTE: f. s. = forma sec iaus

SOURCE

IFO(6298)

CZAS

ATCC-10407

CZAS

SUBSTRATE

15a-hydroxy-4-andros tene -3 ,17-dione

4 - a n d r o s t e n e - 3 , 1 1 , 1 7 - t r i o n e


l l / 3 -hyd roxy- l , 4 - and ros t ad i ene -3,17-dione


17a ,20a ,21 - t r i hydroxy-4 -pregnen-3-one

l l / 3 ,17a ,21 - t r ihydroxy-4 -pregnene-3 ,20-d ione







4 ,16 -p regnad iene -3 , 20-dione


REACTION

11/3-OH; 11-C = 0 (via 11/3-OH)

14a-OH

14a-OH; 11/3-OH; 11-C = 0 (via 11/3-OH)

14a-OH; 11/3-OH-n-c=o l l a - O H ; 11/3-OH; 19-OH

11/3-OH; 19-OH

2 0 - C = O -20/3-OH

oxidation -product not identified






17/3-Ac-> 17a-oxa-17 -C=0

R E F .

T-955

T-955

T-955

T-955

T-957

T-953; T-954

T-953; T-954

C-99

M-602

M-602

M-602

M-602

M-602

M-602

C-99

TABLE I I I

515

T r a n s f o r m a t i o n s by G e n u s : PENICILLIUM

SPECIES

adametzi (in mixed cul ture with Tr ichoderma lignorum [17a-OH) and Wojnowicia graminis [21-OH|)

albidum *

*

*

1 *

aspe rum *

a t ramentosum *

1 *

aurantio - violaceum

auran t io -v i rens

avelianeum

biforme

brefeldianum

brevi -compactum

SOURCE

MCC

NRRL

UÇ

ASRI

CZAA

CZAS

FCUTS

MCC

CZAS

MCC

ASRI

CZAS

MCC

MCC

MCC

CZAS

ASRI

CZAS

FCUTS

MCC

MCC

ATCC-9056

SUBSTRATE

4-pregnene 3,20-dione

Sarsasapogenin

Diosgenin






















REACTION

11a-OH

-

-

-

17j3-Ac-17a-oxa-17-C = 0

17/3-Ac-17a-oxa-17-C = 0

17/3-Ac->17a-oxa-17-C = 0

17/3-Ac-17a-o x a - 1 7 - C = 0

17/3-Ac—17a-o x a - 1 7 - C = 0

none at C - l l

17/3-Ac— 17a-oxa-17-C = 0

none at C - l l

l l a - O H

l l a - O H

none at C - l l

none at C - l l

none at C - l l

-

—

-

-

none at C - l l

none at C - l l


R E F .

M-566

M-587

M-587

M-587

P-726

C-99

C-99

C-99

C-99

D-190

C-99

D-190

C-99

C-99

D-190

D-190

D-190

C-99

C-99

C-99

C-99

D-190

D-190

M-602

516

TABLE I I I

Transformations by Genus: PÉNICILLIUM

SPECIES

br evi - compactum

camember t i

canescens

*

*

*

casei

caseicolum

char les i i

SOURCE

ATCC-9056

CZAS

MCC

CZAS

MCC

ATCC-10419

ASRI

CZAS

MCC

ASRI

FCUTS

MCC

ASRI

CZAA

CZAS

FCUTS

UC

SUBSTRATE


(revision of s t ruc tu re -20a to 20ß - Ref. S-832)








21-hydroxy-4-p regnene-3 ,20-dione aceta te (revision of s t ruc tu re -20a to 20/3 - Ref. S-832)












(revision of s t ruc tu re -20a to 20/3-Ref. S-832)

REACTION

17/3-Ac^ 1 7 - C = 0

2 0 - C = O -20/3-OH

—

none at C-11

—

none at C-11

170-Ac — 1 7 - C = 0


17ß-(20-C=O-21-OAc) -1 7 - C = 0

20-C=O -* 20/3-OH 21-OAc -21-OH

17 /3 -Ac^ l7a -oxa-17-C = 0

17/3-Ac^l7a-o x a - 1 7 - C = 0

none at C-11

-

-

none at C-11

-

-

-

-

17/3-(20-C=O -21-OAc) -> 1 7 - C = 0

20-C=O-> 20j3-OH; 21-OAc -> 21-OH

R E F .

M-637

M-637

C-99

D-190

C-99

D-190

M-637

M-602

M-637

M-637

Çf_99

C-99

D-190

C-99

C-99

D-190

C-99

C-99

C-99

C-99

M-637

M-637

TABLE I I I

Transformat ions by Genus: PÉNICILLIUM

517

SPECIES

chermes inum

chrysogenum *

*

*

*

*

c i t r eo -v i r ide *

SOURCE

CZAS

FCUTS

MCC

ASRI

AY

CZAS

IPB

MCC

MCC(MF-2133)

NRRL

SQ

WISC(48-701)

WISC (49-133)

CZAS

MCC

SUBSTRATE

4-pregnene-3 ,2 0-dione




17a, 21 -dihydroxy -4 -pregnene -3,20-dione (use of conidia)




Diosgenin (dioscorea tuber pulp)

plant saponins

3j3-hydroxy -5 -pregnen-20-one



17a -oxa-D-homo-4-andros tene -3,17-dione




REACTION

—

-

none at C-11

17/3-Ac-17a-o x a - 1 7 - C = 0

17α-ΟΗ-17β-(20-C=O-21-OH) -> 17-C = 0

17/3-Ac-17a-o x a - 1 7 - C = 0

17/3-Ac-1 7 - C = 0

none at C-11

3/3-glycoside (Dioscin) —* 3/3-ΟΗ·3β-ΟΗ - > 3 - C = 0 ; Δ 5 - Δ 4

hydrolysis of gly cos ides to aglycones (sapogenins)

Δ 5 - Δ 4 ; 3/3-ΟΗ - 3 - C = 0

11/3-OH

no tes tol ic acid

17a-oxa-17-C = 0 - > 1 3 , 1 7 -seco-13ö-OH-16-COOH

17j3-Ac—17a-o x a - 1 7 - C = 0

17/3-Ac—13,17-seco-13a-OH-16-COOH

17j3-Ac-17a-o x a - 1 7 - C = 0

none at C-11

R E F .

C-99

C-99

D-190

C-99

V-1048

C-99

C-102

D-190

R-781

K-478·, K-479

P-710

H-328

H-398

H-398

F-270·, F-284

H-398

C-99

D-190

518

TABLE I I I

Transformat ions by Genus: P É N I C I L L I U M

SPECIES

ci t r inum *

*

*

*

*

*

*

SOURCE

ASRI

ATCC-8506

ATCC-10105

CZAS

FRI

I P ß (THOM)

MCC

S

SUBSTRATE


A-nor-17j3-hydroxy-3-androsten-2-one


17a-oxa-D-homo-4-andros tene -3,17-dione




17«, 21-d ihydroxy-4-pregnene-3,20-dione



1 lûf-hydroxy-4-pregnene-3, 20-dione






REACTION

17/3-Ac-^ 17/3-OH

17/3-OH—17a-o x a - 1 7 - C = 0

no tes tol ic acid

17a-oxa-17-C= 0 —13,17-seco-13ö-OH-16-COOH

1 7 ß - A c - 1 7 a -o x a - 1 7 - C = 0

17/3-Ac->13,17-seco-13a-OH-16-COOH


17/3-Ac -» 1 7 - C = 0

1 7 0 - A c -17/3-OH

-

17-C = 0 -17/3-OH

17/3-Ac — 17/3-OH

17/3-Ac -1 7 - C = 0

17/3-Ac — 17/3-OH

17a-OH-17/3-Ac-17/3-OH

17/3-Ac -17/3-OH

none at C - l l

1 7 - C = 0 - 1 7 a -o x a - 1 7 - C = 0

17/3-Ac— 17a-o x a - 1 7 - C = 0

R E F .

C-99

L-500

H-398

H-398

F-270

H-398

M-602

M-637

C-99

S-849

H-336

H-336

C-102

H-336

H-336

H-336

D-190

S-846

S-846


TABLE I I I

519

T r a n s f o r m a t i o n s by G e n u s : PENICILLIUM

SPECIES

ci t r inum

claviforme

clavigerum

commune *

1 *

corylophilum *

1 *

I corymbiferum

SOURCE

S

SQ

CZAA

CZAS

RIDPI

ASRI

CZAS

ASRI

CZAS

ASRI

CZAS

MCC

ASRI

SUBSTRATE





11/3 ,17a ,21- t r ihydroxy-4-preg-nene-3 ,20-dione

1 7a , 21 -dihydr oxy -4 -pr egnene -3 ,11 ,20- t r ione

A-nor-17/3-hydroxy-3 -andr osten -2-one



9 a - f l u o r o - 4 - p r e g n e n e - 3 , 1 1 , 2 0 -t r ione












REACTION

17a-OH-17/3-Ac —17a-oxa-1 7 - C = 0

17/3-(20-C=O-21-OK) -»17a-oxa-17-C = 0

-

20-C = O -20/3-OH

-

-

17/3-OH — 17a-oxa-17-C = 0

17/3-Ac— 17a-o x a - 1 7 - C = 0

17/3-Ac—17a-o x a - 1 7 - C = 0

1 7 ß - A c - 1 7 a -o x a - 1 7 - C - O

-

-

-

-

-

17/3-Ac-17a-o x a - 1 7 - C = 0

17/3-Ac-17a-oxa-17-C = 0

17/3-Ac-17/3-OH

17/3-Ac-17/3-OH

11a-OH

R E F .

S-846

S-846

S-846

S-846

S-846

S-846

L-502

L-502

L-492

L-492

C-99

C-99

C-99

C-99

C-99

C-99

C-99

C-99

C-99

D-190

C-99

520

TABLE I I I

T r a n s f o r m a t i o n s by Genus: PENICILLIUM

SPECIES

corymbiferum

crus tosum

cyaneofulvum *

*

cyaneum

cyclopium

(Westling) *

daleae

*

decumbens *

*

*

*

SOURCE

CZAS

MCC

CZAS

MCC

ASRI

CZAS

MCC

MCC

CZAS

MCC

NG

N R R L -942, 1888, 1889, ERRL-1292

MCC

RIDPI

ASRI

CZAS

FCUTS

IPB

SUBSTRATE



4 -p regnene-3 i 20-d ione








plant sap on in s

plant saponins











REACTION

_

none a t C-11

-

none at C-11

17/3-Ac—17a-o x a - 1 7 - C = 0

17/3-Ac-*17a-o x a - 1 7 - C = 0

none at C-11

none at C-11

-

none at C-11

hydrolysis of glycosides to aglycones (sapogenin)

hydrolysis of glycosides to aglycones (sapogenin)

none at C-11

17/3-Ac-» 17a-o x a - 1 7 - C = 0

17/3-Ac—17a-o x a - 1 7 - C = 0

17/3-Ac-* 17a-o x a - 1 7 - C = 0

17/3-Ac-» 17a-o x a - 1 7 - C = 0

1 7 - C = 0 -> 17/3-OH

17/3-Ac-» 17/3-OH

17/3-Ac-»17j3-OH

17a -OH -17/3 -Ac -»17/3-OH

17/3-Ac-»17/3-OH

R E F .

C-99

D-190

C-99

D-190

C-99

C-99

D-190

D-190

C-99

D-190

K-479

K-478

D-190

C-99

C-99

C-99

C-99

H-336

H-332·, H-336

H-336

H-336

H-336


SPECIES

decumbens

digitatum

diversum *

duponti

egyptaceum *

*

*

*

ehrl ichi i

expansum

SOURCE

MCC

CZAS

MCC

NG (Sandoz-872)

CZAS

FCUTS

MCC

ASRI

CZAS

FCUTS

SSSR

MCC

ASRI

ATCC-7861

CZAA

CZAS

FCUTS

MCC

NRRL

SUBSTRATE




3/3, 6/3, 8/3,14/3-tetrahydroxy-4, 20,22-bufatr ienol ide 6-aceta te 3-glucoside

3ß, 14/3-dihydroxy-5j3-20(22)-cardenolide 3[glucosyl-digitoxosy I -digitoxosy 1 -digitoxoside]











4 - p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e





Sarsasapogenin

Diosgenin


REACTION

none at C - l l

-

none at C - l l

3 / 3 - [ l V g l u c o -s ide l -3 /3 -OH

glucosyl-digitoxosyl-digitoxosyl -digitoxoside -* digitoxosy 1-digitoxosyl-digitoxoside

15/3-OH

15/3-OH

none at C - l l

17/3 - A c - 17a-o x a - 1 7 - C = 0

17/3 - A c - 17a-o x a - 1 7 - C = 0

17/3-Ac->17a-o x a - 1 7 - C = 0

17/3-Ac-17a-o x a - 1 7 - C = 0

none at C - l l

—


17/3-Ac -17-C = 0

-

-

-

none at C - l l

-

-

-

REF.

D-190

C-99

D-190

S-936a

S-936a

C-99

C-99

D-190

C-99

C-99

C-99

C-99

D-190

C-99

M-602

M-637

C-99

C-99

C-99

D-190

M-587

M-587

M-587

TABLE I I I

PENICILLIUM

521


SPECIES

fellutanum

I i requentans *

*

funiculosum

fuscum *

gladioli

godlewskii *

granulatum

helicum

herquei

humuli

implicatum *

islandicum

ital icum

janthinellum *

SOURCE

MCC

SSSR

ASRI

ATCC-10444

CZAS

MCC

MCC

NRRL

CZAS

MCC

CZAS

CZAS

MCC

CZAS

MCC

ASRI

CZAS

MCC

FCUTS

MCC

MCC

CZAS

MCC

ASRI

SUBSTRATE








Sarsasapogenin

Diosgenin




4 -pregnejie -3 ,20-dione







4-pregnene-3 ? 20-d ione







REACTION

none at C - l l

-

17/3-Ac-17a-o x a - 1 7 - C = 0

17/3-Ac-1 7 - C = 0

17/3 - A c - 17a-o x a - 1 7 - C = 0

none at C - l l

none at C - l l

-

-

-

17/3-Ac-17a-o x a - 1 7 - C = 0

none at C - l l

17/3-Ac-17a-o x a - 1 7 - C = 0

-

none at C - l l

-

none at C - l l

-

-

none at C - l l

17/3-Ac-17a-o x a - 1 7 - C = 0

none at C - l l

none at C - l l

-

none at C - l l

17/3-Ac— 17a-o x a - 1 7 - C = 0

R E F .

D-190

C-99

C-99

M-637

C-99

D-190

D-190

M-587

M-587

M-587

C-99

D-190

C-99

C-99

D-190

C-99

D-190

C-99

C-99

D-190

C-99

D-190

D-190

C-99

D-190

C-99

522

TABLE I I I

PENICILLIUM

TABLE I I I


SPECIES

janthinellum

javanicum *

*

jenseni i *

*

*

*

kapuscinskii *

lanoso-coeru leum

lanoso-gr i seum

lanoso-vir ide

lanosum

lavendulum

SOURCE

ATCC-10455

CZAS

MCC

ASRI

CZAS

MCC

NRRL

ASRI

CZAS

FCUTS

MCC

SSSR

SSSR

MCC

NRRL

MCC

MCC

CZAS

ASRI

NRRL

SUBSTRATE







Sarsasapogenin

Diosgenin









Sarsasapogenin

Diosgenin






Sarsasapogenin

Diosgenin

4-dehydrotigogenone

REACTION


17/3-Ac-17a-oxa-17-C = 0

none at C - l l

17/3-Ac-17a-oxa-17-C = 0

17/3-Ac-17a-o x a - 1 7 - C = 0

none at C - l l

-

-

-

17/3-Ac-17a-o x a - 1 7 - C = 0

17/3-Ac-17a-oxa-17-C = 0

17/3-Ac— 17a-o x a - 1 7 - C = 0

none at C - l l

17/3-Ac-17a-o x a - 1 7 - C = 0

17/3-Ac—17a-o x a - 1 7 - C = 0

none at C - l l

-

-

-

none at C - l l

none at C - l l

-

-

-

-

-

R E F .

M-602

C-99

D-190

C-99

C-99

D-190

M-587

M-587

M-587

C-99

C-99

C-99

D-190

C-99

C-99

D-190

M-587

M-587

M-587

D-190

D-190

C-99

C-99

M-587

M-587

M-587

523

524

TABLE I I I



levitum

lilacinum

ASRI

CZAS

ASRI

ATCC-10114







5ß -p regnane -3 ,12 ,20 - t r ione

3α, 11α, 17a-tr ihydroxy-5/3-pregnan-20-one


14a-hydroxy-4-pregnene-3 ,20 -dione




11a, 17a ,21 - t r ihydroxy-4 -p reg -nene-3 ,20-d ione

17/3-Ac^l7a-oxa-17-C = 0

17/3-OH-> 1 7 - C = 0

17/3-OH-17a-o x a - 1 7 - C = 0

17/3-OH-*13,17-seco-13a-OH-16-COOH

17-C = 0—17a-oxa-17-C = 0

1 7 - 0 = 0 - 1 3 , 1 7 -seco-13a-OH-16-COOH

17/3-Ac — 1 7 - C = 0

17/3-Ac — 1 7 - C = 0

17a-OH-17ß-Ac - 1 7 - C = 0


2 0 - C = O -20ß-OH

17j3-Ac-17-C = 0

17/3-Ac->17-C = 0

17a-OH-17/3-Ac - 1 7 - C = 0

17/3-(20-C = O-21-OH)—17-C=C|

17a-OH-17/3-(20-C=O-21-OH)| -»17 -C=0

20-C=O->20/3-OH

17a-OH-17/3-(20-C = O-21-OH)| ->17-C=0

C-99

C-99

C-99

P-737

P-737

P-737

P-737

P-737

M-637

M-637

M-637

M-602

M-637

M-637

E-204; M-637

M-637

M-637

M-637

M-637

M-637

TABLE I I I


525

SPECIES

li lacinum

*

*

(in mixed cul ture with 1 Rhizopus n igr icans

[ l la -OH])

(in mixed cul ture with Rhizopus n igr icans [ l l a -OH])

SOURCE

ATCC-10114

CZAA

CZAS

MCC

NRRL

UC

SUBSTRATE

14a, 17c*,21-tr ihydroxy-4-preg-nene-3 ,20-d ione


17ce,21-dihydroxy-4-pregnene-3 ,11 ,20- t r ione 21-aceta te

3 -ketobisnor -4 -cholen-22 -al




Sarsasapogenin

Diosgenin






REACTION

17α-ΟΗ-17β-(20-C=O-21-O H ) - 1 7 - C = 0

17a-OH-17/3-(20-C=O-21-OH)-*17-C=0

17tf-OH-17/3-(20 -C=O-21-0 A c ) - 1 7 - C = 0

20-H-C = O -20/3-CH2OH

170-Ac—17a-oxa-17-C = 0

17/3-Ac—17a-o x a - 1 7 - C = 0

l l a - O H

-

-

-17/3-Ac->17a-o x a - 1 7 - C = 0

17/3 - A c ^ 17/3-OH

17/3-Ac^l7-c=o 17/3-Ac->17a-o x a - 1 7 - C = 0

17/3-Ac-17/3-OH

20-C=O -20/3-OH

17/3-Ac -17-C = 0

17/3-Ac—17-c=o

17/3-Ac— 17-C = 0

R E F .

M-637

M-637

M-637

E-202; W-1068

C-99

C-99

D-109

M-587

M-587

M-587

P -726 ; S-832

S-832

P -726 ; S-832

S-832

S-832

S-832

S-831; S-83_2_

S-831

S-831

526

TABLE I I I


SPECIES

lividum

*

luteum

mar tens i i

melearginum *

*

melinii *

miczynskii *

*

multicolor *

*

nalgiovensis

*

SOURCE

ATCC-10102

MCC

SSSR

ATCC-10465

CZAS

FRI

CZAS

MCC

ASRI

CZAS

MCC

CZAS

MCC

CZAS

FCUTS

MCC

FCUTS

SSSR

MCC

SSSR

SUBSTRATE

21-hydroxy-4 -p regnene -3 ,20 -dione aceta te

(revision of s t ruc tu re -20a to 20j3 - Ref. S-832)





17ö ,21-d ihydroxy-4-pregnene-3,20-dione















REACTION

17/3-(20-C=O-21-OAc) -1 7 - C = 0

20-C=O -> 20/3-OH;21-OAc - 2 1 - O H

none at C-11

17/3-Ac-17a-o x a - 1 7 - C - O


-

-

-

none at C-11

1 7 / 3 - A c - 1 7 a -o x a - 1 7 - C = 0

17/3-Ac— 17a-o x a - 1 7 - C = 0

none a t C-11

17/3 - A c - 17a-o x a - 1 7 - C = 0

none at C-11

17/3-Ac—17a-o x a - 1 7 - C = 0

17/3-Ac— 17a-o x a - 1 7 - C = 0

none at C-11

17/3-Ac-17a-o x a - 1 7 - C = 0

17/3-Ac-17a-o x a - 1 7 - C = 0

none a t C-11

17/3-Ac— 17a-o x a - 1 7 - C = 0

R E F .

M-637

M-637

D-190

C-99

M-602

C-99

S-849

C-99

D-190

C-99

C-99

D-190

C-99

D-190

C-99

C-99

D-190

C-99

C-99

D-190

C-99

TABLE I I I


527

SPECIES

namyslowskii

n igr icans *

*

*

notatum *

1 *

1 *

(Wastling)

SOURCE

MCC

ASRI

ATCC-10115

CZAA

CZAS

MCC

ASRI

ATCC-9479

CZAS

FAR MIT

FCUTS

IPB

SUBSTRATE





(revision of s t r uc tu r e -20a to 20/3 - Ref. S-832)











5-androstene-3/3 ; 17/3-diol


4 - p r e g n e n e - 3 , 2 0 - d i o n e


REACTION

none at C - l l

17j3-Ac-»17a-o x a - 1 7 - C = 0


17/3-(20-C=O-21-OH) -> 1 7 - C = 0

20-C=O-> 20/3-OH

17/3-Ac-17a-o x a - 1 7 - C = 0

17/3-Ac-»17a-o x a - 1 7 - C = 0

none at C - l l

17/3-Ac-17/3-OH


17/3-Ac — 17ß-OH

15«-OH

3-C = 0—3/3-OH; Δ 4 - 5 α - Η

15α -OH

17β-Ac-17/3-OH

3/3-OH-3-C=0· , . 5 . 4 Δ -*Δ

3 / 3 - O H - 3 - C = 0 ; Δ 5 - Δ 4

1 7 - C = 0 -17/3-OH

17/3-Ac -17/3-OH

17/3-Ac — 17/3-OH

R E F .

D-190

C-99

M-636

M-637

M-637

C-99

C-99

D-190

C-99

M-602

C-99

C-86

C-86

C-86

C-99

H-337

H-337

H-336

H-332; H-336

H-336 1

528

TABLE I I I


SPECIES

nota tu m *

novae-zeelandia

ochraceum

ochro-chlorum *

*

olivino-viride

oxalicum

*

*

pali tans

pallidum

parvum *

SOURCE

IPB

MCC

NG

(Sandoz-831)

ATCC-10473

CZAS

FCUTS

MCC

ASRI

CZAS

MCC

MCC

ATCC-10576

CZAS

FCUTS

MCC

CZAS

MCC

ASRI

ASRI

SUBSTRATE




5-choIesten-3j3-oi (sole carbon source)


3j8, 6ß? 8j3,14ß-tetrahydroxy-4-20,22 -bufatrienolide 6-aceta te 3-glucoside

3/3,14/3-dihydroxy -5/3-20(22)-car denolide - 3 - [glucosyl -digitoxosyl -digitoxosyl -digitoxoside ]

5/3-pregnane-3, 6 ,20- t r ione








4 -p regnene-3 ,2 0-dione









REACTION

17a-OH-17/3-Ac->17j3-OH

17/3-Ac-*17/3-OH

none at C - l l

utilization

utilization

3/3-[l ξ -gluco-sidel —» 3/3-OH

glucosyl-digitoxosyl-digitoxosyl-digitoxoside —* digitoxosyl-digitoxosyl-digitoxoside

17j3-Ac-»17-C=0


--

none at C - l l

17/3-Ac-* 17a-o x a - 1 7 - C = 0

17/3-Ac-17a-o x a - 1 7 - C = 0

none at C - l l

none at C - l l


l l a - O H

11a-OH

none a t C - l l

-none at C -11

-

17/3-Ac-17a-o x a - 1 7 - C = 0

R E F .

H-336

H-336

D-190

S-793c

S-793c

S-936a

S-936a

M-637

M-602

C-99

C-99

D-190

C-99

C-99

D-190

D-190

M-636

C-99

C-99

D-190

C-99

D-190

C-99

C-99


SPECIES

parvum *

patulum

phoenicum

p i sca r ium *

psi t tacinum *

puberulum

pulvil lorum *

1 *

purpurescens *

purpurogenum

pusil lum *

1 *

rac iborsk i i *

1 *

SOURCE

FCUTS

NG (Sandoz-815)

FCUTS

CZAS

MCC

CZAS

ASRI

MCC

ASRI

CZAS

CZAS

MCC

SSSR

ASRI

CZAS

MCC

FCUTS

SSSR

ASRI

CZAS

SUBSTRATE


3/3, 6/3, 8/3,14/3-tetrahydroxy -4 , 20,22 -bufatrienolide 6-aceta te 3-glucoside

3ß,14/3-dihydroxy-5/3-20(22)-cardenolide 3-[glucosyl-digitoxosy 1 -digitoxosy 1 -digitoxoside ]


4 -p regnene-^ , 20-dione

















REACTION

17/3-Ac-17a-o x a - 1 7 - C = 0

3/3-[lVgluco-side ) — 3/3-OH

glucosyl-digitoxosyl-digitoxosyl-digitoxoside— digitoxosyl-digitoxosyl-digitoxoside

17/3-Ac-17a-o x a - 1 7 - C = 0

none at C-11

17/3-Ac-17a-o x a - 1 7 - C = 0

-

none at C-11

17/3-Ac-17a-o x a - 1 7 - C = 0

17/3-Ac-17a-o x a - 1 7 - C = 0

17/3 - A c - 17a-o x a - 1 7 - C = 0

none at C-11

17/3-Ac-17a-o x a - 1 7 - C = 0

-

-

none at C-11

17/3-Ac-17a-o x a - 1 7 - C = 0

17/3-Ac— 17a-o x a - 1 7 - C = 0

1 7 ß - A c - 1 7 a -o x a - 1 7 - C = 0

17/3-Ac-17a-oxa -17 -C^O

R E F .

C-99

S-936a

S-936a

C-99

C-99

D-190

C-99

C-99

D-190

C-99

C-99

C-99

D-190

C-99

C-99

C-99

D-190

C-99

C-99

C-99

C-99

TABLE I I I

PENICILLIUM

529

SPECIES

ra i s t r i ck i i *

*

*

r e s t r i c t u m *

*

*

r e s t r i c tu losum *

*

rolfsi i

roquefort i

1 ro seo -pu rpureum

rubrum

1 rugulosum *

*

sc le ro t io rum *

SOURCE

ASRI

ATCC-10490

CZAA

CZAS

MCC

ASRI

CZAS

FCUTS

MCC

ASRI

CZAS

-MCC

CZAS

FCUTS

MCC

NRRL

MCC

CZAS

ASRI

CZAS

MCC

SSSR

SUBSTRATE
















Sarsasapogenin

Diosgenin








REACTION

17/3-Ac->17a-o x a - 1 7 - C = 0


17/3-Ac-17a-o x a - 1 7 - C = 0

17/3-Ac->17a-o x a - 1 7 - C = 0

none at C - l l

17/3-Ac-17a-o x a - 1 7 - C = 0

17/3-Ac—17a-o x a - 1 7 - C = 0

17/3-Ac->17a-o x a - 1 7 - C = 0

none at C - l l

17/3-Ac-17a-o x a - 1 7 - C = 0

17/3-Ac-17a-o x a - 1 7 - C = 0

none at C - l l

-

-

none at C - l l

-

-

-

none a t C - l l

-

15/3-OH

15/3-OH

none at C - l l

17/3-Ac— 17a-o x a - 1 7 - C = 0

R E F .

C-99

M-602

C-99

C-99

D-190

C-99

C-99

C-99

D-190

C-99

C-99

D-190

C-99

C-99

D-190

M-587

M-587

M-587

D-190

C-99

C-99

C-99

D-190

C-99

530


TABLE I I I

PENICILLIUM

TABLE I I I


531

SPECIES

s impl ic i s s imum *

solitum

soppi *

species

SOURCE

CZAS

MCC

MCC

CZAS

MCC

ATCC-11598

ATCC-12556

SUBSTRATE







D -homo -17a - oxa -1 ,4 -andr osta -d iene-3 ,17-d ione






3/3-hydroxy- 5 -andr osten -17 -one


REACTION

17/3-Ac-17a-o x a - 1 7 - C = 0

none at C-11

none at C-11

17/3-Ac-17a-oxa-17-C = 0

none at C-11

15α-OH; 17/3-OH-17-C = 0

15a-OH

15a-OH

15a-OH


7/3-OH

la -OH

7/3-OH

la-OH

6/3-OH

12/3-OH

15/3-OH

la,6/3-diOH

la-OH

la -OH; 3/3-OH-> 3-C=0;A5—Δ4

l a - O H

2/3-OH

R E F .

C-99

D-190

D-190

C-99

D-190

D-151

D-151

D-158

F-285; F-287

F-285; F-287

F-290

D-163

F-290

T-1036

T-1036

T-1036

T-1036

T-1036

D-163; D-164; D-168; G-293

D-163; D-168

D-163; D-167; D-168

D-163; D-167; D-168

532

T A B L E I I I

T r a n s f o r m a t i o n s by Genus : PÉNICILLIUM


species ATCC-12556

ATCC-13001

EM

IPB

NG


17a-oxa-D-homo-4-andros tene-3,17-dione


16a, 17α-oxido-4-pregnene -3, 20-dione


lia -methyl -5 - a n d r o s t e n - l a , 3β, 17/3-triol

17a, 21 - tr ihydroxy -16 -methylene-1 ,4-pregnadiene-3 , 20-dione


1,3, 5(10)-estrat r iene-3,17/3-diol (sole carbon source)

3 - h y d r o x y - l , 3 , 5 (10) -es t ra t r ien-17-one (sole carbon source)

3a-hydroxy-5/3-cholanic acid (sole carbon source)

la -OH; D-163 5a-H

1α-ΟΗ; Δ — 5a-H; 3-C = 0— 3/3-OH

2/3-OH

2/3-OH

15/3-OH

2/3,15/3-diOH

7/3,15/3-diOH

6/3-OH;15-C = 0 (via 15/3-OH)

7/3-OH

7/3-OH

15/3-OH

3/3-OH->3-C = 0 : Δ 5 - Δ 4

11α-OH

1 7 - C = 0 — 17/3-OH

17/3-Ac-17-C = 0

17/3-Ac-» 17a-oxa-17-C = 0

15β-ΟΗ

llff-OH

17/3-Ac-17/3-OH

17a-OH-17/3-

D-163

T-1036

T^1036

T^1036

T-1036

D-177; T-1036; T-1037

T-1036

T-1036

T-1036; T-1037

T-1036

G-293

M-558

H-336

C-102

C-99; C-102

C^99

C-99; D-190

C-99; C-102; H-336 H-336

Ac—17/3-OK

utilization

T-1033

T-1033

T-1033



TABLE I I I


533

SPECIES

species

(in mixed culture with Rhizopus n igr icans | l l a - O H | - Sporotr ichum su l lu rescens [ l la-OH|)

spicul isporum

spinulosum *

SOURCE

NC

(Sandoz-822, 825,833,834, 838 ,841 ,851 , 858.860,889, 890,909)

(Sandoz-822, 833 ,834,838, 851 ,858,889, 909)

(Sandoz-858, 889)

(Univ. of Texas - Sp. 17 ,18 ,19 ,20)

NG

NRRL

Sear le

SQ

UC

CZAS

ASRI

SUBSTRATE

3a, la, 12a-tr ihydroxy-5/3-cholanic acid (sole carbon source)

3/3, 6/3, 8/3,14/3-tetrahydroxy-4, 20,22 -bufatrienolide 6-aceta te 3-glucoside

3/3,14/3-dihydroxy-5/3-20(22)-cardenolide - 3 -1 glucosy1-digitoxosyl-digitoxosyl-digitoxoside ]

Digilanid A

5 -cholesten -3/3 -ol (suggested precaut ions to be taken before concluding s t e ro l is modified by a culture)


plant saponins

3/3 -hydr oxy - 5 -androsten -17 -one


1 7 a - o x a - D - h o m o - l , 4 - a n d r o s t a -d iene-3 ,17-d ione

4 -pregnene-3 ,20-d ione (revision of s t ruc tu re -20a to 20/3 - Ref. S-832)

21 -hydroxy-4 -p regnene -3 ,20 -dione aceta te (revision of s t ruc tu re - 20a to 20/3- R e t S-832)



REACTION

utilization

3ß-[lVgIuco-side]^3/3-OH

glucosyl-digitoxosyl-digitoxosyl-digitoxoside —» digitoxosyl-digitoxosyl-digitoxoside

select ive c leav-age of glucose from sugar chain

util ization

17ß-Ac->17-C-0

hydrolysis of glycosides to agiycones (sapogenin)

1 α - Ο Η ; Δ 5 - Δ 4 ; 3/3-OH-3-C = 0

1α-ΟΗ; 2/3-ΟΗ

15a-OH

20-C = O -20/3-OH

20-C = O -20/3-OH; 2 1 -O A c - 2 1 -OH

-17/3-Ac—17a-oxa-17-C = 0

R E F .

T-1033

S-936a

S-936a

S-936a

P-732

S-922

K-478

D-162

D-162

P-706

M-637

M-637

C-99

C-99

534

TABLE I I I


SPECIES

spinulosum *

*

steckii *

*

*

* *

stoloniferum

s t r i a tum

subalter itium *

*

t a rdum

* ter l ikowski *

t e r r e s t r e

thomii *

*

*

SOURCE

CZAA

CZAS

MCC

ASRI

CZAS

FCUTS

I P ß

MCC

SSSR

SSSR

CZAS

ASRI

FCUTS

MCC

SSSR

ASRI

MCC

ASRI

CZAS

MCC

ASRI

ATCC-10506

CZAS

FCUTS

MCC

SUBSTRATE























l i a , 17a-dihydroxy-4-pr egnene -3,20-dione

1 l a , 17a -dihydroxy -4 -pr egnene -3,20-dione

l i a , 17a-dihydroxy-4-pregnene -3,20-dione

l i a , 17a-dihydroxy -4 -pregnene -3,20-dione

REACTION

17/3-Ac-17a-o x a - 1 7 - C = 0

17/3-Ac-17a-o x a - 1 7 - C = 0

none at C-11

17/3-Ac-17a-o x a - 1 7 - C = 0

17/3-Ac— 17a-oxa-17-C = 0

17/3-Ac-17a-o x a - 1 7 - C = 0

17ß-Ac-17-C = 0

17/3-Ac-17a-oxa-17-C = 0

none a t C-11

17/3-Ac—17a-o x a - 1 7 - C = 0

--

17/3-Ac-17a-o x a - 1 7 - C = 0

17/3-Ac-17a-o x a - 1 7 - C = 0

l i a - O H

15/3-OH

17/3-Ac-17a-o x a - 1 7 - C = 0

none at C-11

--

none a t C-11

17/3-Ac-17a-o x a - 1 7 - C = 0


170-OH-17/3-A c - 1 7 - C = 0

17a-Ac— 17a-o x a - 1 7 - C = 0

17a-Ac— 17a-o x a - 1 7 - C = 0

none at C-11

R E F .

C-99

C-99

D-190

C-99

C-99

C-99

C-102

C-102

D-190

C-99

C-99

C-99

C-99

C-99

D-190

C-99

C-99

D-190

C-99

C-99

D-190

C-99

M-602

M-637

C-99

C-99

D-190

TABLE I I I


535

SPECIES

thomii

t rzebinski i

turbatum

ur t icae

var iabi le

vermicula tum

ver rucu losum

vinaceum

1 vi r id ica tum

waksmanni

wortmanni

SOURCE

WISC

MCC

MCC

ATCC-10120

CZAA

CZAS

ASRI

MCC

NRRL

MCC

MCC

CZAS

MCC

MCC

MCC

SUBSTRATE

14/3,19-dihydroxy-3-keto-4, 20(22) -car dadienolide

14/3-hydroxy-3,19-dioxo-4, 20(22) -car dadienolide






4 - p r e g n e n e - 3 , 1 1 , 20- t r ione

6a - f l uo ro -4 -p regnene -3 ,11 , 20-tr ione

9 a - f l u o r o - 4 - p r e g n e n e - 3 , 1 1 , 20- t r ione

6û! -methyl -4-pregnene-3 ,11 , 20- t r ione

6α ,9α-d i f luoro-4-pregnene-3 , 11, 20- t r ione

9a - f luo ro -6a -me thy l -4 -p reg -nene -3 ,11 ,20 - t r i one





Sarsasapogenin

Diosgenin





4 - p r e g n e n e - 3 , 20-dione



REACTION

1 9 - O H -19-C = 0

1 9 - C = 0 -19-OH

none a t C-11

none a t C-11

15f-OH

15α-OH

15û-OH

6/3-OH

15α -OH

15α-OH

15α-OH

15α-ΟΗ

15α-OH

15α-OH

--

-none a t C-11

---

none at C-11

none at C-11

-none at C-11

none a t C-11

none at C-11

R E F .

S-892

S-892

D-190

D-190

M-639

M-639

E-202; F-250; M-576; M-577; M-602

E-202

A-31 ; ß - 4 4

A-31

A-31

A-31

A-31

A-31

C-99

C-99

C-99

D-190

M-587

M-587

M-587

D-190

D-190

C-99

D-190

D-190

D-190

536


T r a n s f o r m a t i o n s by G e n U S : PENTATRICHOMONAS (Zoomastigina - Polymastigina) PESTALOTIA (Imperf. - Melanconiales)

SPECIES

PENTATRICHOMONAS (Protozoa)

gal i inarum

hominis

! PESTALOTIA

diospyri

foedans

funerea

royenae

SOURCE

uc

uc

FRI

ATCC-11817 (QM-795)

AY

C

KSC

C

KSC

TNAES

ATCC-11816 (QM-531)

SUBSTRATE

1 la -hydroxy-4-andros tene -3,17-dione


1 ,4-andros tad iene-3 ,17-d ione



16a-ethyl-17a, 21-dihydroxy -1,4 -pregnadiene-3 ,20-dione 21-aceta te

1 la, 21 -dihydr oxy- 16a- methyl -1 ,4-pregnadiene-3 , 20-dione

17ö, 21 -dihydr oxy -4 -pr egnene -3, 20-dione (with spores)

11/3, 21-dihydroxy-3, 20-diketo-4-pregnen - 18-oic acid (18—» 11) lactone


3 /3-hydroxy-5a-pregnane- l l , 20-dione




REACTION

17-C=0-> 17j3-OH

1 7 - C = 0 -17/3 -OH

17-C=0-> 17/3-OH

l l o - O H

11a-OH

l l a - O H ; 2 1 - O A c -21-OH

l l ö - O H

16G-OH

16a-OH

16a-OH

16a-OH

X-OH; 16a-OH

16a-OH

11a-OH

R E F .

S-830

S-830

S-830

S-849

S-882

O-703

O-702

S-835

W-1091

F-265; F-266

W-1092

F-266

F-265; F-266 S-849 1

S-882

537


Transformat ions by Genus: ΡΕΖΓΖΑ PHIALOPHORA

PHOLIOTA PHOMA

(Asco. - Pez iza les ) (Imperf. - Moniliales) (3as id io . - Agaricales) (Imperf. - Sphaeropsidales)

SPECIES

PEZIZA

species

PHIALOPHORA

ve r rucosa

PHOLIOTA

adiposa

squar roso ides

PHOMA

species

SOURCE

C (ETH-M-23)

(ETH-M-26)

FRI

FRI

AL (H-140)

ATCC-13145

SUBSTRATE


d, l -21-hydroxy-4-pregnene-3,20-dione




1 6 a - t e r t - b u t y l - 1 7 a , 2 1 -d ihydroxy-5a-pregnane-3 , 20-dione

16/3-ethyl-17a,21-dihydroxy-5a-pregnane-3 ,20-d ione

17a, 21-dihydroxy-16a-methyl -5a-pregnane-3 ,20-d ione

17a, 21-dihydroxy-16/3-methyl-5a-pregnane-3 ,20-d ione


REACTION

7a-OH

d , l - d - 7 a - O H + 1


l l a - O H

11/3-OH

l l a - O H

l l ß - O H

l l a - O H

11/3-OH

l l a - O H

11/3-OH

6/3-OH

l l a - O H

11/3-OH

R E F .

M-585

W-1102

S-849

S-849

S-825

1-42.

1-422

1-422

1-422

1-422

1-422

1-422

1-422

1-422

1-422

1 -4 .72

538


TABLE I I I

PHOMA PHOMOPSIS PHYCOMYCES

TAXONOMY

(Imperf. - Sphaeropsidales) (Phyco. - Mucorales)

SPECIES

species

PHOMOPSIS

c i t r i

PHYCOMYCES

blakesleeanus

SOURCE

ATCC-13145

FAHU

FRI

TNAES

NRRL

P F

SUBSTRATE


17a ,21-dihydroxy-16a-methyl -4-pregnene-3 ,20-d ione

17a,21-dihydroxy-16/3-methyl-4-pregnene-3 ,20-d ione

16ö-ter t . bu ty l -17a ,21 -dihydr oxy -1 ,4 -pr egnadiene -3,20-dione

16/3-ethyl-17a, 21-dihydr oxy -1,4 -pr egnadiene -3 ,20-dione

17a, 21-dihydroxy-16a-methyl -1,4 -pr egnadiene -3 ,20-dione

17a,21-dihydr oxy-16j3-me thy 1-1 ,4-pregnadiene-3 , 20-dione




Sarsasapogenin

Diosgenin


17a ,21-d ihydroxy-4 ,14-pregnadiene-3 ,20-d ione

REACTION

15/3-OH

l l a - O H

11/3-OH

l l a - O H

11/3-OH

l l a - O H

11/3-OH

l l a - O H

11/3-OH

l l a - O H

11/3-OK

l l a - O H

11/3-OH

l l a - O H

Δ14 - 1 4 a , 15a-oxide

R E F .

1-422

1-422

1-422

1-422

1-422

1-422

1-422

1-422

1-422

1-422

1-422

1-422

1-422

S-849

S-849

S-849

M-587

M-587

M-587

S-865

TABLE I I I

T r a n s f o r m a t i o n s by Genus : PHYCOMYCES

539

SPECIES

blakesleeanus

nitens

pirot t ianus

1 species

SOURCE

SQ

UC

SSSR

SSSR

ATCC-14163

SUBSTRATE


4 - p r e g n e n e - 3 , 20-dione


17a-hydroxy-4-p regnene-3 , 20-dione


1 7a, 21 -dihydroxy- 4 -pregnene -3,20-dione






l l / 3 ,17ö ,21 - t r i hyd roxy-4 -p reg -nene-3 ,20-d ione

17a, 21-dihydroxy-9/3,11/3-oxido-4-pregnene-3 ,20-d ione

9a - f luo ro - l l / 3 ,16α ,17α ,21 - t e t r a -hydroxy-4 -p regnene -3 ,20 -dione 16,17-acetonide

9ö-f luoro- l l /3 ,16α, n a ^ l - t e t r a -h y d r o x y - l ^ - p r e g n a d i e n e -Sj 20-dione 16,17-acetonide

17a, 21 -dihydroxy-4 -pregnene -3 ,11 ,20 - t r ione

9a-f luoro-16a, 17a, 21 -tr ihydroxy-4 - p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e 16,17-acetonide

REACTION

Δ 5 - Δ 4 ; 3/3-ΟΗ ->3-C = 0

7a-OH

15/3-OH

11 -oxygénation

11-oxygénation

11-oxygénation

11-oxygénation

Πα-ΟΗ

-

6/3-OH

6/3-OH

6/3-OH

6/3-OH

6/3-OH

6/3-OH

6/3-OH; 11/3-OH

-n-c=o 6/3-OH

6/3-OH

6/3-OH

R E F .

P-710

F-285; F-286; F-288

F-285; F-286; F-287; F-288

M-601; M-636

M-601; M-636

M-601; M-636

M-601; M-636

E-224

E-224

H-400

H-400

H-400

H-400

H-400

H-400

H-400

H-400

H-400

H-400

540


TABLE I I I

PHYCOMYCES PHYTOMONAS PHYTOPHTHORA

PICHIA

TAXONOMY

(Schizo0 - Pseudomonadales) (Phyco. - Peronospora les ) (Asco. - Endomycetales)

SPECIES

species

theobromatus

PHYTOMONAS (see Xanthomonas)

c i t r i

e icobatryae

malvacearum

PHYTOPHTHORA

ci trophthora

paras i t i ca

PICHIA

membranaefaciens

rosa

SOURCE

NG

UC

TNAES

TNAES

NG

TNAES (CI-16)

FAKU

NRRL

FRI

SUBSTRATE


24/3-methyl-5, 7 ,22-cho les ta -trien-3/3-ol (sole carbon source)


1 7a -hydroxy-4 -p regnene -3 ,20 -dione



17a, 21 -dihydroxy -4 -pregnene-3,20-dione





Sarsasapogenin

Diosgenin



REACTION

utilization

utilization

11-oxygénation

11-oxygénation

11-oxygénation

11-oxygénation

—

-

—

-

—

-

-

-

REF.

S-793c

S-793c

M-601; M-636

M-601; M-636

M-601; M-636

M-601; M-636

S-849

S-849

T-1030

S-849

S-849

M-587

M-587

M-587

S-849

541


TABLE I I I

PILAIRA PIRICULARIA

PLEOSPORA

TAXONOMY

(Phyco. - Mucorales) vlmperf. - Moniliales) (Asco0 - Sphaeriales)


PILAIRA

anomala

PIRICULARIA

oryzae

PLEOSPORA

gaeumanni

NRRL

FAKU

FRI

Sarsasapogenin

Diosgenin


17a ,21-dihydroxy-4-pregnene -3,20-dione



l l /3 -hydroxy-3 ,20-d ike to-4-preg-nen-18-oic acid (18 -* 11) lactone

11/3,21 -dihydroxy -3 ,20 -diketo-4 -p regnen-18-a l

d, 1-21-hydroxy-4-pregnene-3, 20-dione

12a - f l uo ro - l lß -hyd roxy -4 -p reg -nene -3 ,20-dione

12a-fluoro-11/3,17a-dihydroxy -4 -pregnene-3 ,20-d ione

9a-f luoro-11/3,17a,21-tr ihydroxy-4-pr egnene-3 ,20-dione

I 9a - f l uo ro -4 -p regnene -3 ,11 ,20 -tr ione

l l /3 ,21-d ihydroxy-3 ,20-d ike to-1,4 -pr egnadien -18 -al

12a-f luoro-l l /3 ,17a-dihydroxy -l , 4 - p r e g n a d i e n e - 3 , 20-dione

9a- f luoro- l l /3 ,17a ,21- t r ihydroxy-1,4 -pr egnadiene - 3 , 2 0 - dione

6/3-OH

6/3-OH;lla-OH

11a-OH

14a-OH

14a

d,l-+ 1

14a

14a

14a

14a

14a

14a

14a

-OH

-d-14a-OH

-OH

-OH

-OH

-OH

-OH

-OH

-OH

W-

w-

vV-

w-

w-

w-

w-

w-

w-

-1108

-1108

-1102

-1103

-1103

-1108a

-1108a

-1108

-1103

-1108a

S

c

R E F .

M-587

M-587

M-587

S-849

S-849

S-849

542


T r a n s f o r m a t i o n s by G e n u s : PLEUROTUS PLUTEUS

POLYPORUS

(Basidio. - Agaricales) (ßasidio. - Agaricales) (Basidio. - Agaricales)

SPECIES

PLEUROTUS

japonicus

os t rea tus

PLUTEUS

granular is

POLYPORUS

abietinus

brumal i s

caeruleoporus

cinnabar inus

conchifer

frondosus

pubescens

radica ta

SOURCE

IAM

FAKU

FRI

NRRL-2366

AL(C-123)

UC

AL(G-67)

AL(H-126)

AL(G-90)

LED (D-6)

AL(C-255)

IAM

IAM

AL(H-139)

SUBSTRATE



17a,21 -dihydroxy -4 -pr egnene -3,20-dione



not given







17a, 21 -dihydroxy-4-pr egnene -3,20-dione


REACTION

-

-

-


17ß-Ac->17a-o x a - 1 7 - C = 0

oxidation




6/3-OH; 14a-OH; 15/3-OH


-

6j3-OH;lla-OH


R E F .

S-849

S-849

S-849

R-778

S-825

M-601; M-636

S-825

S-825

S-825

B-63

S-825

S-849

S-849

S-825

543

TABLE I I I

T r a n s f o r m a t i o n s by G e n u s : POLYPORUS POLYSTICTUS

PORIA

TAXONOMY

(Basidio. - Agaricales) (Basidio. - Agar icales)

SPECIES

squamosus

sulfureus

tulipiferus

POLYSTICTUS

cinnabar ius

h i r s tus

polyzonus

1 sanguineus

vers ico la

vers ico lorpus

PORIA

cocos

I species

SOURCE

AL (C-180)

AL (C-6)

LAM

ATCC-13489

FAKU

IAM

IAM

IAM

FRI

IAM

S

S

ATCC-13490

FRI

SUBSTRATE






17a, 21 -dihy droxy -4 -pregnene -3, 20-dione



17a, 21 -dihydroxy-4-pregnene -3, 20-dione

17a ,21-d ihydroxy-4-pregnene-3 ; 20-dione



17a -hydroxy-4 -p regnene-3 ,20-3,20-dione



21-hydroxy-4-p regnene-3 , 20-dione



REACTION



—

6/3-OH;14a-OH; 15j3-OH

6j3-OH

14a-OH

15j3-OH

-

-

6j3-OH; l l a - O H

-

l l a - O H

l l a - O H

-

-

6/3-OH; l l a - O H

6ß-OH; l l a - O H

6/3-OH; 14a-OH; 15/3-OH

6^-OH

14a-OH

15j3-OH

—

R E F .

S-825

S-825

S-849

B-63

B-63

B-63

3-63

S-849

S-849

S-849

S-849

S-849

S-849

S-859

S-859

S-859

S-849

B-63

B-63

B-63

B-63

S-849

544



PORIA PROACTINOMYCES (Schizo. - Actinomycetales)

SPECIES

PORIA

vaporar ia

PROACTINOMYCES (Synonym - Nocardia)

act inomorphus

ag re s t i s

aquosus

coeliacus

crystal lophagus

erythropoi is

SOURCE

FRI

NG

NG

NG

NG

NG

NG

SUBSTRATE







l ,3 ,5 v 10) -es t ra t r i ene-3 ,17 /3-d io l

5-androstene-3/3, 17/3-diol



3/3-hydroxy-5-cholenic acid

3-keto-4-cholenic acid



5-cholesten-3/3-ol

REACTION

utilization

utilization

utilization

utilization

utilization

17/3-OH — 1 7 - C = 0

Δ5 - Δ 4 ; 3/3-OH — 3-C = 0

Δ 5 - Δ 4 ; 3 /3-OH-3-C = 0 ; 17/3-OH - 1 7 - C = 0

Δ 5 - Δ 4 ; 3/3-OH -3-C = 0

17/3-OH-1 7 - C = 0

Δ 5 - Δ 4 ; 3/3-OH -3-C = 0

17/3-CH (CH3)CH2CH2 COOH -17/3-COOH

3/3-OH-3 - C = 0

3/3-OH — 3 - C = 0

Δ 5 - Δ 4 ; 3/3-OH — 3 - C = 0

R E F .

S-849

T-1030

T-1030

T-1030

T-1030

T-1030

T-1034

T-1032

T-1032

T-1032

T-1032

T-1032

T-1034

T-1034

T-1032; T-1034

T-1030; T-1031; T-1032; T-1034

TABLE I I I

T r a n s f o r m a t i o n s by Genus : PROACTINOMYCES

545

SPECIES

erythropol is

globerulus

minimus

paraffinae

polychromogenes

1 r e s t r i c t u s

roseus

rubroper t inc tus

species

SOURCE

NG

NG

NG

NG

NG

NG

NG

NG

NG

SUBSTRATE


5-cholesten-3/3-ol aceta te

4-choles ten-3-one

5-st igmasten-3/3-ol

5 ,22-s t igmastadien-3/3-ol




5-cholesten-3/3-oi (sole carbon source)




l , 3 ,5 (10) -es t r a t r i ene -3 ,17 /3 -d io l (ail subs t ra tes-Ref . T-1033) (sole carbon source)

3 -hydroxy-1 ,3 , 5 (10) -es t ra t r i en-17-one

3a -hydr oxy -5a -andr ostan -17 -one

3ß-hydr oxy- 5-androsten -17-one


3a, la, 12a-tr ihydroxy-5/3-cholanic acid


REACTION

utilization

-choiestenone —» r ing A cleavage

17j3-CH(CH3) CH2CH2CH2CH ( C H 3 ) 2 - 17/3-COOH

3/3-OH-3-C = 0 ; Δ 5 - Δ 4

3/3-OH-3-C = 0 ; Δ 5 - Δ 4

utilization

util ization

util ization

utilization

utilization

7ξ-ΟΗ

Δ 5 - Δ 4 ; 3 / 3 - Ο Η -3-C = 0

utilization

utilization

utilization

utilization

utilization

util ization

util ization

utilization

R E F .

T-1030; T-1031

T-1032

T-1034

T-1034

T-1032

T-1032

T-1030

T-1030

T-1030

T-1030

T-1030

K-474; K-475

K-474; K-475

T-1030

T-1033

T-1033

T-1033

T-1033

T-1033

T-1033

T-1033

546

TABLE I I I

TAXONOMY

T r a n s f o r m a t i o n s by Genus : PROACTINOMYCES PROTAMINOBACTER (Schizo. - Pseudomonadales)

SPECIES

species

PROTAMINOBACTER

alboflavum (alboflavus)

SOURCE

NG

ATCC-8458

SUBSTRATE

choles tan-3a-o l

cholestan-3/3-01

5/3-cholestan-3a-ol


5/3-cholestan-3/3-ol aceta te

5a, 6ß-dibromocholestan -3/3-ol

3ß-chloro-5-choles tene

5-cholesten-3/3-ol

5-choiesten-3/3-01 aceta te

d ichoies teryl e ther

4-choies ten-3-one

24/3-methyl -5 ,7 ,22-choles ta t r ien-3/3-01

5-stigmasten-3/3-ol

5,22-st igmastadien-3/3-01

e s t r an -3 -one

5α - andr ostan - 3 - one

17a-hydr oxy - 5a-andr ostan - 3 - one






5a-pregnan-3-one

5/3-pregnan-3-one





REACTION

utilization

utilization

utilization

utilization

utilization

-

-

Δ - Δ ;3/3-OH^ 3 - C = 0

utilization

utilization

util ization

utilization

utilization

utilization

S 4 Δ ; enol.

1,4

Δ

Δ 1 ' 4

1 4

Δ ' 1 4

Δ ' 1

Δ ; enol. 1

Δ 1

Δ 1 4

Δ ' 1 4

Δ '

Λ 1 ' 4

1 4

Δ '

Λ 1 ' 1

1 4

Δ '

R E F .

T-1033

T-1033

T-1033

T-1033

T-1033

T-1033

T-1033

H-406; H-407

T-1033

T-1033

T-1033

T-1033

T-1033

T-1033

S-866

S-866

S-866

S-866

S-866

S-863

S-863

S-863

S-866

S-866

S-866

S-866

S-866

S-866

TABLE I I I

Transformat ions by Genus: PROTAMINOBACTER

547

SPECIES

alboflavum (aiboflavus)

SOURCE

ATCC-8458

SUBSTRATE



11/3-hydroxy-5/3-pregnane-3,20-dione

14a -hydroxy-5/3-pregnane - 3 , 2 0 -dione


21 -hydroxy -5/3-pr egnane -3 ,20 -dione

21 -hydroxy-δξ -p regnane -3 ,20 -dione

1 I ß , 21 -dihydroxy -5/3 -pregnane -3,20-dione

11/3,21 -dihydroxy -5ξ -pregnane -3 ,20-dione

11/3,17«, 21- t r ihydroxy-5/3-preg-nane-3 ,20-d ione

11/3,14a, 17a, 21-tetrahydroxy-5/3-pr egnane-3 ,20-dione


17a, 21 -dihydroxy -5/3 -pr egnane -3 ,11 ,20 - t r ione


11/3,17a -dihydroxy -4 -pregnene -3,20-dione



9a- f luoro- l l /3 ,17a , 21-tr ihydroxy-4 -p regnene-3 ,20-d ione

16/3-fluoro-l l /3,17a,21-tr ihydroxy-4-pregnene-3 ,20-d ione

11/3,14a, 17a, 21 - te t rahydroxy - 4 -pregnene-3 ,20-d ione

REACTION

1 4

Δ

Δ ' l 1

Δ

A ' ' '

L 1

Δ '

Δ 1 ' 4

•1

Δ

1 4

Δ '

Δ

A 1 '*

A'«*

Δ 1 ' 1

1 , 4

Δ '

l

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

R E F .

S-866

S-866

S-866

S-866

S-866

S-866

S-863; S-866

S-866

S-866

S-866

S-866

S-866

S-866

S-863

S-863

S-863

S-863

S-863

B-51

S-863

548

TABLE I I I

Transformations by Genus: PROTAMINOBACTER

SPECIES

alboflavum (alboflavus)

rub rum

SOURCE

ATCC-8458

NRRL

ATCC-8457

SUBSTRATE

17a,21-dihydroxy-14a, 15a-oxido-4-pregnene-3 ,20-d ione

11/3 ,17a,21- t r ihydroxy-14a,15a-oxido-4-pregnene-3 ,20-dione

4 - p r e g n e n e - 3 , 1 1 , 20- t r ione

17a, 21 -dihydroxy -4-pregnene -3 , 1 1 , 2 0 - t r ione

2a-f luoro-17a, 21-dihydroxy-4-pregnene - 3 , 1 1 , 2 0 - tr ione

14a, 17a, 21 - t r ihydroxy-4 -p reg -nene -3 ,11 ,20 - t r i one


17a,21-dihydroxy-4,9(11) -

17a, 21-d ihydroxy-4 ,14-pregna-diene-3 ,20-dione

Sarsasapogenin

Diosgenin


e s t r an -3 -one

5a-andros tan-3-one







5a-pregnan-3-one

5ß-pregnan-3-one




20-hydroxy-5ß-pregnan-3-one


REACTION

Δ

Δ

Δ

Δ

Δ

Δ

Δ

Δ

Δ

-

-

-1 4

Δ ' ; enol.

A ' ' 4

Δ 1>4

Δ 1 4

Δ 1

Δ ; enol. 1

Δ 1

Δ 1 4

Δ 1 ,4

Δ

Λ 1 ' 4

1 4

Δ '

Λ 1 ' 1

Λ 1 ' 4

Λ 1 ' 4

R E F .

S-863

S-863

S-863

S-863

H-401

S-863

S-863

S-863

S-863

M-587

M-587

M-587

S-866

S-866

S-866

S-866

S-866

S-863

S-863

S-863

S-866

S-866

S-866

S-866

S-866

S-866

S-866

pregnadiene-3, 20-dione

T A B L E I I I

Transformations by Genus: PROTAMINOBACTER

549

SPECIES

rubrum

SOURCE

ATCC-8457

SUBSTRATE


l l /3-hydroxy-5/3-pregnane-3, 20-dione


17a -hydr oxy - 5/3 -pr egnane - 3 , 2 0 -dione


21 -hydroxy-5ξ -p regnane -3 ,20 -dione

11/3, 21 -dihydroxy - 5/3-pregnane -3,20-dione

l l /3 ,21-d ihydroxy-54-pregnane-3,20-dione

l l /3 ,17a ,21- t r ihydroxy-5/3-preg-nane-3 ,20-d ione

11/3,14a, 17a ,21- te t rahydroxy-5/3-pregnane-3,20-dione

5a -p regnane -3 ,11 ,20 - t r ione

17a, 21-dihydroxy-5/3-pregnane -3 , 1 1 , 20- t r ione






11/3,14a, 17a, 21 - t e t r ahydroxy-4-pregnene-3 ,20-d ione

17a, 21-dihydroxy-14a, 15a-oxido-4-pregnene-3 ,20-d ione

11/3,17a, 21- t r ihydroxy-14a , 15a-ox ido-4-pregnene-3 ,20-d ione

4 - p r e g n e n e - 3 , 1 1 , 20- t r ione

17a ,21-d ihydroxy-4-pregnene-3 ,11 ,20 - t r i one

REACTION

1 1

Δ ' 1 , 4

Δ

1 4

Δ '

J 4

Δ '

Λ 1 ' 4

Δ

1 4

Δ

4

Δ

Λ 1 ' 4

1 4

Δ

1 , 4

Δ 1 4

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

Δ1

R E F .

S-866

S-866

S-866

S-866

S-866

S-863; S-866

S-866

S-866

S-866

S-866

S-866

S-866

S-863

S-863

S-863

S-863

S-863

S-863

S-863

S-863

S-863

S-863

550

TABLE I I I

T r a n s f o r m a t i o n s by Genus: PROTAMINOBACTER PROTEUS

PSEUDOMONAS

TAXONOMY

(.Schizo. - Eubacter ia les) iSchizo. - Pseudomonadiales)

SPECIES

rubrum

PROTEUS

spec ies

PSEUDOMONAS

aeruginosa

(in mixed cul ture with Mycococcus sp. Ax )

aureofaciens

azoformicans

SOURCE

ATCC-8457

r a t caecum

IAM (HX-19)

NG

IAM (MT)

IAM (Baltimore)

IFO (3505)

IAM

IAM

NG

IAM

IAM

NRRL B-1543

IAM

SUBSTRATE

14a ,17a ,21 - t r i hydroxy-4 -p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e

17a ,21-dihydroxy-4 ,9(11)-pregnadiene-3 ,20-d ione

17a ,21-d ihydroxy-4 ,14-pregnadiene-3 ,20-d ione






11/3 ,17a,21- t r ihydroxy-4-p regnene -3 , 20-dione





17a, 21-dihydroxy - 4 -pregnene-3,20-dione


REACTION

Δ1

1

Δ

Δ1

Δ 1

11/3-OH

utilization

Δ1

oxidation

utilization

oxidation

R E F .

S-863

S-863

S-863

S-863

N-675

S-849

T-1030

S-849

S-849

1-428

1-428

1-414; 1-415

1-414; 1-415

T-1030

1-414; 1-415

1-414; 1-415

S-849

1-414; 1-415

TABLE I I I

Transformat ions by Genus: PSEUDOMONAS

551

SPECIES

azoi 'ormicans

boreopolis

i r rad ia ted mutant

caudata

chlororaphis

SOURCE

IAM

ATCC-13476

IAM

IAM

Take da (109)

Takeda (109)

IAM

IAM

IAM (1511)

SUBSTRATE

17ö,21-d ihydroxy-4-pregnene-3,20-dione

17o , ,21-dihydroxy-4-pregnene-3,20-dione

4-pregnene-3 ,20-dione

17a ,21-d ihydroxy-4-pregnene-3,2C-dione





17/3-hydr oxy -4 -andros ten -3 -one



17a-hydroxy-4-pregnene-3 , 20-dione


l l ß , 2 1 - d i h y d r o x y - 4 - p r e g n e n e -3,20-dione


REACTION

Δ]

Δ1; 20-C = O -20/3-OH

11/3-OH

Δ1; 20-C = O -20/3 -OH

11/3-OK

Δ1; 11/3-OH

Δ ' ; 17 /3-OH-1 7 - C = 0

17/3-OH — 1 7 - C - O

Δ1; 17G-OH-17j3-(20-C=O-21-OH) - 1 7 a -oxa-17-C = 0

Δ1

R E F .

1-414; 1-415

T-96C

T-960

T-96C

1-414; 1-415

1-414; 1-415

N-652

N-652

T-961

1-414; 1-415

1-414; 1-415

N-648

N-648

N-648

N-648

N-648

N-648

N-648

N-648

N-648

N-648

N-648

552

TABLE I I I


SPECIES

chlororaphis

cohaerens

cruciviae

dacunhae

SOURCE

IAM (1511)

IAM

ATCC-13262

IAM

ATCC-13261

IAM (A-6-3)

SUBSTRATE



15a ,17a ,21 - t r i hyd roxy -4 -p reg -nene-3 ,20-d ione

l l / 3 , 1 7 a , 2 1 - t r i h y d r o x y - l , 4 -pr egnadiene -3 ,20 -dione










1 Iß , 21 -dihydr oxy -4 -pr egnene -3,20-dione


REACTION

17a-OH-17/3-(20-C=0-21-OH) — 1 7 - C = 0

Δ1

17α-ΟΗ-17]3-(20-C = 0-21-OH) -17-C = 0

Δ1; 17α-ΟΗ-17/3-(20-C = O-21-OH) - 1 7 - C = 0

17a-OH-17/3-(20-C=0-21-OH) — 1 7 - C = 0

17α-ΟΗ-17β-(20-C = 0 - 2 1 - O H H 1 7 - C = 0

oxidation

-

1

9α-ΟΗ; Δ ; r ev . aldol. , enol.

1

Δ ; rev . aldol. (Formaldehyde Î ) enol„

oxidation

1

Δ

1

Δ

Δ1; r ev . aldol. (Formaldehyde! ) enol.

1

Δ

1

Δ

1

Δ

R E F .

N-648

N-648

N-648

N-648

N-648

N-648

1-414; 1-415

1-414; 1-415

M-597

M-597

1-414; 1-415

1-414; 1-415; S-849

M-597

M-597

S-848

S-848

S-848; S-849

TABLE I I I

553

T r a n s f o r m a t i o n s by G e n u s : PSEUDOMONAS

SPECIES

dacunhae

desmolyt ica

docunhae (probably dacunhae)

f luorescens

(in mixed cul ture with Mycococcus sp. A J

(in mixed cul ture with Mycococcus sp. AJ

SOURCE

LAM(A-6-3)

IAM (G-1-7) (G-1-13) (R-lC-2)

S

IAM

IAM

ATCC-13475

IAM (A-3-8)

IAM(A-3-12)

IAM

SUBSTRATE

l l ß , 17α, 21 - t r i hyd roxy-4 -p reg -nene-3 ,20-d ione

1 Ία, 21 -dihydroxy -4 -pregnene -3 ,11 ,20 - t r ione








17a, 21-dihydroxy-4-pregnene -3 ,11 ,20- t r ione










REACTION

-

-

1

Δ

-

-

1

Δ

1

Δ

Δ1

-

-

oxidation

-

oxidation

-

1 2 0 - C = O ^ k

20/3-OH

-

1

Δ

oxidation

R E F .

S-848

S-848

S-849

S-859

S-859

S-849

S-849

S-849; S-859

S-849

S-849

1-414; 1-415

1-414; 1-415

1-414; 1-415

1-414; 1-415

T-960; U-1039

S-849

S-849

1-414; 1-415

1-414; 1-415

SPECIES

f luorescens


fragi


gaeger i

gelidicola

graveoiens


indoloxidans

SOURCE

IFO(3081)

IFO (3459)

NG

NRRL

Takeda (M-8)

IFO (3458)

IAM

IAM

IFO (3460)

NRRL

NRRL

SUBSTRATE



11/3,17a, 21- t r ihydroxy-4-pr eg -nene-3 ,20-d ione

5-choles ten-3ß-ol

Sarsasapogenin

Diosgenin



11/3,17a, 21 - t r ihydroxy -4 - p r eg -nene-3 ,20-d ione





11/3,17a, 21 - t r ihydroxy - 4 -pregnene-3 ,20-d ione

Sarsasapogenin

Diosgenin


Sarsasapogenin

Diosgenin


REACTION

-

-

1

Δ

-

-

-

-

2 0 - C = O ^ 20/3 -OH

-

1

Δ

oxidation

oxidation

oxidation

-

1

Δ

-

-

-

-

-

—

R E F .

S-849

S-849

1-428

1-428

T-1030

M-587

M-587

M-587

N-652

1-428

1-428

1-414; 1-415

1-414; 1-415

1-414; 1-415

1-414; 1-415; S-849

1-428

1-428

M-587

M-587

M-587

M-587

M-587

M-587

T r a n s f o r m a t i o n s by Genus: PSEUDOMONAS

TABLE I I I

554

TABLE I I I


555

SPECIES

iner t ia

j aeger i

lacunogenes

melanogenes

myxogenes

n i t roreductans

ochracea

oleovorans

SOURCE

IAM

IAM(AHH-23) (AHH-27) (AHH-28)

r a t fèces

IAM

IAM

IAM

IAM

IAM

ATCC-13474

Takeda (SP-125)

SUBSTRATE




5-cholesten-3j3-ol










17a, 21-dihydr oxy-4-pregnene -3,20-dione

17a, 21-dihydr oxy-4 -p regnene-3,20-dione


REACTION

oxidation

-

-

util ization

oxidation

-

-

-

-

-

oxidation

-

-

-

1

Δ

Δ1; 11/3-ΟΗ

Δ1; 20-C = O -20/3-OH

Δ1

R E F .

1-414; 1-415

1-414; 1-415

S-849

W-1067

1-414; 1-415

1-414; 1-415

1-414; 1-415

1-414; 1-415

1-414; 1-415

1-414; 1-415

1-414; 1-415

1-414; 1-415

1-414; 1-415

1-414; 1-415

T-960

T-960

T-960

Ν-652

TABLE I I I

T r a n s f o r m a t i o n s by Genus : PSEUDOMONAS

SPECIES

ovalis

*

pavonacea

per lu r ida

p ic torum

putida

pyocyanea

rathonis

riboflavinus

SOURCE

IAM(A-10-3; C 3 - 3 ; S-5)

IAM

NRRL

IAM

IAM

NG

IAM

NRRL

ra t cecum

IAM

IAM

SUBSTRATE




Sarsasapogenin

Diosgenin






5-cholesten-3/3-ol



Sarsasapogenin

Diosgenin


3a, 7a, 12a- t r ihydroxy-5ß-choianic acid





REACTION

-

oxidation

1

Δ

-

-

-

oxidation

-

-

-

-

-

-

—

-

—

oxidation

1

Δ

oxidation

R E F .

S-849

1-414, 1-415

I 414; 1-415

M-587

M-587

M-587

1-414; 1-415

I 414; 1-415

1-414; 1-415

1-414; 1-415

T-1030

1-414; 1-415

1-414; 1-415

M-587

M-587

M-587

N-675

1-414; 1-415

1-414; 1-415

1-414; 1-415

1-414; 1-415; S-849

556

TABLE I I I


557

SPECIES

roseum

schuylkill

schuylkil i iensis

species

(later - t e s tos t e ron i , ATCC-11966 - Ref. M-560)

SOURCE

IAM

IAM(CB-6; B-6)

IAM

ATCC-13261

ATCC-13262

ATCC-13263

3en May Lab Chicago

SUBSTRATE

4 -p regnene -3 ,20 -d ione








19-hydroxy-4-andros tene -3,17-dione

1,3, 5(10)-es t ra t r iene-3,17/3-diol (all s u b s t r a t e s , this re fe rence using tes tos te rone adapted cells)

3 -hydroxy-1 ,3 , 5 (10) -es t ra t r i en-17-one


3a -hydroxy-5a -androstan-17 -one

3/3 - hydroxy - 5 -androsten -17 -one

3a-hydroxy-5-androsten -17-one

17a-hydroxy-4-andros ten-3-one

17/3-hydroxy-4-androsten-3-one (soie carbon source)


REACTION

oxidation

-

-

oxidation

-

Δ

9α-ΟΗ; Δ ; rev . aldol; enol.

7/3-OH

11a-OH

1

9a-OH; Δ ; rev. aldol. ; enol.

9a-OH; Δ1; rev. aldol; enol. ; 17-C = 0 -17/3-OH

1

Δ ; rev . aldol; (Formaldehyde Î ); enol.

-

oxidation

oxidation

oxidation

oxidation

oxidation

17/3-OH -*17-C=0

—

R E F .

1-414; 1-415

1-414; 1-415

S-849

1-414; 1-415

1-414; 1-415

D-171

D-171

D-171; M-597

D-171; M-597

D-171; M-597

D-171; M-597

D-171; M-597

T-968

T-968

T-968

T-968

T-968

T-968

T-968

T-968

T-968

558

TABLE I I I


SPECIES

species (later - t e s tos te ron i , ATCC-11966 - Ret. M-560)

SOURCE

Ben May Lao Chicago

C

IAM

NG

Searle

Takeda (109)

SUBSTRATE

4-andros teae-3 ,17-d io . ie


11/3 ,17a ,21- t r ihydroxy-4-preg-nene-3 ,20-dione

17a,21 -d ihydroxy-4-pregneie -3? 11 ,20- t r ione

3a-hydroxy- 5a-androstan -17-o;ie

17α, 21 -dihydroxy -4 -pr egnene -3,20-dione

1,3, 5( lC)-es t ra t r iene-3 ,17/3-dioi

subs t r a t e s - T-1C33, S-786, S-787)


3a - hydroxy - 5a - androstan -17 - one

3/3- hy dr oxy - 5 -andr osten -17 -one


4-pregne ie -3 ,20-d ione

3a, 7a, 12a-trihydroxy-5/3-cholanic acid

3-hydroxy-5-cholenic acid

5 ,6-dibromo-choiestane-3/3-oi acetate

3/3-chloro-5-cholesteie

24/3-methyl-5, 7,22 -cho lesta -trien-3/3-oi


19-hydroxy-4-andros tene -3 ,17-dione


REACTION

oxidation

-

-

d, l -3a-OH — d-3 - C = 0 + l -3a-OH

-

-

utilization

utilization

utilization

utilization

utilization

utilization

-

-

utilization

9α-ΟΗ; Δ*; rev . aldoi. ; enol.

Δ ; rev . aldol. (Formaldehyde Î ); enol.

l l ß - O H

R E F .

T-968

T-968

T-968

T-968

W-1102

S-849

T-1033

T-1033

T-1033

T-1033

S-786; S-787

S-787; T-1033

T-1033

T-1033

T-1033

T-1033

T-1033

D-169

D-169

N-652; U-1038

( , s ü ie c a r D on s o u r ce - a l l

TABLE I I I

T ransformat ions by Genus: PSEUDOMONAS

559

SPECIES

species

1 (in mixed cul ture with one of the following: Mycococcus sp . Alt

1 A-io> A14, A15, A18, A ^ , 1 A A A A A

A32

s t r iafac iens

1 vin mixed cul ture with Mycococcus sp. A,)

s tu tze r i

1 synxantha

1 tae t ro lens

SOURCE

Takeda (109)

(109-mutant)

(M-8)

(125)

(B- l )

IFO (3309)

IAM

IAM

IAM

SUBSTRATE

17ß,21-d ihydroxy-4-pregnene-3,20-dione

1 la, 21 -dihy droxy -4 -pr egnene -3,20-dione


11/3,17o,21-tr ihydroxy-4 p r e g -nene-3 ,20-d ione

4 -p regnene -3 ,20 -dione






REACTION

Δ ' ; 2 0 - C - O -20/3 -OH

Δ ' ; 20-C=O 2G/3-OH

Δ1; 11/3-OH

Δ ' ; 2 0 - C - O — 20/3-OH .

Δ'

Δ ' ; 20-C=O -» 2C/3-OH

1

Δ

—

—

oxidation

-

-

-

-

R E F .

U-1038

U-1040

T-961; U-1040

N-652; y_il_03?

N-652; U-1Ü39

U-1039

U-1039

1-428

1-428

1-428

1-414; 1-415

1-414; 1-415

1-414; 1-415

1-414; 1-415

1-414; 1-415

1-414; 1-415

1

Δ

560

TABLE I I I


SPECIES

tes tos te roni

SOURCE

ATCC-11996

SUBSTRATE

Type Reaction for j3-hydroxy s tero id dehydrogenase

3/3 -hydroxy -5 -andr osten -17 -one + D P N + ^ 4 - a n d r o s t e n e - 3 , 17-dione + DPNH + H+

17/3-hydroxy-4-androsten-3-one + DPN+ ^ 4 - a n d r o s t e n e - 3 , 17-dione + DPNH + H+

(see r e f e rences for isolat ion, purif ication, specifici ty, kinet ics and inhibition of enzymeSo )

Type Reaction for 3a-hydroxy s tero id dehydrogenase

3a -hydroxy - 5a -androstan -17 -one + DPN ^ a n d r o s t a n e - 3 , 1 7 -dione + DPNH + H+

(see r e f e rences for isolat ion, purif icat ion, specifici ty, kinet ics and inhibition of enzymes . )

Type Reaction for A 5 -3-ke to -s te ro id i s o m e r a s e

5 -andros tene -3 ,17-d ione-* 4 -andros tene-3 ,17-d ione

(see r e f e rences for isolation purif ication, specifici ty, kinet ics and inhibition of enzymes . )

Ring A dehydrogenation

Δ1 -dehydrogenase

Δ4 -5α-dehydrogenase

Δ4 - 5/3 -dehydrogenase

(see r e f e rences for isolat ion, purif icat ion, specifici ty, kinet ics and inhibition of enzymes and Ref. T-1005 for compar ison with "s te ro id r ing dehydrogenase" from No card ia . )

3α-hydroxy - 5α-androstan -17-one

5a -andros t ane -3 ,17 -d ione -(cell free ex t r ac t s - Ref. L-507)

REACTION

3 / 3 - O H - 3 - C = 0 ; 17 /3-OH-1 7 - C = 0

3 a - O H - * 3 - C = 0

Δ 5 -+Δ 4

Δ ^ Δ 4

3a-OH— 3 - C = 0

Δ1

Δ 1 ' 4

R E F .

D-155; F-241; F-242; M-559; M-560; T-964; T-965; T-966; T-967; T-969

D-155; M-560; R-767; T-964; T-965; T-971

K-43T, K-438; T-583; T-964; T-972; W-1064

L-507; L-508; L-509; T-1005

D-155

L-507; L-508; L-509

L-507; L-508

1

TABLE I I I


561


t es tos te ron i ATCC-11996 5o-andros tane-3 ,17-d ione (cell free ex t rac t s - Ref„ L-507)

17/3-hydroxy-5/3-androstan-3-one

L-508

L-507

A-nor -17/3 -hydroxy-3 -andr osten-2-one

17/3-hydroxy-5a-est ran-3-one


5 -androstene -3j8,17/3-diol

1 la- methyl -5 -andros tene -3/3,17/3-diol


11/3,17/3-dihydr oxy-4-andr osten -3-one




17/3-OH-17-C = 0

Δ1*4

17|3-OH-47-C = 0 ; Δ4

9a-OH; 17/3-OH ->17-C = 0

Δ*; 17/3-OH-» 17-C = 0

Δ1; enol. 17/3-OH—17-C=0

Δ ; enol.

Δ 5 - Δ 4 ; 3 / 3 - Ο Η -3-C = 0 ; 17/3-OH - 1 7 - C = 0

Δ5—Δ4; 3/3-OH-3-C = 0

Δ1

17/3-OH-17-C = 0 ; Δ 1

17/3-OH-17-C=0

1 7 / 3 - O H - 1 7 - 0 0

Δ 5 - Δ 4 ; 3 / 3 - Ο Η -3-C = 0

Δ 5 - Δ 4 ; 3 / 3 - Ο Η -3-C = 0 ; 1 7 - C = 0 -17/3-OH

Δ4; 17-C = 0 -17/3-OH

Δ1; 17-C = 0 -17/3-OH

Δ 1

1 7 - C = 0 — 17/3-OH

L-508

L-508

S-885

L-508

L-507; L-508; L-509

L-508

T-966

T-966

L-507

L-507

D-155; L-508; T-966

T-966

T-966

T-966

L-508

L-508

L-507; L-508

T-966

1

Δ

1

Δ

562

TABLE I I I

T r a n s f o r m a t i o n s by Genus: TAXONOMY

PSEUDOMONAS PSEUDOMYCODERMA (Imperf. - Moniliales)

PSILOCYBE (ßasidio0 - Agaricales)

SPECIES

tes tos teroni

tr ifoli i

xanthe

PSEUDOMYCODERMA

miso

PSILOCYBE

caeru lescens (var. mazatecorum)

SOURCE

ATCC-11996

IAM

IAM

FRI

S i

SUBSTRATE


5 a - l - e s t r e n e - 3 , 1 7 - d i o n e


l ,3 ,5 (10) -es t r a t r i ene -3 ,17 i3 -d io l



(use of inhibi tors to in-c r e a s e 9α-OH)


11/3,17«, 21- t r ihydroxy-4-preg-nene-3 ,20-d ione (use of dr ied cells)







3/3 -hydroxy - 5 -pregnen -20 -one


REACTION

Δ1

4

Δ ; enol0

1

Δ ; enol.

17/3-OH—17-c=o 1 7 - C = 0 ^ 1 7 / 3 -OH

9a-OH

9a-OH

9a-OH

Δ1

Δ -»Δ ; 3/3-OH-3 - C = 0

-

-

-

-

-

3/3-OH-3-C = 0 ; Δ5-»Δ4;11α-ΟΗ

3 ß - O H ^ 3 - C = 0 ; Δ 5 - Δ 4 ; 1 1 α - Ο Η ; 21-OH; l i a , 2 1 -diOH l l a - O H

l l a -OH;21-OH; l l a , 2 1 - d i O H

R E F .

L-508 1

L-508

L-508; L-509

D-155; T-966

T-966

P-740

S-898

S-885

F-231

T-966

1-414; 1-415

1-414; 1-415

1-414; 1-415

1-414; 1-415

S-849

C-113

C-113

C-113

C-113

TABLE I I I

T ransformat ions by Genus: PSILOCYBE

563

SPECIES

cae ru lescens * (var. mazatecorum)

caeru l ipes

mexicana *

semperviva

SOURCE

SY

AL (C-236)

SY

UB

UB

SUBSTRATE

17a, 21 -d ihydroxy-4-pregnene -3,20-dione





14/3-hydroxy-3 -keto-5j3 -20(22) -cardenolide


3/3, 5/3,14j3-trihydroxy-19-oxo-20(22)-cardenolide

3/3,l la,14/3-trihydroxy-5/3-20(22)-cardenolide


3/3, 5/3,14/3,19-tetrahydroxy-20(22)-cardenolide



REACTION

l i a - O H


l i a - O H



7/3-OH

3/3-OH -> 3-C = 0

7/3-OH; 3/3-OH - 3 - C = 0

7/3-OH

12/3-OH






3 -C=0-3 /3 -OH

12/3-OH; 3-C = 0 —3/3-OH

R E F .

C-113

S-825

C-113

W-1075

W-1075

W-1075

W-1075

W-1075

W-1075

W-1075

W-1075

W-1075

W-1075

W-1075

W-1075

W-1075

W-1075

564


TABLE I I I

PSILOCYBE PULLULARIA

PYCNODOTHIS

TAXONOMY

(Imperf. - Moniliales) (Imperf. - Sphaeropsidales)

SPECIES

semperviva

PULLULARIA

pullulans

species

PYCNODOTHIS

species

SOURCE

UB

FRI

NG (Sandoz)

NRRL

ATCC-11721

SUBSTRATE


3/3,11a, 14/3-trihydroxy-5/3-20(22)-cardenolide

3/3,14/3,16j3-trihydroxy-5j3-20(22)-cardenolide

3/3, 5/3,14/3-trihydroxy-19-oxo-20(22)-cardenolide


3/3,6/3, 8/3,14/3-tetrahydroxy-4, 20,22-bufatr ienolide 6-aceta te 3-glucoside

3/3,14/3-dihydroxy-5/3-20(22)-cardenolide 3-[glucosyl-digitoxosy 1 - digitoxosy 1 -digitoxoside]

Digilanid - A

plant saponins




REACTION

12/3-OH



1 9 - C = 0 - > 19-OH

-

3β-[1χξ -gluco-side] — 3/3-OH

-hydrolysis of glycosides to aglycones (sapogenins)

1

Δ

17/3-AC-17-c=o Δ ; 17/3-Ac -» 1 7 - C = 0

Δ1; 17/3-Ac — 17/3-OH

17/3-(20-C=O-21-OH) -> , 1 7 - C = 0 ; Δ

R E F .

W-1075

W-1075

W-1075

W-1075

S-849

S-936a

S-936a

S-936a

K-478

K-450

K-450

K-450

K-450

K-450

565


Transformat ions by Genus: PYCNODOTHIS PYCNOSPORIUM PYRENOPHORA PYRONEMA PYTHIUM

(Imperf. - Sphaeropsidales) vAsco. - Sphaeriales) (Asco. - Pezizales) (Phyco. - Peronosporaies)

SPECIES

species

PYCNOSPORIUM

species

PYRENOPHORA

greminea

t e r e s

PYRONEMA

confluens

PYTHIUM

ultimum

SOURCE

ATCC-11721

ATCC-12231 (QM-703)

FRI

NIHJ^A-17)

NIHJ(A-29)

FRI

FRI

S

SUBSTRATE















REACTION

16

Δ -17-Ac -» 1 7 - C = 0 ; Δ1

11)3-OH

11/3-OH

11/3-OH

2ß-OH

-

6/3-OH;lla-OH

l l a - O H

11/3-OH

17-C = 0 ^ 1 7 a -o x a - 1 7 - C = 0

1 7 ß - A c - 1 7 a -o x a - 1 7 - C = 0

17a-OH-17/3-Ac-*17a-oxa-1 7 - C = 0

17/3-(20-C=O-21-OH)—17a-o x a - 1 7 - C = 0

R E F .

K-450

D-147

D-147

D-147

S-849

S-849

S-849

S-849

S-849

S-846

S-846; S-849

S-846; S-849

S-846; S-849

S-846; S-849

566


T r a n s f o r m a t i o n s by G e n u s : PYTHIUM RAMULARIA RHACODTUM RHIZOBIUM

(Imperf. - Moniliales) (Imperf. - Mycelia Steri l ia) (Schizo. - Eubacter ia les)

SPECIES

ult imum

RAMULARIA

robusta

RHACODIUM

ce l la re

RHIZOBIUM

leguminosarum

SOURCE

S

Leo P h a r m . P r o d u c t s ,

Denmark

ATCC-13243t

SY

SUBSTRATE



17a, 21-d ihydroxy-4-pregnene-3 ,11 ,20 - t r ione


17/3-hydr oxy-17α-methyl -4-androsten -3 -one


3 -hydr oxy -1 ,3 ,5(10) - e s t r a t r ien -17-one










REACTION

2 0 - C = O -20/3-OH

-

—

1

Δ

Δ

l l a - O H

17-C=0-> 17/3-OH

1 7 - C = 0 -17j3-OH

-

-

-

-

20-C=O-> 2 0 | - O H

2 0 - C = O ^ 20ξ-ΟΗ

2 0 - C = O -20ξ-ΟΗ

R E F .

S-846; S-849

S-846; S-849

S-846; S-849

L-525

L-525

G-313

C-114

C-114

C-114

C-114

C-114

C-114

C-114

C-114

C-114

C-114

TABLE I I I

T ransformat ions by Genus: R H I Z O B I U M

567

SPECIES

meliloti

1 phaseoli

trifolii

SOURCE

SY

SY

SY

SUBSTRATE

3-hydroxy-l,3,5(10)-estratrien-17-one


19-nor-4-pregnene-3,20-dione


1la-hydroxy-4-pregnene-3,20-dione



ll/3,17a,21-trihydroxy-4-preg-nene-3,20-dione

17a,21-dihydroxy-4-pregnene-3,11,20-trione

4,16-pregnadiene-3,20-dione

3-hydroxy-1,3, 5(10)-estratrien-17-one


19-nor-4-pregnene-3,20-dione


1la-hydroxy-4-pregnene-3,20-dione



l l ß , 17a,21-trihydroxy-4-preg-nene-3,20-dione

17a, 21 -dihydroxy-4-pr egnene-3,11,20-trione

4,16-pregnadiene-3,20-dione

3-hydroxy-l,3,5(10)-estratrien-17-one


REACTION

1 7 - C = 0 -17ß-OH

17-C=0-> 17/3-OH

-

-

-

-

20-C=O-> 20ξ-ΟΗ

20-C=O-> 204-OH

20-C=O^ 20ξ-ΟΗ

-

1 7 - C = 0 -17/3-OH

17-C=0-> 17/3-OH

-

-

-

-

20-C = O-> 20ξ-ΟΗ

20-C=O-> 20ξ-ΟΗ

2 0 - C = O -20ξ-ΟΗ

-

17-C=0 — 17/3 -OH

17-C=0-+ 17/3-OH

REF.

C-114

C-114

C-114

C-114

C-114

C-114

C-114

C-114

C-114

C-114

C-114

C-114

C-114

C-114

C-114

C-114

C-114

C-114

C-114

C-114

C-114

568


TABLE I I I

RHIZOBIUM RHIZOCTONIA

TAXONOMY

(Imperf. - Mycelia Steri l ia)

SPECIES

trifoli i

RHIZOCTONIA (See - Corticium)

ferrugena

SOURCE

SY

ATCC-13246t or

CBS

SUBSTRATE












11/3,21 -dihydroxy-4 -pregnene -3,20-dione


11a, 17a, 21 - t r ihydroxy-4 -p reg -nene -3 , 20-dione



11/3,17a, 21- t r ihydroxy-6a-me thy 1-4 -pregnene-3 ,20-d ione


REACTION

—

-

-

-

20-C=O — 20ξ-ΟΗ

2 0 - C = O ^ 20ξ-ΟΗ

20-C=O-> 20ξ-ΟΗ

-

l|3-OH; 2/3-OH

1/3-OH; 2/3-OH

1/3-OH; 2ß-OH

1/3-OH; 2/3-OH

1/3-OH

2ß-OH

1/3-OH; 2/3-OH

1/3-OH; 2/3-OH

1/3-OH; 2/3-OH

1/3-OH; 2/3-OH

1/3-OH; 2/3-OH

R E F .

C-114

C-114

C-114

C-114

C-114

C-114

C-114

C-114

G-313

G-313

G-313

G-313

G-312; G-313; G-315

G-312; G-313; G-315

G-313

G-313

G-313

G-313

G-313

569

TABLE I I I

Transformat ions by Genus: RHIZOCTONIA

SPECIES

ferrugena

munerat i i

solani

SOURCE

ATCC-13246t

ATCC-13247t

ATCC-10154, 10157,10187

ATCC-10157, 10187

SUBSTRATE

17a, 21-dihydroxy-4,9(1 l ) -p regna j d iene-3 ,20-d ione





17ö, 21-d ihydroxy-4-pregnene-3,20-dione





1 1 Ö , 1 7 Ö , 21 - t r i hyd roxy -4 -p reg -nene-3 ,20-d ione


9 a - f l u o r o - l l ß , 1 7 a , 2 1 - t r i h y d r o x y -4-pregnene-3 ,20-d ione

l l / 3 ,17a ,21 - t r i hyd roxy-6 -me thy l -4 -p regnene-3 ,20-d ione

l l / 3 , 1 6 a , 1 7 a , 2 1 - t e t r a h y d r o x y - 4 -p regnene-3 ,20-d ione

17a, 21-dihydroxy-4-pregnene -3 ,11 ,20 - t r i one

17a, 21-d ihydroxy-4-pregnene-3 ,11 ,20 - t r i one 21-aceta te

17α, 21 -d ihydroxy-1 ,4 -p regna -d iene-3 ,20-d ione

REACTION

1/3-OH; 2/3-OH

1/3-OH; 2/3-OH

1ξ-ΟΗ; l i a - O H ; 11/3-OH; 11-C = O (via 11/3-OH)

1ξ-ΟΗ; 11α-ΟΗ; 11/3-OH; 1 1 - C = 0 (via 11/3-OH

I4-OH; 11a-OH; 11/3-OH; 11-C= O (via 11/3-OH)

1/3-OH; 11a-OH

Ιξ-OH; l i a - O H ; 11/3-OH; 11-C= O (via 11/3-OH)

1ξ-ΟΗ; 11α-OH; 11/3-OH; 11-C= O (via 11/3-OH)

1ξ-ΟΗ;11α-ΟΗ; 11/3-OH; 11-C= O (via 11/3-OH)

1ξ-ΟΗ; 11α-OH

-

~

-

—

—

—

-

—

R E F .

G-313

G-313

G-313

G-313

G-313

G-313

G-313

G-313

G-313

G-313

G-313

G-313

G-313

G-313

G-313

G-313

G-313

G-313

TABLE I I I

T ransformat ions by Genus: RHIZOCTONIA

SPECIES

solani

SOURCE

ATCC-13248t; C3S

ATCC-13249t; CBS

SUBSTRATE




11a, 17a, 21- t r ihydroxy-4-pr eg-nene-3 ,20-d ione


9 a - f l u o r o - l l ß , 17a,21-tr ihydroxy-4-pregnene-3 ,20-d ione

11/3,17a, 21- t r ihydroxy-6-methy 1-4 -p regnene-3 ,20-d ione

11/3,16a, 17a ,21- te t rahydroxy-4-pr e gnene - 3,2 0 - dione


17a, 21 -dihydroxy -4 -pregnene -3 ,11 ,20 - t r i one 21-aceta te

17a, 21-dihydroxy - 1 , 4 - p r e g n a -d iene-3 ,20-d ione




11a, 17a, 21 - t r i hyd roxy-4 -p reg -nene-3 ,20-d ione



11/3,17a, 21- t r ihydroxy-6-methyI -4 -pregnene-3 ,20-d ione

l l / 3 ,16a ,17a ,21 - t e t r ahydroxy-4-pregnene-3 ,20-d ione

17α, 21 -dihydroxy -4 -pregnene -3 ,11 ,20 - t r ione

REACTION

11a-OH; 11/3-OH

11a-OH; 11/3-OH

l i a - O H ; 11/3-OH; n - c = o (via 11/3-OH)

-

1ξ-ΟΗ

-

-

-

1ξ-ΟΗ

1ξ-ΟΗ

11α-ΟΗ; 11/3-OH; i i - c = o (via 11/3-OH)

1ξ-ΟΗ; 2/3-OH

1ξ-ΟΗ; 2/3-OH

1ξ-ΟΗ; 2/3-OH

-

Ιξ-ΟΗ; 2/3-ΟΗ

1|-ΟΗ; 2/3-ΟΗ

Ιξ-ΟΗ; 2/3-ΟΗ

Ιξ-ΟΗ; 2/3-ΟΗ

Ιξ-ΟΗ; 2/3-ΟΗ

R E F .

G-313

G-313

G-313

G-313

G-313

G-313

G-313

G-313

G-313

G-313

G-313

G-313

G-313

G-313

G-313

G-313

G-313

G-313

G-313

G-313

570

TABLE I I I


571

SPECIES

solani

SOURCE

ATCC-13249t; CBS

ATCC-13250t; CBS

C

SUBSTRATE

17a ,21-d ihydroxy-4-pregnene-3 ,11 ,20 - t r ione 21-aceta te

1 la, 21 -dihydr oxy - 1 , 4 -pr egna -d iene-3 ,20-d ione



11/3, 21 -d ihydroxy-4-pregnene -3,20-dione


11a, 1 la, 21 - t r ihydr oxy -4 -pr eg -nene -3 ,20-dione


9a- f luoro- l l /3 ,17a , 21- t r ihydr oxy-4-p regnene-3 ,20-d ione

l l j 3 ,17a ,21 - t r ihydroxy-6 -me thy l -4 -p regnene-3 ,20-d ione

l l j 3 , 16a ,17a ,21 - t e t r ahyd roxy -4 -pregnene-3 ,20-d ione

1 la, 21 -dihydr oxy -4 -pregnene -3 ,11 ,20 - t r i one

17o, 21 -d ihydroxy-4-pregnene -3 ,11 ,20 - t r i one 21-ace ta te

1 la, 21 -dihydr oxy - 1 , 4 -pr egna -d iene-3 ,20-d ione

l l / 3 -hydroxy-4 -andros t ene -3 ,17 -dione

REACTION

1ξ-ΟΗ; 2/3-OH

-

1ξ-ΟΗ; 2/3-OH

1ξ-ΟΗ; 2/3-OH

1ξ,15ξ-άίΟΗ

6/3,15^-diOH; 20-C=O -» 20 | -OH


1ξ-ΟΗ

2/3-OH; 11-C = 0 (via 11/3-OH)

6 /3 -OH; l l -C=0 (via 11/3-OH)

6/3-OH

1ξ-OH; 2/3-OH

1ξ-ΟΗ

-

-

-

1ξ-ΟΗ; 2β-ΟΗ

Ιξ-ΟΗ; 2/3-ΟΗ

2/3,6/3-diOH

-

6/3-ΟΗ

R E F .

G-313

G-313

G-313

G-313

G-312

G-312

G-312

G-313

G-312

G-312

S-793b

G-313

G-313

G-313

G-313

G-313

G-313

G-313

G-312

G-313

U-1043

572

TABLE I I I


SPECIES

solani (var. lycopersici)

species

SOURCE

CSS

FAKU(B-5; P -20)

IFO (6521)

ATCC-13245

CBS

NRRL-2573

SUBSTRATE



17a, 21-dihydroxy-4-p regnene-3,20-dione






9a- f luoro- l l /3 , 17a,21- t r ihydroxy-4-pregnene-3 ,20-d ione

l l / 3 ,17a ,21- t r ihydroxy-6 -methyI -4 -p regnene-3 ,20-d ione

l l j 3 ,16a ,17a ,21- t e t r ahydroxy-4-pregnene-3 ,20-d ione


17a, 21-dihydroxy-4-pregnene -3 ,11 ,20 - t r ione 21-aceta te

17a, 21-d ihydroxy-1 ,4 -p regna-d iene-3 ,20-d ione




REACTION

1ξ-ΟΗ

-

1

Δ

6/3-OH

2/3-OH;l la-OH

2/3-OH;l la-OH

lß-OH

2/3-ΟΗ

6/3-OH

2/3-OH;l la-OH

-

2β-ΟΗ

-

-

-

2/3-OH

2/3-OH

-

l l a - O H ; l l / 3 - O H

l l a - O H ; l l / 3 - O H

l l a - O H

11/3-OH

l l / 3 - O H ; l l - C = 0(v ia 11/3-OH)

R E F .

G-313

S-849

T-956

T-956

G-313

G-313

G-313; S-793b

G-312

G-312

G-313

G-313

G-313

G-313

G-313

G-313

G-313

G-313

G-313

G-313

G-313

G-312; G-313; S-793b

G-312; G-313; S-793b

G-312; G-313 |


573

Transformat ions by Genus: RHIZOCTONIA RHIZOPUS (Phyco. - Mucorales)

SPECIES

species

(from apple)

RHIZOPUS

a r rh i zus

SOURCE

NRRL-2573

FAHU

Rutgers (Dr. Haenseler)

ATCC-11145 UC(RH-176)

SUBSTRATE

11a, 17a ,21 - t r i hyd roxy -4 -p reg -nene-3 ,20-d ione



11/3,17a, 21- t r ihydroxy-6-methy l -4 -p regnene-3 ,20-d ione


17a, 21 -dihydr oxy -4 -pregnene -3 ,11 ,20 - t r ione

17a, 21-dihydr oxy-4-pregnene-3 ,11 ,20 - t r ione 21-ace ta te

17a, 21-dihydr o x y - 1 , 4 - p r e g n a -d iene-3 ,20-d ione






4 -andros tene -3 ,17-d ione 6α ,7ξ-Η 3

REACTION

-

1ξ-ΟΗ

-

—

-

1ξ-ΟΗ

1ξ-ΟΗ

11α-ΟΗ; 11/3-ΟΗ; 1 1 - C = 0 (via 11^-OH)

2/3-ΟΗ

74-ΟΗ

15α-ΟΗ

6/3-ΟΗ

Ι ΐα -ΟΗ

6/3-ΟΗ

Ι ΐα -ΟΗ

6/3-ΟΗ

Ι ΐα -ΟΗ

Δ ->5α-Η; 6 - C = 0

6/3-ΟΗ

Ι ΐα -ΟΗ

R E F .

G-313

G-313

G-313

G-313

G-313

G-313

G-313

G-313

S-849

G-312

G-312

E-201

E-201

E-201

E-201

E-201

E-201 ; M-601; M-604; M-636; P-728

M-601; M-604; M-636

B-32

B-32

574

TABLE I I I

T r a n s f o r m a t i o n s by Genus: RHIZOPUS


a r rh i zus ATCC-11145 4-pregnene-3 ,20-d ione





3ß-hydroxy-5/3-pregnan-20-one


l l o - O H

, Ι Ια -d iOH

6/3-OH

l l a - O H

6/3-OH

l l ö - O H

6/3-OH; 21-OAc -»21-OH

l i a - O H ; 21-OAc| -» 21-OH

7/3-OH

11-OH

7/3,1 la-diOH

7/3,1 la-diOH

F-247; F-248; H-340; L-518; L-519; M-528; M-601; M-611; M-636; N-649; N-682; P -728 ; P -729 ; S-906

H-343; M-601; M-616; N-682; 0 -697 ; 0 -698 ; P-729

M-580

M-601; M-636; M-580

E-203; M-601; M-631; M-636

E-203; P-728

E-203

E-203

E-202; M-601; M-636

M-601; M-636

E-202; M-601; M-628; M-629

E-202; M-601; M-630

TABLE I I I

T ransformat ions by Genus: RHIZOPUS

575

SPECIES

arrhizus

*

*

*

* *

* *

*

SOURCE

ATCC-11145

SUBSTRATE

19 -no r -4 -p regnene-3 ,20-d ione



1 7a, 21 -dihydroxy -4 -pregnene -3 ,20-dione 21-aceta te

1 7 a , 2 1 - d i h y d r o x y - 4 , 9 ( l l ) -p regnadiene-3 ,20-d ione


l l /3 ,21-dihydroxy-4 ,17(20)-pregnadien-3 -one

3α, 14/3-dihydroxy-5/3-20(22)-cardenolide

3/3,14/3-dihydroxy-5/3-20(22)-cardenolide (Ref. N-683 - method to acce le ra t e r a t e of hydroxyla-tion)

3/3,14/3-dihydroxy-5/3-20(22)-cardenolide 3-aceta te

3/3,14/3 -dihydroxy -5/3,17a-20(22)-cardenolide

14-hydroxy-3-keto-5/3-20(22)-cardenolide

REACTION


6/3-OH (0 21 8 )

6j3-OH

l l a - O H

6/3,l la-diOH

l l a - O H ; 21-OAc — 21-OH

no epoxidation

no epoxidation

6/3-OH; 11/3-OH --> n-c=o 3a-OH — 3 - C = 0

1/3-OH

5ß-OH

7ß-OH

X-OH

7ß-OH; 3ß-OH -» 3-C=0

1/3,7/3-diOH

5ß,7ß-diOH

3ß-OAc—3-C=Oj 7ß-OH

3/3-OH — 3 - C = 0

3 -C=0->3a-OH; 7/3-OH

R E F .

3 -71

H-374

M-601; M-615; M-636; N-682; P-725

N-682

N-682

M-645

B-66

B-66

H-341; H-344

N-681

N-682

N-678· N-682

1-425; J-43"2; N-678; N-682; N-683

J-432

N-678

N-682

N-682

N-678

N-681 ; N-682

N-678

576

TABLE I I I

Transformat ions by Genus: RHIZOPUS

SPECIES

a r r h i z u s

cambodjae

chinensis (-)

chiuniang (Yamazaki)

cohnii

SOURCE

ATCC-11145

C

IAM (R-5-6)

NRRL-R-16

SSSR

FAR MIT

SSSR

ATCC-1227b

IAM (10-10)

SSSR

IAM(14-14B)

ATCC-8996

CZAS(I;II)

SUBSTRATE


3j3,7/3,14/3-trihydroxy-5/3-20(22)-cardenolide

3 -keto -bisnor -4 -cholen -22 -a l

(20S)-20-hydroxy-18,20-cycio-4-pregnen-3-one


l l j3 ,21-dihydroxy-4,17(20)-pregnadien-3 -one

Sarsasapogenin

Diosgenin

4-dehydrotigogenone





17o-hydroxy-4-pregnene-3 ,20-dione


17«, 21-dihydroxy-4-pregnene-3,20-dione




11/3,21 -dihydroxy -4,17(20)-pr egnadien -3 -one


REACTION

7/3-OH

3/3-OH->3-C=0

6/3,1 la -d iOH; 2 2 - C = 0 -22-OH

11a-OH

l l a - O H

6/3-OH;ll/3-OH - + i i - c = o

---

6/3-OH

l l a - O H

6 ß , l l a - d i O H

6/3,1 la-diOH

oxidation

oxidation

oxidation

oxidation

l l a - O H

6/3-OH

l l a - O H

6j3-OH;ll/3-OH

-n-c=o l l a - O H

R E F .

N-678

N-678

M-578

W-1071

A-29

H-341

M-587

M-587

M-587

E-224

C-84

C-84

E-224

M-601; M-636

M-601; M-636

M-601; M-636

M-601; M-636

A-26; A-29

E-224

A-29

H-431

T-1028

TABLE I I I

577

T r a n s f o r m a t i o n s by G e n u s : RHIZOPUS

SPECIES

cohnii

de lemar

1 *

1 * 1 * 1 *

1 *

delemar

formosens is (formosaensis)

japonicus

SOURCE

SSSR

U

ATCC-4858

IAM (19-27)

NI

U

IAM(24-29C) (Nakazawa)

ATCC-8446

SUBSTRATE






11/3,21-dihydroxy-4,17(20)-pregnadien-3-one












REACTION

6/3-OH; l l a - O H ; 11/3-OH

oxidation

oxidation

oxidation

oxidation

6/3-OH; 11/3-OH ^n-c=o 11a-OH

l l a - O H

6/3,1 la -d iOH

6ß-OH

l l a - O H

1/3-OH

3/3-OH—3-C = 0

7/3-OH

5ß,7/3-diOH

7ß-OH

oxidation

oxidation

oxidation

oxidation

l l a - O H

6/3-OH; 11/3-OH -n-c=o

R E F .

E-224

M-601; M-636

M-601; M-636

M-601; M-636

M-601; M-636

H-341

A-29

N-682

N-682

N-682

N-682

N-682

N-682

N-682

N-682

N-682

M-601; M-636

M-601; M-636

M-601; M-636

M-601; M-636

A-29

H-341

578

TABLE I I I


SPECIES

japonicus

javanicus

*

*

* *

*

*

kansho (Yamamoto)

kasanens is

n igr icans

SOURCE

IAM(24-14; 24-14B)

U

IAM(26-23)

NI

IAM(28-14)

ATCC-8998

U

ATCC-6227a

SUBSTRATE









3/3,14/3-dihydroxy-5ß-20(22)-cardenolide



11/3,21-dihydroxy-4,17(20)-pregnadien-3 -one






REACTION

l i a - O H

oxidation

oxidation

oxidation

oxidation

l i a - O H

6/3,1 la -d iOH

l i a - O H

6/3 -OH

11α-ΟΗ

7/3-OH

1/3-OH

3/3-OH-»3-C=0

7/3-OH

11a-OH

6/3,1 la-diOH

6/3-OH-l 1/3-OH -ai-c=o

oxidation

oxidation

oxidation

oxidation


R E F .

A-29

M-601; M-636

M-601; M-636

M-601; M-636

M-601; M-636

A-29

N-682

N-682

N-682

N-682

N-682

N-682

N-682

N-682

A-29

A-26

H-341

M-601; M-636

M-601; M-636

M-601; M-636

M-601; M-636

T-1028

TABLE ! I l

579


SPECIES

nigr icans

(see stolonifer)

(in mixed cul ture with Pénic i l l ium lilacinum [17/3-Ac—» 17/3-OH])

SOURCE

ATCC-6227a

ATCC-6227b

SUBSTRATE





17/3-hydroxy -4 - e s t r en -3 -one

17/3-hydr oxy- 17a -methyl - 4 -e s t r en -3 -one

17/3-hydroxy -4 -androsten -3 -one


REACTION

l l a - O H

l l a - O H

l l a - O H


l l a - O H


6/3-OH

10/3-OH

l l a - O H

l l ö - O H

6/3-OH

l i a - O H

6β-ΟΗ

l i a - O H

11α-OH

R E F .

M-601; M-636; T-1028

M-636

M-636

T-1028

M-636

T-1028

M-642; P-708

M-642; P-708

M-619; M-620; P-708

M-575; M-608

E-201

E-201 ; M-601; M-619; M-620; M-636

E-198; E-201 ; M-619

E-201 ; M-575; M-608; M-624; M-626; M-638

S-831

580

TABLE I I I



n igr icans

(in mixed cul ture with Pénici l l ium li lacinum [17/3-Ac-

17-C=OJ)

ATCC-6227b 4 -andros tene-3 ,17-d ione


6/3-hydroxy-3a, 5a-cyclopregnan-20-one



5/3 -pregnane -3 ,20-dione 11α,12α-Η3

5 /3 -pregnane-3 ,20-d ione- l l a -D

5/3-pregnane -3 ,20-dione -11/3-D

16a, 1 la- oxido- 5a -pregnane -3,20-dione

16a, 17a -oxido -5/3 -pregnane -3,20-dione


20a-hydroxy-4-pregnen-3-one


(20S)-20-hydroxy-18,20-çy_çlp-4-pregnen-3-one


6/3-OH

l i a - O H

l i a - O H

l i a - O H

7/3,1 la-diOH

l l a - O H

l l a - O H

l l a - O H

l i a - H -l l a - O H

l l a - O H ( loss of l l a - D )

l l a - O H (11/3-D)

l l a - O H

l l a - O H

7/3-OH l l a - O H

l l a - O H

no oxidation at C - l l

l l a - O H

E-201

E-201 ; M-601; M-636

S-831

M-601; M-636

M-601; M-636

W-1069; W-1070

E-209; M-601; M-636

E-209; M-601; M-636

H-371

C-137

C-137

K-439

K-440; W

E

S-

S-

-1066

-202

832

832

W-1071

B - 7 1 ; B-73; C-117; C-118; M-636

TABLE I I I

581



n i g n c a n s ATCC-6227b

(in mixed cul ture with Pénici l l ium li lacinum [17/3-Ac-» 17-C=Ol)

4 -pregnene-3 ,20-d ione 11a-OH

l l a - O H ; Δ -» 5a-H

6/3, l la-diOH

l l û - O H




16a-methy l -4 -p re gnene -3 ,20 -dione

16ß-me thy l -4 -p regnene -3 ,20 -dione

6/3-f luoro-17a-hydroxy-4-preg-nene-3 ,20-d ione


E-200; M-601; M-611; M-636; N-650; N-682; P -729 ; R-766; T-1028; W-1069; W-1106

P-729

N-682; P -729 ; W-1069

S-831

6/3-OH

l l a - O H

11a-OH

l l a - O H

l l a - O H ; ^ 2 1 - O H

l l a - O H

(o218)

21-OAc

M-580; M-601; M-607; M-613

E-200; H-391; M-580; M-601; M-607; M-627; M-636

E-203; M-601; M-636

H-374

E-203; M-601; M-636

C-141; L-515; L-517; S-804

l l a - O H

l l a - O H

6/3-OH

L-517

H-

M N-P -

-391

-615; -682; 725

582

TABLE I I I


SPECIES

nigr icans *

SOURCE

ATCC-6227b

SUBSTRATE


1 7a, 21 -dihydroxy -4 -pregnene -3,20-dione 21-aceta te

17a-hydroxy-21-methy l -4 -preg-nene-3 ,20-d ione

21-hydroxy-17a-methy l -4 -preg-nene-3 ,20-d ione aceta te

6α, 16a-d imethyI-4-pregnene-3,20-dione

16a, 17a-méthylène-4-pregnene-3,20-dione

16a, 17a-ox ido-4-pregnene-3 ,20-dione

6a-ch loro-16a , 17a-méthylène -4 -pregnene-3 ,20-d ione

6/3-fluoro-17a-hydroxy-21-methyl -4 -pregnene-3 ,20-d ione

6a-f luoro-16a, 17a-méthylène -4-pregnene-3 ,20-d ione

6/3 -f luor o -16a, 17a -méthylène -4-pregnene-3 ,20-d ione


17α, 21 -dihydroxy - 7 - methyl -4 -p regnene-3 ,20-d ione 2 1 -aceta te

6a - methyl -16a, 17a - méthylène -4-pregnene-3 ,20-d ione

REACTION

l i a - O H

l i a - O H ; Δ-+ 5/3-H

l l a - O H ; 2 1 - O A c - 2 1 - O H

l i a - O H

l l a - O H

l i a - O H

l l a - O H

l l a - O H

l l a - O H

l l a - O H

l l a - O H

l l a - O H

l l a - O H ; 21-OAc ^ 2 1 - O H

l l a - O H ; 21-OAc —21-OH

l l a - O H

R E F .

E-200; M-601; M-636; M-641; M-645; N-682; P-725

M-601; M-606; M-636; P-725

M-601; M-636; M-641; M-645

H-391

H-377

S-923

C-92

B-52; D-160; D-161; E-223; M-644; P-727

C-92

H-391

C-92

C-92

A-8

B-33

C-92

TABLE I I I


583

SPECIES

nigr icans

SOURCE

ATCC-6227b

SUBSTRATE

6a-f luoro-17a ,21-d ihydroxy-16-me thy lene -4 -p regnene -3 ,20 -dione 21-aceta te

17α, 21-dihydroxy-βα, 16α-di-methy l -4 -pregnene-3 ,20-d ione

21-hydroxy-16a ,17a-oxido-4-pregnene-3 ,20-d ione

21-hydroxy-17a-methy l -1 ,4 -pregnadiene-3 ,20-d ione aceta te

16α, 17α -méthylène - 1 , 4 -pregna -d iene-3 ,20-dione

6a-ch loro-16a , 17a-méthylène -1,4 -pregnadiene -3 ,20 -dione

6a-f luoro-16a, 17a-méthylène-1,4 -pr egnadiene -3 ,20-dione

6ß - f lu or o -16a, 17a - méthylène -1,4-pr egnadiene-3 ,20-dione

6a-methyl -16a , 17a-méthylène-1,4 -pr egnadiene-3,20-dione

17a, 21 -dihydroxy- 6a, 16a -d i -methyl -1 ,4 -pr egnadiene - 3 , 20-dione 21-aceta te

6a- f luoro-16a ,17a ,21- t r ihydroxy-1,4 -pr egnadiene -3 ,20-d ione


6-chloro-16a, 17a-méthylène-4 , 6-pr egnadiene-3 ,20-dione

16a, 17a-méthylène-4 , 6-pregna-d iene-3 ,20-d ione

6-methyl-16a, 17a-méthylène -4 , 6 - p r egnad iene-3 ,20-dione



REACTION

l i a - O H · 2 1 -OAc-21 -OH

l i a - O H

l l a - O H

l l a - O H

l l a - O H

l l a - O H

l l a - O H

l l a - O H

l l a - O H

l l a - O H ; 2 1 -O A c - 2 1 -OH

l l a - O H

l l a - O H

l l a - O H

l l a - O H

l l a - O H

no epoxidation

16

11α-ΟΗ; Δ -17-Ac-+17a-Ac

R E F .

A-7

S-903

F-243

H-377

C-92

C-92

C-92

C-92

C-92

S-903

R-771

D-178; M-601; M-621; M-636; P-730

C-92

C-92

C-92

B-66

M-579; M-601; M-605; M-612; M-636

584

TABLE I I I



n igr icans ATCC-6227b

ATCC-7577

ATCC-10404

1 ,4 ,6 -p regna t r i ene -3 ,20-d ione

1 6 a , 1 7 a - m e t h y l e n e - l , 4 , 6 -p regna t r i ene -3 ,20-d ione

6 - chlor o -16a ,17a- méthylène -1 , 4 , 6 - p r e g n a t r i e n e - 3 , 2 0 -dione

6-f luoro-16a, 1 la -méthylène -1 , 4 , 6 - p r e g n a t r i e n e - 3 , 2 0 -dione

6 -methyl -16α, 1 la - méthylène -1 , 4 , 6 - p r e g n a t r i e n e - 3 , 2 0 -dione


3j3,14/3-dihydroxy-5/3-20(22)-cardenolide (Ref. N-683 - method to acce le ra te hydr oxy lation)

b i snor -4 -cho len-22-a l -3 -one


1 la -hydroxy-4-pr egnene-3 ,20-dione





l i a - O H

l l a - O H

l i a - O H

l l a - O H

l l a - O H

7/3-OH

1/3-OH

H-388; O-700

C-92

C-92

C-92

C-92

N-682

N-682;

7/3-OH

1/3,7/3-diOH

5/3,7/3-diOH

3/3-OH->3-C=0

l l a - O H ; 22-C= 0 ^ 2 2 - O H

6/3,1 l a -diOH; 2 2 - C = 0 — 2 2 -OH

15a-OH; 22-C= O - » 22-OH

l l a - O H

l l a - O H

N-683

N-682; N-683

N-682

N-682

N-682

M-578; M-601; M-622; M-636

M-578; M-601; M-636

E-202

M-601

M-636

l l a - O H

l l a - O H

l l a - O H

l l a - O H

M-636

M-636

M-601

M-636

TABLE I I I

585


SPECIES

nigr icans

(in mixed cul ture with

chus [21 -OH ] and Tr icothecium ro seum [17a-OH|)

(in mixed cul ture with low yielding s t r a in of

1 Bacil lus subtl is -Δ1)

SOURCE

ATCC-10404

Char les

CZAS

FRI

Hoechst

SUBSTRATE

21-hydroxy-4 -p regnene -3 ,20 -dione


19 -nor-4 -pr egnene -3 ,20-dione


3/3,21 -dihydr oxy - 5a -pr egnan-20-one

d , l - 4 -p regnene -3 ,20 -d ione




1 Ία, 21 -dihydr oxy -4 -pregnene -3,20-dione


3 ß - hydr oxy - 3 - nor- 5 - andr osten -17-one



REACTION

11a-OH

l l a - O H


6/3-OH; 11/3-OH -» n-c=o 7/3-OH

d , l ^ d - l l a - O H + 1

l l a - O H

l l a - O H

l l a - O H

l l a - O H

l l a - O H

Δ 5 - 5 ξ , 6ξ-oxide

l l a - O H

l l a - O H ; Δ 5 -5 ξ , 6 | -ox ide

Δ^->5ξ, 6 4 -oxide—»5a, 6/3-diol

15a-OH

X-OH

6/3-OH; l l a - O H

Δΐ ( inc reased yield)

R E F .

M-636

M-636

3 - 7 1

H-341

K-433

W-1102

W-1106

W-1100

K-433

K-433

T-1028

P-741

P-741

P-741

P-741

P-741

P-741

S-849

L-521

Ophioboius herpotri-

586

TABLE I I I

Transformat ions by Genus:· RHIZOPUS

SPECIES

nigr icans (in mixed cul ture with low yielding s t r a in of Bacillus subti l is [Δ1] )

( Yamazaki)

(Ehrenberg)

SOURCE

Hoechst

IAM (R-5-4; R - 5 - 7 ; 37-12; 37-27)

IPB

NG (Brit . Drug Houses - No.

153)

NG

NG (Sandoz)

NRRL-1478

NRRL

PIRI

SSSR (VNIKH-F-1-7)

( F - l )

SUBSTRATE




(use of Warburg s tudies a s in-dicator of t ransformat ion -Ref. C-106)

20/3-hydroxy-3-keto-4-pregnen-18-oic acid (18-+20) lactone

17/3-hydroxy-4-methyi-4-andros ten-3-one

16α,17α -ox ido-4 -p regnene-3 ,20-dione

3/3,6/3,8/3,14/3-tetrahydroxy-4, 20,22-bufatr ienolide 6 -acetate 3-glucoside

1 6 a , 1 7 a , 2 1 - [ 3 , l , l - ( 2 - p y r a z o -lino) 1-4-pr egnene-3 ,20-dione

Sarsasapogenin

Diosgenin

4-dehydrotigogenone

4 -p regnene-3 ,20 -dione


REACTION

Δ1

Δ1

11a-OH

11a-OH

7 ξ - Ο Η

l l a - O H

6/3-OH

7a-OH

7/3-OH

l l a - O H

l l a - O H

3/3-[l1 4-glucoside -» 3/3-OH]

l l a - O H

l l a - O H ; 6/3,11a -diOH

l l a - O H

l l a - O H

R E F .

L-521

L-521

A-29

C-103; C-106; C-107

L-488; L-489

L-488; L-489

K-445

K-445

K-445

K-445

E-223

S-936a

W-1113

M-587

M-587

M-587

W-1115

B-42

T-1011

TABLE I I I


587

SPECIES

nigr icans

niveus (Yamazaki)

1 nodosus 1 (Namyslowski )

1 oryzae

1 pseudochinensis

1 ( Yamalaki )

pygmaeus

1 ref lexus

SOURCE

Moscow (very active s t r a in s - 1 , 7 , 1 0 , 1 6 , 1 7 , 1 8 ,

19,58)

(poorly active - 2 , 5 , 6 , 8 , 1 1 , 12,13,14)

SSSR

WC(86)

TSURUMI

IAM (R-5-5 )

IAM (32-29)

ATCC-9363 and

10260

IAM (R-5-7)

CZAS

IAM

SSSR

ATCC-1225

SUBSTRATE


6/3-f luoro-17a,21-dihydroxy-4-pregnene-3 ,20-d ione

4 , l l - p r e g n a d i e n e - 3 , 2 0 - d i o n e



17ö-hydroxy-4-pregnene-3 ,20-dione






17j3-hydroxy-4 - e s t r en -3 -one

REACTION

l i a - O H ; 6/3, l l o - d i O H

l l a - O H

6/3,1 lu-diOH; 11/3-OH; l l a - O F

l l ö - O H

no epoxidation

l l a - O H

l l o - O H

11-oxygénation

11-oxygénation

11-oxygénation

11-oxygénation

l l a - O H

l l a - O H

l l a - O H

6/3-OH

6/3-OH; Δ 4 -* Δ5; ketoniz.

6/3-OH

l l a - O H

R E F .

T-1010

E-224; S-946; T-1009

T-1009; E-224

F-268

K-484

A-29

A-29

M-601; M-636 M-601; M-636

M-601 ; M-636

M-601; M-636

A-29

T-1028

A-29

E-224

M-623

M-618; M-620

M-618; M-620

588

TABLE I I I


SPECIES

reflexus

shanghaiesis (shanghaiensis)

species

SOURCE

ATCC-1225

U

ATCC-10329

U

C

SUBSTRATE


17/3-hydroxy-17a-me thy 1-4-andros ten-3-one

4 -andros t ene -3 ,17-d iene

16α, 17a-ox ido-4-pregnene-3 , 20-dione





l l /3 ,21-dihydroxy-4 ,17(20)-pregnadien-3-one

3/3-hydroxy-14a,15a-oxido-20(22)-cardenolide aceta te





3/3,21 -d ihydroxy-5a-pregnan-20-one



REACTION

6/3-OH

3-C = 0 - A 4 -5 a - H - 3 , 6 - d i -C = 0 (via 6/3-OH; Δ4-*Δ5; ketoniz. )

l l a - O H

6/3-OH

l l a - O H

6/3-OH

l l a - O H

l l a - O H

11-OH

11-OH

11-OH

11-OH

6/3-OH; 11/3-OH

- n-c=o 3/3-OAc^3j3-OH

11-oxygénation

11-oxyge nation

11-oxygenation

11-oxygénation

7/3-OH

l l a - O H

l l a - O H

R E F .

E-201 ; M-618

E-201 ; M-623

E-201

E-201

E-201

E-201

E-201

M-644

M-601; M-636

M-601; M-636

M-601; M-636

M-601; M-636

H-341

M-576; M-577

M-601; M-636

M-601; M-636

M-601; M-636

M-601; M-636

K-433

K-433

K-433

TABLE I I I

589


SPECIES

species

1 stolonifer (synonym for n i g r i -cans)

1 stolonifer in abs t r ac t (n ig r i cans - inRef . T-1011)

SOURCE

C

IAM

NRRL

Sear le

SSSR

SY

ATCC-6227b

SSSR (No. 7,16)

SUBSTRATE

d , l - 2 1 - h y d r o x y - 4 - p r e g n e n e - 3 , 20-dione

17a ,21-hydroxy-4-pregnene-3,20-dione


plant saponins

3/3- hydroxy - 5 -andr osten -17 -one





17a-methyl th io-4-andros ten-3-one

17/3 -methy Isulf iny 1 -4 -andr osten -3-one

17)3-methylsulfonyl-4-androsten-3-one


REACTION

d,l-> d-6/3-OH + 1

l i a - O H

l i a - O H

7a-OH

7/3-OH

7 - C = 0

6/3-OH; l l a - O H

l i a - O H

6/3, l la-diOH

l l a - O H

7/3-OH

l l a - O H ; 17a-SCH3—17a-S(0)CH3

17a-SCH3 -> 17a-S(0)CH3 ( s te reochemis t ry a t S unknown)

1 7 a - S C H 3 ^ 17a-S(0)CH3 (opposite s t e r eo -chemis t ry at S from preceding compound)

Πα-ΟΗ (s te reochemis t ry at S unknown)

l l a - O H (opposite s te reo-chemis t ry a t S from preceding compound)

l l a - O H

l l a - O H

R E F .

W-1102

K-433

A-29

K-478

D-175

D-175

D-175

D-175

T-1010

T-1010

M-554

T-1037

D-174; D-176

D-174

D-174

D-176

D-176

D-176

T-1011

590

TABLE I I I

T r a n s f o r m a t i o n s by Genus: RHIZOPUS RHODOSEPTORIA

TAXONOMY

(Imperf. - Sphaeropsidales)

SPECIES

suinus

tonkinensis

t r i t i c i

RHODOSEPTORIA

1 spec ies

SOURCE

C

IAM (65-10)

SSSR

U

ATCC-1230

IAM (65-5a ; 66-14c; 66-27)

U

ATCC-11833 QM-704

SUBSTRATE

21-hydroxy-4-p . regnene-3 ,20-dione







11/3,21 -dihydroxy-4,17(20) -pr e gnadien - 3 - one







17a, 21-dihydroxy-4-pregnene -3 ,20-dione (use of whole broth or washed mycelium)

REACTION

17]3-(20-C-O-21-OH)-* 1 7 - C = 0

l l a - O H

6/3-OH

11-oxygénation

11-oxygénation

11-oxygénation

11-oxygénation

6/3-OH; 11 /3-OH-n-c=o l l a - O H

oxidation

oxidation

o xidation

oxidation

11/3-OH

11/3-OH

11/3-OH

R E F .

W-1095

A-29

E-224

M-601; M-676

M-601; M-636

M-601; M-636

M-601; M-636

H-341

A-29

M-601; M-636

M-601; M-636

M-601; M-636

M-601; M-636

K-446

K-446

K-446


T r a n s f o r m a t i o n s by G e n u s : RHODOTORULA (imperf. - Monmaies)

591

SPECIES

RHODOTORULA

glutinis

grac i l i s

longiss ima

SOURCE

IFO (0395)

NRRL

SQ (SC-2218)

NRRL-Y-2343

SUBSTRATE



1 7 a , 1 9 , 2 1 - t r i h y d r o x y - 4 - p r e g -nene-3 ,20-d ione

1 7 a , 2 1 - d i h y d r o x y - l , 4 - p r e g n a -d iene-3 ,20-d ione

Sarsasapogenin

Diosgenin



5-cholesten-3/3-01





17/3-hydr oxy -17a -4 -p regnene -3,20-dione



1 I ß , 21-dihydr oxy-4-p regnene-3,20-dione


11a, 17a, 21 - t r ihydroxy-4 - p r e g -nene -3 ,20-d ione


4 - p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e

REACTION

20-C = O ^ 20a-OH

2 0 - C = O -20a-OH

20-C=O-> 20a-OH

2 0 - C = O -20a-OH

-

-

-

-

Δ ^ Δ ;3/3-OH - 3 - C = 0

2 0 - C = O -20a-OH

20-C=O-> 20a-OH

20-C=O-> 20a-OH

2 0 - C = O -20a-OH

-

-

20-C = O ^ 20a-OH

-

20-C=O — 20a-OH

2 0 - C = O ^ 20a-OH

20-C=O-> 20a-OH

2 0 - C = O - * 20a-OH

R E F .

T-958

T-958

T-958

T-958

M-587

M-587

M-587

T-1005

T-1005

C-122

C-122

C-122

C-122

C-122

C-122

C-122

C-122

C-110; C-122

C-122

C-122

C-122

592


T r a n s f o r m a t i o n s by Genus: RHODOTORULA ROSSELLINIA

RUSSULA SACCHAROMYCES

(Asco. - Sphaeriales) (Basidio. - Agaricales) (Asco. - Endomycetales)

SPECIES

longissima

(rubra)

ROSSELLINIA

necat r ix

RUSSULA

delicans

SACCHAROMYCES

NOTE: L i t e ra tu re i s not always c lear on name of spec ies ; top or bot-tom yeas t , b a k e r s , b r ewer s or impover -ished yeas t , nor i s it cer ta in that al l were s t r a ins of ce rev i s i ae . Wherever poss ible the original source and type a r e given.

ce rev i s iae

SOURCE

NRRL-Y-2343

TNAES

ALiC-173)

ATCC-4125

SUBSTRATE

17ö-hydroxy-4 -p regnene-3 ,11 , 20- t r ione


17o ,21 -d ihyd roxy - l , 4 -p r egna -diene - 3 , 1 1 , 2 0 - t r i o n e

17a-hydroxy-9j3,11/3-oxido-1 ,4 ,6 -pregnat r iene - 3 , 2 0 -dione

17a,21-dihydroxy-9/3,11/3-oxido-l , 4 , 6 - p r e g n a t r i e n e - 3 , 2 0 -dione



Note on React ions Attr ibuted to Yeas t : In the y e a r s 1937-1938 many oxidations of s t e ro ids were er roneously repor ted to be c a r -r i ed out by yeas t (see Ref. V-1047). Later work showed that these reac t ions were due to spec ies of corynebac te r ia and f lavobacteria which were con-taminants in the yeas t p r e p a r a -t ions (see Ref. A-17).

Transformat ions r epor t ed in this table show only t h o s e reac t ions actually c a r r i e d out by yeas t . All o thers may be found under the appropr ia te bac te r ia l genus.


9c*-fluoro -1 lß-hydroxy - 1 , 4 -andros tad iene-3 ,17-d ione

REACTION

20-C=O-> 20a-OH

2 0 - C = O -20a-OH

2 0 - C = O ^ 20a-OH

2 0 - C = O -20a-OH

2 0 - C = O -20a-OH


1 7 - C = 0 -17/3-OH

1 7 - C = 0 -17/3-OH

R E F .

C-122

C-122; C-110

C-110

G-303

G-303

S-849

S-825

A-17; K-457; M-552; M-594; V-1047

A-17; E-219; E-220; M-538; M-546; M-553

C-128

N-666

TABLE I I I

T ransformat ions by Genus: SACCHAROMYCES

593

SPECIES

ce rev i s i ae

(dist i l lers)

SOURCE

ATCC-4125

FAR MIT

SUBSTRATE

9a - f luor o -11 ß - hydr oxy -16a -me thy l -1 ,4 -andros tadiene -3,17-dione

9 a - b r o m o - 1 6 a - m e t h y l - 1 , 4 -and ros t ad i ene -3 ,11 ,17 - t r i one

9a-chlor o -16a -me thy l -1 ,4 -and ros t ad i ene -3 ,11 ,17 - t r i one

9 a - f l u o r o - 1 6 a - m e t h y l - l , 4 -and ros t ad i ene -3 ,11 ,17 - t r i one

l l / 3 - h y d r o x y - l , 4 , 6 - a n d r o s t a -t r i ene -3 ,17 -d ione

9a- f luoro-11/3-hydroxy-1 ,4 ,6-andros t a t r i ene -3 ,17 -d ione

l , 4 , 6 - a n d r o s t a t r i e n e - 3 , 1 1 , 1 7 -t r ione

9a -f luoro - 1 , 4 , 6 - andros ta t r iene -3 ,11 ,17 - t r i one

1 ,4 ,9 (11 ) - and ros t a t r i ene -3 ,17 -dione

3ß-hydroxy-16a ,17a-ox ido-5a-pregnan-20-one

l l a - h y d r o x y - 5 a - p r e g n a n e - 3 , 2 0 -dione

l l a - h y d r o x y - 5 a - p r e g n a n e - 3 , 2 0 -dione ace ta te

1 l a -hyd r oxy - 5/3-pr e g n a n e - 3 , 2 0 -dione

17a-hydr oxy-5/3-pr egnane -3 ,20 -dione

21-hydroxy-5/3-pregnane-3 ,20-dione

16a ,17a-oxido-5 /3-pregnane-3 ,20-dione

11/3,17a, 21- t r ihydr oxy-5a-pr eg-nane-3 ,20-d ione 21-ace ta te

REACTION

1 7 - C = 0 -17/3-OH

1 7 - C = 0 - > 17/3-OH

1 7 - C = 0 ^ 17/3-OH

1 7 - C = 0 - > 17/3-OH

1 7 - C = 0 - * 17/3-OH

1 7 - C = 0 -17/3-OH

1 7 - C = 0 -17/3-OH

1 7 - C = 0 - > 17/3-OH

1 7 - C = 0 -17/3 -OH

16α,17α-oxide - 1 6 a - O H ; 1 3 / 3 -CH3->17/3-CH3; 2 0 - C = O - 2 0 a -OH; Δ1 3

3-C = 0 ^ 3 / 3 - O H

no reduction

no reduction

no reduct ion

no reduct ion

16a,17a-oxide-+ 16a-OH;13/3-CH3 — 17/3-CH3; 20-C = O - 2 0 a - O H :

>13

no reduction

R E F .

R-752

R-752

R-752

R-752

G-305

G-305

G-305

G-305

R-775

C-88

C-83; C-89

C-83

C-83

C-83

C-83

C-88; C-90

C-83

594

TABLE I I I

Transformat ions by Genus: SACCHAROMYCES

SPECIES

cerev i s iae (dis t i l lers)

(bread yeast)

(bakers yeast)

SOURCE

FAR MIT

FAR MIT

Kaiser Wihelm I n s t . , Ber l in

SUBSTRATE

5a -pr egnane - 3 , 1 1 , 2 0 - t r ione

5/3-pregnane-3,11,20- t r ione

17a, 21 -dihydroxy - 5a -pr egnane -3 ,11 ,20 - t r ione 21-ace ta te



l l a - h y d r o x y - 1 6 a , 1 7 a - o x i d o - 4 -pregnene-3 ,20-d ione

16a, 17a-ox ido-4-pregnene-3 ,20-dione


3j3,20j3-dihydroxy-4j3, 5j3-oxido-pregnane

3/3-hydroxy-5a, 6a-oxido-pregnan-20-one

3/3,21-dihydroxy-16a, 17a-oxido-5-pregnen-20-one 21-aceta te

4/3, 5j3-oxidopr egnane-3 , 20-dione

l ,3 ,5 (10) -es t r a t r i ene -3 ,17 /3 -d io l propionate

3 - h y d r o x y - l , 3 , 5 ( 1 0 ) - e s t r a t r i e n -17-one aceta te

3 - h y d r o x y - l , 3 , 5 ( 1 0 ) - e s t r a t r i e n -17-one propionate

REACTION

3 - C = 0 -3a-OH

3 - C = 0 - * 3a-OH

no reduction

16a, 17a -oxide -♦ 16a-OH;13/3-CH3 ^17/3-CH3; 20-C = 0 — 20a-OH; Δ13

-

-

16a,17a-oxide-^ 16a-OH; 13ß-CH3 ^17j3-CH,; 20-C=O^>20a3-OH; Δ1 3

no reduction

4/3, 5/3-oxido— 4j3,5a-diol

5a,6a-oxido—» 5a,6j3-diol

16a, 17a- oxide —» 16a-OH; 13ß-CH3 ^ 1 7 ß - C H 3 ; 20-C=O-*20a-OH;

Δ1 3

3-C=0—3/3-OH; 4/3,5/3-oxido-> 4/3,5a-diol

3-OPr->3-OH

3-OAc - 3-OH

3 - O A c ^ 3-OH; 17-C=0-*17/3-OH

3-OPr-*3-OH

3 - O P r ^ 3 - O H ; 1 7 - C = 0 ^ 1 7 / 3 -OH

REF.

C-83; C-89

C-83; C-89

C-83

C-88; C-90

C-88

C-88

C-88; C-90

C-83

C-87

C-87

C-90

C-87; C-90

M-539

M-539

M-539

M-539

M-539

TABLE I I I

T ransformat ions by Genus: SACCHAROMYCES

595

SPECIES

ce rev i s i ae (bakers yeast)

SOURCE

Kaiser Wihelm Inst. , Ber l in

IPB

Max Planck Inst, for

Biochem. , München

SCH

SUBSTRATE

3-hyd roxy -1 ,3 ,5 (10 ) - e s t r a t r i en -17-one butyra te

3α, 5α - cy cloandr ostane - 6 ,17-dione

3/3-hydroxy-5-androsten-17-one aceta te

17/3-hydroxy-5a- l -andros ten-3-one

5α-1 -andros tene -3 ,17-d ione


5a -1 -p regnene-3 ,20-d ione

5 a - l - c h o l e s t e n - 3 - o n e



3 -hyd roxy -1 ,3 , 5 (10) -es t ra t r i en -17-one

5a -andros tane -3 ,17-d ione


4 -andros t ene -3 ,17 -d ione


1,4,9(1 l ) - a n d r o s t a t r i e n e - 3 , 1 7 -dione

3,12-diketo-5/3-cholanic acid

5a-cho les tan-3-one

REACTION

3-Oßu - 3-OH

3-OBu — 3-OH; 1 7 - C = 0 - > 17/3-OH

17-C = 0-17/3-OH

17-C=0-17 /3-OH

Δ1— H; 3 - C = 0 — 3/3-OH

1 7 - C = 0 -17/3-OH

Δ ' - Η ; 1 7 - C = 0 -17/3-OH; 3-C = 0 -3/3-OH

A 4 -5 /3 -H;3 -C = 0 - 3 a - O H ; 1 7 - C = 0 -17/3-OH

-

-

1 7 - C = 0 — 17/3-OH

1 7 - C = 0 -17/3-OH

1 7 - C = 0 -17/3-OH

3-C = 0 - 3 / 3 - O H ; 17-C = 0 -17/3-OH

1 7 - C = 0 -17/3-OH

1 7 - C = 0 -17/3-OH

1 7 - C = 0 -17j3-OH

1 7 - C = 0 -17/3-OH

3 - C = 0 - 3 a - O H

3-C=0—3/3-OH

R E F .

M-539

M-539

B-81

M-539

B-80

ß - 7 8

B-80

S-808

B-80

B-80

C-106

D-143

S-806

M-543

M-543

M-543

H-385

G-308

M-543

M-543

596

TABLE I I I

T r a n s f o r m a t i o n s by Genus : SACCHAROMYCES

SPECIES

cerev is iae (compressed yeast)

(pressed yeast)

(mailand-flockige fermente)

SOURCE

ATCC-4125

C

C

I P ß

NG

(Sandoz)

NRRL

SAG

Instituto Pe rez ion -amento

SUBSTRATE

15/3-hydroxy-4-androstene-3,17-dione

3/3-hydroxy-16,17-oxido-5a-pregnan-20-one

16a- methyl -1 ,4 ,9(11) -andros ta -t r i ene -3 ,17 -d ione

3 - h y d r o x y - l , 3 , 5 (10) -es t ra t r ien-17-one

d, 1-3-hydroxy-l , 3 , 5(10)-es t ra -t r i en-17-one


3-keto-5ß-cholanic acid

3,6-diketo-5/3-choianic acid

3/3, 6/3, 8/3,14/3-tetrahydroxy-4, 20, 22-Dufatrienoiide 6-acetate 3-giucoside

Sarsasapogenin

Diosgenin


12/3-hydroxy-4-androstene-3 ,17-dione

5a -androstane -3 ,17-dione


4-androstene -3 ,17-dione


5a - cholestan - 3-one

REACTION

17-C = 0 -17/3-OH

16,17-oxide-* 16a -OH; 13/3 -Me ->17/3-Me; 20-C = 0—20a-OH; Δ13

1 7 - C = 0 -17/3-OH

17-C = 0 -17/3-OH

d , l - 1 7 - C = 0 -d-17/3-OH + 1-17-C = 0

1 7 - C = 0 -17/3-OH

-

3 - C = 0 -3a-OH

—

-

-

-

1 7 - C = 0 -17/3-OH

3-C = 0-3/3-OH; 17-C=0-17/3-OH

17-C=0-17/3-OH

17-C=0-17j3-OH

Δ — 5a-H; 3 -C = 0— 3/3-OH;17-C = 0 17/3-OH

no reduction

R E F .

H-382

C-85, C-88

R-775

W-1085

V-1055; vV-1094

H-335; H-337

E-221

E-221

S-936a

M-587

M-587

M-587

R-749

M-551; V-1046

M-549

M-550

M-551

M-550

597


T r a n s f o r m a t i o n s by G e n u s : SACCHAROMYCLS

SACCHAROMYCODES SANSEVIERIA

(Asco. - Endomycetales) ^Spermatophyta -Lil i if lorae)

SPECIES

cerev is iae (brewers yeast)

(Fleishmann)

el l ipsoideus

i'ragiiis

lactis

pas tor ianus

SACCHAROMYCODES

ludwigii

SANSEVIERIA (Plant)

zeylanica (cellular extract)

SOURCE

Phys . Chem. Inst. ,

Okayama

P F

NG

ATCC-10022

NRRL

NRRL

ATCC-2366

NRRL

P F

SUBSTRATE

3,12-diketo-5/3-choianic acid

12a -hydr oxy -3 -keto - 5/3 - choianic acid aceta te

11/3,17/3-dihydr oxy-21-methyl -1 ,4 -p regnad iene -3 ,20 ,21 -t r ione

6a,9ö-dif luoro-l l /3,17/3-dihydroxy - 21 - methyl - 1 , 4 - p r egnadiene-3, 20 ,21- t r ione



Sarsasapogenin

Diosgenin


Sarsasapogenin

Diosgenin



Sarsasapogenin

Diosgenin

4-dehydrotigogenone

17/3-hydr oxy-4-andros ten - 3-one

1 la, 21 -d ihydroxy-4-pregnene-3,20-dione

REACTION

3 - C - O - 3 a - O H

3-C = 0 ->3a-OH

2 l - C = 0 - 2 1 - O H

2 1 - C = 0 - 2 1 - O H

17-C = 0 -17/3-OH

17-C = 0 -17/3-OH

1 7 - C = 0 - * 17/3-OAc

-

-

-

-

-oxidation -produc ts not identified

-

-

-

1

Δ 1

Δ

Δ4 - 5/3-H

R E F .

K-441

K-442

Α-6

Α-6

Α-17

Μ-572

Μ-572

Μ-587

Μ-587

Μ-587

Μ-587

Μ-587

Μ-587

Η-328

Μ-587

Μ-587

Μ-587

N-658a

N-658a

N-658a

598

I A B L L I I I TAXONOMY

SARCINA (Schizo. - Eubacter ia les) T r a n s f o r m a t i o n s by G e n u s : SARCINOMYCES (imperf. - Monmaies)

SCENEDESMUS (Chlorphyta - Chlorococcales) SCHIZOPHYLLUM (Basidio. - Agaricales)

SPECIES

SARCINA

albida


albiden

aurent iace

lutea

(in mixed culture with Mycococcus sp. A J

marginata

var iabi l i s

SARCINOMYCES

c rus taceum

SCENEDESMUS (Algae)

species

SCHIZOPHYLLUM

commune

SOURCE

IFO(3063)

IAM

IAM

IAM (PCI-1001)

IFO (3232)

NG

NRRL

IAM

IAM

FRI

SCH (J9-A-21)

IAM

SUBSTRATE





11/3, 17α, 21 - t r i hyd roxy-4 -p reg -nene-3 ,20-dione


Sarsasapogenin

Diosgenin




17a, 21 -d ihydroxy-4 -p regnene-3,20-dione



REACTION

-

l l a - O H

11a-OH

-

-

—

-

-

-

-

l l a - O H

-

6/3-OH

l l a - O H ; 11/3-OH

-

R E F .

1-428

1-428

S-849

S-849

S-849

1-428

1-428

T-1030

M-587

M-587

M-587

S-849

S-849

S-849

L-527

L-527

S-849

599

T A B L E I I I TAXONOMY

T r a n s f o r m a t i o n s bV G e n u s · SCHIZOSACCHAROMYCES (Asco. - Endomycetales) y ' SCLEROTINIA (Asco. - Helotiales)

SPECIES

SCHIZOSACCHARO-MYCES

octosporus

SCLEROTINIA

alii i

fructicoia

fluctigena

l ibert iana

SOURCE

NRRL

TNAES

C

TNAES

IAM

S

SUBSTRATE

Sarsasapogenin

Diosgenin




17a -hydroxy- l , 4 -p regnad iene -3 ,11 ,20 - t r ione


17o ,21-d ihydroxy-4-pregnene-3,20-dione


17û-hydroxy-4-pregnene-3 ,20-dione



11/3, 21-d ihydroxy-4-pregnene-3,20-dione

REACTION

---

-

21-OH

21-OH

-

2/3-OH; 11/3-OH

2/3,15/3-DIOH

2/3,X-DIOH


2/3-OH

l l a - O H

15/3-OH

2ß,15/3-DIOH

2/3,15ß-DIOH; 21-OAc-*21-OH

2/3-OH

15/3-OH

R E F .

M-587

M-587

M-587

S-849

W-1101

W-1101

S-849

S-849

S-849; S-850; S-859; T-983

T-983

T-983

S-849, S-859; T-983

S-849; S-859; T-983

S-850; T-983

S-849

S-840; S-849, S-853

S-840; S-849 S-853

S-840; S-849; S-853

600


TABLE I I I

SCLEROTINIA SCLEROTIUM

TAXONOMY

(Imperf. - Mycelia Steri l ia)

SPECIES

libertiana

sc le ro t io rum

SCLEROTIUM

coffeicolum

hydrophilum

SOURCE

S

TNAES

FAHU

S

OR

NARI

S

SUBSTRATE

17a, 21 -dihydroxy-4-pregnene-3,20-dione

17a,21 -dihydroxy -4 -pr egnene -3,20-dione


17/3-hydroxy-17a-propyl-4-andros ten-3-one


4-pre gnene-3 ,20-dione




REACTION

2/3-OH

11a-OH

11/3-OH

X-OH

2/3-OH; 11/3-OH

2]3-OH; 11/3-OH

2/3-OH

11a-OH

llj3-OH

16/3-OH

6/3-OH; l l a - O H

6/3,1 l a -DIOH

6/3-OH

l l a - O H

6/3-OH; l l a - O H

6/3-OH; 2 1 - O A c -21-OH

l l a - O H ; 21-OAc — 21-OH

R E F .

S-849; S-859; S-860; T-983

S-849; S-859; S-860

S-849; S-859; S-860

T-983

S-849

S-849

S-860

S-860

S-860

S-950

S-849

S-849; S-856; S-859

S-856; S-859

S-849; S-856; S-859

S-856

S-856

S-856

TABLE I I I

TAXONOMY

Transformat ions by Genus: SCLEROTIUM SCOPULARIOPSIS (Imperf. - Moniliales)

601

SPECIES

hydrophilum

(var. i r r egu la r i s )

rolfs i i

SCOPULARIOPSIS

1 amer icana

1 brevicaul is

SOURCE

S

CBS QM-93-A

ATCC-12450

FRI

NRRL-1103

SUBSTRATE

21-hydroxy-4 -p regnene -3 ,20 -dione ace ta te





17ö, 21 -dihydroxy -4 -p r egnene -3,20-dione




17a ,21-d ihydroxy-4- p r egnene -3, 20-dione



REACTION

6/3, l la-diOH; 2 1 - O A c -21-OH

6/3-OH; 11/3-OH-*

n-c=o 15/3-OH; 11/3-OH —

n-c=o 6/3-OH

11a-OH

l l a - O H ; 11/3-OH

l l a - O H ; 11/3-OH

1ξ-OH; l l a - O H ; llj3-OH; 1 1 -C = 0 (via 11/3-OH)

1|-OH; l l a - O H ; 11/3-OH; 1 1 -C = 0 ( via 11/3-OH)

1ξ-OH; l l a - O H ; 11/3-OH; 1 1 -C = 0 (via 11/3-OH)

Ιξ-OH; l l a - O H ; 11/3-OH; 1 1 -C = 0 (via 11/3-OH)

Ιξ-ΟΗ; l l a - O H

l l a , 1 7 a - d i O H

R E F .

S-856

S-849; S-856

S-856

S-849; S-856; S-859

S-849; S-856; S-859

C-313

G-313

G-313

G-313

G-313

G-313

G-313

S-849

D-188

602


TABLE I I I

SCOPULARIOPSIS SEPEDONIUM SEPTOMYXA

TAXONOMY

(Imperf. - Moniliales) (Imperf. - Melanconiales)

SPECIES

brevicaul is

SEPEDONIUM

ampul losporum

SEPTOMYXA

aescul i

SOURCE

NRRL

NRRL-2877

PH

PH

U

SUBSTRATE

Sarsasapogenin

Diosgenin


5 /3 -p regnane -3 , l l , 20 - t r i one


r e t r o - 4 - p r e g n e n e - 3 , 2 0 - d i o n e

£e t ro_-4 ,6 -p regnad iene-3 ,20-dione

17/3 -hydr oxy - r e t r o - 4 -andr osten -3-one

r e t r o - 4 , 6 - p r e g n a d i e n e - 3 , 2 0 -dione

17/3-hydroxy-19-nor-4-androsten-4 -es t rone


17j3 -hydr oxy -1 la - methyl -4 -andros ten-3-one

11/3,17/3-dihydr oxy -17a -methyl -4-andros ten -3-one



REACTION

—

—

~

16a-OH

17a-OH

16a-OH

16a-OH

16a-OH

16a-OH

Δ1; enoL

Δ ; enol. ; 17/3-OH ^ 1 7 - C = 0

Δ1

Δ1; 17/3-OH^ 1 7 - C = 0

Δ1

Δ1

Δ 1

Δ1; 1 7 - C = 0 ^ 17a-oxa-17-C =o Δ1; 1 7 - C = 0 -170-OH

Δ1; 1 7 / 3 - A c -1 7 - C = 0

REF.

M-587

M-587

M-587

F-252

M-646

P - 7 3 5

P - 7 3 5

P - 7 3 5

P - 7 3 5

W-1072

W-1072

W-1072

W-1072

W1072

E-206

W-1072

W-1072

W-1072

W-1072

chrysospermum

TABLE I I I

603

T r a n s f o r m a t i o n s by Genus: SEPTOMYXA

SPECIES

aescul i

SOURCE

U

SUBSTRATE

4-pregnene-3 ,20-d ione (use of washed mycel ium and var ious addit ives changes proport ion of products)





17ce, 21 -dihydroxy-4-pregnene -3,20-dione

1 1/3, 17a, 21 - t r ihydroxy -4 - p r e g -nene -3 ,20-d ione

l l / 3 ,17a ,21 - t r i hyd roxy-6a -methy l -4 -p regnene-3 ,20-d ione

4 - p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e

REACTION

Δ1

Δ1; 17/3-Ac — 17ß-OH

Δ1; 17 /3 -Ac-1 7 - C = 0

Δ1; 17/3-Ac — 17a-oxa-17-C =o

Δ1

Δ1; 17 /3 -Ac-17/3-OH

Δ1; 17/3-Ac-» 1 7 - C = 0

Δ1; 17/3-Ac-» 17/3-OH

Δ1; 1 7 / 3 - A c -1 7 - C = 0

Δ1

Δ1; 17»-OH-17/3-Ac--17/3-OH

1

Δ

Δ1; 17/3-(20-C = 0 - 2 1 - O H ) -17/3-OH

Δ1; 17/3-(20-C = 0 - 2 1 - O H ) -1 7 - C = 0

Δ1; 17/3-(20-C = 0 - 2 1 - O H ) -17a-oxa-17-C =o

Δ1

Δ1

1

Δ

Δ 1

R E F .

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

604

TABLE I I I


SPECIES

aescul i

affinis

SOURCE

UC

ATCC-6737

SUBSTRATE

4 -pregnene - 3 , 1 1 , 2 0 - t r ione

17a ,21-d ihydroxy-4-pregnene-3 , 1 1 , 2 0 - t r ione


In the following reac t ions the use of one or the other of the fol-lowing " a c c e l e r a t o r s , " "indue er s " or " p r o m o t e r s " will be designated by the s y m -b o l ^ A) under substrate . -

Lis t of Acce le ra to r s

l , 4 -andros tad iene-3 ,17-d ione

17ß-hydroxy- l , 4 -andros t ad i ene -3,17-dione

1 7 a - o x a - D - h o m o - l , 4 - a n d r o s t a -d iene-3 ,17-dione


1Ια-hydroxy-4 -p regnene -3 ,20 -dione

l l /3 ,21-dihydroxy-4 ,17(20)-pr egnadiene -3 ,20 -dione

3 -keto -b i snor -4 -cholen -22 -al

3 -keto -b i snor -4-cholen-22 -ol

3 -keto-bisnor -1 ,4 -choladien-22 -al

3 -keto -bisnor -1 ,4 -choladien-22 -ol

3 -ke to -b i sno r -1 ,4 -choladien-22 -oic acid


REACTION

Δ1; 17/3-Ac-» 1 7 - C = 0

Δ1; 17 /3 -Ac-17/3-OH

Δ1

Δ1

Δ1; enol.

Δ1; enol. ; 17/3-OH^ 1 7 - C = 0

R E F .

W-1072

W-1072

W-1072

W-1072

B-43; B-44; F-249; F - 2 5 1 ; F -253 ; H-395; L-513; L-517; M-530; M-531; M-532; M-534; M-647; P -709 ; S-833; S-922; S-924; S-925; S-926; S-927

M-573; W-1072

M-573; W-1072

TABLE I I I

605

T r a n s f o r m a t i o n s by Genus : SEPTOMYXA

SPECIES

affinis

SOURCE

ATCC-6737

SUBSTRATE

17/3-hydroxy -2a -methyl -4 -es -t r en -3 -one

17/3-hydroxy-4-methyl -4-es t ren-3-one

17a-ethinyl-6a-f luoro-17/3-hydroxy-4 -es t r en -3 -one

6a-fluoro-17/3-hydroxy-17a-me thy l -4 - e s t r en -3 -one

6α -flu o r o - 17/3-hydroxy- 17α-methy le th iny l -4 -es t ren-3-one

6a - f luo ro -4 -e s t r ene -3 ,17 -d ione

6/3-f luoro-4-es t rene-3 ,17-dione

6 a - f l u o r o - 4 - e s t r e n e - 3 , 1 1 , 1 7 -t r ione

6 /3 - f luoro-4-es t rene-3 ,11 ,17-t r ione

4, 7 - e s t r ad i ene -3 ,17 -dione

1 7/3 -hydr oxy -4 -andr osten -3 -one

2α, 17/3-dihydroxy-4-andr osten -3-one diacetate

2/3,17/3-dihydroxy-4-andr osten -3-one diacetate

17/3-hydr oxy -17a-methyl -4 - an -dr osten -3 -one

17a-brometh iny l -6a- f luoro-4-andros ten-3-one

17α-bromethinyl -17/3-hydr oxy-4-andros ten-3-one

REACTION

Δ1; enol. ; 17/3-OH — 1 7 - C = 0

Δ ; enol. ; 17/3-OH-> 1 7 - C = 0

Δ ; enol.

1

Δ ; enol.

Δ ; enol.

Δ ; enol.

Δ1; enol.

Δ1; enol.

Δ ; enol.

Δ1; enol.

Δ1

Δ1; 17/3-OH — 1 7 - C = 0

Δ1; 17/3-OH -» 17a-oxa-17-C

=o 2a-OAc — 2a-OH; 17/3-OAc -> 17/3-OH

2/3-OAc — 2/3-OH; 17/3-OAc - 17/3-OH

2/3-OAc — 2/3-OH; 17/3-OAc - 1 7 - C = 0

Δ1

Δ1

1

Δ

R E F .

P -731

P-731

C-93

C-93

C-93

P-709

P-709

P-709

P-709

3-72

W-1072

W-1072

W-1072

H-399

H-399

H-399

E-205; W-1072

0 -694 ; 0 -695

0 -694 ; 0 -695

606

TABLE I I I

T r a n s f o r m a t i o n s by G e n u s : SEPTOMYXA

SPECIES

affinis

SOURCE

ATCC-6737

SUBSTRATE

1 la -br omethinyl -17/3 - methoxy -4 -andros ten-3-one

17a-chlorethinyl-17/3-hydroxy-4 -andr osten -3 -one

17a-chlorethinyl-17/3-methoxy-4 -andr osten -3 -one

17a-ethinyl-6a-fluoro-17/3-hydroxy-4 -andr osten -3 -one

1 7α- ethyl -6α -fluor o - l 7/3-hydroxy-4-andros ten-3-one

l l ß , 17/3-dihydroxy- 17α -methyl -4-andros ten -3-one

6a-fluoro-17/3-hydroxy-17a-methyl -4 -andr osten -3 -one

17a -br omethinyl -6a -ch loro-17ß -hydroxy-4-andros ten-3-one

17a-bromethinyl-6a-f luoro-17/3-methoxy-4-andros ten-3-one

17a-bromethinyl-17/3-hydroxy-6a -methy l -4 -andros ten -3 -one

6a-chloro-17a-chlorethinyl-17/3-hydroxy -4 -andr osten -3 -one

17a-chlorethinyl-6a-f luoro-17/3-hydroxy-4 -andr osten -3 -one

17a-chlorethinyl-6a-f luoro-17/3-methoxy-4-andros ten-3-one

17a -chlor ethinyl-17/3- hydroxy -6a-methyl -4 -andr osten -3 -one

9a-fluoro-ll j3,17/3-dihydroxy-17a-methyl -4-andr o s t e n - 3 -one (+A)

6a - f luor o -17/3 - hydr oxy -17a -methy le th iny l -4 -andros ten-3-one

17/3-hydroxy-17a-methyl-9/3,11/3-oxido-4-andros ten-3-one (+A)

6a-f luoro-17/3-hydroxy-4-andro-s t e n e - 3 , l l - d i o n e

4 -andros tene-3 ,17-d ione (testolic acid was not produced by cu l tu res forming lac tone-Ref. H-398)

REACTION

Δ 1

Δ1

Δ1

Δ1

Δ 1

Δ1

Δ1

Δ1

Δ 1

Δ1

Δ 1

Δ 1

Δ1

Δ1

Δ 1

Δ1

Δ1

Δ1

Δ1

R E F .

0 - 6 9 4 ; 0 -695

0 -694 ; 0 -695

0 -694 ; 0 -695

C-93

C-93

E-206

C-93

0 -694 ; 0 -695

0 -694 ; 0 -695

0 -694 ; 0 -695

0 -694 ; 0 -695

0 -694 ; 0 -695

0 -694 ; 0 -695

0 -694 ; 0 -695

M-647

C-93

M- 647

P-709

H-399; W-1072

TABLE I I I

607


SPECIES

affinis

SOURCE

ATCC-6737

SUBSTRATE

4-andr os tene-3 ,17-d ione (testolic acid was not produced by cu l tu res forming lac tone-Ref. H-398)

6a- f luoro- l l /3 -hydroxy-4-andro-s tene-3 ,17-d ione (+A)

6/3-f luoro-l l /3-hydroxy-4-andro-s tene-3 ,17-d ione (+A)

6a -fluor o -4 -andr ostene - 3 , 1 1 , 1 7 -tr ione

17a-oxa-D-homo_-4-androstene-3,17-dione

17a-chlorethinyl-6 -fluor 0-17/3 -hydr oxy -4 ,6 -andr ostadien - 3 -one

17a-chlorethinyl-6-f luoro-17/3-me thoxy -4 ,6 - and ros t ad i en -3 -one

17a -chlor ethiny 1 -17/3 -hydr oxy -6 - m e t h y l - 4 , 6 - a n d r o s t a d i e n - 3 -one

6-chloro-17a-chlorethinyl-17/3-hyd roxy -4 ,6 - and ros t ad i en -3 -one

6-ch loro-17a-ch lore th iny l -17ß-methoxy -4 ,6 -andr ostadien -3 -one

17a-bromethinyl -6-chlor o-17/3-hydroxy -4 ,6 -andr os tadien-3 -one

17a-bromo-6-chloro-17j3-m e t h o x y - 4 , 6 - a n d r o s t a d i e n - 3 -one

17a-bromethinyl-6-f luor 0-17/3-hydroxy-4 ,6 -andr o s t a d i e n - 3 -one

17a-bromethinyl-6-f luor 0-17/3-methoxy - 4 , 6 -andr ostadien - 3 -one

17a-bromethinyl-17/3-hydroxy-6 -me thy l -4 ,6 -and r o s t ad i en -3 -one

REACTION

Δ1; 17 -C=0-> Πβ-ΟΉ

Δ1; 1 7 - C = 0 -17a-oxa-17-C =o

1

Δ

Δ1

Δ1

no tes to l ic acid

1

Δ

Δ1

Δ1

Δ1

Δ1

Δ1

1

Δ

Δ1

Δ1

Δ1

R E F .

W-1072

H-398; W-1072

P-709

P-709

P-709

H-398

0 -694 ; 0 -695

0 -694 ; 0 -695

0 -694 ; 0 -695

0 -694 ; 0 -695

0 -694 ; 0 -695

0 -694 ; 0 -695

0 -694 ; 0 -695

0 -694 ; 0 -695

0 -694 ; 0 -695

0 -694 ; 0 -695

608

TABLE I I I


SPECIES

affinis

SOURCE

ATCC-6737

SUBSTRATE


6a- f luoro-17a-hydroxy-5a-pregnane-3 ,20-d ione

3ß-hydroxy-5a-pregnane-11 ,20-dione 20-cycloethyleneketal (+A)

3j3,17a-dihydroxy-5a-pregnane-11,20-dione 20-cycloethylene-ketal (+A)

3/3,21 - d ihydroxy-5a-pregnane-11,20-dione 20-cycloethylene-ketal (+A)

3/3,17a, 21 - t r ihydroxy-5a -p reg -nane-11,20-dione 20-cyclo-ethy leneketal (+ A)

5a -p regnane -3 ,11 ,20 - t r i one (+A)

6/3-fluoro-3/3, 5a-d ihydroxy-preg-nan-20-one 20-cycloethylene-ketal (+A)

3/3,5a-dihydroxy-6/3-methyl-preg-nan-20-one 20-cycloethylene-ketal (+A)

6a-fluor o -17a-hydroxy - 5/3-preg-nane-3 ,20-d ione

5 ß -pregnane - 3 , 1 1 , 2 0 - t r i o n e (compare with ethyleneketal der ivat ive - Ref. R-251)

5/3-pregnane-3,11,20- t r ione 20-cycloethyleneketal (+A)

3/3-hydroxy-5-pregnen-20-one (+A)

3/3-hydroxy-5-pregnen-20-one 20-cycloethyleneketal (+A)

3/3-hydroxy-5-pregnen-20-one 20-methyl enol ether (+A)

REACTION

1

Δ 1

Δ

Δ ^ β - Ο Η -3-C = 0

Δ ; 3/3-OH — 3 - C = 0

Δ ; 3/3-OH -> 3 - C = 0

Δ ; 3j3-OH — 3 - C = 0

Δ ; 17/3-Ac -» 1 7 - C = 0

Δ1; 3 / 3 - O H -3 - C = 0

Δ1; 3 / 3 - O H -3 - C = 0

1

Δ

oxidized to an-dros tane s e r i e s

Δ1; 1 7 / 3 - A c -1 7 - C = 0

Δ

oxidized to an-dros tane s e r i e s

1 5 4

Δ ; Δ - Δ ; 3 /3 -OH-3-C=0

1 5 4

Δ ; Δ - Δ ; 3/3-ΟΗ — 3 - C = 0

R E F .

Β-72

Β-34

F-251

F-251

F-251

F-251

Ε-207; Μ-573; W-1072

F-251

F-251

Β-34

F-251

Ε-207; Μ-573; W-1072

F-249; F - 2 5 1 ; F-253

F-251

F-251

F-251

TABLE I I I

609



affinis ATCC-6737 3/3-hydroxy-16ce -methyl - 5 - p r e g -nen-20-one 20-cycloethylene-ketal


[occur rence of tes to l ic acid by cu l tures repor ted to p r o -duce testololactone-Ref. H-398; with spo re s - Ref. S-901; use of washed mycel ium and changing proport ion of products by var ious addit ives-Ref.W-10721



17a -hydroxy-4 -p regnene -3 ,20 -dione (with s p o r e s -Ref. S-901)

17ö-hydroxy-4 -p regnene-3 ,20-dione ace ta te

Δ1; Δ 5 - Δ 4 ; 3 /3-OH-3 - C = 0

F-251

H-399:

Δ1; 17 /3 -Ac-17/3-OH

Δ1; 17/3-Ac -1 7 - C = 0

Δ1; 1 7 / 3 - A c -17a-oxa-17-c=o

Δ 1

Δ1; 1 7 / 3 - A c -17/3-OH

Δ1; 17/3-Ac-> 1 7 - C = 0

Δ1

Δ1; 1 7 / 3 - A c -17/3-OH

Δ1; 1 7 / 3 - A c -1 7 - C = 0

Δ1

Δ1; 170-OH-17/3-Ac — 17/3-OH

Δ1; 17Q-OH-1 7 / 3 - A c -1 7 - C = 0

Δ1; 170-OH-1 7 / 3 - A c -17a-oxa-17-C =o

S-901; W-1072

S-901; W-1072

S-901; W-1072

H-398; S-901; W-1072

E-208; W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

S-901; W-1072

S-901

S-901

B-36

1

Δ

1

Δ

610

TABLE I I I


SPECIES

affinis

SOURCE

ATCC-6737

SUBSTRATE

21-hydroxy-4 -p regnene-3 ,20-dione (with spo re s -Ref. S-901)

1 la -ethyl -4 -pregnene -3 ,20 -dione (with spores)

dione (with spores)

21 -fluoro -4 -pregnene -3 ,20-dione (with spores)

6 a - f l u o r o - l l a -hydroxy-4 -p reg -nene-3 ,20-d ione

6a-fluoro-11/3-hydroxy -4 - p r e g -nene -3 ,20-dione

6ö- f luoro-17a-hydroxy-4-preg-nene-3 ,20-d ione

6j3-f luoro-l la-hydroxy -4 - p r e g -nene -3 ,20-dione

6/3-fluor o - l 1/3-hydroxy -4 - p r e g -nene -3 ,20-dione

6 /3 , l ia -d ihydroxy-4-pregnene -3,20-dione (+A)

l i a , 17a-dihydroxy-4-pregnene -3,20-dione (+A)

11/3,17a-dihydroxy-4-pregnene-3,20-dione (+A)

REACTION

Δ1

Δ1; 17/3-(20-C = 0-21-OH) — 17/3 -OH

Δ1; 17/3-(20-C = 0 - 2 1 - O H ) ^ 1 7 - C = 0

Δ1; 17/3-(20-C = 0 - 2 1 - O H ) -17a-oxa-17-C =o

Δ1

1

Δ

Δ1; 17/3-(20-C = 0 - 2 1 - F ) -17/3-OH

Δ1; 17/3-(20-C = 0 - 2 1 - F ) - * 1 7 - C = 0

Δ1; 17/3-(20-C = 0 - 2 1 - F ) -17a-oxa-17-C =o

Δ1

Δ1

Δ1

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

R E F .

W-1072

S-901; W-1072

S-901; W-1072

S-901; W-1072

S-901

S-901

S-901

S-901

S-901

C-91

C-91

B-34

C-91

C-91

M-647

M-647

M-647

17û-methyl-4-pr egnene-3,20-

TABLE I I I

611


SPECIES

affinis

SOURCE

ATCC-6737

SUBSTRATE


17a, 21-d ihydroxy-4-pregnene-3,20-dione (with spo re s - Ref. S-901)

21-fluoro-17a-me thy 1-4-preg-nene-3 ,20-d ione (with spores )

21 -hydroxy-17a -me thy l -4 -p reg -nene-3 ,20-d ione ace ta te (with spores)

6α, 17a-d imethy l -4 -pregnene-3,20-dione

9 a - c h l o r o - l 1/3,21-dihydroxy-4-pregnene-3 ,20-d ione

9 a - f l u o r o - l l ß - h y d r o x y - 6 a -methyl-4 -pregnene -3 ,20-d ione (+A)

l l ß , 1 7 a , 2 1 - t r i h y d r o x y - 4 - p r e g -nene-3 ,20-d ione [(+A)- Ref. M-647, reac t ion k ine t ics , washed cells-Ref. C-132, use of dr ied thal i i Ref.-F-231]

6a- isobutyl- l l j3,17a, 21- t r ihy-d roxy-4-p regnene-3 ,20-d ione (+A)

7a -cyano- l l / 3 ,17a ,21 - t r ihydroxy-4-pregnene-3 ,20-d ione

7/3-cyano-11/3,17a,21-trihydroxy-4-pregnene-3 ,20-d ione

6a-f luoro-11/3,17a-dihydroxy-2a-methy l -4 -p regnene-3 ,20-d ione (+A)

REACTION

Δ1; 17/3-(20-C = 0-21-OH)-+ 17/3-OH

Δ1; 17/3-(20-C = 0 - 2 1 - O H ) -1 7 - C = 0

Δ1

Δ1; 17a-OH-17/3-(20-C=O-2 1 - O H ) - 17/3-OH

Δ1; 17a-OH-17/3-(20-C=O-21-OH)-» 17-C = 0

1

Δ

Δ1; 2 1 - O A c -21-OH

Δ1

Δ1; 17ß-(20-C = 0 - 2 1 - O H ) -1 7 - C = 0

Δ1

Δ1

1

Δ

1

Δ

1

Δ

Δ 1

R E F .

S-901

S-901

S-901; W-1072

S-901

S-901

S-901

S-901

S-901

H-399

S-923; S-927

C-132; F - 2 3 1 ; M-647; W-1072

H-395

B-75

ß - 7 5

B-43

612

TABLE I I I


SPECIES

affinis

SOURCE

ATCC-6737

SUBSTRATE

9a-f luoro- l l /3 ,17a-d ihydroxy-6 a - m e t h y l - 4 - p r e g n e n e - 3 , 2 0 -dione (+A)

9a- f luoro- l l /3-hydroxy-6a , 16a-dimethyl -4 -pr egnene -3 ,20 -dione

6a- f luoro- l l /3 ,17a , 21- t r ihy-droxy -4 -pregnene-3 ,20-d ione 21-aceta te [(+A)-Ref. M-530 ,531 ,532 , 647]

6/3-fluoro-11/3,17a, 21 - t r ihy-droxy -4 -pregnene-3 ,20-d ione 21-ace ta te (+A)

6α -hexy 1 -11 β, 17α, 21 - t r ihydr oxy -4 -pregnene-3 ,20-d ione (+A)

l l a , 1 7 a , 2 1 - t r i h y d r o x y - 6 4 -methy l -4 -pr egnene-3 ,20-dione (+A)

11 β, 17a, 21 - t r ihydroxy - 2a - mettyl 4 -pregnene-3 ,20-d ione (+A-Ref. M-647)

l l / 3 ,17a ,21- t r ihydroxy-6a -methyl-4 -pr egnene -3 ,20-dione (+A-Ref. H-395; S-833; S-922)

l l /3 ,17a ,21- t r ihydroxy-6/3-methy l -4 -pregnene-3 ,20-d ione (+A-Ref. H-395; S-833)

l l / 3 ,17a ,21 - t r ihydroxy-6 -methy lene -4 -pr egnene - 3 , 2 0 -dione

11/3,17a, 21- t r ihydroxy-6a-penty l -4 -pregnene-3 ,20-d ione (+A)

11/3,17a, 21- t r ihydroxy-6a-pheny 1 -4 -pregnene - 3 ,20 -dione (+A)

11/3,17a, 21 - t r ihydroxy-6a - i so -p ropy l -4 -p regnene-3 ,20-d ione (+A)

11/3,15a, 17a, 21 - t e t r ahydroxy-4-pregnene-3 ,20-d ione (+A)

REACTION

Δ 1

Δ 1

Δ1; 2 1 - O A c ^ 21-OH

Δ1; 21-OAc — 21-OH

1

Δ

1

Δ

Δ 1

Δ 1

1

Δ

1

Δ

1

Δ

1

Δ

Δ 1

Δ 1

R E F .

L-513

S-923

H-396; M-530; M-531; M-532; M-647; S-924; S-926

S-925; S-926

H-395

S-833

H-394; M-573; M-647

H-395; L-512; M-573; M-647; S-833; S-922; W-1072

H-395; L-512; S-833

F-264

H-395

H-395

H-395

B-44

TABLE I I I

613


SPECIES

affinis

SOURCE

ATCC-6737

SUBSTRATE

11/3,15/3,17a, 21 - t e t r ahydroxy-4 -pregnene-3 ,20-d ione (+A)

9a -b r omo-6a-f luoro-11/3,17α-dihy dr oxy-2α-methy l -4 -pr eg-nene-3 ,20-d ione (+A)

9a-bromo-6/3-f luoro- l l /3 , 17a, 21- t r ihydroxy-4-pregnene -3,20-dione 21-ace ta te

9a-chloro-6a-f luoro-11/3 ,17a-dihy droxy- 2a -methyl -4 -pr eg-nene -3 ,20-dione (+A)

9a-chloro-6/3-fluoro-11/3,17a, 2 1 -t r i h y d r o x y - 4 - p r e g n e n e - 3 , 2 0 -dione 21-aceta te

6a-fluoro-11/3,17a, 21 - t r ihydroxy J 2 a - m e t h y l - 4 - p r e g n e n e - 3 , 2 0 -dione (+A)

6a-fluoro-11/3,17a, 21 - t r ihy -d roxy-16a -me thy l -4 -p r eg-nene-3 ,20-d ione 21-ace ta te

6a- f luoro- l l j3 ,17a , 21 - t r ihy-droxy -16β -methyl -4 -pr eg-nene -3 ,20-d ione 21-ace ta te

6/3-fluoro-11/3,17a, 21 - t r ihydroxy -2 a - m e t h y l - 4 - p r e g n e n e - 3 , 2 0 -dione (+A)

9a-fluoro-11/3,17a, 21 - t r ihy -droxy -6a -methy l -4-pregnene -3 ,20-dione (+A)

9a-fluoro-11/3,15a, H a ^ l - t e t r a -h y d r o x y ^ - p r e g n e n e - S , 20-dione (+A)

9a-fluoro-11/3,15/3,17a, 21 - t e t r a -hydroxy-4 -p regnene -3 ,20 -dione (+A)

6a, 9a -dif luoro -11/3,17a -dihy -dr oxy-2a -me thy l -4 -p r egnene -3,20-dione (+A)

6a ,21-d i f luoro- l l /3 ,17a-d ihy-d roxy-2a -me thy l -4 -p r egnene-3,20-dione (+A)

6 a , 9 a , 2 1 - t r i f l u o r o - l l / 3 , 1 7 a - d i -hyd roxy-4 -p regnene -3 ,20 -dione (+A)

REACTION

Δ1

Δ 1

Δ1; 21-OAc— 21-OH

1

Δ

Δ1; 21-OAc-* 21-OH

Δ 1

Δ1; 2 1 - O A c -21-OH

Δ1; 2 1 - O A c ^ 21-OH

Δ 1

Δ 1

Δ 1

Δ 1

Δ1

Δ1

Δ 1

R E F .

B-44

B-43

S-926

B-43

S-926

B-43

L-517

L-517

B-43

S-921

B-44

B-44

B-43

B-43

M-534

614

TABLE I I I


SPECIES

affinis

SOURCE

ATCC-6737

SUBSTRATE

6/3 ,9a-d i f luoro- l l /3 ,17a ,21- t r i -hydroxy-4 -p regnene -3 ,20 -dione 21-aceta te

l l / 3 ,17a ,21- t r ihydroxy-16a-methyl-6 - mé thy lène -4 -p reg -nene-3 ,20-d ione

11/3,15/3,17a, 21- te t rahydroxy-15a -me thy l -4 -p regnene -3 ,20 -dione (+A)

l l / 3 ,16a ,17a ,21 - t e t r ahydroxy-6 a - m e t h y l - 4 - p r e g n e n e - 3 , 2 0 -dione

9a -b romo-6a ,21 -d i f l uo ro - l l / 3 , 17a-d ihydroxy-2a-methyl -4-pregnene-3 ,20-d ione (+A)

9 a - c h l o r o - 6 a , 2 1 - d i f l u o r o - l l / 3 , 17a-d ihydroxy-2a-methyl -4-pregnene-3 ,20-d ione (+A)

9a- f luoro- l l j3 ,15 /3 ,17a ,21- te t ra -hydr oxy-15a -me thy l -4 -p reg -nene-3 ,20-d ione

9 a - f l u o r o - l l / 3 , 1 6 a , 1 7 a , 2 1 - t e t r a -hydroxy-6a -me thy l -4 -p reg -nene-3 ,20-d ione

6a, 9a, 21 - t r i f luoro-11/3,17a-di-hydr oxy-2a -methy l -4 -p r eg -3 ,20-dione

4 -pregnene - 3 , 1 1 , 2 0 - t r ione

REACTION


6 /3-f luoro-4-pregnene-3 ,11,20-t r ione

6a -me thy I -4 -p r egnene -3 ,11 ,20 -t r ione

3 -me thy l -4 -p regnene -3 ,11 ,20 -tr ione

Δ ; 21-OAc-21-OH

Δ1; 17/3-Ac-17/3-OH

Δ1; 17/3-Ac-1 7 - C = 0

Δ1; 17/3-Ac-17/3-OH

Δ1; 17/3-Ac-1 7 - C = 0

Δ1; 17/3-Ac-17/3-OH

R E F .

S-926

F-264

B-44

L-517

B-43

B-43

B-44

L-517

B-43

E-M W

208; -574; -1072

W-1072

W -1072

C-91

C-91

R-780

R-780

R-780

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

TABLE I I I

615


SPECIES

affinis

SOURCE

ATCC-6737

SUBSTRATE

6/3-methyl -4-pregnene-3 ,11 ,20-t r ione

9a -fluoro -6a - methyl -4 -pr egnene -3 ,11 ,20 - t r i one

17a, 21 -dihydroxy -4 -pregnene -3 ,11 ,20 - t r ione (with spo re s -Ref. S-901)

6a- f luoro-17a-hydroxy-2a-m e t h y l - 4 - p r e g n e n e - 3 , l l , 2 0 -t r ione

2a-f luoro-17a, 21-dihydroxy-4-pregnene - 3 , 1 1 , 2 0 - t r ione

6a-f luoro-17a, 21-dihydroxy-4-p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e 2 1 -aceta te (+A)

6ß-f luoro-17a, 21 -d ihydroxy-4-p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e 21-aceta te (+A)

9a-f luoro-6a , 16a-d imethyl -4-p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e

17a, 21 -d ihydroxy-6a-methyl -4 - p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e ( + A-Ref. L-512)

17a,21-dihydroxy-6/3-methyl-4-p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e

15a, 17a, 21 - t r i hyd roxy-4 -p reg -nene - 3 , 1 1 , 2 0 - t r ione

15/3,17a, 21 - t r i hyd roxy-4 -p reg -n e n e - 3 , 1 1 , 2 0 - t r i o n e

9a-bromo-6a- f luoro-17a-hydroxy-2 a - m e t h y l - 4 - p r e g n e n e - 3 , 1 1 , 20- t r ione (+A)

9a-bromo-6 /3- f luoro-17a ,21-d ihyd roxy-4 -p regnene -3 ,11 , 20- t r ione 21-aceta te

REACTION

Δ1; 17j3-Ac-* 1 7 - C = 0

Δ 1

Δ 1

Δ1; 17α-ΟΗ-17/3-(20-C = O-2 1 - O H ) - 17ß-OH

Δ1; 17α-ΟΗ -17/3-(20-C = O-2 1 - O H ) -1 7 - C = 0

1

Δ

Δ 1

Δ1; 21-OAc-* 21-OH

Δ ;21-OAc-> 21-OH

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

Δ1; 21 -OAc-» 21-OH

R E F .

R-780

S-923; S-927

S-901; W-1072

S-901

S-901

B-43

H-401

M-530; M-531; M-532; S-924; S-926

S-925; S-926

S-923

L-512; S-833

S-833

ß - 4 4

B-44

B-43

S-926

616

TABLE I I I

T ransformat ions by Genus: SEPTOMYXA

SPECIES

affinis

SOURCE

ATCC-6737

SUBSTRATE

9a-chloro-6a-f luoro-17a-hydroxy-2 a - m e t h y I - 4 - p r e g n e n e - 3 , l l , 20- t r ione (+A)

9a - chlor o - 6/3 -fluor o -17a, 21 -di -hyd roxy-4 -p regnene -3 ,11 , 20- t r ione 21-aceta te

6a- f luoro-17a ,21-d ihydroxy-2a-m e t h y l - 4 - p r e g n e n e - 3 , 1 1 , 2 0 -tr ione (+A)

6/3-fluoro-17a, 21 -dihydroxy-2a-m e t h y l - 4 - p r e g n e n e - 3 , 1 1 , 2 0 -t r ione (+A)

9a - f luoro -15a ,17a ,21- t r ihydroxy-4 -pr egnene - 3 , 1 1 , 2 0 - t r i o n e ( + A )

9a-f luoro-15/3 ,17a,21- t r ihydroxy-4 -pr egnene - 3 , 1 1 , 2 0 - t r ione (+A)

6a, 9a -dif luor o -17a -hydr oxy - 2a -methyl -4-pr e g n e n e - 3 , 1 1 , 2 0 -t r ione (+A)

6/3,9a-dif luoro-17a,21-dihydroxy-4 -p regnene -3 ,11 ,20 - t r i one 21 -aceta te

6α, 21 -d i f luoro-17a-hydroxy-2a-m e t h y l - 4 - p r e g n e n e - 3 , 1 1 , 2 0 -t r ione (+A)

15/3,17a, 21-trihydroxy-15a-meth5fl -4 -pr egnene - 3 , 1 1 , 2 0 - t r ione (+A)

9a -b romo-6a ,21-d i f luoro -17a-hydroxy-2a -me thy l -4 -p reg -nene -3 ,11 ,20 - t r i one (+A)

9a -ch lo ro -6a , 21 -dif luoro-17a-hydroxy-2a-methy l -4 -pr eg-nene -3 ,11 ,20 - t r i one (+A)

9a-f luoro-15/3 ,17a,21- t r ihydroxy-1 5 a - m e t h y l - 4 - p r e g n e n e - 3 , 1 1 , 20- t r ione (+A)

6a ,9a ,21- t r i f luo ro -17a-hydroxy-2a -methy l -4 -p r egnene-3 ,11 ,20-t r ione

20-methoxy-4,17(20)-pregnadien-3-one

REACTION

1

Δ

Δ 1 ; 2 1 - O A c -21-OH

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

Δ ; 2 1 - O A c - * 21-OH

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

1

Δ

R E F .

B-43

S-926

B-43

B-43

ß-44

B-44

B-43

S-926

B-43

B-44

B-43

B-43

B-44

B-43

E-251

TABLE I I I

Transformat ions by Genus: SEPTOMYXA

617

SPECIES

affinis

SOURCE

ATCC-6737

ATCC-13425

SUBSTRATE

11/3,21-dihydroxy-4,17(20)-pr e gnadie n - 3 - one

(use of inc rementa l addition for de hydrogénation a t con-cent ra t ions exceeding solubi l -ity of subs t ra te - Ref. C-130, react ion kinet ics and use of washed cel ls - Ref. C-132 , continuous t ransformat ion -Ref. R-766 (+A) -Ref . M-647)

6a - fluor o-11/3,21-dihydroxy -4 , 17(20) -pregnadien-3 -one 21-aceta te (+A)

11/3,21 -d ihydroxy-2a-methy l -4 , 17(20)-pregnadien-3-one

11/3,21 -d ihydroxy-6a-methy l -4 , 17(20) -pregnadien-3-one

11/3,16a, 21 - t r ihydroxy-4 ,17(20) -cis -pregnadien-3-one 2 1 -aceta te

11/3,21 -dihydroxy-6a, 16a -d i -methyl -4 ,17(20)-pregnadien-3-one (+A)

l l /3 ,21-dihydroxy-6a,16/3-di-methyl-4,17(20) -pregnadien-3-one (+A)

6 ,17a -d ime thy l -4 ,6 -p regnad iene -3,20-dione (with conidia)

l l / 3 , 17a ,21 - t r i hyd roxy -6 -methy l -4 ,6 -pr egnadiene - 3 , 20-dione (+A)

17a, 21 -d ihydroxy-6 -me thy l -4 ,6 -p r e g n a d i e n e - 3 , l l , 2 0 - t r i o n e (+A)

1 l a - h y d r o x y - 4 - p r e g n e n e - 3 , 2 0 -dione (demonstrat ion of indueible enzyme- Ref. K-456)

11/3,17a, 21 - t r ihydroxy-4 - p r e g -nene-3 ,20-d ione (see note above)

l l j ß ,17a ,21 - t r ihydroxy-6a -methy l -4 -p regnene-3 ,20-d ione (see note above)

REACTION

1

Δ

Δ ; 2 1 - O A c - » 21-OH

1

Δ

1

Δ

Δ 1

Δ1

1

Δ

Δ 1

1

Δ

Δ 1

1

Δ

1

Δ

Δ 1

REF.

C-130; C-132; M-647; R-766; S-922; W-1072

L-517

H-394; M-573; S-927

M-573; S-928

M-529

L-517

L-517

S-901

H-395

H-395

K-456

K-456

K-456

618

TABLE I I I


SPECIES

affinis

corni

SOURCE

ATCC-13425

AY

ATCC-13416 CBS

SUBSTRATE

17a ,21-d ihydroxy-4-pregnene-3 ,11 ,20 - t r ione (see note above)

11)3,21 -dihydroxy-4,17(20) -p reg -nadien-3-one (see note above)

17ß-hydroxy-4-andros tene -3 ,17-dione (with conidia)

4 -pregnene-3 ,20-d ione (with conidia)

17a, 21 -dihydroxy -4 -pr egnene - 3 , 20-dione (with conidia)





11/3,17/3 -dihydroxy -17a -methyl -4 -andros ten-3-one


5a -pre gnane -3 ,11 ,20 - t r ione

4 -pregnene-3 ,20-d ione • (use of washed mycel ium and

var ious addit ives changes p r o -port ion of products)

REACTION

Δ1

Δ 1

Δ 1 · 17j3-OH-+ 1 7 - C = 0

X

Δ

1

Δ

1

Δ

Δ1; enol.

Δ ; enol. ; 17/3-OH^ 1 7 - C = 0

1

Δ

Δ1; 17/3-OH^ 1 7 - C = 0

Δ1

1

Δ

Δ 1

Δ1; 1 7 - C = 0 -17a-oxa-17-C

=o Δ1; 17 -C=0-> 17/3-ΟΗ

Δ1; 17/3-Ac-» 1 7 - C = 0

Δ1

Δ1; 17/3-Ac — 17/3-OH

Δ1; 17/3-Ac^ 1 7 - C = 0

R E F .

K-456

K-45 6

S-835

S-835; V-1048

S-835; V-1048

S-835

W-1072

W-1072

W-1072

W-1072

W-1072

E-206

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

TABLE I I I

619


SPECIES

corni

SOURCE

ATCC-13416 CBS

SUBSTRATE

4-pregnene-3 ,20-d ione (use of washed mycel ium and var ious addit ives changes p r o -port ion of products)


l l / 3 -hydroxy-4 -p regnene -3 ,20 -dione



17a ,21-d ihydroxy-4-p regnene-3 , 20-dione


11/3,17a, 21 - t r ihydroxy-6a-methy l -4 -p regnene-3 ,20-d ione

4 - p r e g n e n e - 3 , 1 1 , 20-tr ione

REACTION

Δ1; 17/3-Ac-> 17a-oxa-17-C =o

Δ1

Δ1; 17 /3-Ac^ 17/3-OH

Δ1; 17/3-Ac — 1 7 - C = 0

Δ1· 17ß-Ac-> 17/3-OH

Δ1; 17/3-Ac-+ 1 7 - C = 0

Δ1

Δ1; 17α-OH-17/3-Ac^ 17/3-OH

1

Δ

Δ1; 17j3-(20-C = 0-21-OH) -17/3-OH

Δ1; 17/3-(20-C = 0-21-OH) -» 1 7 - C = 0

Δ1; 17ß-(20-C = 0-21-OH) -» 17a-oxa-17-C =o

1

Δ

1

Δ

1

Δ

Δ1

Δ1; 17/3-Ac ^ 1 7 - C = 0

Δ1; 17/3-Ac^ 17/3-OH

R E F .

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

TABLE I I I

Transformat ions by Genus.· SEPTOMYXA

SPECIES

corni

sal ic ina

SOURCE

ATCC-13416 CBS

U

SUBSTRATE

17a, 21 -d ihydroxy-4-pregnene-3 ,11 ,20 - t r ione

l l ß , 21-dihydroxy-4,17(20)-pregnadien-3 -one



17ß-hydroxy-17a-methyl -4-andros ten-3-one

1 I ß , 17ß-dihydroxy- 17α -methyl -4 -andros ten-3-one


5a -pregnane - 3 , 1 1 , 2 0 - t r ione

4 -pregnene-3 ,20-d ione (use of washed mycel ium and var ious addit ives changes proport ion of products)



REACTION

Δ 1

Δ 1

Δ ; enol.

Δ ; enol. ; 17ß-OH — 1 7 - C = 0

Δ 1

Δ1; 1 7 β - Ο Η -1 7 - C = 0

1

Δ

Δ1

Δ 1

Δ1; 1 7 - C = 0 -17a-oxa-17-C

=o Δ1; 17-C = 0 -> 17ß-OH

Δ1; 17ß-Ac-* 1 7 - C = 0

Δ1

Δ1; 1 7 ß - A c -17ß-OH

Δ1; 1 7 ß - A c -1 7 - C = 0

Δ1; 17ß-Ac — 17a-oxa-17-C

=o Δ1

Δ1; 1 7 ß - A c -17ß-OH

Δ1; 17ß-Ac-> 1 7 - C = 0

Δ1; 1 7 ß - A c ^ 17ß-OH

R E F .

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

E-206

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

620

SPECIES

sal icina

1 tulasnei

SOURCE

U

SUBSTRATE

l l / 3 -hydroxy-4 -p regnene -3 ,20 -dione

17«-hydroxy-4-p regnene-3 ,20-dione



l l j 3 ,17o ,21 - t r i hyd roxy-4 -p reg -nene-3 ,20-d ione

l l j 3 ,17a ,21- t r ihydroxy-6a -methy 1-4-pr egnene - 3 ,20-dione

4 - p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e

17«, 21-d ihydroxy-4-pregnene-3 ,11 ,20 - t r i one

l l /3 ,21-d ihydroxy-4 ,17(20) -preg-nadien-3-one

17/3-hydroxy-4-es t ren-3-one


REACTION

Δ1; 1 7 / 3 - A c -1 7 - C = 0

Δ1

Δ1; 17a-OH-17/3-Ac-* 17/3-OH

Δ1

Δ1; 17/3-(20-C= 0-21-OH)-> 17/3-OH

Δ1; 17/3-(20-C = 0 -21-OH)-> 1 7 - C = 0

Δ1; 17/3-(20-C = 0 -21-OH)-+ 17a-oxa-17-C =o

Δ1

1

Δ

1

Δ

1

Δ

Δ1; 17 j3 -Ac-1 7 - C = 0

Δ1; 1 7 / 3 - A c -17/3-OH

Δ1

1

Δ

Δ1; enol.

Δ1; enol. ; 17/3-OH-* 1 7 - C = 0

Δ 1

Δ1; 17/3-OH — 1 7 - C = 0

R E F .

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072


TABLE I I I

SEPTOMYXA

621

TABLE I I I


SPECIES

tulasnei

SOURCE

U

SUBSTRATE

1 7/3 - hydr oxy -17a - methyl - 4 -andros ten-3-one

11/3,17j3-dihydroxy-17a-methyl-4 -andros ten-3-one


5 a - p r e g n a n e - 3 , l l , 2 0 - t r i o n e

4 -pregnene-3 ,20-d ione (use of washed mycel ium and var ious addit ives changes propor t ion of products)


1 Iß -hyd roxy-4 -p regnene -3 ,20 -dione



REACTION

Δ1

1

Δ

Δ 1

Δ1; 1 7 - C = 0 -17a-oxa-17-C = 0 î

Δ1; 1 7 - C = 0 -17/3-OH

Δ1; 1 7 / 3 - A c -1 7 - C = 0

Δ 1

Δ1; 1 7 / 3 - A c -17/3-OH

Δ1; 1 7 / 3 - A c -1 7 - C = 0

Δ1; 1 7 / 3 - A c -17a-oxa-17-C =o

Δ 1

Δ1; 1 7 / 3 - A c -17/3-OH

Δ1; 1 7 / 3 - A c -1 7 - C = 0

Δ1; 17jS-Ac-> 17/3-OH

Δ1; 17/3-Ac — 1 7 - C = 0

Δ 1

Δ1; 17a-OH-17/3-Ac-> 17/3-OH

1

Δ

Δ1; 17/3-(20-C= 0-21-OH) — 17/3-OH

R E F .

W-1072

E-206

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

622

623

TABLE I I I

TAXONOMY

T r a n s f o r m a t i o n s by Genus: SEPTOMYXA SERRATIA (Schizo. - Eubacteriales)

SPECIES

tulasnei

SERRATIA

m a r c e s c e n s

SOURCE

U

ATCC-13477

IAM (1-2;

1-3; 1-7; 1-9; 1-10)

(2-1 2-2)

(2-3)

(2-5; 2-7)

(2-10)

IFO(3046)

SUBSTRATE



l l j 3 , 17a ,21 - t r i hyd roxy -4 -p reg -nene-3 ,20-d ione

11/3 ,17a,21- t r ihydroxy-6a-methyl-4 -pr egnene -3,20-dion€

4 -pr egnene - 3 , 1 1 , 2 0 - t r i o n e

17ö, 21 -dihydroxy -4 -pr egnene -3 ,11 ,20 - t r ione

l l j3 ,21-d ihydroxy-4 ,17(20)-preg-nadien-3-one



REACTION

Δ1; 17/3-(20-C =0-21-OH) -1 7 - C = 0

Δ1; 17j3-(20-C = 0-21-OH) -17a-oxa-17-C =o

Δ 1

1

Δ

1

Δ

1

Δ

Δ1; 17/3-Ac^ 1 7 - C = 0

Δ1; 17/3-Ac^ 17/3-OH

1

Δ

1

Δ

Δ 1

Δ1

Δ 1

Δ 1

Δ 1

Δ1

2j3-OH

—

2/3-OH

Δ1

Δ1; l l a - O H

R E F .

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

W-1072

T-960

S-849

S-849

S-849

S-849

S-849

S-849

S-849

624


T r a n s f o r m a t i o n s by Genus.· SERRATIA

SHIYUDAKE SORDARIA

SPHACELOMA SPICARIA

(Taxonomy Unclear) (Asco. - Sphaeriales) (Imperf. - Melanconiales) (Imperf. - Moniliales)

SPECIES

marcescens


plymuthica

SHIYUDAKE

spec ies

SORDARIA

spec ies

SPHACELOMA

species

SPICARIA

s impl ic i s s ima

species

violacea

SOURCE

IFO (3046)

IFO (3048)

NG

ATCC-13478

S

NRRL

TNAES

ATCC-13595

LED(Z-118)

NRRL

NRRL

SUBSTRATE




24 /3-methyl -5 ,7 ,22-choles ta t r ien-3/3-ol (sole carbon source)



plant saponins




plant saponins

Sarsasapogenin

REACTION

-

-

-

-

—

1

Δ

11a-OH

-

-

15/3-OH

15/3-OH

-

R E F .

1-428

1-428

S-849

S-793c; T-1030

S-793c

T-960

S-849

K-478

S-849

A-9 ; B-58

B-56

K-478

M-587


Transformat ions by Genus: SPICARIA SPONDYLOCLADIUM (Imperf. - Moniliales)

625

SPECIES

violacea

v i r idans

SPONDY LOC L ADIUM

aus t ra l e

1 xylogenum

SOURCE

NRRL

FRI

ATCC-12728

ATCC-12727

SUBSTRATE

Diosgenin


17α, 21 -dihydr oxy -4 -pregnene -3 ,20-dione









6a- f luoro-17a ,21-d ihydroxy-16-methylene -4 -pregnene - 3 , 2 0 -dione 21-propionate

1,4 -pregnadiene -3 ,20-d ione

17a, 21 -d ihydroxy-1 ,4 -p regnad i -ene-3 ,20-d ione


4-andros , tene-3 ; 17-dione







1,4 -pregnadiene -3 ,20-d ione

17a, 21-dihydroxy - 1 , 4 - p r e g n a -d iene-3 ,20-d ione

REACTION

11a-OH; 11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH; 2 1 - P r ^ 2 1 - O H

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

11/3-OH

R E F .

M-587

M-587

S-849

S-790

S-790

S-790

S-790

S-790

S-790

H-391; S-790

H-391; S-790

A-7

S-790

S-790

S-790

S-790

S-790

S-790

S-790

S-790

S-790

S-790

S-790

S-790

626


TABLE I I I

SPOROBOLOMYCES SPORORMIA

SPOROTRICHUM

TAXONOMY

(Imperf. - Moniliales) (Asco. - Sphaeriales) (Imperf. - Moniliales)

SPECIES

roseum

SPORORMIA

fasciculata

leporina

minima

montana

pol lacci i

SPOROTRICHUM

as té ro ïdes

bombycinum

epigaeum

SOURCE

FRI

PH

PH

NRRL-2475

PH

PH

FRI

ATCC-7139

ATCC-7145

SUBSTRATE


retro_-4-pr egnene -3 ,20 -dione

r e t r o - 4 -pr egnene - 3 ,20 -dione


l l /3 -hydroxy-4-p regnene-3 ,20-dione







5/3-pregnane -3 ,20-dione (reaction depends on a i r r a t e -low -hvdr oxylation only-high -hydroxylation + side chain cleavage - R e t M-582) a i r r a t e not c r i t i ca l if subs t ra te has no side chain a t C-17)

4 -pregnene-3 ,20-d ione (see note this ref. )

4 -p regnene-3 ,20-d ione 20-cyclo-ethyleneketal


REACTION

17/3-Ac-» 17/3-OH

17/3-Ac-» 17/3-OH

17a-OH

17a-OH

17a-OH

17a-OH

17/3 -Ac — 17/3-OH

17/3-Ac-» 17/3-OH

11a-OH

11a-OH

11a-OH; or 11a-OH; 17/3-Ac-» 17/3-OH

11a-OH; or 11a-OH; 17/3-Ac-+ 17/3-OH

11a-OH

17/3-Ac — 17/3-OH

R E F .

S-849

P-734

P-734

D-182a

D-182a

D-182a

D-182a

P-734

P-734

S-849

M-582

M-582

M-582

M-582

F-251

M-582

TABLE I I I

T ransformat ions by Genus·. SPOROTRICHUM

627

SPECIES

epigaeum

1 gougeroti

sulfur es cens

1 va r . beyman

SOURCE

ATCC-7145

IFO (5982)

ATCC-7159

CBS

U

SUBSTRATE

17a-hydroxy-4 -p regnene-3 ,20-


l i a , 21-dihydroxy-4-pregnene -3,20-dione

17a,21 -dihydroxy-4-pregnene -3,20-dione

21-hydroxy-1 ,4 -p regnad iene -3,20-dione (low a i r ra te )

(high a i r ra te )


17a, 21 -d ihydroxy-1 ,4 -p regna-d iene-3 ,20-d ione

5/3 -andr ostane -3 ,17 -dione

17/3-hydr oxy-17a-methy l -4 -andros ten-3-one

17/3 -hydr oxy-1 ,4 -andr ostadien -3-one

17α, 21 -d ihydroxy-4-pregnene-3,20-dione (low a i r ra te )

(high a i r ra te)

3 -keto -bisnor-4 -cholenic acid

22 -hydroxy-bisnor-4 -cholen-3 -one


17/3-hydr oxy-17a-me thy 1-1,4-andr os tadien-3 -one



REACTION

17a-OH-17/3-Ac-> 17/3-OH

17/3-(20-C = O-2 1 - O H ) -17/3-OH

17/3-(20-C=O-2 1 - O H ) -17/3-OH

17a-OH-17j3-(20-C=O-21-OH) - 17/3-OH

l i a - O H

l i a - O H ; 17β-(20 -C=O-21-OH) -> 17/3-OH

2 0 - C = O -20/3-OH

2 0 - C = O -20/3-OH

l i a - O H

l l a - O H

l l a - O H

l l a - O H

l l a - O H ; 17a-OH-17/3-(20-C=O - 2 1 -O H ) - 17β-ΟΗ

l l a - O H

l l a - O H

l l a - O H

l l a - O H

l l a - O H

l l a - O H ; 17/3-Ac—17/3-OH

R E F .

M-582

M-582

M-582

M-582

M-582

M-582

T-958

T-958

M-582

M-582

„M-582

M-582

M-582

M-582

M-582

M-582

E-205; M-582

M-582

S-831

628



SPQROTRICHUM STACHYBOTRYS (Imperf. - Moniliales)

STACHYLIDIUM (Imperf. - Moniliales)

SPECIES

sulfur escens in sequential f e rmen-tation with Pén ic i l -l ium sp. (initial sub-s t r a t e 4 -p regnene-3,20-dione)

STACHYBOTRYS

spec ies

STACHYLIDIUM 1 (possible synonym -

Vert ici l l ium) bicolor

(in mixed cul ture with Bacil lus sphaer icus A T C C - 7 0 5 5 O 1 ] )

1 theobromae

SOURCE

U

NRRL

NG (Sandoz)

ATCC-12672

FRI

IFO (6647)

S

ATCC-12474

SUBSTRATE


plant saponins

3/3,6/3,8/3,14/3-tetrahydroxy-4, 20,22-bufatr ienolide 6 - ace -ta te 3-glucoside





l l j3 ,21-d ihydroxy-4-pregnene-3,20-dione





17a, 21-dihydroxy-4-pregnene -3,20-dione 21-aceta te

REACTION

11a-OH

3ß [ l ^ - g l u c o -side]-> 3/3-OH

11/3-OH

l l a - O H ; 11/3-OH

l l a - O H ; 11/3-OH

l l a - O H ; 11/3-OH

11/3-OH

14a-OH

11/3-OH

11/3-OH

11/3-OH

l l a - O H ; 11/3-OH

11/3-OH; 2 1 - O A c ^ 21-OH

R E F .

S-831

K-478

S-936a

D-146

S-849

K-468; K-468

K-468

S-843; S-849

S-843; S-849

S-843; S-849

S-841; S-843; S-849; S-851

S-843; S-849

D-146

D-146

D-146

629


T r a n s f o r m a t i o n s by Genus: STACHYLIDIUM STAGONOSPORA STAPHYLOCOCCUS STAUROPHOMA

(Imperf. - Sphaeropsidales) (Schizo. - Eubacteriales) (Imperf. - Sphaeropsidales)

SPECIES

theobromae

STAGONOSPORA

cur t i s i i

STAPHYLOCOCCUS

albus

aureus (Pyogenes aureus)

STAUROPHOMA

species

SOURCE

AY

CBS

PH

NG (rat cecum)

LAM (FAD-209p)

NG (ra t cecum)

NG

ATCC-14288

SUBSTRATE

4-pregnene-3 ,20-d ione (use of conidia)

1 Ία, 21 -dihydr oxy -4 -pregnene -3,20-dione (use of conidia)

17a, 21 -dihydr oxy -4 -pregnene -3,20-dione (use of conidia)

r e t r o -17j3-hydroxy - 4-andr os ten-3-one


retro_-4,6 -pregnadiene- 3 ,20 -dione

3a, 7a, 12a- t r ihydroxy-5ß-cholanic acid


3a, 7a, 12a- t r ihy dr oxy - 5/3-cholanic acid


24ß -me thy l -5 ,7 ,22 -cho l e s t a -trien-3/3-ol




REACTION

11a-OH; 14a-OH

14a-OH

l l ß - O H

l i a - O H ; l l ß - O H

16a-OH

16a-OH

16a-OH

-

l l ß - O H

-

-

-

16a-OH

16a-OH

16a-OH

R E F .

S-835; V-1048

S-835; V-1048

S-835

D-146

P-736

P-736

P-736

N-675

S-849

N-675

S-793c; T-1030

S-793c

H-397

H-397

H-397

630


T r a n s f o r m a t i o n s by G e n u s : STEMPHYLIUM STEREUM

STERIGMATOCYSTIS

(Imperf. - Moniliales) (Basidio. - Agaricales) (Imperf. - Moniliales)

SPECIES

STEMPHYLIUM

botryosum

species

STEREUM

fasciatum

induratum

STERIGMATOCYSTIS

japonica

STIGMINA

platani (in mixed culture with Hendersonia rubra [21-OH] or Tricho-derma nigrovirens [17a-OH])

STREPTOCOCCUS

pyogenes

SOURCE

FRI

Takeda

NG (Sandoz)

NRRL

IFO (9994)

IAM

FRI

MCC

NG

STIGMINA (Imperf - Moniliales) STREPTOCOCCUS (Schizo. - Eubacteriales)

SUBSTRATE




3/3,6j3,8/3, 14/3-tetrahydroxy-4,20(22) -bufatrienolide 6-acetate 3-glucoside

plant saponins

17/3 -hydroxy- 17a -methyl -4 -androsten-3-one





5-choIesten-3/3-oI (sole carbon source)

REACTION

-

14a-OH

14a-OH

3/3-[lVgluco-s i d e ] ^ 3/3-OH

-

1

Δ

1

Δ

Δ1; 2 0 - C = O -20/3-OH

—

-

11/3-OH

REF.

S-849

N-661

N-661

S-936a

K-478

T-959

T-959

T-959

S-849

S-849

M-566

T-1030

631


T r a n s f o r m a t i o n s by G e n u s : STREPTOMYCES (Scnizo. - Actinomycetaies)

SPECIES

STREPTOMYCES (occasionally

Actinomyces)

albidoflavus

albidus * (Actinomyces)

a lbosporeus

1 albus

(Rossi-Dor ia)

1 (Actinomyces)

SOURCE

Shionogi

CZAS

ATCC-3003

ATCC-3004, 3351

C

CZAS

NG

NRRL

Shionogi

SSSR (3006)

SUBSTRATE


11β, 17α, 21 - t r ihydroxy -4 - p r e g -nene -3 ,20 -dione





11/3,17a, 21 - t r ihydroxy -4 - p r e g -nene -3 ,20-d ione

d , l - l , 3 , 5 ( 1 0 ) - e s t r a t r i e n e - 3 , 17/3-diol


l , 3 ,5 (10) -es t r a t r i ene -3 ,17 i3 -d io l

Sarsasapogenin

Diosgenin



l l j 3 , 17a ,21 - t r i hyd roxy -4 -p reg -nenex3,20-dione


11/3,17a, 21 - t r i hyd roxy -4 -p reg -nene-3 ,20-d ione


l l / 3 , 1 7 a , 2 1 - t r i h y d r o x y - l , 4 -p r egnadiene -3 ,20 -dione

REACTION

20-C=O-> 20/3-OH

2 0 - C = O -20/3-OH

16α-ΟΗ

20-C=O » 20/3-OH

2 0 - C = O -20/3-OH

2 0 - C = O ^ 20/3-OH

2 0 - C = O ^ 20/3-OH

d,l-17/3-OH-> d - 1 7 - C = 0 + 1-17/3-OH

use of osc i l lo -polarographic detection of t r ansf or mations of s t e ro ids

17/3-OH -1 7 - C = 0

-

-

-

20-C=O-> 20/3-OH

2 0 - C = O -20/3-OH

2 0 - C = O -20/3-OH

2 0 - C = O -20/3-OH

2 0 - C = O -20/3-OH

2 0 - C = O -20/3-OH

R E F .

K-470

K-470

V-1060

K-470

K-470

K-470

K-470

W-1102

S-929

W-1082

M-587

M-587

M-587

K-470

K-470

K-458

K-459

K-459

K-459

632

TABLE I I I

Transformat ions by Genus: STREPTOMYCES

SPECIES

albus

annulatus * (Actinomyces)

antibioticus

argenteolus (species ATCC-11009 Ref. F -265 , H-380, P - 7 1 6 , P - 7 1 9 - ident-ified a s argenteolus in Ref. F-267)

*

SOURCE

SSSR

CZAS

ATCC-8663

ATCC-11891

NG

ATCC-11009 SQ (MD-248)

SUBSTRATE

1 7 a , 2 1 - d i h y d r o x y - l , 4 - p r e g n a -d i e n e - 3 , l l , 2 0 - t r i o n e


17a, 21 -dihydroxy-4 -pregnene -3 ,11 ,20 - t r ione




11/3, 1 7 Q , 21 - t r ihydroxy-4 -p reg -nene-3 ,20-d ione


11/3,16α, 17α, 21- te t rahydroxy-4-pregnene-3 ,20-d ione


9a- f luoro- l l /3 ,17a ,21- t r ihydroxy-6a - methy l -1 ,4 -pregnadiene -3,20-dione

5-cholesten-3/3-ol

24/3-methyl-5 ,7 ,22-choles ta t r ien-3j3-ol



REACTION

2 0 - C = O -20/3-OH

16a-OH

1

Δ

l | - O H

1ξ-OH

1ξ-ΟΗ

1ξ-ΟΗ

Ιξ-ΟΗ

1ξ-ΟΗ

1ξ-ΟΗ

Ιξ-ΟΗ

-

-

16α-ΟΗ

Δ ^ Δ * ; 3/3-ΟΗ - 3 - C = 0

Δ ^ Δ ; 3/3-ΟΗ ^ 3 - C = 0 ; 16α-ΟΗ

R E F .

Κ-459

V-1060

C-125

F-234

F-234

F-234

F-234

F-234

F-234

F-234

F-234

S-793C

S-793C

F-265 ; F-267

F-267; P-710; P -712 ; P-716

F-265; F-267; P -712 ; P-716

TABLE I I I

T ransformat ions by Genus: STREPTOMYCES

633

SPECIES

argenteolus

aureofaciens

SOURCE

ATCC-11009 (SQ-MD-248)

ATCC-10762

SUBSTRATE

4-pregnene-3 ,20-d ione (effect of ant ibiot ics - Ref. P-719 - adaptive enzyme inhibitors - Ref. P-711)


21-hydroxy-4-p regnene-3 , 20-dione ace ta te

17a, 21 -dihydroxy -4 -pregnene -3,20-dione 21-ace ta te

12a- f luoro- l l j3 ,17a ,21- t r ihydroxy -4 -pregnene-3 ,20-d ione

9a - f luo ro - l l /3 ,17a ,21- t r ihydroxy-2f -methy l -4 -pregnene - 3 , 2 0 -dione

12a- f luoro- l l /3 ,17a ,21- t r ihydroxy -1 ,4 -pregnadiene- 3 ,20-dione

9a - f luoro - l l j3 ,17a ,21- t r ihydroxy-2 - methyl -1 ,4 -pregnadiene -3,20-dione




9a -f luoro -1 I ß , 17a, 21 - t r ihydroxy -4 -p regnene-3 ,20-d ione

9 a - f l u o r o - l l / 3 , 1 6 a , 1 7 a , 2 1 - t e t r a -hydroxy-4-pregnene-3 ,20-d ione

9a- f luoro- l l /3 ,16a , H a ^ l - t e t r a -h y d r o x y - l ^ - p r e g n a d i e n e - S ^ O -dione

REACTION

16a-OH

2/3,16a-diOH

Δ -*5/3-H; 16a-OH

16a-OH

16a-OH; 21-OAc - 2 1 - O H

16a-OH; 21-OAc - 2 1 - O H ; Δ 4 -5/3-H

2/3-OH; 21-OAc - 2 1 - O H

16a-OH

16a-OH

16a-OH

16a-OH

I f -OH

1ξ-ΟΗ

1ξ-ΟΗ

1ξ-ΟΗ

1ξ-ΟΗ

1ξ-ΟΗ

REF.

F-265; F-267; P - 7 1 1 ; P -716 ; P - 7 1 8 ; P-719

F-267; P -716 ; P-718

F-267; P -716 ; P-718

F-288

F-265; F-267; P-716

F-267

F-265; F-267; P-716

H-380

H-380

H-380

H-380

F-234

F-234

F-234

F-234

F-234

F-234

634

TABLE I I I


SPECIES

aureofaciens

*

bikiniensis

bobilae

SOURCE

ATCC-10762

NRRL-2209

SQ

ATCC-3309

>

NG

SSSR (11062)

(E-55-LL) Shionogi

SUBSTRATE

3)3,14/3-dihydroxy-5j3-20(22)-cardenolide







11/3, 17a, 21 - t r ihydroxy -4 -p r eg -nene-3 ,20-d ione

9 a - f l u o r o - l l ß , 17α, 21- t r ihydroxy-4-p regnene-3 ,20-d ione




l , 3 , 5 ( 1 0 ) - e s t r a t r i e n e - 3 , 1 7 a - d i o l

1 ,3 ,5(10)-es t ra t r iene-3 ,17/3-dio l


17α, 21 -d ihydroxy-4-pregnene-3,20-dione


REACTION

7/3-OH

Δ 5 - Δ 4 ; 3j3-OH - ' 3 - C = 0

6/3-OH

9a-OH

6/3,9a-diOH

9a-OH

Δ -»Δ*; 3/3-OH ->3-C=0

1ξ-ΟΗ

16a-OH

16a-OH

16a-OH

Δ 4 ^ 5 α - Η ; 3 -C=0-3 /3 -OH

1ξ-ΟΗ; 16a-OH

16a-OH

16a-OH

16a-OH

15a-OH

16a-OH

16a-OH

16a-OH

2 0 - C = O -20/3-OH

20-C=O — 20/3-OH

REF.

T-1013

P-712

F-288; P-713

F-288; P-713

P-714

P-715

P-710

F-234

P-745

P-745

P-745

K-471

F-234; P-745

P-745

P-745

V-1060

F-285; F-287

S-935

S-935

S-935

K-458

K-470

aureus 4-pregnene-3,20-dione

C Z A S

WC( 3569, 3676)

TABLE I I I

T ransformat ions by Genus.· STREPTOMYCES

635

SPECIES

bobilae

cal ifornicus

*

celluloflavus

SOURCE

(E-55-LL) Shionogi

Shionogi (5119)

\VC (3312)

AMCY

SUBSTRATE


1 7a, 21 -dihydroxy -4 -pr egnene -3 ,20-dione



3o, 7a, 12a-tr ihydroxy-5/3-cholanic acid (sole carbon source)

3a, 7a, 12a-tr ihydroxy-5/3-cholanic acid conjugated with glycine-glycocholic acid (sole carbon source)

3α, 7α, 12a-tr ihydroxy-5/3-cholanic acid conjugated with t aur ine- taurochol ic acid (sole carbon source)

3 ,7 ,12- t r iketo-5/3-cholanic acid (sole carbon source)





17a, 21-dihydroxy-4-pr egnene-3,20-dione 21-ace ta te

9a- f luoro- l l j3 ,17a , 21 - t r ihydroxy-4-pregnene-3 ,20-d ione

l l / 3 , 1 7 a , 2 1 - t r i h y d r o x y - l , 4 -pregnad iene-3 ,20-d ione

9a - f luo ro - l l / 3 ,17a ,21 - t r ihydroxy-1,4 -pregnadiene-3 ,20-d ione

4 -pregnene -3 ,20-d ione


11/3,17a, 21 - t r i h y d r o x y - 4 - p r e g -nene-3 ,20-d ione

REACTION

20-C=O-> 20/3-OH

20-C=O-> 20/3-OH

2 0 - C = O ^ 20/3-OH

uti l ization

util ization

util ization

util ization

uti l ization

16a-OH

16a-OH

16a-OH

16a-OH; 21-OAc - 2 1 - O H

16a-OH; 21-OAc - 2 1 - O H

16a-OH

16a-OH

16a-OH

l | - O H

1ξ-ΟΗ

l | - O H

R E F .

K-470

K-470

K-470

S-785

H-357; S-784; S-785

S-785

S-785

S-785

L-491

L-491

L-491

L-491

L-491

L-491

L-491

L-491

F-234

F-234

F-234

636

TABLE I I I


SPECIES

celluloflavus

c h a r t r e u s i s

chrysomal lus *

coelicolor

*

dias ta t icus (Krainsky)

1 * I d ias ta tochromogenes

1 endus

1 e ry th reus

exfoliatus

SOURCE

AMCY

Shionogi

CZAS

C

CZAS

WC (3593)

ATCC-3315

AY

CZAS

CZAS

U (9-20)

P F

CZAS

SUBSTRATE

11/3,16α, 17α,21- te t rahydroxy-4-pregnene-3 ,20-d ione

9 a - f l u o r o - l l / 3 , 1 6 a , 1 7 a , 2 1 -t e t r ahydroxy-4 -p regnene -3,20-dione

11/3, 17α, 21- t r ihydroxy-6α-methyl - l , 4 - p r e g n a d i e n e - 3 , 2 0 - d i o n e

17α, 21 -dihydroxy -4 -pr egnene -3 ,20-dione



d , l -17a , 21-d ihydroxy-4-preg-




21-hydroxy-4 -p regnene-3 ,20-dione ace ta te

17α, 21 -d ihydroxy-4-pregnene-3,20-dione


1 ,3 ,5 (10) -es t ra t r i ene-3 ,17 /3-diol (using spores)




11/3,17a-dihydroxy-21-methyl-l , 4 - p r e g n a d i e n e - 3 , 2 0 , 2 1 -t r ione


REACTION

I4-OH

l | - O H

l | - O H

20-C=O -20/3-OH

2 0 - C = O -20/3-OH

16a-OH

d , l - 2 0 - C = O -d-20/3-OH + 1

2 0 - C = O -20/3-OH

2 0 - C = O -20/3-OH

16a-OH

16a-OH; 21-OAc - 2 1 - O H

2 0 - C = O -20/3-OH

2 0 - C = O -20/3-OH

17/3-OH -» 1 7 - C = 0

16a-OH

6/3-OH; 6/3,11a-diOH

11-oxygénation

2 0 - C = O -20/3-OH

6/3-OH; 6/3,11a-diOH

R E F .

F-234

F-234

F-234

K-470

K-470

V-1060

W-1094

K-470

K-470

L-491

L-491

K-470

K-470

S-835; V-1048

V-1060

S-929

H-328

A-6

S-929

nene-3,20-dione

TABLE I I I

Transformat ions by Genus·. STREPTOMYCES

637

SPECIES

f imicar ius

*

flaveolus *

1 f lavogriseus

1 fradiae

SOURCE

CBS

CZAS

CZAS

Shionogi (D-551)

Shionogi (H-4449)

Tokyo Univ. (4449)

C

CZAS (6 ,9 ; 6 ,10; 6 , 1 1 ; 6 ,15 ; 6 ,16; 6,17)

SUBSTRATE



17of, 21-d ihydroxy-4-pregnene-3,20-dione

11/3,17a, 21- t r i hydroxy-4 -p reg -nene-3 ,20-d ione







11/3,17a, 21-tr ihy d r o x y - 4 - p r e g -nene-3 ,20-d ione


d, l -3 /3-hydroxy-5-pregnen-20-one



11/3-hydroxy· 4 - p r e g n e n e - 3 , 2 0 -dione

REACTION

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH 1

Δ

Δ1; 2 0 - C = O -20/3-OH

1

Δ

Δ1; 2 0 - C = O -20/3-OH

20-C=O > 20/3-OH

2 0 - C = O -20/3-OH

3 a - O H - 3 - C = 0 ; 1 2 a - O H - 12-C = 0 ; Δ4

3 a - O H - 3 - C = 0 ; 12a-OH-+12-C = 0;17/3-CH(CH3) -CH2CH2COOH -17/3-CH(CH3)-COOH

d, l -3/3-OH—d-3-C=0+1-3 /3-OH; ά , 1 - Δ 5 -ά-Δ4+ 1-Δ5

6/3-OH; 6/3,11a-diOH

6/3-OH

6/3-OH

R E F .

P-745

P-745

P-745

P-745

P-745

V-1060

V-1060

K-470

K-470

K-470

K-470

K-470

K-470

H-357

S-784; S-785

W-1102

S-929; V-1061

V-1061

V-1061

TABLE I I I


SPECIES

fradiae

fulvissimus

gelat icus (Actinomyces)

SOURCE

CZAS (6 ,9 ; 6 ,10; 6 , 1 1 ; 6 ,15 ; 6 ,16; 6,17)

SQ

WC (3535)

NRRL B-1453

Okayama Univ. Med. School(1164)

SUBSTRATE

17a-hydroxy-4 -p regnene-3 ,20-dione




4 -p r egnene -3 ,11 ,20 - t r i one








3α, 7α, 12a-tr ihydroxy-5/3-cholanic acid

REACTION

6/3-OH; 6/3,11a-diOH

6/3-OH; 6/3,11α-diOH

6/3-OH; 6/3,11a-diOH

6/3-OH

6/3-OH

6/3-OH

Δ 5 - Δ 4 ; 3/3-OH-* 3 - C = 0

Δ 5 ^ Δ 4 ; 3/3-OH-3 - C = 0

6/3-OH

11/3-OH

11/3-OH

11/3-OH; 1 1 - C = 0 (via 11/3-OH)

l | - O H

17/3-CH(CH3)-CH2CH2COOH-17/3-COOH; 3/3-O H - 3 - C = 0 ; Δ5—Δ4; Χ-ΟΗ

3a-OH-»3-C=0; 12a-OH—12-C = 0 ; A4;17/3-CH (CH3)- CH2 -CH2-COOH—17/3-CH (CH3)-COOH

1 2 a - O H - 1 2 - C = 0;17/3-CH(CH3) -CH2-CH2-COOH -17/3-CH(CH3)-COOH

3a-OH— 3 - C = 0 ; 7 α - Ο Η - Δ β ; 1 2 α -OH - 1 2 - C = 0 ; Δ4

R E F .

V-1061

V-1061

V-1061

V-1061

V-1061

V-1061

P-710

P-712

H-328

C-134

C-112; C-134; C-135; H-328

C-134; C-135; H-328

F-234

H-364

H-354; H-355; H-356; H-360; S-785

H-359

H-359; H-361

638

TABLE I I I


639

SPECIES

gelat icus (Actinomyces)

globisporus

SOURCE

Okayama Univ. Med. School(1164)

Shionogi (1164)

IPB

SUBSTRATE

3a, 7ö, 12o-trihydroxy-5]3-cholanic acid

3α, 7α, 12a-tr ihydroxy-5/3-cholanic acid (sole carbon source)

3 ,7 ,12 - t r ike to -5ß-cho lan ic acid


11/3, 17a, 21 - t r i hyd roxy-4 -p reg -nene-3 ,20-d ione


5-androstene-3j3,17/3-diol

3/3-hydr oxy - 5 -andr osten -17 -one (influence of s t e ro id on microbia l resp i ra t ion)


REACTION

7α-ΟΗ-*Δ6;3α-ΟΗ->3-0=Ο;Δ 4 ; 17ß-CH(CH3)-(CH 2)2-COOH-17/3-CH(CH3)-COOH

3a-OH—3-C = 0

12a-OH-> 1 2 - C = 0

3 a - O H - 3 - C = 0 ; 12a-OH-»12-

c=o 3a-OH—3-C=0; 1 2 Λ - Ο Η - > 1 2 -C = 0 : 7 a - O H - > Δβ; Δ'4

util ization

7-C=0->7a-OH: Δ4

7-C = 0-*7a-OH;

-(CH2)2-COOH-> 17/3-CH(CH3)-COOH

2 0 - C = O -20)3-ΟΗ

2 0 - C = O -20/3-OH

Δ5—Δ ; 3/3-OH— 3 - C = 0

Δ5—Δ4;3β-ΟΗ— 3 - C = 0

Δ5—Δ ;3/3-OH— 3-C=0 ;17ß-OH ->17-C = 0

Δ —Δ ; 3/3-OH - 3 - C = 0

Δ ->Δ ; 3/3-OAc - 3 - C = 0

5 4

Δ —Δ ;3/3-OAc - 3 - C = 0 ; 1 7 -C=0-*17/3-OH

R E F .

H-359

H-366

H-366

H-366

H-366

S-784

H-3 63

H-363

K-470

K-470

H-337

H-337

H-337

C-106; C-107

H-335

H-335

Δ ;17i3-CH(CH3) 4

TABLE I I I

Transformations by Genus: STREPTOMYCES

SPECIES

globosus * (Actinomyces)

g r i seocarneus

gr i seo lus

g r i seus (var. casteneous) (var. cinnibarinus) (var. violaceus) (WC)

SOURCE

CZAA

ATCC-12628

CZAS

AMCY (LED-AD-1431)

AMCY (LED)

ATCC-13968

SUBSTRATE



9a - f luo ro - l l /3 ,17a ,21- t r ihydroxy-4-pregnene-3 ,20-d ione

11/3, 16α, 17α, 21 - te t rahydroxy-4-pregnene-3 ,20-d ione

9a- f luoro- l l /3 ,16α ,17α ,21- te tΓa-hydroxy-4 -p regnene -3 ,20 -dione






11/3,17a, 21- t r ihydr oxy - 1 , 4 -pregnadiene-3 ,20-d ione




11/3,17a, 21 - t r ihydroxy-4 - p r e g -nene -3 ,20-dione


11/3,17a, 21- t r ihydr o x y - 1 , 4 -pregnadiene-3 ,20-d ione

11/3,16a, 17a ,21- te t rahydroxy-4-pregnene-3 ,20-d ione 16 ,17 -acetonide

9a- f luoro- l l /3 ,16a , 17a, 2 1 - t e t r a -hydroxy-4 -p regnene -3 ,20 -dione 16, 17- acetonide

REACTION

16a-OH

I4-OH

1ξ-ΟΗ

1ξ-ΟΗ

1ξ-ΟΗ

6/3-OH

6/3,1 la-diOH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

2/3-OH

2/3-OH

R E F .

V-1060

F-234

F-234

F-234

F-234

S-929

S-929

P-745

P-745

P-745

P-745

P-745

P-745

P-745

P-745

P-745

P-745

P-745

F-235; F-236

F-235; F-236

640

TABLE I I I

Trans format ions by Genus: STREPTOMYCES

641


griseus ATCC-13968 6a, 9a-difluoro-ll/3,16a, 17a, 21 -tetrahydroxy-4-pregnene-3,20-dione 16,17-acetonide

9a:fluoro-ll/3,16a,17a,21-tetra-hydroxy -1,4-pr egnadiene-3,20-dione 16,17-acetonide

5a-androstane-3,17-dione


5a-pregnane-3,20-dione

21-hydroxy-5a-pregnane-3,20-dione

17a, 21-dihy droxy-5a-pregnane-3,20-dione




11/3,21-dihydroxy-4-pr egnene -3,20-dione


11/3,17a, 21-trihydr oxy-4-pr eg-nene-3,20-dione

17a, 21 -dihydroxy -4-pregnene -3,11,20-trione

2/3-OH

2-OH

3-C=0—3/3-OH

Δ4-5α-Η

Δ4^5α-Η; 3-C=0-3/3-OH

3-C=0-3/3-OH

3-C=O-»30-OH

3-C=0—3/3-OH

Δ4^5α-Η

Δ -5a -H; 3-C=0-3/3-OH

Δ4—5α-Η; 3-C=0-3/3-OH

Δ4-5α-Η

Δ - 5 α -H; 3-C=0-3/3-OH

Δ4-5α-Η; 3-C=0-*3|3-OH

Δ4-5α-Η

Δ -5α-Η; 3-C=0-3ß-OH

3-C=O-3/3-0H; Δ4—5α-Η

3-C = 0—3/3-OH; Δ4-5α-Η

F-235; F-236

F-235: F-236

V-1059: W-1097

V-1059; W-1097

V-1059; W-1097

V-1059; W-1097

V-1059: W-1097

V-1059; W-1097

V-1059; W-1097

V-1059: W-1097

V-1059; W-1097

V-1051; V-1059; W-1097

V-1059: W-1097

V-1059; W-1097

V-1059; W-1097

V-1059; W-1097

W-1097

W-1097

c

642

TABLE I I I


SPECIES

gr i seus *

halstedii

SOURCE

CZAS

NG

SCH (FC-103)

Shionogi

SQ

WC (No. 4; 3478)

ATCC-13499

SUBSTRATE


1 ,3 ,5 (10 ) -e s t r a t r i ene -3 ,17a -d io l

l , 3 ,5 (10) -es t ra t r i ene-3 ,17 j3 -d io l



24 /3-methyl -5 ,7 ,22-choles ta t r ien-3j3-ol (sole carbon source)



l l / 3 , 1 7 a , 2 1 - t r i h y d r o x y - l , 4 -pr e gnadiene - 3 , 2 0 - dione

1 la, 21 -dihydroxy - 1 , 4 -pregna -diene - 3 , 1 1 , 2 0 - t r ione


11/3; 17a, 21 - t r ihydroxy-4 -p reg -nene-3 ,20-d ione



l ,3 ,5 (10) -es t r a t r i ene -3 ,17 /3 -d io i

3 - h y d r o x y - l , 3 , 5 (10) -es t ra t r ien-17-one


9a-fluor o -11 j3,17a, 21- t r ihydroxy-4-pregnene-3 ,20-d ione 2 1 -aceta te

9a- f luoro- l l /3 ,17a , 21 - tr ihydroxy -4-pregnene-3 ,20-d ione 2 1 -propionate

REACTION

16a-OH

16a-OH

16a-OH

16a-OH

-

—

2 0 - C = O -20/3-OH

2 0 - C = O -20/3-OH

20-C=O-> 20/3-OH

2 0 - C = O - * 20/3-OH

2 0 - C = O -20/3-OH

2 0 - C = O -20/3-OH

Δ 5 -Δ 4 ;3 /3-ΟΗ - 3 - C = 0

Δ —Δ*;3/3-ΟΗ - 3 - C = 0

16a-OH

16a-OH;17/3-OH - 1 7 - C = 0

16a-OH

16a-OH;17-C = 0—17/3-OH

16a-OH

16a-OH;21-OAc - 2 1 - O H

16a-OH; 2 1 -OPr—21-OH

R E F .

V-1060

S-935

S-935

S-935

S-793c

S-793c

C-110

C-110

C-110

C-110

K-470

K-470

P-710

P-712

K-448

K-448

K-448

K-448

K-447

K-447

K-447

TABLE I I I


643

SPECIES

halstedii

1 hydrogenans

SOURCE

ces

IAM (3199)

NRRL B-2138

Hoechst (FAM)

(FHP-678)

SUBSTRATE





9 a - f l u o r o - l l ß , 1 7 a , 2 1 - t r i h y d r o x y -4-pregnene-3 ,20-d ione

9 a - f l u o r o - l l j 3 , 1 6 a , 1 7 a , 2 1 - t e t r a -hydroxy-4 -p regnene -3 ,20 -dione

3α, 7α, 12a-tr ihydroxy-5j3-cholanic acid (sole carbon source)

s eve ra l bile ac ids

l , 3 ,5 (10) -es t r a t r i ene -3 ,17 /3 -d io l


9a - f luoro- l l j3 ,17a ,21- t r ihydroxy-4-pregnene-3 ,20-d ione 2 1 -aceta te



17a, 21 -dihydroxy -4 -pregnene -3,20-dione (induction of 20ß-hydroxy-dehydrogenase , Ref. N-656 -isolation and specificity , Ref. N-657 - purification and crys ta l l iza t ion , Ref. H-408; H-409; H-410; S-802; S-803)


REACTION

I4-OH

1ξ-ΟΗ

1ξ-ΟΗ

1ξ-ΟΗ

I f -OH

I l - O H

utilization

utilization

16a-OH

16a-OH;17/3-OH - 1 7 - C = 0

16a-OH

16a-OH; 17-C = 0 ->17β-ΟΗ

16a-OH;21-OAc - 2 1 - O H

-

2 0 - C = O -20/3-OH

2 0 - C = O -20/3-OH

REF.

F-234

F-234

F-234

F-234

F-234

F-234

H-357; S-784

S-785

K-448

K-448

K-448

K-448

K-447

L-522

L-522

H-408; L-522; N-656

H-408; L-522

644

TABLE I I I


SPECIES

hydrogenans

1 hygroscopicus

lavendulae

SOURCE

Hoechst (F AM)

(FHP-678)

AMCY

AMCY (LED)

ATCC-8664

SQ (SC-1620)

AY

SUBSTRATE



l l j 3 , 1 7 a , 2 1 - t r i h y d r o x y - l , 4 -pregnadiene -3 ,20-dione

17a, 21-d ihydroxy-1 ,4 -p regna-d i ene -3 ,11 ,20 - t r i one


9a- f luoro- l l j3 , 17a ,21- t r ihydroxy-4-pregnene-3 ,20-d ione


9 a - f l u o r o - l l ß , 1 6 a , 1 7 a , 2 1 - t e t r a -hydroxy-4 -p regnene -3 ,20 -dione

11/3,17a, 21- t r ihydroxy-6a-methyl -1 ,4 -p regnad iene -3 ,20-d ione




4-pregnene-3 ,20-d ione (adaptive enzyme; effect of antibiotics)


5-cholesten-3/3-ol


REACTION

20-C=O-+ 20/3-OH

2 0 - C = O -20/3-OH

2 0 - C = O -20/3-OH

2 0 - C = O ^ 20/3-OH

14-OH

1ξ-ΟΗ

1ξ-ΟΗ

1ξ-ΟΗ

1ξ-ΟΗ

I l - O H

I l -OH

1 Δ ; enol.

17/3-Ac — 1 7 - C = 0

Δ1; enol. 17/3-Ac-17/3-OH

17/3-Ac—17a- x o x a - 1 7 - C = 0 ^ ; enol.

Δ1; 17/3-Ac -1 7 - C = 0

1 Δ

Δ —Δ ; 3/3-OH - 3 - C = 0

1 Δ

2 0 - C = O -20/3-OH 1

R E F .

H-408; L-522; S-801

L-522

H-408; L-522

L-522

F-234

F-234

F-234

F-234

F-234

F-234

F-234

G-317

G-317

G-317

G-317

P-719

T-1005

T-1005

S-835; V-1048

S-835

TABLE I I I


645

SPECIES

lavendulae

SOURCE

C

CZAS

NG

Shionogi (O-20-60)

(Waksman s t ra in)

WC (3440-14)

SUBSTRATE

d, 1-17α, 21 -dihydroxy-4 - p r e g -nene-3 ,20-d ione


5-cholesten-3/3-01

24/3-methyl -5 ,7 ,22-choles ta t r ien-3/3-01


11/3 ,17û,21- t r ihydroxy-4-preg-nene-3 ,20-d ione



17/3 -hydr oxy -1 ,4 -andr ostadien -3-one





REACTION

d , l - 2 0 - C = O ^ d-20/3-OH + 1

16a-OH

-

Δ1; 2 0 - C = O ^ 20/3-OH

Δ1; 20-C = O -20/3-OH

20-C = O -20/3-OH

2 0 - C = O -20/3-OH

17/3-OH -1 7 - C = 0

17/3-Ac-17-C

17/3-Ac-17/3-OH; Δ1

ΔΧ;Πβ-Αο -> 17-C = 0

1

Δ ;17/3-Ac — 17/3-OH

20-C = O -20/3-OH

1

Δ

17/3-Ac-*17/3-OH

Δ1; 2 0 - C = O -20/3-OH

2 0 - C = O -20/3-OH

1

Δ

REF.

W-1094

V-1060

S-793c

S-793c

K-470

K-470

K-470

K-470

P-733

F-251

F-251

F - 2 7 1 ; F-284; P -733

F - 2 7 1 ; F-284; P-733

F - 2 7 1 ; F-284

F-251

F - 2 7 1 ; F-288

F - 2 7 1 ; F -273 ; F-288

F - 2 7 1 ; F -273 ; F-288

F-272

646

TABLE I I I


SPECIES

lipmanii

*

mediocidicus

*

*

*

*

*

microflavus

1 * I n i t rosporeus

SOURCE

ATCC-3331

CZAS

ATCC-13278

ATCC-13279

ATCC-3332

CZAS

AMCY

SUBSTRATE







l ,3 ,5 (10) -es t ra t r i ene-3 ,17 j3 -d io l




9a -fluor o -17a, 21 -dihydroxy - 4 -pr egnene - 3 , 1 1 , 2 0 - t r ione

l , 3 , 5 (10 ) - e s t r a t r i ene -3 ,17 /3 -diol



9a- f luoro- l l /3 , 17a ,21- t r ihydroxy-4-pregnene-3 ,20-d ione





11/3,17a, 21- t r ihydroxy-6a-methy l -1 ,4-pregnadiene-3 ,20-dione

REACTION

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH;17j3-OH - 1 7 - C = 0

16a-OH

16a-OH; 17-C = 0 ^17/3-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

1ξ-ΟΗ

1ξ-ΟΗ

1|-ΟΗ

1ξ-ΟΗ

R E F .

P-745

P-745

P-745

P-745

P-745

V-1060

K-448; S-788

K-448

K-448

K-448

S-788

S-788

S-788

S-788

S-788

P-745

P-745

V-1060

F-234

F-234

F-234

F-234

TABLE I I I


647

SPECIES

n i t rosporeus

olivaceus *

olivochromogenus

parvus *

purpureochromogenus

SOURCE

IAM (O-20)

CZAS

WC (3688)

ATCC-3336

ATCC-13025 MCC (MA-320)

CZAS

NRRL

ATCC-3133

SUBSTRATE


3Q, 7o, 12a- t r ihydroxy-5ß-cholanic acid (sole carbon source)

3α, la, 12a-trihydroxy-5/3-cholanic acid conjugated with glycine-glycocholic acid (sole carbon source)

3a, la, 12a-tr ihydroxy-5/3-cholanic acid conjugated with taur ine -taurocholic acid (sole carbon source)

3 ,7 ,12- t r iketo-5/3-cholanic acid (sole carbon source)


17/3-hydr oxy -4 -androsten -3 -one






9a - f luoro - l l /3 ,17a ,21- t r ihydroxy-4-pregnene-3 ,20-d ione 2 1 -aceta te


Sarsasapogenin

Diosgenin



REACTION

utilization

utilization

utilization

utilization

utilization

16a-OH

16a-OH

16«-OH

16a-OH

16a-OH

1

Δ

1

Δ

Ιξ-ΟΗ-21-OAc —21 -OH

20-C = O->20/3-OH;21-OAc -21-OH

6/3-OH;21-OAc ->21-OH

21-OAc-21-OH

16a-OH

-

-

-

16a-OH

R E F .

S-785

H-357; S-784

S-785

S-785

S-785

S-929; V-1060

F-265

F-265; F-267

F-265; F-267

F-265; F-267

C-125

C-125

M-569; S-941

M-569; S-941 '

M-569; S-941

S-941

V-1060

M-587

M-587

M-587

P-745

648

TABLE I I I


SPECIES

purpureochromogenus

*

r imosus

1 roseochromogenus

SOURCE

ATCC-3133

CZAS

AY

CZAS

LED (T-1686B)

NG

NRRL-2234

SQ

AMCY (LED)

SUBSTRATE






l ,3 ,5 (10) -es t ra t r i ene -3 ,17 i3 -d io l (with spores)



l , 3 , 5 ( 1 0 ) - e s t r a t r i e n e - 3 , 1 7 a - d i o l

l ,3 ,5 (10) -es t ra t r i ene-3 ,17)3-d io l



4-pr e gnene - 3,2 0 - dione

5-cholesten-3/3-ol



21-(n-ace ty lamino)-9a-f luoro-l l ß , 17a-dihydroxy-4-pregnene-3,20-dione

21-amino-9a- f luoro- l l /3 ,17a-d ihydroxy-4-p regnene-3 ,20-dione hydrochloride

9a - f luoro - l l /3 ,17a ,21- t r ihydroxy-1,4 -pr egnadiene -3 ,20-d ione

21 - (n -acety lamino) -9a -fluor o -11/3 ,17a-d ihydroxy- l ,4-pregna-d iene-3 ,20-d ione

REACTION

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

1 7 / 3 - O H -1 7 - C = 0

6/3-OH

6/3, l la-diOH

6/3-OH

16a-OH

16a-OH

16a-OH

Δ5—Δ ; 3/3-OH - 3 - C = 0

1

Δ

Δ 5 ^ Δ 4 ; 3/3-OH - 3 - C = 0

Δ 5 - Δ \ · 3/3-OH - 3 - C = 0

21-OH-»21-AcNH

2β-ΟΗ (tentative)

2 1 - N H 2 - 2 1 -AcNH

21-OH-^21-AcNH

—

R E F .

P-745

P-745

F-234; P-745

P-745

V-1060

S-835; V-1048

S-929

S-929

S-909

S-935

S-935

S-935

P-712

T-1005

T-1005

P-710

S-911

S-911

S-911

S-911

S-911

TABLE I I I


649


roseochromogenus AMCY (LED-409)

ATCC-3347

9a - f luoro-11ß-hydroxy-4-androstene-3,17-dione

4-estren-3-one

16a-hydroxy-4-estren-3-one


4-estren-3,16-dione

3/3-bromo-19-nor-5-pregnen-20-one

3/3-chloro-19-nor-5-pregnen-20-one

3/3-fluoro-19-nor-5-pregnen-20-one

3/3-hydroxy-19-nor-5-pregnen-20-one

11/3,21 -dihydroxy-4-pregnene-3,20-dione


9a -fluoro -1 Iß, 21 -dihydroxy -4-pregnene-3,20-dione

lla,17a,21-trihydroxy-4-preg-nene-3,20-dione

11/3,17a,21-trihydroxy-4-preg-nene-3,20-dione

16a-OH

16a-OH

16/3-OH

16-C=0(via either 16a or 16/3 -OH)

16a-OH^16/3-OH (vial6-C=0)

16a-OH^16-c=o

16/3-OH — 16-C=0

1 6 - C = 0 -16/3-OH

16a-OH

B-62

S-793a

S-793a

S-793a

S-793a

S-793a

S-793a

S-793a

Z-1128

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH; 16a, 17a-diOH-17/3-(20-C=O-21-OH) —>D-homo-16a, 17aa-diOH-17a/3-CH 2 OH-17-C=0

16a-OH

Z-1128

Z-1128

Z-1128·, Z-1129

H-399

H-399

H-403

G-295; G-297

G-297

G-295; G-297; H-399

650

TABLE 111


SPECIES

roseochromogenus

SOURCE

ATCC-3347

SUBSTRATE


9a -ch lo ro - l l j 3 ,17a ,21 - t r ihydroxy-4-pregnene-3 ,20-d ione

6a - cyano -9a - f l uo ro - l l / 3 , 17a ,21 -t r i hyd roxy -4 -p regnene -3 ,20 -dione


(s t rain var ia t ion - Ref. G-298)

(Ref. G-297, p r e s e n c e of

a non-biologie i somer ization of th is subs t ra te to D-homo compound)

9a -ch lo ro -2 /3 , l l | 3 ,17a ,21 - t e t r a -hydroxy-4 -p regnene -3 ,20 -dione

9a -ch lo ro - l l / 3 ,16a , H a ^ l - t e t r a -h y d r o x y ^ - p r e g n e n e - S , 20-dione

9a-fluoro-2/3,11/3,17a, 2 1 - t e t r a -hydroxy-4 -p regnene -3 ,20 -dione (see note Ref. G-297)


6a - cyano -17a, 21-dihydr oxy-4-p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e

l l / 3 , 1 7 a , 2 1 - t r i h y d r o x y - l , 4 -pregnadiene-3 ,20-d ione (see note Ref. G-297)

6a - f luoro- l l /3 ,17a ,21- t r ihydroxy-1,4-pr egnadiene - 3 ,20-dione

REACTION

16a-OH; 16a, 17a-diOH-17ß-(20-C=O-21-OH) —>D-homo -16a -17aa-diOH-17aß-CH 2 OH-17-C=0

2/3-0H

16a-OH

2ß-OH

2/3-OH

16a-OH

16a-OH;17a-OH-17/3-(20-C=O-21-OH)-*17aa-OH-17aß-CH2OH-1 7 - C = 0

2/3,16a-diOH

16a-OH

2/3-OH

16a-OH

2/3-OH

16a-OH

16a-OH

16a-OH

R E F .

G-297

S-913

3 -74

G-298; S-913

S-912

G-295; G-297; L-505; S-913

G-295; G-297; G-298; L-505; S-910; S-912; S-913

G-298; S-912; S-913

S-913

S-913

S-912; G-297

S-913

B-74

G-295; G-297

H-399

ferrie or ferrous ion leads to

TABLE I I I


651


roseochromogenus

(Krainsky)

ATCC-3347

AY

CZAS

Shionogi ^0-36)

SQ

WC(3689)

9a - f luoro- l l /3 ,17a ,21- t r ihydroxy 1 ,4-pregnadiene-3 ,20-d ione (Δ1 of subs t ra te blocks 2/3-OH)

6 a - c y a n o - 1 7 a , 2 1 - d i h y d r o x y - l , 4 -pr egnadiene - 3 , 1 1 , 2 0 - t r ione

17a, 21-dihydroxy-4-pregnene -3,20-dione (with conidia)

3/3-hydroxy -19 -nor_-5a -pregnan-20-one


11/3,21 -dihydroxy -4 -pr egnene -3,20-dione 18-oic acid (18^11)- lac tone

4-pregnene ^3,20-dione



D - homo -17a - oxa - 1 , 4 - andr o s t a -d iene-3 ,17-d ione







A - n o r - D - h o m o - 1 7 a - o x a - 3 -andros tene -2 ,17-d ione

D - homo-17a -oxa -1 ,4 -and r osta -d iene-3 ,17-d ione

9a - f luoro- l l /3 -hydroxy-4-andro-s t ene -3 ,17-d ione

16a-OH

16a-OH

16a-OH;17a-OH -17/3-(20-C=O-2 1 - O H ) - 1 7 a a -OH-17a/3-CH2OH - 1 7 - C = 0

16a-OH

16a-OH

3/3-OAc->3/3-OH; 16a-OH

16a-OH

16a-OH

Δ1; 20-C = O 20/3 -OH

Δ1; 20-C=O 20/3-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

G-298

ß - 7 4

G-297

S-835; V-1048

W-1093

W-1092

vV-1091

V-1060

K-470

K-470

P-706

L-502

F-288

F-288

F-288

F-265

F-265 ; F-267

L-503

T-1000

T-1008

c

652

TABLE I I I


SPECIES

roseochromogenus

SOURCE

WC (3689)

SUBSTRATE

9 a - c h l o r o - 4 - a n d r o s t e n e - 3 , 11 ,17-t r ione

9ö - f luo ro -4 -and ros t ene -3 ,11 ,17 -t r ione




12a-bromo-11/3-hydroxy-4-pregnene-3 ,20-d ione

12a-ch loro- l l /3 -hydroxy-4-pregnene-3 ,20-d ione

nene-3 ,20-d ione

12a-fluoro-11/3-hydroxy -4 - p r e g -nene -3 ,20-dione

12ö-f luor0-21-hydroxy-4-preg-nene-3 ,20-d ione


1 l/3-hydroxy-6a- methyl - 4 -pregnene-3 ,20-d ione

11/3-hydroxy - 12a -me thy l -4 -p reg -nene-3 ,20-d ione

21 -hydroxy-11/3,12/3-oxido-4-pregnene-3 ,20-d ione

6a- f luoro- l l /3 ,17a-d ihydroxy-4-pregnene-3 ,20-d ione

9a- f luoro- l l /3 , 17α-dihydroxy -3 ,20-d ike to -4-pregnene-21-a l

11/3,17a-dihydroxy-6a-methyl-4-pregnene-3 ,20-d ione

9a-f luoro-11/3,17a-dihydroxy-6a-methy l -4 -pregnene-3 ,20-d ione

21-f luoro- l l /3 ,17a-d ihydroxy-6a-me thy l -4 -p regnene -3 ,20 -d ione

REACTION

Ιβα-ΟΗ

16α-OH

16α-ΟΗ

16α-OH

16α-OH

16α-OH

16α-OH

16α-OH

16α-OH

16α-OH

16α-OH

16α-OH

16α-ΟΗ

16α-OH

16α-OH

2 1 - C = 0 - > 21-OH

2 1 - C = 0 ^ 21-OH; 20-C = O —20/3-OH

16a-OH

16a-OH

16a-OH

R E F .

T-1008

T-1008

L-506

F-265; F-267

F-265; F-267

F-256

F-256

B-35

F-256; F-257

F-256

F-256

S-834

F-257

D-156; D-157

M-530

S-907

S-907

L-511

L-511

L-510

6o!-fluoro-ll/3-hydroxy-4-preg-

TABLE I I I


653


roseochromogenus WC (3689) 6a ,21 -d i f luo ro - l l / 3 ,17a -d i -hydroxy-4 -p regnene -3 ,20 -dione


9a- f luoro- l l j3 ,17a ,21- t r ihydroxy-4-p regnene-3 ,20-d ione (s t rain var ia t ion , Ref. G-298)

16a-OH

16a-OH

12a-f luoro- l l /3 ,17a,21- t r ihydroxy- | 4 -p regnene-3 ,20-d ione

6a - f luoro- l l j3 ,17a ,21- t r ihydroxy-9 a - m e t h y l - 4 - p r e g n e n e - 3 , 2 0 -dione

9a - f luo ro - l l / 3 ,17a ,21 - t r ihydroxy-12a -me thy l -4 -p regnene -3 ,20 -dione

6 a , 9 a - d i f l u o r o - l l / 3 , 1 7 a , 2 1 - t r i -hyd roxy-4 -p regnene -3 ,20 -dione

6 a , 1 2 a - d i f l u o r o - l l ß , 17α, 2 1 -t r i h y d r o x y - 4 - p r e g n e n e - 3 , 2 0 -dione

9a, 21-dif luoro-l l /3,17a-dihydroxy- | 6 a - m e t h y l - 4 - p r e g n e n e - 3 , 2 0 -dione

6a, 9a, 2 1 - t r i f l u o r o - l l ß , 17a-d i -hydroxy-4 -p regnene -3 ,20 -dione

1 2 a - b r o m o - 4 - p r e g n e n e - 3 , 1 1 , 2 0 -t r ione

1 2 a - c h l o r o - 4 - p r e g n e n e - 3 , 1 1 , 2 0 -t r ione

6 a - f l u o r o - 4 - p r e g n e n e - 3 , 1 1 , 2 0 -t r ione

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

M-532

M-533;

2/3-OH

16a-OH

2/3,16a-diOH

2 0 - C = O -20/3-OH

16a-OH; 20-C=O-20/3-OH

16a-OH

16a-OH

M-534; M-586

G-298; S-913

G-298; S-913; T-1002

G-298

S-907

S-907

F-256; F-257

F-260

F-260

M-533; M-586

F-261

L-510

M-532

F-256

F-257

B-35

654

TABLE I I I


SPECIES

roseochromogenus

SOURCE

WC (3689)

SUBSTRATE

12a - f luo ro -4 -p regnene -3 ,11 ,20 -t r ione

6 a - m e t h y i - 4 - p r e g n e n e - 3 , 1 1 , 2 0 -t r ione

12a- f luor0-21-hydroxy-4-preg-n e n e - 3 , l l , 2 0 - t r i o n e

12a -chloro -1 la, 21 -dihydroxy -4 -p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e

12a-f luoro-17a ,21-dihydroxy-4-p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e

12a -ch lo ro -6a - f luo ro -17a ,21 -d ihydroxy-4 -p regnene -3 ,11 , 20- t r ione

21-hydroxy- l l /3 ,12/3-oxido- l ,4-pregnadiene-3 ,20-d ione

11/3,1 la -dihydr oxy- 6a- methyl -l , 4 -p regnad iene -3 ,20 -d ione

l l / 3 , 1 7 a , 2 1 - t r i h y d r o x y - l , 4 -pr egnadiene -3 ,20-dione

6a- f luoro- l l /3 , 17a ,21- t r ihydroxy-1,4 -pr egnadiene -3 ,20-dione

9a - f luo ro - l l /3 ,17a ,21- t r ihydroxy-1,4-pr egnadiene-3 ,20-dione (Δ1 of subs t ra te blocks 2/3-OH -Ref. G-298)

12α-fluoro-11/3,17a,21-tr ihydroxy - 1 , 4 - p r egnadiene-3 ,20-dione

9o-f luoro-l l j3 ,17α-dihydr oxy-6α-me thy 1-1,4-pr egnadiene - 3 , 20-dione

2 1 - f i u o r o - l l ß , 17α -dihydr oxy -6a -m e t h y l - l , 4 - p r e g n a d i e n e - 3 , 2 0 -dione

6a, 21-difluor o- l l /3 ,17a-dihydr oxy - l , 4 - p r e g n a d i e n e - 3 , 2 0 - d i o n e

l l /3 ,17a ,21- t r ihydroxy-6a-methy l - l , 4 - p r e g n a d i e n e - 3 , 2 0 - d i o n e

9a - f luoro- l l /3 ,17a ,21- t r ihydroxy-6 a - m e t h y l - l , 4 - p r e g n a d i e n e -3,20-dione

9a, 21-difluoro-11/3,17a-dihydr oxy -6a -me thy 1-1,4-pr egnadiene-3,20-dione

REACTION

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

16a-OH

REF.

F-256

S-834

F-256

F-256; F-257

F-256

F-261

D-157

L-511

F-257

M-531

G-298; T-1002

F-256; F-257

L-511

L-510

M-532

F-257

F-257

L-510

TABLE I I I


655

SPECIES

roseochromogenus

ruber

rubescens

SOURCE

WC (6389)

NRRL (B - 1268)

IAM (Z-52)

SUBSTRATE

6 a , 9 a , 2 1 - t r i f l u o r o - l l / 3 , 1 7 a -dihydroxy - 1 , 4 -pr egnadiene -3,20-dione

12a-f luoro-17a, 21 -dihydroxy- i , 4 -p regnad iene-3 ,11 ,2G- t r ione




9 a - f l u o r o - l l ß , 17a ,21- t r ihydroxy-4-pregnene-3 ,20-d ione


9a- f luoro- l l /3 ,16a , 17a, 21 - t e t r a -hydroxy-1 ,4-pregnadiene -3,20-dione


3a, 7a, 12a- t r ihydroxy-5ß-choianic acid (sole carbon source)

3α, 7α, 12a-tr ihydroxy-5j3-cholanic acid conjugated with glycine-glycocholic acid (sole carbon source)

3a, 7a, 12a-tr ihydroxy-5/3-cholanic acid conjugated with taur ine -taurochol ic acid (sole carbon source)

3 ,7 ,12 - t r ike to -5ß -cho lan ic acid (sole carbon source)

REACTION

16a-OH

16a-OH

1ξ-ΟΗ

l | - O H

1ξ-ΟΗ

1ξ-ΟΗ

1ξ-ΟΗ

1ξ-ΟΗ

utilization

util ization

3a-OH-+3-C=0; 7α-ΟΗ->Δ6;12α-O H ^ 1 2 - C = 0 ; 5β-Η-*Δ4

3 a - O H - 3 - C = 0 ; Δ4-(5/3-Η)

3a-OH-*3-C=0; 12a-OH-+12-C=0 Δ4-(5/3-Η)

3a-OH->3-C=0; 7 α - Ο Η - Δ 6 ; Δ4-(5β-Η)

uti l ization

util ization

uti l ization

R E F .

M-532

F-256

F-234

F-234

F-234

F-234

F-234

F-234

S-785

H-357; S-784

H-365

H-365

H-365

H-362

S-785

S-785

S-785

656

TABLE I I I


SPECIES

rubr i r e t i cu l i

rubrocyanodias ta t icus

r u t g e r s e n s i s

scabies

setonii

spec ies

(species l a te r ident-ified a s argenteolus)

SOURCE

AMCY (LED)

Shionogi

NRRL

IAM (3111)

SUBSTRATE

CZAS

AMCY (LED-AC-

209)

ATCC-11009

C (A-7747)


9a- f luoro- l l /3 , 17α, 21 - tr ihydroxy -4 -pregnene-3 ,20-d ione



Sarsasapogenin

Diosgenin



3a, 7a, 12a - t r ihydr oxy - 5/3 -cholanic acid (sole carbon source - Ref. S-784)

3α, 7α, 12a-tr ihydroxy-5/3-cholanic acid conjugated with glycine-glycocholic acid (sole carbon source)

3a, 7a, 12a - tr ihydroxy -5/3-cholanic acid conjugated with taur ine- taurochol ic acid (sole carbon source)

3 ,7 ,12- t r ike to -5ß-cho lan ic acid (sole carbon source)


2 - f l uo ro -17a ,21 -d ihyd roxy - l , 4 -p regnad iene -3 ,11 ,20 - t r i one


3/3-hydroxy-19-j ior-5a-pregnan-20-one


3/3-hydroxy-5/3-pregnan-20-one

9a-fluoro-3/3, l l /3-dihydroxy-5a-pregnan-20-one

REACTION

14-OH

I l - O H

2 0 - C = O ^ 20/3-OH

2 0 - C = O ^ 20ß-OH

utilization

util ization

util ization

utilization

util ization

16a-OH

REF.

3/3-OH->3-C=Oj Δ 5 - Δ 4

16a-OH

16a-OH

16a-OH

16a-OH

F-234

F-234

K-470

K-470

M-587

M-587

M-587

S-785

H-357; S-784

S-785

S-785

S-785

V-1060

A ^ H ( 2 a - F ) IH-402

F-267 P-710; P-712 P-716

W-1093

N-653: W-1092

W-1092

W-1092

TABLE I I I


657

SPECIES

species

SOURCE

C (A-7747)

MCC (MA-449)

NG

QM-1086

S (8)

(27)

SUBSTRATE

3/3-hydroxy-5a-9(ll)-pregnen -20-one acetate


d, l-21-hydroxy-4-pregnene-3,20-dione

l lß , 21 -dihydroxy-4-pregnene-3,20-dione 18-oic acid (18^11) lactone

17a, 21 -dihydroxy -4 -pregnene -3,11,20-trione

5-cholesten-3/3-ol 14

5-cholesten-3/3-ol 4-C 14

5-cholesten-3/3-ol 26-C

17a, 21 -dihydroxy-4-pregnene-3,20-dione

ll/3,17a,21-trihydroxy-4-pregnene-3,20-dione

17a, 21 -dihydroxy -4-pregnene -3,11,20-trione

ll/3,17a,21-trihydroxy-l,4-pr e gnadiene -3,20- dione

17a, 21 -dihydroxy -1,4 -pregna-diene-3,11,20-trione








REACTION

16a-OH; 3/3-OAc ^3ß-OH

16a-OH

d,l^d-16a-OH + 1

16a-OH

Δ4-5β-Η; 3-C=0—3a-OH

utilization

utilization

utilization

20-C=O-» 20/3-OH

20-C=O-20/3-OH

20-C=O-20/3-OH

20-C=O-20/3-OH

20-C=O-* 20/3 -OH

16a-OH

-

—

16a-OH

-

-

REF.

W-1092

V-1054

W-1102

W-1091

B-41

D-145

D-145

D-145

C-110

C-110

C-110

C-110

C-110

S-847; S-849; S-859

S-859

S-859

S-847; S-859

S-849; S-859

S-849

S-849; S-859

658

TABLE I I I


SPECIES

species (s t ra in 8 ,27 ,41 ,44 -Actinomyces)

SOURCE

S (41)

(44)

(72)

(103)

(161)

SCH (DS-81B,FC-6 - 5 3 S , F C - 7 -206)

(FC-B-222)

Shionogi (1-13)

SUBSTRATE









17ûi-hydroxy-4-pregnene-3,20-dione





17a, 21-dihy dr oxy-4-pr egnene -3,20-dione

REACTION

6/3,1 la-diOH

-

16a-OH

-

-

16a-OH

6/3-OH

6/3,1 l a -diOH

-

6ß-OH

l l a - O H

6/3-OH

l l a - O H

16a-OH

2/3-OH

2 0 - C = O -20/3-OH

1

Δ

20-C = O -20/3 -OH

Δ1; 2 0 - C = O -20/3-OH

R E F .

S-859

S-859

S-859

S-847; S-859

S-859

S-859

S-847

S-847; S-854; S-859

S-847; S-854; S-859

S-859

S-847; S-849

S-847; S-849

S-847; S-849; S-854

S-847; S-854

S-847

H-383

C-110

K-470

K-470

K-470

TABLE I I I


659

SPECIES

spec ies

tanashiens is

tendae

thioluteus

SOURCE

Shionogi (1-13)

SQ (SC-1646, SC-3309, SC-3310, SC-3311)

SY (J-6-11)

uc

(BC-17 ,H-3 9 , K - 9 3 , W -4)

(H-39)

WC (3676)

WC (3808)

Shionogi

Shionogi (ETH-11313)

Shionogi (OKAMI)

SUBSTRATE



5-cholesten-3/3-01


21 -hydroxy-4 -p regnene -3 ,20 -dione (revision of s t ruc tu re a t 20 -see Ref. S-832)

17α, 21 -dihydroxy -4-pregnene -3,20-dione


17a, 21 -d ihydroxy-1 ,4 -p regna -d i e n e - 3 , 1 1 , 2 0 - t r i o n e

17a, 21 - dihydroxy -16a - methyl -1,4 -p r egnad i ene -3 ,11 ,20 -t r ione


l l / 3 , 17a ,21 - t r i hyd roxy -4 -pregnene-3 ,20-d ione


11/3,17a, 21 - t r ihydroxy-4 - p r e g -nene -3 ,20-d ione


11/3,17a, 21 - t r i h y d r o x y - 4 - p r e g -nene-3 ,20-d ione

REACTION

Δ1; 2 0 - C = O -20/3-OH

20-C=O-> 20/3-OH

1

Δ 1

Δ

Δ 5 -Δ 4 ;3 /3-ΟΗ - > 3 - C = 0

6/3-OH

11/3-OH

6/3,11/3-diOH

2 0 - C = O -20/3-OH

11-oxygénation

oxidation

15α-OH

Δ4-»5/3-Η

Δ 4 - 5 β - Η

Δ1; 20 -C=O-> 20/3-OH

Δ1; 2 0 - C = O -20/3-OH

2 0 - C = O -20/3-OH

2 0 - C = O -20/3-OH

2 0 - C = O - » 20/3-OH

2 0 - C = O ^ 20/3-OH

REF.

K-470

K-470

K-470

T-1005

T-1005

C-112

C-112

C-112

E-202

H-328

H-328

F-285; F-287

G-314

G-314

K-470

K-470

K-470

K-470

K-470

K-470

SPECIES

vinaceus *

v i r idans

vir idifaciens

v i r id is

*

vir idochromogenes (Actinomyces)

SOURCE

ATCC-11861

Shionogi

ATCC-11389

AY

CZAS

WC (3690)

CZAS

IPB

SUBSTRATE




11)3 ,17a ,21- t r ihydroxy-4-preg-nene-3 ,20-d ione


l l ß , 17a, 21 - t r i hyd roxy-4 -p reg -nene-3 ,20-d ione

9a - f luoro- l l j3 ,17a ,21- t r ihydroxy-4-pregnene-3 ,20-d ione

17a, 21 -dihydroxy-4,9(11) -p regna-d iene-3 ,20-d ione

17a, 21 -dihydroxy-4-pregnene -3,20-dione (with spores)









3ß-hydroxy-5-andros ten-17-one aceta te

REACTION

16α-OH

16a-OH;21-OAc - 2 1 - O H

20-C = O-> 20/3-OH

2 0 - C = O ^ 20j3-OH

1ξ-ΟΗ

1ξ-ΟΗ

1ξ-ΟΗ

14-OH

16α-OH

16α-OH

16α-OH

16α-ΟΗ

16α-OH

16α-OH

3/3-OH->3-C = 0 ; Δ 5 - Δ 4 ; 17)3-OH - 1 7 - C = 0

3)3-OH^3-C = 0 : Δ 5 - Δ 4

3 )3-OAc^3-C=0: Δ —»Δ

3/3-OAc—3-C=0; Δ 5 - Δ 4 ; 1 7 - 0 = 0 ^17)3-OH

R E F .

L-491

L-491

K-470

K-470

F-234

F-234

F-234

F-234

S-835; V-1048

V-1060

F-265

F-265 ; F-267

F-265 ; F-267

F -265 ; F-267

S-929

H-337

H-337

H-335

H-335

TABLE I I I

STREPTOMYCES T r a n s f o r m a t i o n s by Genus:

660

661


T r a n s f o r m a t i o n s by Genus: STREPTOMYCES STROPHARIA

STYSANUS SYNCEPHALASTRUM

(Basidio. - Agar ica les) (Imperf. - Moniliales) (Phyco. - Mucorales)

SPECIES

vi r idochromogenes

wil lmorei

STROPHARIA

cubensis

nordmanii

STYSANUS

1 médius

SYNCEPHALASTRUM

1 c incereum 1 (cinereum)

1 r acemosum

1 *

SOURCE

NRRL

NRRL B-1332

SY

AL (SS-74)

FRI

SSSR

IAM (6801)

SUBSTRATE

Sarsasapogenin

Diosgenin



9a -f luor o -1118,17a, 21 - t r ihy dr oxy -4 -p regnene-3 ,20-d ione





4 -p regnene-3 ,20-d ione (Ref. T-1025 c o r r e c t s con-figuration at 7 to 7/3 in Ref. A - 2 6 , 2 7 , 3 0 ; T-1020,1021) (species identified a s r a c e m o s u m in Ref. A-27)

REACTION

-

-

-

16a-OH

16a-OH

l l a - O H


6/3-OH; l l a - O H

l l a - O H

15/3-OH

6/3,1 la -d iOH •

6/3,15/3-diOH

7/3,15/3-diOH

7/3,14a, 15/3-tr iOH

Δ4-+5α-Η; 15/3-OH; 6 - C = 0 (via 6/3-OH)

R E F .

M-587

M-587

M-587

P-745

P-745

C-113

S-825

S-849

E-224

S-793

S-793

S-793

A-26; A-27; A-30; S-793; T-1020; T-1025

A-26; A-27; A-30; S-793; T-1021; T-1025

S-793

662


T r a n s f o r m a t i o n s by Genus: SYNCEPHALASTRUM SYNCEPHALIS (Phyco. - Mucorales)

TAPHRINA (Asco. - Taphrinales) THAMNIDIUM (Phyco. - Mucorales)

SPECIES

racemosum

spec ies

SYNCEPHALIS

nodosa

reflexa

TAPHRINA

diformans (deformans)

pruni

THAMNIDIUM

elegans

SOURCE

IAM (6801)

SSSR

NRRL

UC

UC

TNAES

TNAES

SQ

SSSR

SUBSTRATE

l l a - h y d r o x y - 4 - p r e g n e n e - 3 , 20-dione

6/3, l l a - d i h y d r o x y - 4 - p r e g n e n e -3,20-dione

7j3,15/3-dihydroxy-4-pregnene-3,20-dione


11/3,1 la, 21 - t r ihydr oxy -4 - p r e g -nene-3 ,20-d ione


plant saponins

not given

not given


17a ,21-d ihydroxy-4-pregnene-3 ,20-dione

4 ,9(11)-pregnadiene-3 ,20-dione


REACTION

6/3-OH

-

14a-OH

l l a - O H

-

6/3-OH; l l a - O H ; 11/3-OH

-

oxidation

oxidation

—

—

6/3,12a-diOH

l l a - O H ; 11/3-OH; 1 1 - C = 0 (via 11/3-OH)

REF.

A-27; T-1020

A-27

T-1021

A-27; T-1020

A-27

E-224

K-478

M-601; M-636

M-601; M-636

S-849

S-849

F-277; F-279

E-224

663


T r a n s f o r m a t i o n s by Genus: THIEL A VIA

THYROSPORA TIEGHEMELLA

TILLETIOPSIS

(Asco. - Eurot ia les) (Imperf. - Moniliales) (Phyco. - Mucorales) (Imperf. - Moniliales)

SPECIES

THIELAVIA

basicola

t e r r i co l a

THYROSPORA

as t r aga l i

TIEGHEMELLA 1 (synonym - Absidia)

1 coerulea

1 cyl indrospora

hyalospora

1 orchidis

r epens

spinosa

I t ieghemii

turkes tan ica

TILLETIOPSIS

lli lacina

SOURCE

FRI

C

FRI

SSSR

SSSR

SSSR

SSSR

SSSR

SSSR

SSSR

SSSR

FRI

SUBSTRATE


no specific subs t ra te - used in mixed cul ture











REACTION

6j3-OH

17a-OH

2/3-OH

l l a -OH; l l j 3 -OH; 1 1 - C = 0 (via 110-OH)

l l a - O H

l l a - O H ; l l ß - O H

l l a - O H ; 11/3-OH; 1 1 - C = 0 (via l l ß - O H

11α-ΟΗ

11α-ΟΗ;11β-ΟΗ

11α-ΟΗ;11/3-ΟΗ

11α-ΟΗ;11]3-ΟΗ; 1 1 - C = 0 ( via 11/3-ΟΗ)

-

R E F .

S-849

W-1106; W-1107

S-849

E-224

E-224

E-224

E-224

E-224

E-224

E-224

E-224

S-849

664


T r a n s f o r m a t i o n s by Genus: TOMENTELLA

TORULA TORULOPSIS

TRAMETES TRICHODERMA

(BasidiOo - Agaricales) (Imperf. - Moniliales) (Imperf. - Moniliales) (Basidio. - Agaricales) (Imperf. - Moniliales)

SPECIES

TOMENTELLA

spec ies

TORULA

species

TORULOPSIS

ae r i a

Candida

TRAMETES

dickinsii

pini

TRICHODERMA

album (in mixed cul ture with Aspergi l lus niger [ l l a -OH] -Hende r son i a acicola [21-OH])

glaucum

SOURCE

FRI

NG

FRI

NRRL

IAM

LAM

MCC

LED (Z-696)

SUBSTRATE


5-choIesten-3ß-oI

24/3-methyl -5 ,7 ,22-choles ta-trien-3/3-ol


Sarsasapogenin

Diosgenin








16a, 17a, 21 - t r ihydr oxy -4 -p reg -nene-3 ,20-d ione 16 ,17 -acetonide

REACTION

-

—

-

-

-

-

-

—

—

17a-OH

17/3-OH — not es te r if ied

21-OH — not e s t e r if ied

2 1 - O H -not es ter i f ied

21-OH — 21-OAc

R E F .

S-849

S-793c

S-793c

S-849

M-587

M-587

M-587

S-849

S-849

M-566

H-404

H-404

H-404

H-404

TABLE I I I

Transformat ions by Genus: TRICHODERMA

665

SPECIES

glaucum

(in mixed cul ture with 1 Cunninghamella

blakesleeana [11β-ΟΗ] 1 Wojnowicia g ramin i s

[21-OH])

1 koningi *

l ignorum 1 (in mixed cul ture with 1 Pénici l l ium adametz i

[ l i a -OH] Wojnowicia graminis [21-OH])

1 *

I n igrovi rens 1 (in mixed cul ture with 1 Hendersonia rubi

[21-OH] Stigmina platana[l l /3-OH])

1 spec ies

1 v i r ide

SOURCE

LED (Z-696)

MCC

SSSR (8,23)

(23)

MCC

SSSR ( 2 , 3 , 4 , 5 , 1 0 , 16,22)

MCC

NRRL

MCC

NRRL-2473

SUBSTRATE

11/3,16a, 17a, 21- te t rahydroxy-4-pregnene-3 ,20-d ione 16,17-acetonide

9a- f luoro- l l /3 ,16a , 17a, 21 - t e t r a -hydroxy-4 -p regnene -3 ,20 -dione

9 a - f l u o r o - l l ß , 16α, 17α, 2 1 - t e t r a -hyd roxy-4 -p regnene -3 ,20 -dione 16a, 17a-bora te (sodium salt)

9 a - f l u o r o - l l / 3 , 1 6 a , 1 7 a , 2 1 - t e t r a -hydroxy-4 -p regnene -3 ,20 -dione 16,17-acetonide

9 a - f l u o r o - l l / 3 , 1 6 a , 1 7 a , 2 1 - t e t r a -h y d r o x y - l , 4 - p r e g n a d i e n e - 3 , 20-dione 16α, 17α-or thof or mate

9a- f luoro- l l /3 ,16a , 17a, 2 1 - t e t r a -hydroxy-1 ,4-pregnadiene -3 ,20-dione 16,17-acetonide



4-pr e g n e n e - 3 , 1 1 , 2 0 - t r ione



4 - p r e g n e n e - 3 , 1 1 , 2 0 - t r i b n e


plant saponins



REACTION

2 1 - O H -21-OAc

21-OH — not es ter i f ied


2 1 - O H -21-OAc


21-OH — 21-OAc

17a-OH

6/3,l la-diOH

17a-OH

17a-OH

6/3,1 la -d iOH


17α-ΟΗ

-

17α-OH

17α-OH

R E F .

H-404

H-404

H-404

H-404

H-404

H-404

M-566

T-1010

T-1010

M-566

T-1010

T-1010

M-566

K-478

M-565

D-185

666


T r a n s f o r m a t i o n s by Genus: TRICHODERMA TRICHOLOMA

TRICHOMONAS (Basidio. - Agar icales) (Zoomastigina - Poiymastigina)

SPECIES

vir ide (in mixed cul ture with Curvular ia lunata [11/3-OH] Omphal ia t ra lucida [11/3-OH] and vVojnowicia graminis [17a-OH])

*

TRICHOLOMA

nudum

species

TRICHOMONAS (Protozoa)

foetus

SOURCE

NRRL-2473

PIRI (FA-3-1)

SSSR

NRRL-2371

AL (G-88)

NG

SUBSTRATE


11/3-hydroxy-4-pr egnene -3 ,20 -dione



3a-hydroxy-5ß-cholanic acid


4 -pregnene - 3 , 1 1 , 2 0 - t r i o n e






l l / 3 -hyd roxy -4 -e s t r ene -3 ,17 -dione

4 - e s t r e n e - 3 , 1 1 , 1 7 - t r i o n e

3a -hydroxy- 5/3-androstan-17 -one

REACTION

17o-OH

17a-OH

17a-OH

11a-OH

oxidation

6/3,1 la -d iOH

17a-OH




1 7 - C = 0 -17/3-OH

17/3-OH — 1 7 - C = 0

1 7 - C = 0 - > 17/3-OH

1 7 - 0 = 0 - ^ 17/3-OH; Δ ; enol.

17-C = 0 -170-OH

1 7 - C = 0 - * 17/3-OH

R E F .

M-566; M-567

D-185

D-185

W-1119

W-1119

T-1010

T-1010

T-1010

R-778

S-825

S-829

S-829

S-830

S-830

S-830

S-830


TABLE I I I

TRICHOMONAS

667

SPECIES

foetus

(in mixed cul ture with Corynebacter ium equi

1 (in mixed cul ture with 1 Corynebacter ium equi

1 gallinae

SOURCE

NG

NG

SUBSTRATE

3a-hydroxy-5/3-androstan-17-one aceta te




11/3,17/3-dihydroxy-4-androsten-3-one


17ß -hyd roxy -4 -and ros t ene -3 ,11 -dione

l l a - h y d r o x y - 4 - a n d r o s t e n e - 3 , 1 7 -dione

l l / 3 -hydroxy-4 -andros t ene -3 ,17 -dione


l , 4 - a n d r o s t a d i e n e - 3 , 1 7 - d i o n e


4 - e s t r e n e - 3 , 1 1 , 1 7 - t r i o n e

3 - h y d r o x y - l , 3 , 5 (10) -es t ra t r i en-17-one

17/3-hydroxy-4-es t ren-3-one

4 -es t r ene -3 ,17 -dione

11/3-hydroxy-4-es t ren-3 ,17-dione

4 - e s t r ene - 3 , 1 1 , 1 7 - t r ione

3a - hydr oxy - 5/3-andr ostan -17-one

REACTION

1 7 - C = 0 -17/3-OH; 3 Q - O A C -*3a-OH

1 7 - C = 0 -17/3-OH

17-C = 0 ^ 17/3-OH; 3ß-OAc -3/3-OH

17/3-OH -1 7 - C = 0

17ß-OH -> 1 7 - C = 0

1 7 - C = 0 -17/3-OH

17/3-OH -1 7 - C = 0

1 7 - C = 0 -17/3-OH

1 7 - C = 0 17/3-OH

1 7 - C = 0 — 17/3-OH

1 7 - C = 0 - * 17/3-OH

1 7 - C = 0 - > 17/3-OH

1 7 - C = 0 -17/3-OH

1 7 - C = 0 -17/3-OH

17 /3 -OH^ 1 7 - C = 0

17-C = 0 -17/3-OH

1 7 - C = 0 — 17/3-OH; Δ1; enol.

1 7 - C = 0 ^ 17/3-OH

1 7 - C = 0 — 17/3-OH

R E F .

S-830

S-829; S-830

S-829

S-829

S-829

S-829

S-829

S-829

S-829

S-829; S-830

S-829

S-830

S-830

S-829; S-830

S-829

S-830

S-830

S-830

S-830

1

Δ

1

Δ

668

TABLE I I I

Transformat ions by Genus: TRICHOMONAS

SPECIES

gallinae

(in mixed cul ture with Corynebacter ium simplex [Δ1] )

(in mixed cul ture with Corynebacter ium equi [Δ1!)

vaginalis

SOURCE

NG

NG

SUBSTRATE

3a-hydroxy-5/3-androstan-17-one aceta te


3ß-hydroxy-5-andros ten-17-one aceta te


11/3,17/3-dihydr oxy-4-andr os ten-3-one


17/3-hydroxy-4-andros tene-3 ,11-dione

1 l a -hydr oxy -4 -androstene - 3 , 1 7 -dione

l l / 3 -hydroxy-4 -andros tene -3 ,17-dione

4 - a n d r o s t e n e - 3 , 1 1 , 1 7 - t r i o n e


4 - and ros t ene -3 ,11 ,17 - t r i one

11/3-hydroxy-4-androstene-3,17-dione

l l ß - h y d r o x y - 4 - e s t r e n e - 3 , 1 7 -dione

3a -hydr oxy - 5ß -andr ostan -17 -one


REACTION

17-C = 0 - > 17/3-OH

1 7 - C = 0 - > 17/3 -OH

3/3-OAc->3/3-OH

1 7 - C = 0 - > 17/3-OH

1 7 - C = 0 -17/3-OH; 3ß-OAc -3/3-OH

17/3-OH -» 17-C = 0

17/3-OH-* 1 7 - C = 0

17-C = 0 -17/3-OH

17/3-OH^ 1 7 - C = 0

1 7 - C = 0 - > 17/3-OH

1 7 - C = 0 ^ 17/3 -OH

1 7 - C = 0 - * 17/3-OH

1 7 - C = 0 — 17/3-OH

1 7 - C = 0 - » 17/3-OH

1 7 - C = 0 — 17/3-OH

17-C = 0 - > 17/3-OH

17-C = 0 - > 17/3-OH

1 7 - C = 0 — 17/3-OH

R E F .

S-830

S-829

S-829

S-829; S-830

S-829

S-829

S-829

S-829; S-830

S-829

S-829; S-830

S-829; S-830

S-829; S-830

S-829

S-830

S-830

S-830

S-830

S-830


T r a n s f o r m a t i o n s by Genus : TRICOPHYTON (imperf. - Monmaies) TRICHOTHECIUM (Imperf. - Moniliales)

669

SPECIES

TRICOPHYTON

concentr icum

TRICHOTHECIUM (see Cephalothecium)

ar rhenopum

candidum

cystospor ium

domest icum

lute urn

SOURCE

FRI

uc

uc

CBS

C3S

CBS

SUBSTRATE



1 Iß -hydroxy-4 -p regnene -3 ,20 -dione


4 -p r egnene -3 ,11 ,20 - t r i one




4 -pregnene - 3 , 1 1 , 2 0 - t r ione








4 -pregnene - 3 , 1 1 , 2 0 - t r ione




4 - p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e

REACTION

6/3-OH;l la-OH; 11/3-OH

17a-OH

17a-OH

17a-OH

17a-OH

17a-OH

17a-OH

17a-OH

17a-OH

17a-OH

17a-OH

17a-OH

17a-OH

17a-OH

17a-OH

17a-OH

17a-OH

17a-OH

17a-OH

17a-OH

17a-OH

REF.

S-849

M-600

M-600

M-600

M-600

M-600

M-600

M-600

M-600

M-600

M-600

M-600

M-600

M-600

M-600

M-600

M-600

M-600

M-600

M-600

M-600

670

TABLE I I I

Transformat ions by Genus: T R I C H O T H E C I U M

SPECIES

plasmoparae

polybrochum

roseum

SOURCE

uc

uc

Armour and Co.

ATCC-8685

ATCC-12519

ATCC-12543 (QM-102E)

C

SUBSTRATE


1 Iß -hydroxy-4 -p regnene -3 ,20 -dione


4 -p r egnene -3 ,11 ,20 - t r i one


l l /3 -hydroxy-4-p regnene-3 ,20-dione


4 -p r egnene -3 ,11 ,20 - t r i one

4 -pregnene-3 ,20-d ione ( t rea tment of nut r ien ts ; s ter i l iza t ion withH202 -use of cata lase)

9ce-fluoro-11/3, 21-dihydroxy-4-pregnene-3 ,20-d ione

9a - f luoro-21-hydroxy-1 ,4 -pr egnadiene - 3 , 1 1 , 2 0 - t r i o n e



17a, 21 -dihydroxy -4 -pregnene - 3 , 20-dione




REACTION

17a-OH

17a-OH

17a-OH

17a-OH

17a-OH

17a-OH

17a-OH

17a-OH

11a-OH

17a-OH

17a-OH

7ß-OH

l i a - O H 16

Δ

11/3-OH

11a-OH

11/3-OH

11/3-OH

6/3-OH

17a-OH

6/3-OH

17a-OH

17a-OH; 11/3-OH - + i i - c = o

R E F .

M-600

M-600

M-600

M-600

M-600

M-600

M-600

M-600

W-1122

N-668

N-668

T-1013

T-1013

T-1013

T-1003

T-1003

T-1003

S-878

M-584

M-584

N-654

M-584

F-584

TABLE I I I

T ransformat ions by Genus: T R I C H O T H E C I U M

671

SPECIES

roseum

(in mixed cul ture with Cunninghamella blakesleeana [ l l ß - O H ; l l - C = O v i a l l ß - O H ] Ophiobolus he rpo-t r i chus L21-OH) and Rhizopus n igr icans [ l la-OH])

(in mixed cul ture with Calonectr ia decora [Δ1] Curvular ia lunata [11/3-OH] and Didymella iycopers ic i [A'I) (in mixed cul ture with

1 Ophiobolus herpo-t r i chus [21-OH])

1 (in mixed cul ture with 1 Calonectr ia decora

ιΔ;ι1 Ophiobolus herpo-t r i chus [21-OH|)

(in mixed cul ture with 1 Cunninghamella

blakesleeana [ l l ß - O H ; l l - C = 0 - v i a l l ß - O H ] )

(in mixed cul ture with 1 Calonectr ia decora

[Δ1 ] Cunninghamella blakesleeana [ 11/3-OH; 1 1 - C = 0 - v i a l lß -OH])

1 (in mixed cul ture with 1 Cunninghamella

blakesleeana [ l l ß -OH; l l - C = 0 - v i a l l ß -OH] )

(in mixed cul ture with Didymella Iycopersici [A1] )

(in mixed cul ture with Ophiobolus he rpo-t r i chus [21 -OH]

1 Wojnowicia graminis [21-OH] )

SOURCE

C

SUBSTRATE

21-hyd roxy -4 -p regnene -3 ,11 ,20 -t r ione

d , l - l l ß , 2 1 - d i h y d r o x y - 3 , 2 0 -diketo -4 -pr egnen -18 -al (18—»11) hemiace ta l





l l ß - h y d r o x y - 4 - p r e g n e n e - 3 , 20-dione



d, 1-21-hydroxy-4-pregnene-3,2C-dione

21-hydroxy-9ß, l l ß - o x i d o - 4 -pregnene-3 ,20-d ione ace ta te

9 o - f l u o r o - l l ß , 2 1 - d i h y d r o x y - 4 -p regnene-3 ,20-d ione 2 1 -aceta te

4 - p r e g n e n e - 3 , 1 1 , 2 0 - t r i o n e

REACTION

17a-OH

d,l->d-17a-OH + 1

17a-OH

17a-OH

17a-OH

17a-OH

17a-OH

17a-OH

17a-OH

d , l - d - 1 7 a - O H + 1

17a-OH

17a-OH

17a-OH

R E F .

M-584

W-1102

W-1106

W-1107

W-1106

W-1106

W-1107

W-1106

W-1107

W-1102

W-1107

W-1107

W-1106

672

TABLE I I I

Transformat ions by Genus: TRICHOTHECIUM

SPECIES

ro seum (in mixed cul ture with Cunninghamella blakesleeana [11/3-OH; 1 1 - C = 0 ] Ophiobolus herpotr ichus [21-OH|)

(in mixed cul ture with Ophiobolus herpo-t r ichus [21-OH])

(in mixed cul ture with Ophiobolus he rpo-t r ichus [21-OH])

(Link) (also pseudovert ic i l l ium for m)

(= Cephalothecium roseum - ATCC-8685)

SOURCE

C

CBS

FRI

NRRL

NRRL-1665

SUBSTRATE

1,4 -pregnadiene -3 ,20-dione

1 Iß -hydroxy-1,4-pregnadiene -3,20-dione

1,4 -pregnadiene - 3 , 1 1 , 2 0 - t r ione


11ß-hydroxy-4-pregnene-3 ,20-dione



3/3,14/3-dihydroxy-5j3-20(22)-cardenolide


Sarsasapogenin

Diosgenin



l l j3 -hydroxy-4-pregnene-3 ,20-dione


11/3,21-dihydroxy-4-pr egnene -3, 20-dione


4 - p r e g n e n e - 3 , 1 1 , 2 0 - t r ione

REACTION

17a-OH

17«-OH

17a-OH

17a-OH

17a-OH

17a-OH

17a-OH

3 ß - O H - 3 - C = 0

7/3-OH

12j3-OH

-

---

17a-OH

17a-OH

6ß,17a-diOH; 21-OAc^21-OH

l l a , 1 7 a - d i O H ; 21-OAC—21-OH

17a-OH;ll /3-OH -n-c=o l l a - O H

17a-OH

R E F .

W-1106

W-1106

W-1106

M-600

M-600

M-600

M-600

J-432

J-432

J-432

S-849

M-587

M-587

M-587

M-600

M-600

M-600

M-600

M-600

M-600

M-600

673


TABLE I I I

TRICHOTHECIUM TRITIRACHIUM

TUB ARIA UNIDENTIFIED

TAXONOMY

(Imperf. - Moniliales) (Basidio. - Agaricales)

SPECIES

roseum

TRITIRACHIUM

purureum

TUBARIA

conspersa

UNIDENTIFIED (listed alphabetically by reference)

1 bacter ium

SOURCE

NRRL-1665

NRRL-2576 (QM-936)

NRRL-2577 (QM-599)

SQ

SSSR (s t ra ins 17 through 26)

V E 3

FRI

AL(SS-32)

SCH (FC-C-78)

SUBSTRATE




6 a - c h l o r o - 1 6 a , 1 7 a , 2 1 - t r i -hydroxy-4 -p regnene -3 ,20 -dione 16,17-acetophenonide

6 a - f l u o r o - 1 6 a , 1 7 a , 2 1 - t r i -hyd roxy-4 -p regnene -3 ,20 -dione 16 ,1 7 -acetonide



4 -pregnene - 3 , 1 1 , 2 0 - t r ione

4 - p r e g n e n e - 3 , 20-dione




11/3,17a, 21 - t r i hyd roxy-4 -p reg -n e n e - 3 , 20-dione

17a, 21 -d ihydroxy-4-pregnene-3 , 1 1 , 2 0 - t r ione

REACTION

17a-OH

l l a , 1 7 a - d i O H

l l a , 1 7 a - d i O H

11a-OH

11a-OH

6/3,1 la -d iOH

l l a , 1 7 a - d i O H

-

-

6j3,14a-diOH

-


2 0 - C = O -20/3-OH

20-C=O-+ 20/3-OH

2 0 - C = O ^ 20/3-OH

R E F .

M-600

D-188

D-188

D-159

D-159

T-1010

T-1010

T-1010

T-1010

S-811

S-849

S-825

C-110

C-110

C-110

SPECIES

bac ter ium (listed alphabetically by reference)

(actually g ram + coccus . )

bac ter ium isolated from yeas t cake

"faulnis bac té r i en" (putrefactive -anaerobic)

intest inal mic roorgan-1 i s m s 1 (from male albino 1 r a t s )

SOURCE

SCH (FC-C-78)

Univ. of Milan

(IK; IKC; IKR 0 - 4 , Y-12)

Okayama Univ. Med.

School (CE-1)

NG

TAKEDA (A,B,C)

NG

NG

NG

SUBSTRATE


1 7 a , 2 1 - d i h y d r o x y - l , 4 - p r e g n a -d i ene -3 ,11 ,20 - t r i one

5-cholesten-3/3-ol

4 -cholesten - 3 -one

choles teryl acetate

3a, la, 12a-trihydroxy-5/3-cholanic acid (sole carbon source)

not given


3/3 -hydr oxy - 5 -andr osten -17 -one (product then reduced by yeas t - 17-C = 0 -»17/3-OH -to t e s tos te rone - 17/3-hydroxy -4-andros ten-3-one)

17a -methyl - 5 -andros tene -3/3,17/3-diol


5-choles ten-3ß-ol

5a -andros tane -3 ,17-d ione



5-choles ten-3a-o l

5-cholesten-3/3-ol

5 -choles ten-3 -one

4 ,4-dimethyl-5-choles ten-3/3-ol

5,7-cholestadien-3/3-ol

24-ethyl-5 ,22-choles tadien-3/3-ol

REACTION

2 0 - C = O -20/3-OH

2 0 - C = O ^ 20/3-OH

utilization

utilization

util ization

3 a - O H - 3 - C = 0 ; Δ4

1

Δ 1

Δ ; further oxidation

Δ ^ Δ ;3/3-OH ->3-C=0

Δ5—Δ4; 3β-ΟΗ - 3 - C = 0

Δ5—Δ4; 3/3-OH ->3-C=0

-

3-C = 0 ^ 3 a - O H ; 3-C = 0^3/3-OH

Δ ^ 5 / 3 - Η ; 3 - C = 0 - 3 a - O H

Δ4—5a-H; 3-C = 0-+3/3-OH

Δ4->5α-Η

Δ 5 - 5 β - Η ; 3a-OH-3/3-OH

Δ 5 ^ 5 β - Η

Δ 5 -5/3-Η; 3-C = 0—3ß-OH

-

Δ ^ 5 / 3 - Η

Δ5^5/3-Η

REF.

C-110

C-110

C-136

C-136

C-136

E-194; H-357

H-387

1-427

M-538

M-542

M-540

M-540

M-548

M-547; M-548

M-547; M-548

M-547

N-655

N-655

N-655

N-655

N-655

N-655


TABLE I I I

UNIDENTIFIED

674

TABLE I I I

T ransformat ions by Genus: U N I D E N T I F I E D

675

SPECIES

intestinal microorgan-isms (from male albino rats)

bacteria - (22 isolates from 10 different source materials)

(cholesterol - sole carbon source)

(particularly active bacterium no. 5)

1 basidiomycete (MEX - 25,° 228)

bacterium (feces)

1 soil microorganisms

SOURCE

NG

NG

AL (SS-70) (SS-50)

AL (Z-9;12)

NG

NG

SUBSTRATE

24/3-methyl-5,7,22-cholesta-trien-3/3-ol

3α, 7α, 12a-trihydroxy-5ß-cholanic acid

l,3,5(l0)-estratriene-3,17ß-diol

1,3, 5(10)-estratriene-3,16a, 17/3 -triol

17ß-hydroxy-4-androsten-3-one

3/3 -hydr oxy - 5 -andr osten -17 -one


5-cholesten-3ß-ol

5-cholesten-3ß-ol acetate

5-cholesten-3/3-ol palmitate

24/3 - methyl -5,7,22 -cholesta -trien-3/3-ol




3a, 7a, 12a-trihydroxy-5ß-cholanic acid



5-cholesten-3ß-ol

potassium 5a-cholestan-3ß-ol sulfate

REACTION

Δ5-5β-Η

7a-OH->7-C = 0

7a-OH - H

12a-OH->12-C = 0;7a-OH-*H

3a-OH-3-C=0; 12a-OH^12-C = 0;7a-OH--»H

utilization

utilization

utilization

—

utilization

utilization

-

—

utilization

—

—

utilization



Δ5-5β-Η

A ring cleavage

REF.

N-655

N-676

N-676

N-676

N-676

S-793c

S-793c

S-793c

S-793c

S-793c

S-793c

S-793c

S-793c

S-793c

S-793c

S-793c

S-793c

S-793c

S-825

S-825

S-914

S-940

676


T r a n s f o r m a t i o n s by G e n u s : UNIDENTIFIED USTILAGO VENTURIA

VERTICILLIUM

(Basidio. - Usti laginales) (Asco. - Sphaeriales) (Imperf. - Moniliales)

SPECIES

soil mic roorgan i sms

bac ter ia (soil)

fungus belonging to family - Dematiaceae

fungus belonging to order - Melanconiales and Moniliales

USTILAGO

zeae

VENTURIA

p i rma (pirina)

VERTICILLIUM

a lbo-a t rum

dahliae

malthousii

SOURCE

NG

NG

NG

Lepetit

NG

NRRL

TNAES

IFO (5922)

IFO (5916; 6119; 6126; 6150)

IFO (6624)

SUBSTRATE

5-cholesten-3j3-ol

potass ium 5-cholesten-3/3-ol sulfate ( subs t ra te used to diver t attack from 3-C position)

5-cholesten-3/3-ol ( subs t ra te added to soil to demonst ra te degradation is the r e su l t of microbia l action)


17a, 21-d ihydroxy-1 ,4 -p regna-d iene-3 ,20-dione


Sarsasapogenin

Diosgenin






REACTION

Δ 5 - Δ 4 ; 3j3-OH ->3-C=0

7-C = 0 (probably not microbiological)

utilization

2 0 - C = O -20/3-OH

l l a - O H

11/3-OH

14a-OH

Δ -»Δ*; 3β-ΟΗ - 3 - C = 0

-

-

-

-

—

—

6j3-OH

l l a - O H

R E F .

S-940

S-940

T-1029

V-1045

T-990

T-990

T-990

P-710

M-587

M-587

M-587

S-849

K-468

K-468

K-468

K-468

677


τ . . . . η VERTICILLIUM T r a n s f o r m a t i o n s by G e n u s : VIBRIO (Schizo. - Pseudomonadaies)

VOLUTELLA (Imperf. - Moniliaies) vVOJNOWICIA (Imperf. - Sphaeropsidales)

SPECIES

nieveost ra tosum

species

theobromae

(in mixed cul ture with Bacil lus sphaer icus -ATCC-7C55 [ Δ 1 ] )

VIBRIO

cyclosi tes

metschnikovu

percolans

(but in mixed culture with Mycococcus sp . A,)

tyrogenes

VOLUTELLA

ciliata

WOJNOWICIA

graminis

(in mixed culture with 1 Trichothecium r o s e u m

[ 1 7 a - O H ] )

SOURCE

FRI

IFO (6625)

NG

CBS

NG

IAM

IFO (3348)

IAM

Leo P h a r m , P r o d u c t s , Denmark

C

SUBSTRATE




24 /3-methyl -5 ,7 ,22-choles ta t r ien-3/3-ol (sole carbon source)







17j3-hydroxy- 17a -methyl - 4 -andros ten-3-one

17a, 21 -dihydr oxy-4-pregnene-3,20-dione

d, l - l l ^ - h y d r o x y - 3 , 2 0 - d i k e t o - 4 -pregnen-18-o ic acid ( 18—^ 11) lactone

d, i - l l / 3 -hydroxy-4 -p regnene-3 , 18 ,20- t r ione

REACTION

-

6/3-OH

-

—

11a-OH

11/3-OH

11a-OH; l l ß - O H

-

—

1

Δ

—

1

Δ 1

Δ

1

Δ

d , l - d - 2 1 - O H + 1

d , l >d-21-OH +1

R E F .

S-849

K-468

S-793c

S-793c

K-468

K-468

K-468

T-1030

S-849

1-428

1-428

S-849

L-525

L-525

L-525

W-1102

W-1102

678

TABLE I I I

Transformat ions by Genus: WOJNOWICIA

SPECIES

graminis

(in sequential fe rmen-tation with one or the other of Curvular ia lunata [110-OH] Tr ichoderma [17a-OH] Cunninghamella [11/3-OH] Pénic i l l ium [ l l a -OH]Ompha l i a t r a

1 [11/3-OH])

SOURCE

CBS

NRRL -2472

SUBSTRATE






11/3-hydr oxy-4-pr egnene-3 ,20-dione



11/3,12/3-oxido-4-pregnene-3,20-dione

11/3,120-oxido-1,4-pregnadiene-3,20-dione


REACTION

6/3-OH

12a-OH

14a -OH ;17/3 -OH - 1 7 - C = 0

16a-OH

16j3-OH

1 6 - C = 0

17/3-OH -1 7 - C = 0

14 Δ ; 12a-OH

16a-OH; Δ -» 5£-H;3-C = 0 ?

6/3-OH

1 7 - C = 0 -17/3-OH

16a-OH;17-C=0 -17/3-OH

21-OH

21-OH

21-OH

21-OH

21-OH

21-OH

21-OH

21-OH

21-OH

R E F .

H-381

H-381

H-381

H-381

H-381

H-381

H-381

H-381

H-381

H-381

H-381

H-381

M-564

D-183; D-184

D-183; D-184

D-184

D-184

D-184

D-156; D-157

D-157

M-566; M-567

TABLE I I I

679

TAXONOMY

T r a n s f o r m a t i o n s by Genus: W O J N O N V I C I A XANTHOMONAS XEROMPHALINA

XYLARIA YEAST

(Schizo. - Pseudomonadales) (Basidio. - Agar icales) (Asco. - Sphaeriales)

SPECIES

gramin is (in sequential f e rmen-tation with Curvular ia lunata[l l j3-OH])

XANTHOMONAS (see Phytomonas)

c i t r i

malvacerum

(in mixed cul ture with Mycococcus sp . Ax)

XEROMPHALINA

tenuipes

XYLARIA

1 polymorpha

1 species

YEAST

see under the following genera;

CANDIDA DE3ARYOMYCES ENDOMYCES EREMASCUS HANSENULA KLOECKERA MONILIA NADSONIA OÏDIUM OOSPORA PICHIA PSEUDOMYCODERMA RHODOTORULA

1 (continued)

SOURCE

NRRL-2472

FAKU

IFO (3383)

AL (SS-6)

FRI

Sear le (M-40-6)

SUBSTRATE



l l ß , 17a ,21 - t r i hyd roxy-4 -p reg -nene-3 ,20-d ione




REACTION

21-OH

l

Δ

-

—


I I G - O H

1/3-OH

7/3-OH

15/3-OH

1/3,6/3-diOH

R E F .

M-566; M-567

S-849

1-428

1-428

S-825

S-849

D-165

D-165

D-165

D-165

680



YEAST ZYGORHYNCHUS (Phyco, - Mucorales)

SPECIES

see under the following genera:

SACCHAROMYCES SACCHAROMYCODES SPOROBOLOMYCES TORULA TORULOPSIS ' *

ZYGORHYNCHUS

heterogamus

moel ler i

SOURCE

SSSR

U

SSSR

U

SUBSTRATE





17ö,21-d ihydroxy-4-pregnene-3, 20-dione

17o,21-dihydroxy-4-pregnene-3,20-dione





REACTION

6/3-OH;lla-OH

oxidation

oxidation

oxidation

oxidation

6/3-OH

oxidation

oxidation

oxidation

oxidation

R E F .

E-224

M-601; M-636

M-601; M-636

M-601; M-636

M-601; M-636

E-224

M-601; M-636

M-601; M-636

M-601; M-636

M-601; M-636

CHAPTER VI

BIBLIOGRAPHY

Adams, W. J . , Patel , D. K. , Petrow, V . , and Stuart-Webb, I. A. , J. Chem. Soc . , p. 297 (1956).

Agnelle-, E. J . , Bloom, B. M. , and Laubach, G. D . , J. Am. Chem. Soc. 77, 4684 (1955).

Agnello, E. J . , Bloom, B. M . , and Laubach, G. D . , U .S . Patent 2,835,683 (May 20, 1958) .

Agnello, E. J . , Bloom, B. M . , and Laubach, G. D . , U .S . Patent 2 ,835,684 (May 20, 1958).

Agnello, E. J. , Bloom, B. M . , and Laubach, G. D . , U .S . Patent 2 ,976 ,283 (March 21 , 1961).

Agnello, E. J . , Figdor, S. K. , Hughes, G. M. K. , Ordway, H. W. , Pinson, R . , J r . , Bloom, B. M . , and Laubach, G. D . , J. Org. Chem. 28, 1531 (1963).

Agnello, E. J . , Laubach, G. D . , and Moreland, W. T . , U .S . Patent 3 ,067,197 (December 4 , 1962).

Allen, W. S . , Bernstein, S . , Feldman, L. I. , and Weiss , M. J . , J. Am. Chem. Soc. 82, 3696 (1960).

Allen, W. S . , and Feldman, L. I . , U .S . Patent 3 ,010,877 (November 28, 1961).

Amiard, G. , andHeymes , R . , U .S . Patent 3 ,005 ,816 (October 24, 1961).

Amiard, G. , and Heymes, R . , U .S . Patent 3 ,033 ,863 (May 8, 1962).

Amiard, G. , andHeymes , R . , U .S . Patent 3 ,052 ,697 (September 4 , 1962).

Amiard, G . , Heymes, R . , and Thuong, T. V. , U .S . Patent 3 ,081 ,300 (March 12, 1963).

Arnaudi, C . , Boll . Sez. Ital. Soc. Intern. Microbiol. 11 , 208 (1939).

Arnaudi, C . , Boll . 1st. Sieroterap. Milan. 21 , 1 (1942).

Arnaudi, C . , Zentr. Bakteriol . , Parasi tenk. , Abt. I. Orig. 105, 352 (1942).

Arnaudi, C . , Boll . 1st. Sieroterap. Milan. 21 , 1-12 (1942).

Arnaudi, C . , Experientia 2 , 138 (1946).

Arnaudi, C . , Rend. Ist. Lombardo Sei. Lettere, Pt. I 83, 151-164 (1950).

Arnaudi, C . , Experientia 7, 81 (1951). REVIEW.

Arnaudi, C. , Appl. Microbiol. 2 , 274 (1954). REVIEW.

Arnaudi, C. , and Colla, C . , Experientia 5, 120 (1949).

681

References A-l through Z-1134 are included in this chapter.

A - l

A-2

A-3

A-4

A-5

A-6

A-7

A-8

A-9

A-10

A - l l

A-12

A-13

A-14

A-15

A-16

A-17

A-18

A-19

A-20

A-21

A-22

682 VI. BIBLIOGRAPHY

Arnaudi, C . , and Ercol i , A. , Boll. 1st. Sieroterap. Milan. 20, 137 (1941).

Arth, G. E . , Beyler , R. E . , and Sarett, L. H . , U .S . Patent 3 ,004,994 (October 17, 1961).

Arth, G. E . , Beyler , R. E . , and Sarett, L. H . , U.S . Patent 3 ,054 ,811 (September 18, 1962).

Asai , T . , Aida, K. , Ohki, E . , Tanaka, T . , and Hattori, M . , J. Agr. Chem. Soc. Japan 32 , 723 (1958).

Asai , T . , Aida, K. , Tanaka, T . , Ohki, E . , Matsuhisa, T . , Takeda, Y . , and Inui, T. , J. Gen. Appl. Microbiol. (Tokyo) 5, 127 (1959).

Asai , T . , Aida, K. , Tanaka, T . , and Sato, Yoshihiro, J. Agr. Chem. Soc. Japan 35, 122 (1961).

Asai , T . , Tsuda, K. , Aida, K. , Ohki, E . , Tanaka, T . , Hattori, M . , and Machida, H . , J. Gen. Appl. Microbiol. (Tokyo) 4 , 63 (1958).

Asai , T . , Tsuda, K. , Aida, K. , Ohki, E . , Tanaka, T . , and Hattori, M . , J. Gen. Appl. Microbiol. (Tokyo), 4 , 79 (1958).

Ayer, D. E . , U .S . Patent 3 ,056 ,808 (October 2 , 1962).

Baba, S . , Brodie, H. J . , Hayano, M . , Peterson, D. H . , and Sebek, O. K. , Steroids l , 151 (1963).

Babcock, J. C . , and Campbell, J. A. , U .S . Patent 2 ,838,534 (June 10, 1958).

Babcock, J. C. , Campbell, J. A . , and Hogg, J. A . , U .S . Patent 2 ,838,531 (June 10, 1958).

Babcock, J. C . , Campbell, J. A . , Hogg, J. A . , and Sebek, O. K. , U .S . Patent 2 ,838,544 (June 10, 1958).

Babcock, J. C . , and Pederson, R. L . , U.S. Patent 2 ,971,886 (February 14, 1961).

Badia, D. J . , and Sardinas, J. L . , U .S . Patent 3 ,010 ,876 (November 28, 1961).

Bagli, J. P . , Morand, P. F . , Wiesner, K. , and Gaudry, R . , Tetrahedron Letters, p. 387 (1964).

Baichikov, A. G . , Barmenkov, A. S . , and Eroshin, V. K. , Med. Prom. SSSR 13, 15 (1959). REVIEW.

Barber, G. W. , Peterson, D. H . , and Ehrenstein, M . , J. Org. Chem. 25, 1168 (1960).

Barkemeyer, H. R . , Stoudt, T. H . , Chemerda, J. M . , Kozlowski, M. A . , and McAleer, W. J . , Appl. Microbiol. 8, 237 (1960).

Barmenkov, A. S. , Fedotiva, M. V . , Eroshin, V. K. , Gusakova, E. G . , and Ogareva, O. B . , Med. Prom. SSSR 15, 39 (1961).

Beal , P . F . , Hogg, J. A . , and Jackson, R. W., U .S . Patent 2 ,989,523 (June 20, 1961).

Beal, P . F . , and Kagan, F . , U.S . Patent 3 ,053 ,864 (September 11 , 1962).

Beesch, S. C. , and Shull, G. M . , Ind. Eng. Chem. 47 , 1857 (1955). REVIEW.

Beesch, S. C . , and Shull, G. M . , Ind. Eng. Chem. 4 8 , 1585 (1956). REVIEW.

Beesch, S. C . , and Shull, G. M . , Ind. Eng. Chem. 49 , 1491 (1957). REVIEW.

Beesch , S. C . , and Tanner, F . W . , Jr . , Ind. Eng. Chem. 50, 1341 (1958). REVIEW.

A-23

A-24

A-25

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BIBLIOGRAPHY 687

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CHAPTER VII

BIBLIOGRAPHICAL APPENDIX

References Ap-1 through Ap-100 are included in this chapter.

Ap-l Afonso, A. , Herzog, H. L. , Federbush, C. , and Charney, W. , Steroids 7, 429 (1966). Conversion of 1,3,5(10) - cholestatrien-3-ol into estrone by Nocardia restr ictus.

Ap-2 Bellet , P . , Nomine, G. , and Mathieu, J. , Compt. Rend. 263C, 88 (1966). Stereo-specific reduction of an optically inactive ketonic precursor in a total synthesis of steroids using Rhizopus arrhizus to give an optically active intermediate which could be converted to estradiol of the natural s e r i e s . Same principle as Gibian reference (Ap-24).

Ap-3 Benn, W. R. , Tiberi, R. , and Nussbaum, A. L. , J. Org. Chem. 29, 3712 (1964). Oxidation of 5,16-pregnadiene-3/3,20/3-diol and the corresponding 20a-o l with Flavo-bacterium dehydrogenans to 16-dehydroprogesterone.

Ap-4 Bolt, C. C. , Mijs, W. J. , Zeelen, F. J. , Szpilfogel, S. A . , de Fl ines , J. and van der Waard, W. F . , Rec. Trav. Chim. 84, 626 (1965). lj3-Hydroxylation of 19-nortestosterone with Botryodiplodia malorum.

Ap-5 Brannon, D. R. , Martin, J. , Oehlschlager, A. C. , Durham, N. N. , and Zalkow, L. H . , J. Org. Chem. 30, 760 (1965). Aspergillus tamarii on progesterone gave testololactone and 11/3 -hydroxytestosterone. 11/3-Hydroxyprogesterone gave 11/3-hydroxytestosterone. l la-Hydroxyprogesterone gave 11a-hydroxytestosterone. 4-Androstene-3,17-dione and testosterone gave testololactone.

Ap-6 Bridgeman, J. E. , Cherry, P. C . , Cottrell , W. R. T . , Jones , E. R. H . , Le Quesne, P. W. , and Meakins, G. D . , Chem. Commun, p. 561 (1966). 1/3,6a-Dihydroxylation of 5a-androstan-17-one with unnamed organism.

Ap-7 Canonica, L. , Jommi, G. , Pagnoni, U. M . , Pel l izzoni , F . , Ranzi, B. M. , and Scolastico, C . , Gazz. Chim. Ital. 96, 820 (1966). 7j3-Hydroxylation and oxidation of 3-hydroxyl to ketone in glycyrrhetic acid by Curvularia lunata.

Ap-8 Capek, A . , Hanc, O . , Tadra, M . , and Tuma, J. , Cesk. Farm. 4 , 198 (1966). Improved preparation of cortisone from Re ichs tem^ Compound S.

Ap-9 Capek, A . , Tadra, M . , and Tuma, J . , Folia Microbiol. (Prague) 9, 380-382 (1964).

Ap-10 Casas-Campil lo, C. , and Baut is ta, M . , Appl. Microbiol. 13 , 977 (1965). 1 5 a -Hydroxylation of estrone and estradiol with Fusarium moniliforme. 6/3-Hydroxyla-tion of estradiol 3-methyl ether with same organism.

Ap-11 Casas-Campil lo , C . , Esparza, F . , and Balandrano, D . , Bacteriol . Proc . p. 93 (1965).

Ap-12 Cherry, P. C . , Jones , E. R. H . , and Meakins, G. D . , Chem. Commun, p. 587 (1966). 3/3-Hydroxylation and 12/3-hydroxylation of 5-androsten-7-one by Calonectria decora. Tentative 4j3-hydroxylation of the same substrate by the same organism.

721

722 VII. BIBLIOGRAPHICAL APPENDIX

Ap-13 Coombe, R. G. , Tsong, Y. Y. , Hamilton, P. B. , and Sih, C. J. , J . Biol. Chem. 241, 1587 (1966). Degradation of estrone by Nocardia sp. via 4-hydroxylation.

Ap-14 Curtis, P. J . , Biochem. J. 97, 148 (1965). Demethylation of totally-synthetic, phenolic 8-azasteroid 3-methyl ether by Aspergillus flavus and Cunninghamella blakesleeana. Reduction of 17a-carbonyl group in same substrate to 17aa-ol and 17a/3-ol by Aspergillus ochraceus.

Ap-15 Davidson, S. J . , and Talalay, P. , J . Biol. Chem. 241, 906 (1966). Soluble 5/3-dehydrogenase from Pseudomonas testosteroni.

Ap-16 deFlines, J . , van der Sijde, D. , and van der Waard, W. F. , Rec. Trav. Chim. 85, 701 (1966). Fermentation of 9/3,10α -progesterone with Sporomia pollaccii yielded mainly 9/3,10a -testosterone. Fermentation with Helicosporium lumbricopsis afforded 9j3, 10α? -androst-4-ene-3,17-dione. Fermentation with Colletotrichum gloeosporioides afforded 15a-hydroxy-9/3,10a-progesterone. This product was converted with Helicosporium lumbricopsis to 15a-hydroxy-9/3,10a-androst-4-ene-3,17-dione. Fermentation of 6-dehydro-9/3,10α-progesterone with Mastigosporium heterosporium afforded 9/3,10a-androsta-4,6-diene-3,17-dione.

Ap-17 Deghenghi, R. , Revesz, C. , and Gaudry, R. , J . Med. Chem. £, 301 (1963). Failure of Septomyxa affinis and Streptomyces lavendulae to degrade the side chain to 17a-alkyl derivatives of progesterone.

Ap-18 Dodson, R. M. , Langbein, G. , Muir, R. D. , Schubert, A. , Siebert, R. , Tamm, C , and Weiss-Berg, E. , Helv. Chim. Acta 48, 1933 (1965). Identity of "6/3,15α·-di-hydroxyprogesterone" (G-319) and " l i a , 15/3-dihydroxyprogesterone" (M-596) with 12/3,15α -dihydroxyprogesterone.

Αρ-19 El-Tayeb, O. , Knight, S. G. , and Sih, C. J . , Biochim. Biophys. Acta 93, 402 (1964). Cylindrocarpon radicicola on 16a,17a-oxidoprogesterone (I) gave 20a-hydroxy-16a,17a-oxido-4-pregnen-3-one (II), 20a-hydroxy-16a,17a-oxido-l,4-pregnadien-3-one (III), 16a-hydroxy-17a-oxa-l,4-androstadiene-3,17-dione (IV) and 16a,17a-dihydroxy-l,4-androstadien-3-one (V). Sequence and mechanism of degradation are discussed. 16a-Hydroxy-4-pregnene-3,20-dione gave (V) only. 16a-Hydroxy-4-androstene-3,17-dione gave (IV) and (V).

Ap-20 El-Tayeb, O. , Knight, S. G., and Sih, C. J. , Biochim. Biophys. Acta 93, 411 (1964). 17a-Hydroxyprogesterone with Pénicillium citrinum gave 12/3-hydroxylation and 15/3-hydroxylation. Cylindrocarpon radicicola gave 17a-oxa-l,4-androstadiene-3,17-dione from either 17a-hydroxyprogesterone or 16-dehydroprogesterone.

Ap-21 Eroshin, V. K. , Med. Prom. SSSR 16, 23-25 (1962).

Ap-22 Fukushima, D. K. , J . Biol. Chem. 239, 1748 (1964). 3a-Hydroxy-5/3-androstane-17-one and 5/3-androstane-3,17-dione were hydroxylated at 7/3- by Pénicillium sp.

Ap-23 Fukushima, D. K. , and Noguchi, S. , Federation Proc. 24, 414 (1964). Andro-sterone and Pénicillium sp. gave 12/3-hydroxylation. Epiandrosterone with the same organism gave la-hydroxylation. 5a-Androstane-3,17-dione gave some l a , 3/3-dihydroxy-5a-androstan-17-one. 3/3-Hydroxy-5/3-androstan-17-one gave the 7/3-ol and 7/3-hydroxy-5/3-androstane-3,17-dione.

Ap-24 Gibian, H., Kieslich, K., Koch, H. J . , Kosmol, H. , Rufer, C . , Schröder, E . , and Vossing, R. , Tetrahedron Letters 21, 2321 (1966). Asymmetric reduction with Saccharomyces sp. and Bacillus thuringiensis of a carbonyl group in a totally synthetic, optically inactive steroid precursor.

Ap-25 Gibson, D. T . , Wang, K. C. , Sih, C. J. , and Whitlock, H. , J r . , J . Biol. Chem. 241, 551 (1966). The structures of several nonsteroidal degradation products from the action of Nocardia restrictus on A4-3-ketosteroids, and insights into the mech-anism of degradation derived therefrom; also J . Am. Chem. Soc. 87, 1386 (1965).

BIBLIOGRAPHICAL APPENDIX 723

Ap-26 Greenspan, G. , Rees , R . , Smith, L. L. , and Alburn, H. E. , J. Org. Chem. 30, 4215 (1965). 11a -Hydroxylation and 12/3-hydroxylation of steroidal alkaloids (funt-umine and funtumidine) by Aspergillus ochraceus.

Ap-27 Greenspan, G . , Smith, L. L. , Foel l , T. J . , and R e e s , R . , U .S . Patent 3 ,231 ,589 (1966). Hydroxylation of 18-homo-19-nortestosterone at lß,6ß,10/3, a n d l l a b v

Aspergillus ochraceus.

Ap-28 Greenspan, G. , Smith, L. L . , Rees , R. , Foel l , T. J . , and Alburn, H. E. , J. Org. Chem. 31 , 2512 (1966). Microbial transformation of steroids of the unnatural ( / ) s e r i e s , and simultaneous transformation of other d- and I -substrates by the same cultures.

Ap-29 Grozdyak, P. I . , Med. Prom. SSSR 16, 26-28 (1962).

Ap-30 Holmlund, C. E . , Sax, K. J. , Blank, R. H. , and Evans, R. H. , Jr . Steroids 5, 459 (1965). 7/3-Hydroxylation and deacetylation of 16a -methy l -17a , 21-dihydroxy-4-pregnene-3,20-dione 21-acetate with Rhizopus nigricans. 1 la-Hydroxylation and deacetylation of the same substrate with Dactylium dendroides.

Ap-31 Iida, M. , Townsley, J. D. , Hayano, M . , and Brodie, H. J. , Steroids, Suppl. 1, p. 159 (1965). Reversible A1-dehydrogenating-hydrogenating enzyme system i s o -lated from Bacillus cyclo-oxydans. Dependence on cofactors and enzyme induction discussed.

Ap-32 Irmscher , K. , Bier Stecher, W. , Metz, H. , Watzel, R . , and Bork, K. H. , Ber . 97, 3363 (1964). A1-Dehydrogenation of 7α-hydroxytestosterone and 7a-acetoxy-methyltestosterone by Corynebacterium simplex. 7a-Hydroxylation of methyltes-tosterone and testosterone by Curvularia lunata and Cunninghamella blakesleeana.

Ap-33 Jeruss i , R. , and Ringold, H. J. , Biochemistry £» 2113 (1965). Enzyme kinetics of 1,2-dehydrogenation using cellfree preparations of Bacillus sphaericus. Comments on mechanism.

Ap-34 Kogan, L. M . , Ulezlo, I. V . , Kozlova, I. K. , Suvorov, N.. N. , Portnova, S. L . , ^ Skryabin, G. K. , and Torgov, I. V. , Izv. Akad. Nauk SSSR, Ser. Khim. No. 11 , p. 2008-2015 (1964).

Ap-35 Kogan, L. M. , Vorshvil lo, W. E . , Skryabin, G. K. , and Torgov, I. V . , Dokl. Akad. Nauk SSSR 160, 346-348 (1965).

Ap-36 Kondo, E . , Kogyo Kagaku Zasshi 67, 724-727 (1964).

Ap-37 Kondo, E. , and Mitsugi, T . , J. Am. Chem. Soc. 88, 4737 (1966). Degradation of spiroketal side chain in diosgenin and tigogenin by Fusarium solani and Corynebac-terium simplex. Formation of l ,4-androstadiene-3 ,16-dione in 65% yield. D i s -cussion of mechanism.

Ap-38 Kondo, E . , Mitsugi, T . , and Tori, K. , J. Am. Chem. Soc. 87, 4655 (1965). 18-Hydroxylation of corticosterone by Corynespora cass i icola and Corynespora melonis . Microbial synthesis of aldosterone.

Ap-39 Kurosawa, Y. , Shimojima, H. , and Osawa, Y. , Steroids Suppl. 1, p. 185 (1965). Resolution of totally synthetic steroid precursors by yeast and pancreatic enzymes.

Ap-40 Koscheenko, K. A . , Skryabin, G. K. , Eroshin, V. K. , Kogan, L. M . , and Torgov, I. V . , Prikl . Biokhim. i Mikrobiol. 1', 127-130 (1965).

Ap-41 Kuchaeva, A. G. , and Capek, A . , Microbiology (USSR) (English Transi .) 32 , 843-846 (1964).

Ap-42 Laskin, A. I . , Fried, J. , Cohen, A. I. , Meyers , C . , Grabowich, P. , Junta, B. , Pa lmere , R. M. , and Dias s i , P. A . , Steroids 5, 57 (1965). 2/3 -Hydroxylation of

724 Vu. BIBLIOGRAPHICAL APPENDIX

deoxycorticosterone, 6α-fluoro-4-pregnene-16a , 17α, 21-triol-3,20-dione 16,17-acetonide, 16a-methyl- 17α ,21 -dihydroxy-4-pregnene-3,20-dione, and progesterone with Gnomonia fragariae. 14a-Hydroxylation and 2jS, 16a-dihydroxylation of proges-terone by the same organism.

Ap-43 Laskin, A. I . , Grabowich, P . , Meyers, C. DeL. , and Fried, J. , J . Med. Chem. 7, 406 (1964). Eburicoic acid was transformed by Glomerella fusarioides into 3,4-seco-Δ8?M (28) -eburicadien-4-ol-3,21 -dioic acid.

Ap-44 Malhotra, S. K., and Ringold, H. J. , J . Am. Chem. Soc. 87, 3228 (1965). The mechanism of action of isomerase derived from Bacillus sphaericus.

Ap-45 Mallett, G. E. , Fukuda, D. S. , andGuynes, G. J. , Abstr. 150th Meeting Am. Chem. S o c , Atlantic City, 1965, p. 12Q.

Ap-46 Manson, A. J. , Sjogren, R. E. , and Riano, M. , J . Org. Chem. 30, 307 (1965). Reduction of 17a-ethinyl-17ß-hydroxy-2-hydroxymethylene-4-androsten-3-one by Rhizopus stolonifer to the corresponding 2a-hydroxymethyl product.

Ap-47 Martinkova, J . , and Dyr. J. , Collection Czech. Chem. Commun. 30, 2994 (1965).

Ap-48 Marx, A. F . , Beck, H. C. , van der Waard, W. F. , and de Flines, J. , Steroids 8, 421 (1966). Incubation of concessine with atachybotrys parvispora gave Δ4 -conenin-3-one and lla-hydroxy-Δ4 -conenin-3-one. Fermentation with Gloeo-sporium fructigenum gave 7a-hydroxyconessine, 7/3-hydroxyconessine, and 11a-hydroxyconessine.

Ap-49 Marx, A. F. , Beck, H. C. , van der Waard, W. F. , and de Flines, J . , Steroids 8_, 391 (1966). 9a-Hydroxylation and 12a-hydroxylation of conessine with Botryodi-plodia theobromae.

Ap-50 Modelli, R. , Ann. Chim. (Rome) 55, 205 (1965). 16a-Hydroxylation of 17a-methyltestosterone and 4-hydroxy-17a-methyltestosterone by Nocardia italica.

Ap-51 Modelli, R. , Ann. Chim. (Rome) 55, 310 (1965). 2a-Hydroxylation and 16a-hydroxylation of 4-estrene-3,17-dione and 19-nortestosterone by Nocardia italica.

Ap-52 Neidleman, S. L. , Diassi, P. A. , Junta, B. , Palmere, R. M. , and Pan, S. C. , Tetrahedron Letters, p. 5337 (1966). 17a-Chlorination and 17a-bromination of 16-ketoprogesterone and 16 -keto - A- nor -progesterone by enzymes from Caldario-myces f urn ago together with hydrogen peroxide and a source of halide ion. 16,16-Dibromination of 15-keto-1-denydrotestololactone under same conditions. Proofs of structure by comparison with samples prepared by nonenzymatic halogenation. No enzymatic halogenation occurred with substrates lacking the /3-dicarbonyl structural element. Also 15a-hydroxylation of 1-dehydrotestoloactone by Pénicillium sp. Work by Brown and Hager [J. Am. Chem. Soc. 89, 719 (1967)] indicates that the enzymatic reaction involves generation of Cl from Cl~ and hydrogen peroxide. The inference may be drawn that there is no steroid-enzyme interaction required in the halogenation examples shown by Neidleman.

Ap-53 Noda Institute for Scientific Research, Netherlands Patent 6,502,883 (1965) (Japanese Patent 30915 (1964); Derwent Abstr. 19, 293). Degradation of choles-terol, sitosterol, or stigmasterol by Corynebacterium simplex and other known 1-dehydrogenating species, in the presence of agents which chelate copper or iron, to give 4-androstene 3,17-dione, 1,4-androstadie ne-3,17-dione, and other products.

Ap-54 Noguchi, S. , and Fukushima, D. K. , J . Org. Chem. 30, 3552 (1965). Pénicillium sp. with 3a-hydroxy-5a-androstan-17-one gave 12j3-hydroxy product. The same organism with 3j3-hydroxy-5a-androstan-17-one gave the Ια-hydroxy product and with 3j3-hydroxy-5j3-androstan-17-one gave the 7j3-hydroxy product and 7/3-hydroxy-5j3-androstane-3,17-dione.


Ap-55 Okada, M. , and Hasunuma, M., J. Pharm. Soc. Japan 86̂ , 67 (1966). 7ß-Hydroxy-lation of digitoxigenin with Cunninghamella blakesleeana.

Ap-56 Okada, M. , Hasunuma, M. , and Saito, Y. , J . Pharm. Soc. Japan 85, 1092 (1965). 12/3-Hydroxylation of bufalin and resibufogenin with Gibberella saubinetti.

Ap-57 Okada, M. , and Saito, Y. , Steroids £, 651 (1965). Assignment of structure to Ία., 15a-dihydroxylated product from Gibberella saubinetti on dehydroepiandrosterone.

Ap-58 Okada, M. , Yamada, A. , and Ishidate, J . Pharm. Soc. Japan 85, 816 (1965). 7a -Hydroxylation of dehydroepiandrosterone with Gibberella saubinetti. 15a-Hydroxy-lation of progesterone, deoxycorticosterone, and testosterone with the same organism.

Ap-59 Okumura, T . , Nozaki, Y. , and Satoh, D. , Chem. & Pharm. Bull. (Tokyo) 12, 1143 (1964). 3/3, 14jS, 21-Trihydroxy-5/3-pregnan-20-one gave 1/3-hydroxylation with Absidia orchidis. From 4,5-dehydrodigitoxigenone the 7/3-hydroxy and 7/3,12/3-dihydroxy products were characterized.

Ap-60 Peterson, G. E. , and Davis, J. R. , Steroids 4, 677 (1964). Degradation of cho-lesterol by Streptomyces sp.

Ap-61 Prochazka, Z . , and Sorm, F . , Collection Czech. Chem. Commun. 30, 1874 (1965). l i a -Hydroxylation of 14/3,18-cycloprogesterone (10j3-methyl-13/3,14/3-cyclomethy-lene-17/3-acetyl-4-gonen-3-one) with Rhizopus nigricans.

Ap-62 Prouva, J. , Schwartz, V. , and Syhora, K. , Folia Mikrobiol. (Prague) 9, 218-221 (1964).

Ap-63 Rahim, M. A. , and Sih, C. J . , J . Biol. Chem. 241, 3615 (1966). In vitro studies of oxygenase and esterase from Cylindrocarpon radicicola. Degradation of proges-terone , 17a? -hydroxyprogesterone, 16-dehydroprogesterone, deoxycorticosterone, and 16a , 17a-oxidoprogesterone to C-19 steroids.

Ap-64 Raman, P. B. , and Per on, F. G., Steroids 5, 249 (1965). 11/3-Hydroxylation of 18,21-dihydroxy-4-pregnene-3,20-dione with Cunninghamella blakesleeana.

Ap-65 Reimann, H. , Sarre, O. Z. , and Oliveto, E. P . , Steroids 7_, 505 (1966). Con-version of a 3/3-hydroxy-Δ5 -steroid to a 3-keto-Δ4 -steroid with Flavobacterium dehydrogenans.

Ap-66 Sato, Y. , Waters, J. A. , and Kaneko, H. , J . Org. Chem. 29, 3732 (1964). 9a -Hydroxylation and 7/3-hydroxylation of 5,6-dihydrosolasodine by Helicosytum pir i -forme.

Ap-67 Saucy, G., Eis, H. , Miksch, F . , and Fürst , A. , Helv. Chim. Acta 49, 1529 (1966). lia-Hydroxylation of 9/3,10α -substrates ("retrosteroids") by Aspergillus ochraceus.

Ap-68 Sax, K. J . , Holmlund, C. E. , Feldman, L. I. , Evans, R. H. , J r . , Blank, R. H. , Shay, A. J . , Schultz, J . S. , and Dann, M., Steroids 5, 345 (1965). I a , 2 a - D i -hydroxylation of 17a-ethynyl-17/3-hydroxy-4-androsten-3-one, 9a-fluoro-ll/3,17/3-dihydroxy-17a-methyl-4-androsten-3-one, and ll/3,21-dihydroxy-16a ,17a-isopro-pylidenedioxy-4-pregnene-3,20-dione by inducible enzyme from Nocardia corallina. Same reaction with a Δ1 -substrate, proposed as intermediate in this process.

Ap-69 Schubert, K., Böhme, K. H. , and Hörhold, C. , Z. Naturforsch. 18b, 988 (1963). Degradation of deoxycorticosterone acetate by Mycobacterium smegmatis. Isolation of fragment with only C and D rings from original skeleton intact.

Ap-70 Schubert, K., Groh, H. , and Ho'rhold, C. , Naturwiss. 52, 20 (1965). Degradation of cholesterol and 4-cholesten-3-one by Mycobacterium smegmatis to 9,10-seco-Δ ι, 3,5 do >_andr ostatr ien-3 -ol -9,17 -dione.

VII. BIBLIOGRAPHICAL APPENDIX

Ap-71 Schubert, K. , Schlegel, J . , and Ho'rhold, C., Steroids, Suppl. 1, p. 175 (1965). Clostridium paraputrificum reduces 3-keto-Δ4-steroids to 3a?-hydroxy-4,5ß-di-hydrosteroids; 3-keto-Δ1*4 -steroids to 3-keto-A1 -4,5/3-dihydrosteroids and 3αι-hydroxy-l,2,4,5/3-tetrahydrosteroids; 3-keto-Δ4»6-steroids into Δ6 -3a-hydroxy-4,5/3-dihydrosteroids; and 3-keto-AM?6-steroids to Δ6-3o?-hydroxy-1,2,4,5/3-tetr ahy drosteroids.

Ap-72 Schubert, A. , and Schwarz, S., Experientia 21, 562 (1965). Dehydrogenation at 1- with Mycobacterium sp. and lla-hydroxylation with Rhizopus nigricans using several unusual twenty-carbon substrates.

Ap-73 Schupbach, M. , and Tamm, C. , Helv. Chim. Acta 47, 2217 (1964). Incubation of 14ß,15ß-epoxy-14-anhydro-digitoxigenin with Fusarium lini gave the 12j3-hydroxy product. The same organism with resibufogenin also gave 12/3-hydroxy product.

Ap-74 Schupbach, M. , and Tamm, C. , Helv. Chim. Acta 47, 2226 (1964). Marinobu-fagenin with Fusarium lini gave the 12/3-hydroxy product.

Ap-75 Schuytema, E. C. , Hargie, M. P. , Merits, I. , Schenck, J . R. , Siehr, D. J . , Smith, M. S. , and Varner, E. L. , Biotechnol. Bioeng. 8, 275 (1966). Use of basidiomycetes to hydroxylate (6β, 11α, 17α), reduce (5a-H), and degrade (17/3-Ac —♦ 17a-oxa-17-ketone) progesterone.

Ap-76 Schwarz, V. , Ulrich, M. , and Sy hor a, K. , Steroids 4, 645 (1964). Production of the 1/3-hydroxy product, along with cortisol and 11-epicortisol, by Absidia orchidis on Compound S.

Ap-77 Shaw, D. A., Borkenhagen, L. F . , and Talalay, P . , Proc. Natl. Acad. Sei. U.S. 54, 837 (1965). Identification of amino acids into which fragments of androstene-dione, formed by degradation with Pseudomonas testosteroni, are incorporated.

Ap-78 Shirasaka, M. , Sankyo Kenyusho Nempo 15, 1-35 (1963).

Ap-79 Sih, C. J. , Lee, S. S. , Tsong, Y. Y. , and Wang, K. C. , J . Am. Chem. Soc. 87, 1385 (1965). Nocardia restrictus on 6/3,19-oxido-4-androstene-3,17-dione gave the 9a -hydroxy product. 9a , 19-Dihydroxy-4-androstene-3,17-dione gave 3,19-di-hydroxy-9,10-seco-l, 3,5(10) -androstatriene-9,17-dione. 2,17/3-Dihydroxy-l,4-androstadien-3-one gave 2£,9a-dihydroxy-4-androsten-3,17-dione. 2-Methoxy-17/3-hydroxy-1,4-androstadien-3-one gave 2-methoxy-3,4-dihydroxy-9,10-seco-l,3,5(10)-androstatrien-9,17-dione. 4,9a,17/3-Trihydroxy-4-androsten-3-one gave 3,4-dihydroxy-9,10-seco-l,3,5(10)-androstatriene-9,17-dione which in turn could be degraded further by N. restrictus. Comments on mechanism of degradation.

Ap-80 Sih, C. J. , Lee, S. S. , Tsong, Y. Y. , and Wang, K. C. , J . Biol. Chem. 241, 540 (1966). Degradation mechanisms with Nocardia restrictus.

Ap-81 Sih, C. J. , Lee, S. S. , Tsong, Y. Y. , Wang, K. C. , and Chang, F. N. , J . Am. Chem. Soc. 87, 2765 (1965). 6j3,19-Oxido-4-cholesten-3-one with Nocardia restrictus gave 6/3,19-oxido-4-androsten-3,17-dione ( I ) . 3/3-Acetoxy-5-cholesten-19-ol with organism CSD-10 gave estrone in 72% yield. 3/3-Acetoxy-5a-chloro-6/3,19-oxidocholestane with CSD-10 gave ( I ) .

Ap-82 Sih, C. J . , Lee, S. S. , Wang, K. C . , and Tsong, Y. Y. , Bacteriol. Proc. p. 93 (1965). Mechanism of A-ring degradation by Nocardia restrictus. See also Ap-79.

Ap-83 Sih, C. J . , and Wang, K. C. , J. Am. Chem. Soc. 87, 1387 (1965). 19-Hydroxy-4-cholesten-3-one with Nocardia restrictus gave estrone. 19-Hydroxy-/3-sitost-4-en-3-one gave estrone.

Ap-84 Singh, K., Sehgal, S. N. , and Vezina, C. , Can. J . Microbiol. 11, 351 (1965). Detailed study of the influence of medium and other environmental conditions on the 1-dehydrogenation of Compound S by spores of Septomyxa affinis. Evidence that

726


the required enzyme is constitutive and not induced. Mention of a variety of other spore-forming organisms, spores from which Δ1 -dehydrogenate Compound S.

Ap-85 Skryabin, G. K. , Zryagintseva, I. S. , and Sokolova, L. V. , Izv. Akad. Nauk SSSR, Ser. Biol. 29, 715-20 (1964).

Ap-86 Smith, L. L. , Greenspan, G. , Rees, R. , and Foell, T . , J . Am. Chem. Soc. 88, 3120 (1966). Aspergillus ochraceus on racemic 19-nortestosterone gave Z-l/3-hy-droxy, d-6/3-hydroxy, Z-10j3-hydroxy, and d-l la-hydroxy products. Similar, but not identical, results with racemic higher 18-homologs.

Ap-87 Sokolova, L. V. , Grinyuk, T. I. , Yaroslavtseva, Z. A. , Kovylkina, N. F. , Gusa-kova, E. G. , Skryabin, G. K. , and Suvorov, N. N. , Med. Prom. SSSR 16, 26-28 (1962).

Ap-88 Suvorov, N. N. , Novikova, V. M., Sokolova, L. V. , and Kovylkina, N. F . , Med. Prom. SSSR 14, 22-24 (1960).

Ap-89 Talalay, P . , and Boy er , J . , Biochim. Biophys. Acta 105, 389 (1965). Preparation of crystalline Δ 5 -isomerase from Pseudomonas testosteroni on a large scale.

Ap-90 , Tori, K., and Kondo, E. , Steroids 4, 713 (1964). NMR method for determination of position of hydroxyl group introduced by microbiological transformation. 15a-Hydroxylation from Helminthosporium sigmoideum on Compound S. 15/3-Hydroxy-lation from Cercospora melonis on Compound S. 7 α, 14α -Dihydroxylation from Curvularia lunata on Compound S. 6/3,llo?-Dihydroxylation by Cunninghamella echinulata on progesterone.

Ap-91 Tsong, Y. Y. , Wang, K. C. , and Sih, C. J . , Biochim. Biophys. Acta 93, 398 (1964). Reduction of Δ6 in 17ß-hydroxy-4,6-androstadien-3-one by Nocardia r e -strictus. Other products include 9a-hydroxy-4,6-androstadien-3,17-dione and 9a , 17/3-dihydroxy-4,6-androstadien-3-one.

Ap-92 van der Sijde, D., de Flines, J . , and van der Waard, W. F . , Rec. Trav. Chim. 85, 721 (1966). Fermentation of 17a,21-dihydroxy-9/3,10a-pregn-4-ene-3,20-dione with Aspergillus ochraceus yielded 11a, 17a,21-trihydroxy-9/3,10a-pregn-4-ene-3,20-dione and 15a,17a,21-trihydroxy-9/3,10a-pregn-4-ene-3,20-dione. Fermen-tation of 9/3,10α -progesterone with Aspergillus ochraceus afforded 11a-hydroxy-9ß, 10a -progesterone. Fermentation of the latter product with Sporomia pollaccii and Helicosporium lumbricopsis afforded 1 l a -hydroxy-9/3,10a -testosterone and 11a-hydroxy-9/3,10a-androst-4-ene-3,17-dione. Fermentation of 9β, 10α-testos-terone with Aspergillus ochraceus yielded 1 l a -hydroxy-9)3,10a -testosterone and 11a -hydroxy-9ß, 10a -androst-4-ene-3,17-dione. Fermentation of 17a -hydroxy-9/3,10a-progesterone with Aspergillus ochraceus afforded l la,17a-dihydroxy-9/3,10a-progesterone and 11a-hydroxy-9/3,10a-androst-4-ene-3,17-dione.

Ap-93 van der Waard, W. F . , van der Sijde, D., and de Flines, J . , Rec. Trav. Chim. 85, 712 (1966). Fermentation of progesterone, 9β, 10α-progesterone, 6-dehydro-9/3, 10a-progesterone, and 9/3,10a-testosterone with Sepedonium ampullosporum af-forded the respective 16a-hydroxy derivatives.

Ap-94 Wacker, A. , Drews, J. Pratt , W. B. , Lawrent, H. , and Petzoldt, K. , Z. Natur-forsch. 20b, 547 (1965). Study of steroid-initiated enzyme induction in Pseudo-monas testosteroni with respect to kinetics, strengths of various inducers, and other factors.

Ap-95 Wang, K. C. , Lee, S. S. , Tsong, Y. Y. , Sih, C. J . , Abstr. 150th Meeting Am. Chem. Soc., Atlantic City, 1965, p. 13Q. Failure of Nocardia and Mycobacteria sp. to convert l,3,5(10)-cholestatrien-3-ol into estrone.

Ap-96 Wiechert, R. , Kerb, U. , and Kies lieh, K. , Ber. 96, 2765 (1963). 11/3-Hydroxy-lation of l a -methyl Compound S with Çurvularia lunata.

728 VII. BIBLIOGRAPHICAL APPENDIX

Ap-97 Wiecher t , R. , Z. Naturforsch. 19b, 944 (1964). 1 Iß-Hydroxy 1 ation of la -me thy l -t e s tos te rone and l a -methyl Compound S with Curvu la r i a lunata.

Ap-98 Wilson, J . , and Vest l ing, C. S. , Arch . Biochem. Biophys. 110, 401 (1965). P r e p -ara t ion of a cel l f ree 15a-hydroxyla t ing sys tem from Bacil lus mega te r ium.

Ap-99 Zakrzewski , Z. , Raczkowska, S . , and Lewenstein, W. , P r z e m y s l . Chem. 4 3 , 564-565 (1964).

Ap-100 Zvyagintseva, I. S. , and Skryabin, G. K . , Izv. Akad. Nauk SSSR, Ser . Biol . 24, 525-532 (1964).

Microbial Transformations of Steroids. A Handbook

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