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Journal of Molecular Catalysis B: Enzymatic 97 (2013) 278– 282

Contents lists available at ScienceDirect

Journal of Molecular Catalysis B: Enzymatic

jo u r n al homep age: www.elsev ier .com/ locate /molcatb

nantioselective reduction of 4-chromanone and its derivatives byelected filamentous fungi

omasz Janeczkoa,∗, Jadwiga Dmochowska-Gładysza,b, Antoni Szumnya,dyta Kostrzewa-Susłowa

Department of Chemistry, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, PolandDepartment of Cosmetology, Wrocław College of Physiotherapy, Kosciuszki 4, 50-038 Wrocław, Poland

r t i c l e i n f o

rticle history:eceived 7 March 2013eceived in revised form 27 August 2013ccepted 2 September 2013vailable online 9 September 2013

a b s t r a c t

Biotransformation of 4-chromanone and its derivatives in the cultures of three biocatalysts: Didymo-sphaeria igniaria, Coryneum betulinum and Chaetomium sp. is presented. The biocatalysts were chosendue to their capability of enantiospecific reduction of low-molecular-weight ketones (acetophenone andits derivatives and �- and �-tetralone). The substrates were reduced to the respective S-alcohols withhigh enantiomeric excesses, according to the Prelog’s rule. In the culture of Chaetomium sp. after longer

eywords:iotransformationtereoinversionnantiospecific reduction-Chromanoneilamentous fungi.

biotransformation time an inversion of configuration of the formed alcohols was also observed. Thehighest yield of transformation was observed for 6-methyl-4-chromanone. In all the tested cultures, thehigher was the molecular weight of a chromanone, the lower conversion percent was observed.

© 2013 Elsevier B.V. All rights reserved.

. Introduction

Enantiomerically pure alcohols play an important role in organicynthesis. Among others, they are used as chiral building blocks inynthesis of larger molecules, which are useful in pharmaceuticalndustry [1–3].

Enantiopure (S)-chromanol is a synthon of compound CP-99,331 (Fig. 1), which may find application in treatment of asthma4,5]. Chromanol 293B (Fig. 1), a chiral derivative of 4-amino-,2-dimethylchromane, is a potential class III antiarrhythmic drughat inhibits cardiac IKs potassium channels [6,7]. Yang et al. [8]onclude that the (2)-[3R,4S] enantiomer of chromanol 293B is aelective inhibitor of KvLQT11minK and therefore a useful tool fortudying IKs.

Enantiopure chiral compounds can be obtained via stereose-ective reduction (either biological or chemical one) [9–12]. A

ethod that meets the criteria of green chemistry technology isn asymmetric reduction of ketones with the help of biocatalysts

13–16]. Using whole cells of microorganisms of both growing andesting-state cultures eliminates problems with regeneration of co-actors cooperating with enzymes [17–19]. Additionally, low costs

∗ Corresponding author. Tel.: +48 71 320 52 52; fax: +48 71 3284124.E-mail addresses: janeczko13@interia.pl, tomasz.janeczko@up.wroc.pl

T. Janeczko).

381-1177/$ – see front matter © 2013 Elsevier B.V. All rights reserved.ttp://dx.doi.org/10.1016/j.molcatb.2013.09.004

and simple experimental procedure are the important benefits ofthis method, being an interesting alternative to methods usingsynthetic catalysts [20–22]. Using living organisms for organicsynthesis have also some limitations. Metabolic processes are ofcomplex nature and living biocatalysts have their substrate speci-ficity, so they are not universal. Therefore, it is important to studythe scope of this type catalyst.

2. Experimental

2.1. Materials

The substrates: 4-chromanone (1a), 6-methyl-4-chromanone(1b) and 6,7-dimethoxy-2,2-dimethyl-4-chromanone (1d) werepurchased from Sigma–Aldrich. 7-Hydroxy-2,2-dimethyl-4-chromanone (1e) was obtained in the reaction of resorcinolwith 3-methylbut-2-enoic acid in the presence of zinc chloride.7-Methoxy-2,2-dimethyl-4-chromanone (1c) was obtained inthe reaction of 7-hydroxy-2,2-dimethyl-4-chromanone (1e) withmethyl iodide (Scheme 1).

All the microorganisms: Didymosphaeria igniaria KCh 6670,Chaetomium sp. KCh 6651, and Coryneum betulinum KCh 6538 were

isolated from forest environment (south Poland) from dead parts ofleafy plants and identified in the Department of Forest Phytopatho-logy of the University of Agriculture in Kraków, Poland. The strainswere cultivated on a Sabouraud agar consisting of: aminobac 5 g,

T. Janeczko et al. / Journal of Molecular Catalysis B: Enzymatic 97 (2013) 278– 282 279

O

O

N

S

OH

F

F O

NHSO2CF

3

O

OH

NSO

2

NC

CP-199,331 Chromanol 293B

Fig. 1. Biologically active chromanol derivatives.

xy-2,

p2

2

rwcTtt

2

T(msHshpaGr3gtF

S

Scheme 1. Synthesis of 7-Metho

eptone K 5 g, glucose 40 g and agar 15 g in 1 l of distilled water at8 ◦C and pH 5.5 and stored in refrigerator at 4 ◦C.

.2. Alcohol reference standards

Reference standards of racemic alcohols were obtained byeduction of 4-chromanone (1a) and 6-methyl-4-chromanone (1b)ith NaBH4. Whereas, under the same conditions 2,2-dimethyl-4-

hromanones gave the products of alcohol dehydration (Scheme 2).he desired products (alcohols) were achieved by cooling the reac-ion mixture to 0 ◦C and using the alkaline solution to decomposehe catalyst.

.3. Analytical methods

The course of biotransformation was controlled by means ofLC. Analytical TLC was carried out on silica gel G 60 F254 platesMerck). Chromatograms were developed using hexane/acetone

ixture (3:1, v/v) as the eluent. Compounds were detected bypraying the plates with 1% Ce(SO4)2 and 2% H3[P(Mo3O10)4] in 10%2SO4. Products were separated by column chromatography using

ilica gel (SiO2, Kieselgel 60, 230–400 mesh, 40–63 �m, Merck) andexane/acetone mixture (3:1, v/v) as the developing system. Com-osition of biotransformation mixtures was established by GC. GCnalysis was performed using a Hewlett-Packard 5890A (Series II)C instrument fitted with a flame ionization detector (FID). The chi-

al, capillary column (for 2a: Supelco Beta DEXTM225, Fused Silica

0 m × 0.25 mm × 0.25 �m; temperature program 120 ◦C (1 min),radient 0.4 ◦C/min to 131 ◦C, gradient 30 ◦C/min to 200 ◦C (3 min)R (R) 13.0 min, tR (S) 14.1 min; for 2b: Supelco Gama DEXTM225,used Silica 30 m × 0.25 mm × 0.25 �m; temperature program

cheme 2. Reduction of 2,2-dimethyl-4-chromanones in room temperature.

2-dimethyl-4-chromanone (1c).

120 ◦C (1 min), gradient 0.4 ◦C/min to 135 ◦C, gradient 30 ◦C/min to200 ◦C (3 min) tR (R) 17.7 min, tR (S) 18.6 min; for 2c: Supelco GamaDEXTM225, Fused Silica 30 m × 0.25 mm × 0.25 �m; temperatureprogram 145 ◦C (1 min), gradient 1.5 ◦C/min to 165 ◦C, gradient30 ◦C/min to 200 ◦C (3 min) tR (R) 7.5 min, tR (S) 7.9 min and for 2d:Supelco Gama DEXTM225, Fused Silica 30 m × 0.25 mm × 0.25 �m;temperature program 145 ◦C (1 min), gradient 1.5 ◦C/min to 170 ◦C,gradient 30 ◦C/min to 200 ◦C (3 min) tR (R) 13.6 min, tR (S) 13.9 min)was used to determinate the composition and enantiomericexcesses of product mixtures. Authentic reference samples of theracemic alcohol were prepared by reducing the ketones withsodium borohydride in methanol. The NMR spectra were recordedon a DRX 300 MHz Bruker spectrometer and measured in CDCl3.Optical rotations were measured on an Autopol IV automaticpolarimeter (Rudolph). The absolute configuration of the productswas determined by comparison of their optical rotation value withliterature data.

2.4. Screening procedure

Erlenmeyer flasks (300 ml), each containing 100 ml of themedium consisting of 3 g glucose and 1 g aminobac dissolved inwater, were inoculated with a suspension of microorganisms andthen incubated for 3–7 days at 25 ◦C on a rotary shaker (190 rpm).After full growth of the culture (about 12 g of cell dry weight/l) 20,40, 60, 80 and 100 mg of a substrate dissolved in 1 ml of acetonewas added. After 1, 3, 6 and 9 days of incubation under the aboveconditions, portions of 10 ml of the transformation mixture weretaken out and extracted with CHCl3 (3× 10 ml). The extracts weredried over MgSO4, concentrated in vacuo and analyzed by GC. Allthe experiments were repeated three times.

2.5. Preparative biotransformation

The same transformations were performed on the preparativescale in 2000 ml flasks, each containing 500 ml of the cultivationmedium. The cultures were incubated under the same conditionsand then 200 mg of substrate dissolved in 2 ml of acetone wasadded to the grown D. igniaria culture (the strain selected for

detailed studies). After 6 days of incubation the mixtures wereextracted with CHCl3 (3× 300 ml), dried (MgSO4) and concentratedin vacuo. The transformation products were separated by columnchromatography and analyzed (TLC, GC, 1H NMR).

2 r Catalysis B: Enzymatic 97 (2013) 278– 282

2

bmd

C1

1H(

([14J

p26

u

J8

p[CJH(1

p1(a

n(13H

3

cr

wS

op(owRt

t

1a 2a 1R = H

2R = H

3R = H

4R = H

1b 2b 1R = H

2R = CH3

3R = H

4R = H

1c 2c 1R = H

2R = OCH3

3R = CH3

4R = CH3

1d 2d 1R = OCH3

2R = OCH3

3R = CH3

4R = CH3

1e 2e 1R = H

2R = OH

3R = CH3

4R = CH3

O

O

R

R

R

R O

OH

R

R

R

R

1

2

3

4

1

2

3

4

microbial

reduction

1 2

Scheme 3. Microbial reduction of selected 4-chromanones.

the content of the R enantiomer is continuously increasing withtime, whereas the amount of the S-alcohol (2c) drops (Fig. 4). Theseindicate that with longer reaction time it is possible to achieve anenantiomeric excess of the R-alcohol. In the culture of Chaetomium

80 T. Janeczko et al. / Journal of Molecula

.6. Identification of products

Structures of the biotransformation products were confirmedy 1H NMR. The absolute configuration of the products was deter-ined by comparison of their optical rotation value with literature

ata.(S)-chroman-4-ol (2a): pale yellow oil; [�]D

23 = −47.6◦ (c 1.8,HCl3) (73% ee) (lit. [�]D

25 = −66.0◦ (c = 3.03, CHCl3), 97% ee [23].H NMR (300 MHz, CDCl3) ı (ppm): 1.84 (br s, 1H; OH), 2.02 (m,H, H-3), 2.10 (m, 1H, H-3), 4.26 (m, 2H, H-2), 4.78 (t, 1H, J = 4.0 Hz,-4a), 6.83 (d, 1H, J = 7.8 Hz; H-8), 6.91 (t, 1H, J = 7.8 Hz, H-6), 7.20

td, 1H, J = 7.8, 1.6 Hz; H-7), and 7.32 (dd, 1H, J = 7.8, 1.6 Hz, H-5).(S)-6-methylchroman-4-ol (2b): pale yellow oil; [�]D

23 = −20.5◦

c 0.9, CHCl3) (63% ee) (lit. [�]D23 = −38.6◦ (c = 1.50, CHCl3), 100% ee

24]. 1H NMR (300 MHz, CDCl3) ı (ppm): 1.85 (s, 1H, OH); 2.00 (m,H, H-3); 2.09 (m, 1H, H-3); 2.26 (s, 3H, CH3), 4.22 (m, 2H, H-2),.74 (t, 1H, J = 4.0 Hz, H-4a), 6.72 (d, 1H, J = 8.3 Hz, H-8), 6.91 (dd, 1H,

= 8.3, 2.0 Hz, H-7), and 7.10 (d, 1H, J = 2.0 Hz, H-5).7-methoxy-2,2-dimethylchroman-4-one (1c): pale yellow

owder; 1H NMR (300 MHz, CDCl3) ı (ppm): 1.43 (s, 6H, 2 x CH3),.64 (s, 2H, H-3), 3.81 (s, 3H, OCH3), 6.35 (d, 1H, J = 2.4 Hz, H-8),.55 (dd, 1H, J = 2.4, 8.8 Hz, H-6), and 7.81 (d, 1H, J = 8.8 Hz, H-5).

7-methoxy-2,2-dimethylchrom-3-ene (3c) (elimination prod-ct): colorless oil; 1H NMR (300 MHz, CDCl3) ı (ppm): 1.41 (s, 6H,CH3), 3.79 (s, 3H, OCH3), 5.45 (d, 1H, J = 9.7 Hz, H-3), 6.30 (d, 1H,

= 9.7 Hz, H-4), 6.36 (d, 1H, J = 2.45 Hz, H-8), 6.43 (dd, 1H, J = 2.45,.2 Hz, H-6), and 6.91 (d, 1H, J = 8.2 Hz, H-5).

(S)-7-methoxy-2,2-dimethylchroman-4-ol (2c): pale yellowowder; [�]D

23 = −23.0◦ (c 1.4, CHCl3) (93% ee) (lit. (R)-1c,�]D

25 = +22.1◦ (c = 0.72, CHCl3, 100% ee (S) [25]. 1H NMR (300 MHz,DCl3) ı (ppm): 1.31 (s, 3H, CH3), 1.45 (s, 3H, CH3), 1.84 (dd, 1H

= 13.5, 8.3 Hz, H-3), 1.98 (s, 1H, OH), 2.14 (dd, 1H J = 13.5, 6.1 Hz,-3), 3.75 (s, 3H, OCH3), 4.79 (dd, 1H, J = 8.3, 6.1 Hz, H-4a), 6.33

d, 1H, J = 2.5 Hz, H-8), 6.51 (dd, 1H, J = 8.5, 2.5 Hz, H-6), and 7.33 (d,H, J = 8.5 Hz, H-5).

6,7-dimethoxy-2,2-dimethylchrom-3-ene (3d) (eliminationroduct): colorless needles; 1H NMR (300 MHz, CDCl3) ı (ppm):.40 (s, 6H, CH3), 3.85 (s, 3H, OCH3), 3.86 (s, 3H, OCH3), 5.48d, 1H, J = 9.7 Hz, H-3), 6.27 (d, 1H, J = 9.7 Hz, H-4), 6.44 (s, 1H, H-8),nd 6.56 (s, 1H, H-5).

(S)-6,7-dimehtoxy-2,2-dimethylchroman-4-ol (1d): colorlesseedles; [�]D

23 = −36.40◦ (c = 0.64, CHCl3) (75% ee); 1H NMR300 MHz, CDCl3) ı (ppm): 1.30 (s, 3H, CH3), 1.42 (s, 3H, CH3),.82 (dd, 1H, J = 13.5, 8.3 Hz, H-3), 2.14 (dd, 1H, J = 13.5, 6.1 Hz, H-3),.80 (s, 3H, OCH3), 3.83 (s, 3H, OCH3), 4.78 (dd, 1H, J = 8.3, 6.1 Hz,-4a), 6.35 (s, 1H, H-8), and 6.92 (s, 1H, H-5).

. Results and discussion

The strains of D. igniaria, C. betulinum and Chaetomium sp. werehosen as biocatalysts, due to their capability to enantiospecificeduction of low-molecular-weight ketones [18,26–29].

The only microorganism that transformed four of the substratesas D. igniaria. In each case a considerable enantiomeric excess of

-alcohol was observed in the product mixture (Scheme 3, Table 1).The results of biotransformations performed in the culture

f Chaetomium sp.1 are interesting mainly with respect to com-osition of the product mixture. In the case of substrates 1a4-chromanone) and 1b (6-methyl-4-chromanone), after one dayf biotransformation the respective S-alcohols predominated, buthen the reaction was carried out longer, the content of the

-alcohols gradually increased. After three days it was the R enan-iomer that prevailed (Figs. 2 and 3).

The observation of 6-methyl-4-chromanone (1b) transforma-ion process led to the conclusion that at first the carbonyl group

Fig. 2. Time dependence of transformation of 4-chromanone (1a) in Chaetomiumsp. KCh 6651 culture.

reduction occurs, giving the S-alcohol (2b) with low enantioselec-tivity, and then this enantiomer is selectively oxidized back to thesubstrate. As a result, after nine days of biotransformation (R)-6-methyl-4-chromanol is obtained as a single product (Scheme 4).

For substrate 1c (7-mehtoxy-2,2-dimethyl-4-chromanone) thereaction pattern is not the same, however one can observe that

Fig. 3. Time dependence of transformation of 6-methyl-4-chromanone (1b) inChaetomium sp. KCh 6651 culture.

T. Janeczko et al. / Journal of Molecular Catalysis B: Enzymatic 97 (2013) 278– 282 281

Table 1Microbial reduction of 4-chromanone and its derivatives.

Substrate Microorganism Reaction time [days] Substrate conversion [%] Product (alcohol)

Ee [%] Configuration

1aDidymosphaeria igniaria 3 100 73 SChaetomium sp.1 3 89 19 RCoryneum betulinum 6 65 88 S

1bDidymosphaeria igniaria 6 98 63 SChaetomium sp.1 9 100 100 RCoryneum betulinum 3 93 96 S

1cDidymosphaeria igniaria 9 56 93 SChaetomium sp.1 1 75 84 SCoryneum betulinum 9 0 – –

1dDidymosphaeria igniaria 6 50 75 SChaetomium sp.1 9 0 – –Coryneum betulinum 9 0 – –

1eDidymosphaeria igniaria 9

Chaetomium sp.1 9

Coryneum betulinum 9

O

OH

O

O

O

OH

(S)-2b 1b (R)- 2b

SC

ssd1aFtc

Crhw(st

Fc

cheme 4. Transformation of 6-methyl-4-chromanone (1b) in the culture ofhaetomium sp. KCh 6651.

p. KCh 6651 substrate 1c is transformed in analogous way to sub-trates 1a and 1b, but the process is much slower. This is probablyue to the presence of additional substituents in the structure ofc, compared to 1a and 1b, which make it less compatible with thective site of the dehydrogenases present in this microorganism.urther confirmation of this conclusion is a complete lack of bio-ransformation products for substrates 1d and 1e incubated in theulture of this strain.

During incubation of substrates 1a, 1b and 1c in the culture ofhaetomium sp. KCh 6651 there are continuous processes of ketoneeduction to both S and R-alcohols and oxidation of the formed alco-ols back to the ketones. These four competitive processes proceed

ith different speed, changing during the biotransformation time

induction of dehydrogenases by substrates and products). Even amall change in speed of one of the competitive processes leadso a complete change in composition of the reaction mixture (and

ig. 4. Time dependence of transformation of 6-methoxy-2,2-dimethyl-4-hromanone (1c) in Chaetomium sp. KCh 6651 culture.

0 – –0 – –0 – –

different final results of reduction of 1a, 1b and 1c). The analo-gous changes in products composition were described in our earlierwork [29].

Among all the tested microorganisms the strain C. betulinumtransformed the least number of substrates. Nevertheless, theyields and the enantiomeric excesses of products for this microor-ganism were satisfying. Transformation of 4-chromanone (1a) and6-methyl-4-chromanone (1b) by means of C. betulinum gave therespective S-alcohols, in accordance with the Prelog’s rule.

For the strains C. betulinum i Chaetomium sp.1 the presence ofan additional methyl group in a xenobiotic molecule (substrate1b) increased the percent of substrate conversion, as well as theenantiomeric excess of resulting alcohol. Whereas, in the cultureof D. igniaria it was 4-chromanone (1a) that was reduced withmuch higher yield compared to 6-methyl-4-chromanone (1b) andthe resulting 4-chromanol (2a) was of much higher enantiomericexcess than its methyl derivative (2b).

The presence of methyl groups in the non-aromatic ring ofthe other substrates (1c–1e) had decreasing effect on the reactionyield. This was probably because of the steric hindrance associatedwith these substituents. 6-Hydroxy-2,2-dimethyl-4-chromanone(1e) was reduced by neither of the tested microorganisms.

The effect of size of substituents on effectiveness of micro-bial conversion of aliphatic-aromatic ketones was described byCarballeira et al. [30]. Another paper on this topic concerns bio-transformations of aliphatic-aromatic ketones by the strain D.igniaria KCh 6670. Also in this case a considerable decrease insubstrate conversion was observed for the following substrates:acetophenone, tetralone and 9,10-phenantrene (0%) [18].

Acknowledgments

This research was supported financially by the European Unionwithin the European Regional Development Found (grant no.POIG.01.03.01-00-158/09-06).

References

[1] K. Goldberg, K. Schroer, S. Lütz, A. Liese, Appl. Microbiol. Biotechnol. 76 (2007)249.

[2] R. Wohlgemuth, Curr. Opin. Microbiol. 13 (2010) 283.[3] D.M. Solano, P. Hoyos, M.J. Hernáiz, A.R. Alcántara, J.M. Sánchez-Montero, Biore-

sour. Technol. 115 (2012) 196.[4] A.V. Kuperman, A.S. Kalgutkar, A. Marfat, R.J. Chambers, T.E. Liston, Drug Metab.

Dispos. 29 (2001) 1403.

[5] R.J. Chambers, A. Marfat, G.W. Antognoli, J.B. Cheng, D.B. Damon, A.V. Kuper-

man, T.C. Liston, C. Mebus, J.S. Pillar, J.T. Shirley, J.W. Watson, Bioorg. Med.Chem. Lett. 9 (1999) 2773.

[6] J. Schreieck, Y. Wang, V. Gjini, M. Korth, B. Zrenner, A. Schomig, C. Schmitt, J.Cardiovasc. Electrophysiol. 8 (1997) 1420.

2 r Catal

[

[[

[[

[[[

[

[

[

[[

[

[

[

[

[

[

82 T. Janeczko et al. / Journal of Molecula

[7] C. Lerce, I. Bruhova, H. Lerce, K. Steinmeyer, A.D. Wei, N. Strutz-Seebohm, F.Lang, A.E. Busch, B.S. Zhorov, G. Seebohm, Mol. Pharmacol. 71 (2007) 1503.

[8] I.C.-H. Yang, M.W. Scherz, A. Bahinski, P.B. Bennett, K.T. Murray, J. Pharmacol.Exp. Ther. 294 (2000) 955.

[9] E.J. Corey, R.K. Bakshi, S. Shibata, J. Am. Chem. Soc. 109 (1987) 5551.10] K. Nakamura, R. Yamanaka, T. Matsuda, T. Harada, Tetrahedron-Asymmetry 14

(2003) 2659.11] Y. Kawanami, K. Hoshino, W. Tsunoi, Tetrahedron-Asymmetry 22 (2011) 1464.12] J. Wettergren, A. Bøgevig, M. Portier, H. Adolfsson, Adv. Synth. Catal. 348 (2006)

1277.13] W.-Y. Lou, W. Wang, T.J. Smith, M.-H. Zong, Green Chem. 11 (2009) 1377.14] Z.-H. Yang, L. Luo, X. Chang, W. Zhou, G.-H. Chen, Y. Zhao, Y.-J. Wang, J. Ind.

Microbiol. Biotechnol. 39 (2012) 835.15] G. Aina, G. Nasini, O.V. de Pava, J. Mol. Catal. B: Enzym. 11 (2001) 367.16] M. Furuta, M. Shoji, T. Ugai, J. Mol. Catal. B: Enzym. 82 (2012) 8.17] E.B. Kurbanoglu, K. Zilbeyaz, N.I. Kurbanoglu, H. Kilic, Tetrahedron-Asymmetry

18 (2007) 1159.18] A. Swizdor, T. Janeczko, J. Dmochowska-Gładysz, J. Ind. Microbiol. Biotechnol.

37 (2010) 1121.19] E. Kyslíková, P. Babiak, H. Maresová, A. Palyzová, J. Hájícek, P. Kyslík, J. Mol.

Catal. B: Enzym. 67 (2010) 266.

[

[

ysis B: Enzymatic 97 (2013) 278– 282

20] M.A. Quezada, J.D. Carballeira, J.V. Sinisterra, Bioresour. Technol. 112 (2012)18.

21] G.W. Huisman, J. Liang, A. Krebber, Curr. Opin. Chem. Biol. 14 (2010) 122.22] E.B. Kurbanoglu, K. Zilbeyaz, N.I. Kurbanoglu, Tetrahedron-Asymmetry 22

(2011) 345.23] C.V. Ursini, G.H.M. Dias, J.A.R. Rodrigues, J. Organomet. Chem. 690 (2005)

3176.24] I. Bichlmaier, A. Siiskonen, M. Finel, J. Yli-Kauhaluoma, J. Med. Chem. 49 (2006)

1818.25] M. Majeric, M. Gelo-Pujic, V. Sunjic, A. Lévai, P. Sebök, T. Timàr, Tetrahedron-

Asymmetry 6 (1995) 937.26] T. Janeczko, J. Dmochowska-Gładysz, M. Kuzbik, T. Kowalski, Chem. Agric. 7

(2006) 181.27] T. Janeczko, J. Dmochowska-Gładysz, E. Kostrzewa-Susłow, Przem. Chem. 88

(2009) 458.28] T. Janeczko, J. Dmochowska-Gładysz, E. Kostrzewa-Susłow, World J. Microbiol.

Biotechnol. 26 (2010) 2047.29] T. Janeczko, A. Panek, A. Swizdor, J. Dmochowska-Gładysz, E. Kostrzewa-

Susłow, Curr. Microbiol. 65 (2012) 189.30] J.D. Carballeira, M. Valmaseda, E. Alvarez, J.V. Sinisterra Gago, Enzyme Microb.

Technol. 34 (2004) 611.