CHAPTER 6: ARRAYS Introduction to Computer Science Using Ruby (c) 2012 Ophir Frieder et al.
The scientific legacy of Frieder W. Lichtenthaler · 2021. 1. 20. · CHAPTER THREE The scientific...
Transcript of The scientific legacy of Frieder W. Lichtenthaler · 2021. 1. 20. · CHAPTER THREE The scientific...
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CHAPTER THREE
The scientific legacy of FriederW. LichtenthalerFranz Dietrich Klingler∗Formerly of the Clemens Sch€opf Institut f€ur Organische Chemie und Biochemie, Technische Universit€atDarmstadt, Darmstadt, Germany∗Corresponding author: e-mail address: [email protected]
Professor Frieder W. Lichtenthaler was born in Heidelberg, Germany, on
19 January 1932 as the oldest of five sons of Wilhelm, a schoolteacher,
and his wife Emma.
He started his scientific career at the University of Heidelberg where
he completed his Dr. rer. nat. in the group of Prof. Friedrich Cramer.
He investigated the chemistry of enol phosphates, the results of which he
developed into a comprehensive review article in 1961.1 In 1959 he joined
the laboratory of Prof. Hermann O. L. Fischer, son of Emil Fischer, at the
University of California, Berkeley, where he started his research work on the
nitromethane cyclization of dialdehydes. When this technology was applied
to glyoxal, a stunning fourfold addition led to a mixture of 1,4-dinitro
inositols from which the neo-1,4-isomer, the most hydrophilic, crystallized
due to its two intramolecular NO2–OH hydrogen bonds (Scheme 1).2
The compound’s configuration was established by 1H NMR spectros-
copy, which in 1960 was one of that technology’s very early straightforward
applications. The spectra were run at the research facilities of Varian
Associates in Palo Alto, CA, on an experimental 30-MHz instrument.
O
O
O
O
O
O
O pH 10
O
N
N
H HO
NO2
NO2
HO
OH
OH O
O
OHO
OH
1,4–neo–
H
H
N NO
O
O
H
H H
Me
Me
Scheme 1 Glyoxal–nitromethane cyclization to 1,4-dideoxy-1,4-dinitro-neo-inositol.
Advances in Carbohydrate Chemistry and Biochemistry, Volume 77 # 2020 Elsevier Inc.ISSN 0065-2318 All rights reserved.https://doi.org/10.1016/bs.accb.2020.05.001
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Similarly, the dialdehyde [(2R,3S,4S)-trihydroxypentanedial (trihydroxy-
glutaraldehyde)] resulting from periodate cleavage of 1,2-O-isopropylidene-
D-glucose and subsequent acid treatment gave a mixture of the
1-deoxy-1-nitro-scyllo- and -neo-inositols (Scheme 2), which upon catalytic
hydrogenation led to the respective inosamines, at the time important
synthetic targets due to their occurrence in aminoglycoside antibiotics.3
Frieder Lichtenthaler‘s independent work started at the Technische
Universit€at Darmstadt, Germany, where he continued to explore the dia-ldehyde–nitromethane cyclization by extending it initially to simple aliphaticand aromatic dialdehydes. Applications of the methodology to a broad range
of monosaccharide-derived dialdehydes offered an excellent synthetic route
to 3-amino-3-deoxy sugars. The 3-deoxy-3-nitro-pyranoses that formed
initially were transformed by hydrogenation into the corresponding
3-amino-3-deoxy derivatives. Prof. Lichtenthaler reviewed this early work
in 1964.4
An interesting three-component reaction of the dialdehydes, nitro-
methane and primary amines was worked out. Treatment of dialdehydes
with primary amines, and condensation with nitromethane as the methylene
component, formed nitro-diamines (Scheme 3),5 which after catalytic
hydrogenation resulted in all-trans-1,2,3-triamines.
Further exploitation of the nitromethane cyclization of dialdehydes
derived from ribo-nucleosides (Scheme 4),6 and D-fructose (Scheme 5)
led upon hydrogenation to 30-aminohexosyl-nucleosides and 4-amino-hexosuloses.7
OH +OH
HOHO
CHO
1.MeNO2
2. H+
~30%
OH–HOHO
HO
OH OHO
HOCHO
HO
NO2
OHHO
HOHO
NO2
OH
O
O1. IO¯
–
2. H+
Scheme 2 Glucose-derived trihydroxyglutaraldehyde cyclization with nitromethane.
CHO1. H2NBn
NHBn
H2, cat.
NHBn
NO2
NH2
NH2
NH2
2. MeNO2
CHO
Scheme 3 Nitromethane cyclization of dialdehydes in the presence of amines.
122 Franz Dietrich Klingler
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Two major advancements of the dialdehyde–nitromethane cyclizationwere successfully elaborated. These were the extension of the methylene
component to higher nitroalkanes8 and to nitro acetic acid,9 which allowed
the preparation of amino acids (Scheme 6).
Having attained a tenure position at the Technische Universit€atDarmstadt, Frieder Lichtenthaler substantially expanded his research topics.
Based on the nitroalkane condensation, he started working on purine and
pyrimidine nucleosides that had one or more amino functions in the
NRHO
OH OH
ONR 1. MeNO2 OH
OHNR
HOH2N
2. Ni, H2HO
NaIO¯
O O
O O
Scheme 4 Synthesis of 30-amino-hexosyl nucleosides.
1. Redn.
Amino-hexosuloses2. H+
HO
O2N
OO
OHO
OH
OO
OHO
AcNHO2N
OO
NHAcO
37%(2 st.) ~25% (4 st.)
1. MeNO22. NH3,MeOH3. Ac2O
OHC
MeNO2
OHC
O
OO
HO
2 steps NaIO¯D-Fructose
O
Scheme 5 Synthesis of amino-hexosuloses from D-fructose.
CHO COOEt
COOEt
COOEt
CHO
OH OH
OH
OH OH
OH
Me
NO2 NH2
NO2
EtNO2
O2N
H2, cat.
Scheme 6 Extension of the nitromethane cyclization to nitroethane and to ethyl2-nitroacetate.
123The scientific legacy of Frieder W. Lichtenthaler
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carbohydrate part. The dialdehydes obtained from periodate cleavage
of ribo-nucleosides were condensed with nitromethane, and the nitro
intermediates were subsequently reduced to the aminohexosyl nucleosides.
The stereochemistry of the newly formed chiral centers during the nitro-
methane cyclization in the 20, 30 and 40-positions were analyzed by 1HNMR spectroscopy, a technique that was at the time just being established
at German universities.
Along this generally applicable scheme, analogs of the nucleoside
antibiotic puromycin were synthesized in order to improve its pharmaco-
logical properties (Scheme 7).10,11
In addition to the gluco-configured analog, the manno- and galacto-
compounds were isolated and fully characterized.11 Analogously, 30-aminohexosyl hypoxanthine12 and theophylline nucleosides were
synthesized.13 In the course of this research, the “acetyl resonance rule”
was developed for the unequivocal determination of the configuration
of the sugar portions of nucleosides from their 1H NMR spectra.14
By using nitroethane instead of nitromethane and following the same
scheme, a number of C-30-methyl-branched nucleosides were synthe-sized.15 These compounds were of considerable interest due to their
cytotoxic and antiviral activities. A number of theses in Lichtenthaler’s
group dealt with research on dipeptyl-amino-sugar nucleosides that were
NMe2
1. CICOOMe, TEA
MHCIC
COOH
O
2. H2, cat.
62% (2 st.)
N N
N
1. NalO¯
~25%
2. MeNO23. H2,cat.
N
O
OHHO
HO
NMe2
N N
NN
O
OH
O
NH
HO
NH2NH
Puromycin
O
NMe2
H2N
N
HO
OH
HO
N N
N
NMe2
N
HO
HO
NH2 NH OH
N N
N
O
O
O
O
Scheme 7 Synthesis of a pyranoid puromycin analog.
124 Franz Dietrich Klingler
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structurally related to gougerotin.16,17 In collaboration with the Czech
Academy of Science in Prague, analogs of the antibiotics gougerotin,
blasticidine, amicetin and plicacetin were synthesized and tested for their
effects on ribosomal peptidyltransferase.18–21
Finally, efficient total syntheses of the antibiotic compounds gougerotin
(Scheme 8) and aspiculamycin from D-galactose were developed.22,23
The necessity of an efficient nucleoside coupling for this total synthesis
caused the development and the optimization of a generally applicable
Friedel–Crafts catalyzed N-glycosidation of silylated pyrimidines tohexuronic acids and amino sugars.24 Using this methodology a high
selectivity for 9-β-purine nucleosides was achieved (Scheme 9).
NH
N
N O
NH2
H2NOC
gougerotin
D-Galactose6 steps
1. NaOMe
75%2. H
2, cat.
30%
NH2
N
N O
NHAc
N
N ON3
MeOOC
HO OHOMe
O
HO OHOH
OH
2N
MeOOC
HO OH
O
N3
MeOOC
67%
NTMGAc
OTMG
1. Ac2O,H+
1. Boc-Sar.-D-Ser.DCC
2. NH3
3. H+75%
2. SnCI¯OAcAcO
O
NH
O
OHN
N
N
Scheme 8 Total synthesis of gougerotin.
SnCI¯
CI CI
60–70°C
NBzTMS
OAc +
OAc
NHBz
N
N N
NTMS
N N
NN
O
OAc
O
Scheme 9 9-β-selective nucleoside coupling of purines.
125The scientific legacy of Frieder W. Lichtenthaler
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This basic work still plays an important role in the development of
industrial processes for the production of nucleosides. Especially in the
synthesis of allopurinol ribosides, this process proves more effective than
the classical Hilbert–Johnson method.25,26
The ribosyl nucleotides of allopurinol, a major tool for the treatment of
gout and related metabolic disorders, had a high potential as antiviral and
antitumor agents as well as antiparasitic properties in dephosphorylated
form.26 In the course of this work, angularly and linearly extended allopu-
rinols and their ribosides were synthesized in collaboration with a Swiss
pharmaceutical company.27–29
The newly developed coupling method was also successfully used in
the syntheses of disaccharide nucleosides of hexosyl-ribosyl inosides and
hypoxanthines.30 The assignment of the glycosidation sites in hexopyranosyl-
D-ribo-nucleosides could unequivocally be determined by elaborate 13C
NMR spectroscopy.31
The antibiotic psicofuramine and its α-anomer could be totallysynthesized by using this coupling methodology (Scheme 10).32
Starting from 1,2:4,5-di-O-isopropylidene-D-fructose, the pentabenzoyl-
psicofuranose was synthesized via oxidation, reduction, isomerization,
deprotection and benzoylation in an impressive 55% yield. The coupling with
bis-(trimethylsilyl)-N6-benzoyladenine in presence of tin tetrachloride
2 : 1
NHBz
N N
NN
OOBz
OBzBzO
BzO
OBz
SnCI¯, MeCN
64%
NHBz
60%
NH3, MeOH
NHBz
N N
NN
OOH
OH
psicofuramine
HO
HO
OBz
OBz
OBz
BzO
BzO1. H2SO¯
DMP2. NaBH¯
2. H+3. BzCI
1. PCC
65%
86%
O
N
N
OBzBzO+
BzOO
OO
OO
OHO
OO
OO
OH
O
N
N N
NTWO
CI CI
M 6=TLIC
N
N
Scheme 10 Total synthesis of psicofuramine.
126 Franz Dietrich Klingler
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delivered an easily separable anomeric mixture of the nucleosides in an
α/β-ratio of 1:2. The final, fully characterized product, psicofuramine,could be obtained in 60% yield.
Alongside his work on nucleosides in the 1960s, Lichtenthaler began
work to transform those monosaccharides that naturally occur in large
quantities, into chiral, enantiopure building blocks. Many different methods
were developed in his group to transform sugars, which are over-
functionalized with hydroxyl-groups of similar reactivity, into simple chiral
units containing useful functional groups like C]C and C]O doublebonds. Besides the normal carbonyl reactivity, the selective oxidation of
one hydroxyl group generated a gradated CdH acidity depending onthe substitution pattern. By a controlled elimination reaction, “sugar
enolones” were created, which were easily accessible and very useful chiral,
enantiopure building blocks.
Depending on the order of the chemical steps, the carbonyl function could
be introduced in the 2- (2-ulsoe), 3- (3-ulsose), or 4- (4-ulose) positions.
Sugar enolones have been postulated as intermediates in the formation
of kojic acid and hydroxymaltol. A straightforward synthesis of the
corresponding 2- and 4-enolones from simple derivatives of D-galactose
and of D-glucose was achieved as well as the transformation into the natural
products kojic acid and hydroxymaltol (Scheme 11).33,34
A well-established laboratory procedure for the preparation of these two
sugar enolones appears in Methods in Carbohydrate Chemistry.35
An alternative approach, which gives access to 1-O-acyl-3,2-enolones,
was also developed. By addition of chlorine to the easily available
2-hydroxyglycal esters and subsequent hydrolysis in presence of a mild base,
the 3,2-enolone was formed in ca. 60% isolated yield (Scheme 12).36,37
Me
OH
hydroxymaltol
75%
82%
1. TFA
DMSO,Ac
2O
DMSO,Ac
2O
OH
O
BzOOBz
OBz
BzO
BzO
OBz OBzO
OMe52%
69%OMe
OMe
O
TFA
2. Zn, HCI
O
O
benzoyl kojic acid
O
O
HO
OBzBzO
BzOOH
OBz
OMeO
O
O
O
Scheme 11 Simple syntheses of hydroxymaltol and benzoyl kojic acid.
127The scientific legacy of Frieder W. Lichtenthaler
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Detailed investigations of the chlorination and bromination of
2-hydroxyglycal esters in terms of stereochemistry and the hydrolysis to
3,2-enolones were performed.38
The structural features of the 2,3-and 4,3-enolones promise a high
synthetic potential for deoxy, amino, and branched-chain sugars.
In the 3,4-enolone, the enolic double bond readily can be selectively
hydrogenated into an easily separable mixture (3:1) of the two 2-deoxy
derivatives (Scheme 13).39
A general account on pyranoid sugar enolones with respect to their
preparation, their use as synthetic building blocks, and their conversion into
several natural products was provided by Frieder Lichtenthaler in 1978.40
A novel, highly stereoselective rearrangement of 2,3-and 4,3-enolones
was reported, which proved to be important for future research work in
the group (Scheme 14).41
CI2, H2O,
NaHCO3
60%
OBz
OBzBzO O
OOBz
OBz
OBz
BzO
O
Scheme 12 Formation of a 3,2-enolone from a 2-hydroxyglycal ester.
OMeBzO
OBz
O
O
OMe
1 : 4
H2, cat.+
OBz
OBz
O
O
OMe
OBz
OBzO
O
Scheme 13 2-Deoxy sugars from sugar enolones.
MeOH,K2CO3DMSO
MeOH,K2CO3DMSO
OBz
O
MeOOBz 69% 41%
O
OBzO
MeO
MeO
MeO
OBz
OBz
O
BzO
O
Scheme 14 Rearrangement of 2,3- and 4,3-enolones.
128 Franz Dietrich Klingler
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A new alternative process to 3,2-endioles via per-O-acetyl-hex-2-uloses
was also developed by the peroxidation of 2-hydroxy-D-glucal esters
(Scheme 15).42
The β anomer crystallized directly from the reaction mixture (a mixtureof anomers) as the monohydrate.
During that work on the 2-uloses, a generally applicable and very useful
methodwas developed for a selective deacylation of enol esters with hydrox-
ylamine (Scheme 16).43
An impressive series of pyranoid and furanoid enol esters were selectively
hydrolyzed in the presence of other ester functions.
This essentially simple process opened up a way to liberate the parent
ketone from furanoid and pyranoid enol esters. After saponification of the
ester functionality, the hydroxylamine was removed from the oxime prod-
uct by treatment with acetaldehyde (Scheme 17).44 None of the resulting
free 1,5-anhydro ketoses had been known before.
RCOOOHAcCIpyr. (cat.)
55% 64%OAc
OAc
OAc
OAc
O
OAc
OAc
OAc OAcOH
OH
O
OAc
OAc
OAcOAc
OAc
O
Scheme 15 3,2-Enediols via peroxidation of 2-hydroxyglycal esters.
OAc
OAc
OAcNOH
O
OAc
HONH2
•HCIpyr., 25°C
86%OAc
OAcOAc
O
Scheme 16 Selective deacylation of enol esters with hydroxylamine.
HONH2×HCI, NaOMe,
MeOHMeCHO,HCI, MeCNpyr, 25°C
93% 65% 60%OBz
OBz
OBz
OBz
O
OBz
OBz
OBz
NOH
O
OH
OH
OH
NOH
O
OH
OH
OH
O
O
Scheme 17 Synthesis of free-hydroxy 1,5-anhydro ketoses.
129The scientific legacy of Frieder W. Lichtenthaler
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Based on this chemistry, a stereospecific synthesis of (S,S)-palythazine, a
marine natural product, was developed. Only after this synthesis could the
structure and the absolute configuration of the natural product be clearly
assigned (Scheme 18).45
Another marine natural product, a branched pyranoid system, bissetone,
isolated from a soft coral, was synthesized starting from the same building
block used for the synthesis of palythazine (Scheme 19).46
The attack of the lithium enolate of acetone from the pro-axial side with
a 4:1 preference is followed by a benzoyl-group shift. The dibenzoate thus
formed gives the desired (S,S)-bissetone simply by O-debenzoylation.
The short and efficient syntheses of (S,S)-palythazine and (S,S)-bissetone
are impressive examples of the use of sugar-derived chiral, enantiopure
building blocks for the synthesis of non-carbohydrate natural products.
1. MeCHO, HCI, MeCN
1. NH2OH,
2. NaOMe, MeOH,–10°C2. NaOAc
>90%OBz
OBz
OBz
NOH
O
BzO
OBz
O
O
OH
NOH
O
O
OH
=
NH2
O
O
82%
OHO
O
OHO
OH pH 9,airNH
2
H2, cat.
69% (2 st.)
(S,S)-Palythazine
O
N
N
Scheme 18 Synthesis of (S,S)-palythazine.
OBz
OBz 60%
o u
O
O
OBzO
OO
BzO
OHO
OO
HO
(S,S)-Bissetone
NaOMeMeOH
92%
Scheme 19 Total synthesis of (S,S)-bissetone.
130 Franz Dietrich Klingler
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In practice, the generation of enantiopure building blocks from readily
available sugars is of practical value only if the individual reactions employed
allow for simple reagents, proceed uniformly, and consist of a few high-
yielding steps.
The sugar-enolones were one way of converting those sugars that
are cheap and accessible in large amounts, into enantiopure, suitably
functionalized building blocks.
In Lichtenthaler’s group, other chiral units from mono- and disaccha-
rides were developed, and their utilization in natural product synthesis
was demonstrated.
An important and very useful example of the transformation of sugars
into versatile building blocks is the Lewis acid-mediated peroxidation of
glycal- and hydroxyglycal esters. The respective ene- and enol-lactones
are formed in a single step (Scheme 20).47,48
Initiated by a BF3-induced removal of the allylic acyloxy function to
form the allylcarboxonium ion (analogous to the Ferrier reaction), the
m-chloroperoxybenzoic acid (MCPBA) attacks solely at C-1 as expected
from a “hard” nucleophile. The resulting 1-perester intermediate undergoes
fragmentation to yield the ene-lactone or enol-lactone.
This reaction works very well with many mono- and disaccharide
derived glycals or hydroxyglycal esters.48
The synthetic utility of these now easily accessible ene- and enol-
lactones was demonstrated in Lichtenthaler’s group by their conversion into
a number of natural products. Di-O-acetyl-L-rhamnal, which itself is acces-
sible from L-rhamnose in a one-pot procedure, is readily transformed into
the acetyl derivative of osmundalactone,48 the aglycon of the glycoside
osmundaline from a fern. This intermediate was converted in two simple
high-yielding steps into (S)-parasorbic acid (Scheme 21),49 which is a con-
stituent of mountain ash berries.
OBz
OBz
X
O
O
OBz
OBz
OBz
BF3 Et2O, MCPBA,
X = H (80%)X = OBz (91%)
CH2CI2, -20°C
X
X = H, OBz
O
O
Scheme 20 BF3-mediated peroxidation of glycal esters.
131The scientific legacy of Frieder W. Lichtenthaler
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While the BF3-mediated peroxidation of, for example, tri-O-acetyl-D-
glucal in dichloromethane at �20 °C affords the pyranoid ene-lactone ingood yield, the same reaction, performed at room temperature, takes a quite
different course. Oxidative cleavage of the olefinic double bond occurs to
yield the acyclic pentenal (Scheme 22).48
Both enantiomers of these simple and very useful C-6 building blocks
are available based on D-glucose or L-rhamnose as starting materials.
The D-glucose-based approach (Scheme 23)50,51 starts from tri-O-acetyl-
D-glucal via the known α,β-unsaturated ethyl hexenoside, which wasconverted under enforced tosylation conditions (TsCl, pyridine, 50°C)into the 4-chloro compound. Reductive removal of the tosyloxy and
the chloro groups was effected either separately or in one operation
(Scheme 23).
O O
AcO Zn-Hg,HCI, Et2O
Me Me
DBU, THF
90% 87% 91%Me
AcO
OAc
MCPBA,BF3
OO O O Me
(S)-Parasorbic acid
O
Scheme 21 Synthesis of (S)-parasorbic acid.
AcO
OAc
O
O
AcO
OAC
90%
NaHCO3,MeOH
84%
MCPBA,BF3,
H H
+25°C
OAc
MCPBA, BF3,
–20°CO
AcO
OCHO
O AcO
OH
O
Scheme 22 Different pathways of MCPBA oxidation of tri-O-acetyl-D-glucal.
132 Franz Dietrich Klingler
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These routes opened a short and efficient way to the (5R)-hydroxyhexenal
in its cycloacetal form.
The enantiomeric (5S) version is as readily accessible from L-rhamnose
via the di-O-acetyl-L-rhamnal using essentially the same methodology.49
The enantiopure 5-hydroxy-C-6 units were used in the total syntheses of
macrolides of the phoracantolides,52 the diplodialides, and a minor but costly
constituent of civet, a glandular secretion of the catlike civet (Viverridae),
which is used in perfumery (Fig. 1).51
These types of 5-hydroxy-C-6 building blocks were also used for the
syntheses of a series of natural products.
One prominent example is the (+)-anamarine which is isolated from
certain African shrubs. It consists of a pyranoid C-6 unit and a C-6
side chain with four chiral centers (Scheme 24). The readily accessible
4-deoxy-6-O-tosyl-2,3-unsaturated ethyl glycoside51 was smoothly trans-
formed into the crystalline phosphonium salt,53 which could be coupled
with the side-chain aldehyde by a Wittig reaction. The aldehyde was syn-
thesized following standard procedures from methyl 6-deoxy-D-glucoside.
1. BF3, EtOH2. TEA
70%
AcO
OAc
OAc
O
OH
HO OEt
TsCI, pyr.50°C
86%
O
LAH,RT
H2, cat.
quant.
82%
CI
OEt
Me
O
OEt
O
NiCI2,
NiCI2,
LAH, THF65°C
LAH
H2, cat.
quant.
68%
65%
76% 85%
NaBH¯
NaBH¯
OEt
Me
O
OEt
Me
O
OEt
Me
O
CI
OTs OTs
OEt
O
Scheme 23 Chiral C-6 building blocks from tri-O-acetyl-D-glucal.
133The scientific legacy of Frieder W. Lichtenthaler
-
The deprotonation of the phosphonium salt had to be performed at
low temperature (�78 °C) in order to avoid β-elimination of the ylid.The Wittig coupling resulted in an 8:1 mixture of epimers that were
separated after oxidation by crystallization of the ene-lactone. After
COOH
A: R1, R2 = O
R1R2
B: R1= H, R2 = OH
"Civet" Phorocantholide-J Diplodialides
O
OO
O
MeMe
Me O
Fig. 1 Synthetic targets made from the C-6 units of Scheme 23.
OH OH
DMP, H+
R = CH(SEt)2
R = CHO
83%
85%
OHOHSEt
EtS Me
MeOTs
OEt
OEt
n-BuLi
60%
Me
1. Nal,78%
PPh3 + I–
PPh3 + I–
EtO
2. TPP
Me
OMe
EtSH, H+
88%
OH
OH
OH
OO
O
OEtO
OO
R OO
OO
OAc
OAc
(+)-Anamarine
1, MCPBA, BF3
OAc
Me
OAc
O
OO
2. Ph2S2, hv3. TFA4. Ac2O 20%
OO
Scheme 24 Total synthesis of (+)-anamarine.
134 Franz Dietrich Klingler
-
photochemical epimerization, deprotection and acetylation, (+)-anamarine,
identical to the natural product, was isolated.
An alternative approach regarding the synthesis of the two C-6 building
blocks was developed parallel to this work in Lichtenthaler’s group.54
A similar, more complex natural product, the ACRL-toxin, produced by
a fungus found on lemon and lime citrus species, which causes a harvest-
threatening necrosis, was synthesized from 1,2:5,6-di-O-isopropylidene-D-
glucose via 3-deoxy-1,2-O-isopropylidene-3-C-methyl-α-D-allofuranose asthe key building block (Scheme 25).55
1. BuLi, –78°C
CHO
O O
Me
O O
O
Me
OTBDMS
Me
Me
Me
Me Me
OH
LDA,1.
OH OH
OH
Me
ACRL-toxin
2. Deprot. ~25%
2. Na(Hg), –30°C3. HgCI
2, HgO
50%
OTBDMS
6 steps~30%
8 steps~15%
Me
Me
HO1. TsCI2. LAH3. PCC
70%
HO
Me
Me
SMeOHC
O O
O
O
OO
O
O
Me Me
SO2Ph
O
O
O O
O
OMe
= O O
Scheme 25 Total synthesis of ACRL-toxin.
135The scientific legacy of Frieder W. Lichtenthaler
-
Selective tosylation, hydride reduction and PCC oxidation afforded
the 6-deoxy-5-keto-derivative in 76% yield over three steps. From these
basic building blocks the two units to be coupled by a Julia coupling were
synthesized in a straightforward manner in six and eight steps, respectively.
The coupling of the phenylsulfone with the aldehyde proceeded smoothly.
After acetylation, reduction and deprotection, the complete side chain was
ready for annelation of the remaining C-4 unit. Following a difficult
optimization process, the trimethyl-1,3-dioxinone was found to be the
most suitable for the introduction of the acetoacetic ester unit. After
deprotonation with LDA at a low temperature, the coupling was achieved
in 35% yield. By acidification and standard methylation, followed by
deprotection, the crystalline product was isolated and fully characterized.55
In the period of the 1980s until the early 2000s, a number of total
syntheses of natural products out of carbohydrates were elaborated in
Lichtenthaler’s group.
One prominent example was the synthesis of (�)-daucic acid, aC-7-dicarboxylic acid with three chiral centers found in carrots, sugar beets,
sunflowers, and other plants. Daucic acid was isolated and structurally
described in the late 1960s. After a total synthesis was completed in
Lichtenthaler’s group, the physicochemical and NMR data were found to
be significantly different from those of the natural product. Therefore, four
different possible isomers were synthesized and compared to the natural
product, which was provided by the original workers. After revision of
the configuration,56 all syntheses of all four isomers were published.57
The synthesis of daucic acid starts from D-galactose (Scheme 26), which
is converted along known procedures into tetra-O-acetyl-β-D-galactosylcyanide. Base hydrolysis, esterification and oxidation affords the
1. NaOMe, MeOH1. NaOAc, Ac2O, 100°C
2. TMSCN,BF3
O
OAc
OH
OH
COOHHOOC
daucic acid
OAc HO
HOOH
O
COOMe
COOMe
1. Acetone, H2SO¯2. MsCI, pyr. 65%
COOMe
COOMe
OMs
O
O
O
AcO
79%
D-Galactose
AcO
CN
1. Lutidine, AI2O32. TFA, H2O,
CHCI3, RT, 1h
3. TFA, H2O 55%
3. HCI, MeOH4. TEMPO, NaOCI5. HCI, MeOH
65%
2. NaOH, 100°C
Scheme 26 Total synthesis of daucic acid.
136 Franz Dietrich Klingler
-
corresponding diester. After isopropylidenation of the 4,5-diol and
mesylation, the lutidine-induced elimination and deprotection by aqueous
trifluoroacetic acid gave the lyxo-configurated dimethyl daucate. After a
very mild saponification with aqueous trifluoroacetic acid for two days at
room temperature, the free (�)-daucic acid was isolated in crystalline form,which was identical to the natural product.
The chiral building blocks that played the most important role in Frieder
Lichtenthaler’s group in terms of their utilization are the so-called “ulosyl
bromides”. Structurally these are 2-oxo-glycopyranosyl bromides (Fig. 2).
The unexpected stability and the graduated reactivity made these
compounds very versatile for glycosidation reactions.
The ulosyl bromides are easily accessible from 2-acyloxyglycals. This
conversion can be done in two ways (Scheme 27): either via a high-yielding
three-step procedure involving hydroxylaminolysis of enediol ester,
deoximination and photo bromination at the push-pull substituted anomeric
center,58,59or, alternatively, via a straightforward one-step process simply
R3
R1
R2
O
O
Br
Fig. 2 General structure of “ulosyl bromides.”
NBS, MeOH
MeCHO, H+
NH2OH NBS, hv
NOH
R1 R1
R1 R1
R2
R2
R2 R2
R2
R2
R2R2
RO
O
O O
O Br
O
O
O
Scheme 27 Two ways of synthesizing “ulosyl bromides.”
137The scientific legacy of Frieder W. Lichtenthaler
-
comprising exposure of the respective 2-acyloxy-glycal in dichloromethane
to a slight excess of N-bromosuccinimide or bromine in the presence of
methanol.60
Most of these ulosyl bromides, especially the peracylated analogues, are
stable substances that can be stored for weeks without noticeable decompo-
sition. Methodologies were worked out in Lichtenthaler’s group for highly
selective glycosidation reactions. As the glycosyl-2-ulosyl bromides lack a
participating group next to the anomeric center, the stereochemical out-
comes of glycosidations greatly depend on the catalyst. The use of insoluble
silver salts, such as silver carbonate, -silicate or -alumosilicate as promoters
invariably results in the formation of β-glycosiduloses. The electron-withdrawing functionality at C-2 obviously favors the SN2-type attack of
the alcohol compound.
Glycosidation with ulosyl bromides can also be conducted in a highly
α-selective manner simply by mediating the reaction with soluble silver salts,silver triflate being the most effective one. The initially formed anomeric
β-triflate, stabilized by the inductive effect of the carbonyl group, is predom-inantly attacked by the alcohol to form the α-glycoside.
The mechanistic details and many examples of these glycosidations have
been summarized by Lichtenthaler in a 40-page review article.61
An interesting further development of this reaction is the glycosidation
with bifunctional acceptors.When exposing ulosyl bromides in the presence
of insoluble silver salts to vicinal diols or their amino- and thio-analogues,
the essentially β-specific glycosidation is followed by an intramolecularhemiketalization with the 2-carbonyl group (Scheme 28).62,63
Based on this chemistry, some pharmaceutically interesting natural
products were synthesized. One target was the broad-spectrum antibiotic
spectinomycin, which consists of a sugar moiety (actinospectose) doubly
connected via a β-glycosidic and hemiketal linkage to an N,N-dimethyl-1,3-diamino-myo-inositol. It forms a pyran-dioxane-cyclohexane system
in cis-cisoid-trans-arrangement (Scheme 29).
BzO
OBz
BzO
Br
O
O
BzO
86%
BzO
BzO
OO OO
OBz
BzO=
BzO
OH
OO
OH
, Ag2CO
3HO
HO
Scheme 28 Reaction of ulosyl bromides with 1,2-diols.
138 Franz Dietrich Klingler
-
The readily available 6-deoxy-di-O-benzoyl-D-glucal was transformed
into the 6-deoxyulosyl chloride in two steps. In this case, the chloride
proved to be advantageous over the bromide as the anomeric leaving group.
The best catalyst for the glycosidation of the highly functionalized cyclo-
hexane was found, after substantial experimentation, in silver alumosilicate.
The desired isomer was formed in high selectivity in 51% isolated yield, and
after deprotection spectinomycin was obtained.64
Other target molecules were the cardiac glycosides, which contain a struc-
turally similar feature. They are constituents of the plant Asclepiadaceae that
belongs to themilkweed family. A 4,6-dideoxy sugar is doubly connected to a
cardenolide bearing a 2,3-diol group in the A-ring. The synthesis of
gomphoside is shown here as an example (Scheme 30). The gomphogenine
O
OO
OH
OH
Me
Ag triflate, THF,3h, –78°C
57%
OBzOBz
OHHO
HO
OH
NZMe
NZMe
NZMe
NZMe
O
OO
OH
OH
Me
OOH
Spectinomycin
NHMe
NHMe
1. K2CO3, MeOH2. H2, cat.
O
O
CIMeO
OBz 1. CI2,H2O2. NaHCO3
47%
71%
OBz OBzBzO
Me
Scheme 29 Total synthesis of spectinomycin.
O
OO
OHOHO
O
OMe
O
OMe
O
O
O
OMe
OBz
BzOOH
OH
ca. 5 : 1
1, TBAOAc, MeCN,H
2O, RT 89%
2, K2CO
3, MeOH, RT
95%
Me
Ghomphoside
H2,Rh-C,
MeOH, H2O
NaBH ,MeOH, 0°C
81%RT, 80%
O
OH
OH
O
OBz
BzOOH
Me
HO
HO
Ag2CO
3, MS,
Ag2CO
3, MS,
DCM, 40°C, 54%
DCM, RT, 75%
OH
OH
O
OH
O
OH+
O
O O
O
O
CIMe
OBz
O
O
Br
BzO
Me
OBz
O
O
O
O
O
†
Scheme 30 Total synthesis of ghomphoside.
139The scientific legacy of Frieder W. Lichtenthaler
-
was prepared fromdigitoxin by a known, eight-step synthesis and glycosidated
with the ulosyl bromide as well as the ulosyl chloride, which gave a slightly
better selectivity of the two expected products.
The naturally fused product was the major product, which could be sep-
arated by chromatography65 and isolated in 55% yield. AfterO-debenzoylation
and exposure to mild base, the 30-dehydro gomphoside was isolated, whichproved identical in all respects to the naturally derived product. By hydroge-
nation of the keto group with rhodium-on-carbon catalyst, the gomphoside
could be isolated. Sodium borohydride reduction formed stereospecifically
the 30-epi-gomphoside. Finally, the structure was analyzed by single-crystalX-ray-diffraction.
The synthetic methodology based on ulosyl bromide chemistry is only
described here by way of a very few selected examples. The process was
expanded to many mono-, di- and trisaccharides in Lichtenthaler’s group.
The 2-oxo- and 2-oximino-glycosyl halogenides proved to be surprisingly
versatile glycosyl donors also for expedient construction of β-D-mannose-,β-L-rhamnose- and β-D-mannosamine-containing oligosaccharides.66
The utilization of inexpensive, accessible, renewable disaccharides,
available in bulk scale, as organic rawmaterials was a general research subject
in Lichtenthaler’s group for many years.
Sucrose, occupying the key position amongst the readily accessible
disaccharides, is produced in well over 100 million tons per year and is the
cheapest of these enantiopure molecules. The reaction potential inherent in
sucrose and other disaccharides was utilized towards the acquisition of versatile
building blocks. The glucose portion of sucrose, for example, was converted
into dihydropyranones with carbonyl functions at C-2 or C-4 or was trans-
formed into enediolone, enelactone or enollactone structures (Fig. 3).
Another novel entry reaction into O-functionalized disaccharide
derivatives, the cathodic deprotonation and subsequent trapping of the
mono-anion with suitable reagents, was evaluated in terms of understanding
the regioselectivity attainable through computer simulations of relevant
conformers of sucrose in solution, and the corresponding molecular
electrostatic potential (MEP) profiles.67
In collaboration with Prof. C. H. Hamann, the selective
O-functionalization of sucrose by cathodic deprotonation, following
etherification and esterification, was shown.68
The different conformers of sucrose in DMSO solution, determined by
NMR studies, were compared to the calculated data generated by force-field
140 Franz Dietrich Klingler
-
calculations and showed surprisingly close agreement. For predicting the
electrochemical properties of sucrose from its solution behavior, i.e., how
the sucrose molecule is oriented in an electric field and, hence, arrives at
the cathode, the MEP (molecular electrostatic potential) of the two relevant
conformers in solution were calculated. In both cases it was evident that the
proton of the 2-OH-group of the glucose part was characterized by highly
positive electrostatic potential, indicating its enhanced acidity over other
protons.69,70
Similar studies and applications towards useful building blocks have
been performed with other disaccharides such as lactose, maltose and
isomaltulose.68,71 Investigations were also extended to higher oligosaccha-
rides, most notably the cyclodextrins, which are easily accessible from starch
on the ton-scale level. Their use, in this context, lies less in the elaboration of
building blocks to be incorporated into complex target molecules, but in the
OO
O
O
PivO
PivO
OBz OH
AcOOBzO
O
OOBz
OBz
BzOBzO
BzO
OAcO
OAc
OAcAcO
AcO
OH
HOHO
OBz
OBzO
O
O
BzOBzO
38% (3 steps) from sucrose 14% (4 steps) from sucrose
70% (1 step) from isomaltulose60% (3 steps) from isomaltulose
58% (2 steps) from maltose 52% (2 steps) from lactose
PivO
PivO
OPiv
OPiv
OO
O
OPivO
PivO
PivO
PivO
OPiv
OPiv
OO
O
O CHO
O
O O
O
Fig. 3 Versatile building blocks from readily available disaccharides.
141The scientific legacy of Frieder W. Lichtenthaler
-
design of novel flexible host molecules with which to study and eventually
understand recognition phenomena at a molecular level. A molecular
modeling study of the (1!4)-linked cyclooligosaccharides containingfive- and six-α-D-glucose, α-D-mannose, and β-D-galactose units, respec-tively, provided a clear conception of their overall conformation, their con-
tact surfaces, and their cavity proportions. AMOLCAD-based generation of
their molecular lipophilicity potential (MLPs) gave a lucid picture of their
hydrophobic and hydrophilic surface areas, and hence, a first estimation
of their inclusion properties.72–76
Besides chiral building blocks based on aldoses, Lichtenthaler investigated
inexpensive ketoses, available in bulk scale, mainly D-fructose, L-sorbose and
isomaltulose over many years. Their utilization as organic rawmaterials in the
chemical industry was modest as their chemistry was not developed at a rate
comparable to that of other common monosaccharides.
Lichtenthaler developed improved procedures for the practical pre-
paration of either acyclic, furanoid or pyranoid, tautomerically fixed fructose
derivatives in order to exploit a defined follow-up chemistry for the
formation of useful chiral building blocks (Scheme 31).77
The pyranoid tetrabenzoate was isolated in 80% yield after treatment of
D-fructose in a cooled (�10 °C) mixture of pyridine and chloroform withfour equivalents of benzoyl chloride. The less reactive tertiary anomeric
hydroxyl group was nearly unaffected under those conditions. When the
benzoylation was performed at ambient temperature, the outcomewas quite
different. A mixture of pyranoid tetra- and pentabenzoates, the furanoid
OR
RO
OR OR
OR
ORRO
RO
OR
OOH
OR
O
ORORRO
R = Bz, Ac R = Bz, Ac
D-Fructose
R = Bz, Piv
OH
O
Scheme 31 Useful pyranoid, furanoid, and acyclic fixed derivatives of D-fructose.
142 Franz Dietrich Klingler
-
tetrabenzoate and the acyclic pentabenzoate was formed. The open-chain
product was isolated after chromatographic separation in 20% yield.
Benzoylation of fructose in pyridine at 60–70 °C led to the furanoidtetrabenzoate in 60% yield.77
The exo- and endo-glycals of D-fructose and of L-sorbose were also
investigated, and practical routes for their acquisition were developed.78,79
Dehydrobromination of benzoylated β-D-fructopyranosyl- and α-L-sorbopyranosyl bromides were examined in order to obtain suitable conditions
to achieve the elimination towards the exo- as well as the endo-positions.
In the fructose case (Scheme 32), exposure to DBU in acetonitrile
generates the exo-hydroxy fructal ester (81%), while in refluxing xylene
the endo-analog (53%) is formed. The utility of such C-6 building blocks
has also been demonstrated.78 Lichtenthaler provided a summary on the
utility of ketoses as organic raw materials in an account in Carbohydrate
Research in 1998.80
Frieder Lichtenthaler’s name is closely associatedwith the promotion of the
use of inexpensive, renewable carbohydrates, available in bulk scale, as chiral,
enantiopure building blocks, and thus their ennoblement in a scientific and
in an economic sense. He formed an internationally renowned compe-
tence center for carbohydrate chemistry at the Technische Universit€atDarmstadt in Germany.
Besides chemical research on carbohydrates, he published a notable
number of essays on the history of carbohydrate chemistry. His interest in
the history of organic chemistry in general was awakened during his time
in Berkeley, when he was asked by Mrs. Fischer to go through the personal
BzO
D-Fructose
1. BzCI2. HBr
BzO BzO
DBU, MeCN81%
OBzOBz
OBzOBz
OBz OBz
OBz
1. Nal, acetone2. Xylene, 100°C
53%
OBz
O O
OBz
Br
O
Scheme 32 Synthesis of exo- and endo-fructals.
143The scientific legacy of Frieder W. Lichtenthaler
-
manuscripts, letters, pictures and books of Emil Fischer, which had been
donated to the Bancroft Library at the University of California-Berkeley.
Lichtenthaler focused especially on reviewing the scientific and personal
achievements of Emil Fischer.81,82 He was a featured speaker and delivered
a most notable lecture on the life and contributions of Emil Fischer in a
commemorative symposium at the American Chemical Society National
Meeting in 1992 in San Francisco.83
FriederW. Lichtenthaler was blessed with a fulfilling family life. His wife
Evemaria, a well-known architect, was a tremendous rock of support
throughout his career, and from this happy marriage resulted two sons
(Matthias and Johannes), a daughter (Kathrin) and eventually eight
grandchildren, of all of whom he was very proud.
In his final years, Lichtenthaler participated in the activities of the
Clemens Schoepf Institute, was engaged in extensive refereeing for various
journals and consultations with industrial companies, and took the effort to
help propagate the paradigm shift in the chemical industry to replace
petroleum-based raw materials with renewable ones from the cornucopia
of carbohydrate compounds.
Professor FriederW. Lichtenthaler passed away peacefully on 6 November
2018 in his home near Darmstadt, Germany, leaving behind an impressive
scientific legacy documented in over 300 publications and many intriguing
ideas to be explored by future generations of chemists.
References1. Lichtenthaler, F. W. Chemistry and Properties of Enol Phosphates. Chem. Rev. 1961,
61, 607–649. Based, in part, on: Lichtenthaler, F. W. €Uber die Reaktivit€at vonEnolphosphaten, Dissertation, Universit€at Heidelberg, 1959.
2. Lichtenthaler, F.W.; Fischer, H. O. L. Cyclizations of DialdehydesWith Nitromethane,VII. Preparation of Neo-Inosadiamine-1.4. J. Am. Chem. Soc. 1961, 83, 2005–2012.
3. Lichtenthaler, F. W. Nitromethan-Kondensation mit Dialdehyden, II. Zur Synthesevon myo-Inosit aus Glucose. Angew. Chem. 1963, 75, 93; Angew. Chem., Int. Ed.Engl. 1963, 1, 662.
4. Lichtenthaler, F. W. Cyclisierung von Dialdehyden mit Nitromethan. Angew. Chem.1964, 76, 84–97; Angew. Chem., Int. Ed. Engl. 1964, 3, 211–224.
5. Lichtenthaler, F. W.; Nakagawa, T.; El Scherbiney, A. Nitromethan-Kondensation mitDialdehyden, X. Synthese cyclischer 1,2,3-Triamine durch Umsetzung vonDialdehyden mit Nitromethan und Benzylamin. Angew. Chem. 1967, 79, 530–531;Angew. Chem., Int. Ed. Engl. 1967, 6, 568–569.
6. Lichtenthaler, F. W. Konfiguration der bei Cyclisierung von 6-Nitro-D-glucosegebildeten Desoxy-nitro-inosite und ihre Isomerisierungen mit Alkali. Chem. Ber.1961, 94, 3071–3085.
7. Lichtenthaler, F. W.; Pashalidis, A.; Lindner, H. J. Studies on Ketoses, 3. Conversion ofD- Fructose Into 4-Amino-, 4-Amino-4-C-methyl-, and 3,4,5-Triamino-Derivatives ofL-Sorbose. Carbohydr. Res. 1987, 164, 357–372.
144 Franz Dietrich Klingler
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-
8. Lichtenthaler, F.W.; Fleischer, D. Nitromethane CondensationWith Dialdehydes, XX.Formation of Cyclohexane Versa Tetrahydropyrane Derivatives on Reaction ofGlutaraldehyde With Nitroalkanes. J. Org. Chem. 1972, 37, 1670–1672.
9. Lichtenthaler, F. W.; Bambach, G. Nitromethane Condensations With Dialdehydes,XIX. C–O-Migration of an Ethoxycarbonyl Group. J. Org. Chem. 1972, 37,1621–1624.
10. Lichtenthaler, F. W.; Albrecht, H. P. Nucleoside, IV. Synthese eines Puromycin-Analogons. Angew. Chem. 1968, 80, 440–441; Angew. Chem., Int. Ed. Engl. 1968, 7,457–458.
11. Lichtenthaler, F. W.; Albrecht, H. P. Nucleoside, V. 6-Dimethylaminopurin-Nucleosideder 3-Amino-3-Desoxy-β-D-Glucose, -Mannose und -Galactose. Chem. Ber. 1969, 102,964–970.
12. Lichtenthaler, F. W.; Emig, P.; Bommer, D. Nucleoside, VI. Nucleosid-Umwandlungenin der Reihe der 30-Aminohexosyl-hypoxanthine. Chem. Ber. 1969, 102, 971–985.
13. Lichtenthaler, F. W.; Nakagawa, T.; Yoshimura, J. Nitromethan-Kondensation mitDialdehyden, VI; Nucleoside II. Theophyllin-Nucleoside der 3-Amino-3-Deoxy-β-D-Glucose, -Mannose und -Galactose. Chem. Ber. 1967, 100, 1833–1844.
14. Lichtenthaler, F. W.; Bambach, G.; Emig, P. Nucleoside, VIII. ZurKonfigurationszuordnung von Zuckern und Hexopyranosyl-Nucleosiden mit Hilfeder Acetyl-Resonanzen-Regel. Chem. Ber. 1969, 102, 994–1004.
15. Lichtenthaler, F. W.; Zinke, H. Nucleosides, XIII. Nitromethane Condensations WithDialdehydes, XVIII, Synthesis and Interconversions of C-Methyl branched 1-(3-Amino-3-deoxy-β-D-hexopyranosyl)uracils. An Empirical Method for ConfigurationalAssignments at the Branch Point by NMR. J. Org. Chem. 1972, 37, 1612–1621.
16. Lichtenthaler, F. W.; Trummlitz, G.; Emig, P. Nucleosides, X. Synthesis of DipeptidylAminosugar Nucleosides Structurally Related to Gougerotin. Tetrahedron Lett. 1970, 11,2061–2064.
17. Lichtenthaler, F. W.; Trummlitz, G.; Bambach, G.; Rychlı́k, I. Nucleosides, XI.Synthese eines biologisch aktiven Gougerotin-Analogons. Angew. Chem. 1971, 83,331–332; Angew. Chem., Int. Ed. Engl. 1971, 10, 334–335.
18. Cerná, J.; Lichtenthaler, F. W.; Rychlı́k, I. Nucleosides, XII. The Effect of Gougerotin-Analogues on Ribosomal Peptidyl Transferase. Fed. Eur. Biochem. Soc. Lett. 1971, 14,45–48.
19. Cerná, J.; Rychlı́k, I.; Lichtenthaler, F. W. Nucleosides, XIV. The Effect of theAminoacyl-4-Amino-Hexosyl-Cytosine Group of Antibiotics on Ribosomal PeptidylTransferase. Fed. Eur. Biochem. Soc. Lett. 1973, 30, 147–150.
20. Lichtenthaler, F. W.; Trumlitz, G. Nucleosides, XVII. Structural Basis of InhibitionProtein Synthesis by the Aminoacyl Aminohexosyl Cytosine Group of Antibiotics.Fed. Eur. Biochem. Soc. Lett. 1974, 38, 237–242.
21. Lichtenthaler, F. W.; Cerná, J.; Rychlı́k, I. Nucleosides, XXIV. The Effect ofOxamicetin and Some Amicetin Analogs on Ribosomal Peptidyl Transferase. Fed.Eur. Biochem. Soc. Lett. 1975, 53, 184–187.
22. Lichtenthaler, F. W.; Morino, T.; Winterfeldt, W.; Sanemitsu, Y. Nucleosides,XXVI. An Alternate Synthetic Approach to Gougerotin. Tetrahedron Lett. 1975, 16,3527–3530.
23. Lichtenthaler, F. W.; Morino, T.; Winterfeldt, W. Nucleosides, XXIX. Total Synthesisof Aspiculamycin. Nucleic Acids Res. Spec. Publ. 1975, 1, 33–36.
24. Lichtenthaler, F. W.; Heerd, A.; Strobel, K. Nucleosides, XIX. Hexuronic Acid andAminosugar Nucleosides Via SnCl4-Catalyzed Glycosidations of SilylpyrimidinesWith Peracyl Sugars. Chem. Lett. 1974, 449–452.
25. Cuny, E.; Lichtenthaler, F. W. Nucleosides, XXVIII. Synthesis of Allopurinol-Ribosides. Nucleic Acids Res. Spec. Publ. 1975, 1, 25–28.
145The scientific legacy of Frieder W. Lichtenthaler
http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0045http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0045http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0045http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0050http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0050http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0050http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0055http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0055http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0055http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0060http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0060http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0060http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0060http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0065http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0065http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0065http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0070http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0070http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0070http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0070http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0075http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0075http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0075http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0080http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0080http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0080http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0080http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0080http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0085http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0085http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0085http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0090http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0090http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0090http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0095http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0095http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0095http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0100http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0100http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0100http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0105http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0105http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0105http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0110http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0110http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0110http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0115http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0115http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0115http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0120http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0120http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0125http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0125http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0125http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0125http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0130http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0130
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26. Lichtenthaler, F. W.; Cuny, E. Nucleosides, 38. The Ribonucleosides of Allopurinol.Chem. Ber. 1981, 114, 1610–1623.
27. Cuny, E.; Lichtenthaler, F.W.; Jahn, U. Nucleosides, 39. Angular und Linear erweiterteAllopurinole: Pyrazolo[4,3-f] und [4,3-g]Chinazolinone. Chem. Ber. 1981, 114,1624–1635.
28. Cuny, E.; Eberhard, W.; Lichtenthaler, F. W. Nucleosides, 43. Synthesis ofBenzologously Extended Allopurinol Ribosides and Formycins. Nucleic Acids Res.Spec. Publ. 1981, 9, 77–81.
29. Lichtenthaler, F. W.; Moser, A. Nucleosides, 44. Benzo-separated Pyrazolopyrimidines:Expeditious Syntheses of [3,4-g]- and [3,4-h]-linked Pyrazoloquinazolinones.Tetrahedron Lett. 1981, 22, 4397–4400.
30. Kraska, B.; Lichtenthaler, F.W.Nucleosides, 41. (1-5)-verkn€upfte Glucopyranosyl- undGalactopyranosyl-ribosen. Chem. Ber. 1981, 114, 1636–1648.
31. Lichtenthaler, F. W.; Eberhard, W.; Braun, S. Nucleosides, 45. Assignment ofGlycosylation Sites in 5’-O-Hexopyranosyl-Ribonucleosides by 13C-NMR.Tetrahedron Lett. 1981, 22, 4401–4404.
32. Alexandrova, L. A.; Lichtenthaler, F. W. Nucleosides, 46. A New Synthesis of theAntibiotic Psicofuranine. Nucleic Acids Res. Spec. Publ. 1981, 9, 263–266.
33. Lichtenthaler, F. W.; Heidel, P. Zuckerenolone, I. Zwischenprodukte der Bildung vonγ-Pyronen aus Hexose-Derivaten; eine einfache Synthese von Kojis€aure undHydroxymaltol. Angew. Chem. 1969, 81, 998–999; Angew. Chem., Int. Ed. Engl.1969, 8, 978–979.
34. Lichtenthaler, F.W.; Ogawa, S.; Heidel, P. Sugar Enolones, VII. Synthesis and γ-PyroneFormation of α, β-Unsaturated Hexopyranosid-4-uloses. Chem. Ber. 1977, 110,3324–3332.
35. Lichtenthaler, F. W. Sugar Enolones, II. Unsaturated Glycopyranosiduloses. MethodsCarbohydr. Chem. 1972, 6, 348–349.
36. Fischer, E.; Lichtenthaler, F. W. Zuckerenolone, III. Ergiebige Synthese von Zucker-3,2-enolonen aus Hydroxyglycalen und ihre Umwandlung in γ-Pyrone. Angew. Chem.1974, 86, 590–592; Angew. Chem., Int. Ed. Engl. 1974, 13, 546–548.
37. Lichtenthaler, F. W.; Kraska, U. Sugar Enolones, V. Preparation and Some Reactions ofBenzoylated 4-Deoxy-D-glycero-hex-3-enosuloses. Carbohydr. Res. 1977, 58, 363–377.
38. Lichtenthaler, F. W.; Sakakibara, T.; Oeser, E. Sugar Enolones, VI. Tetrabenzoyl-2-halo-hexopyranosyl Halides: Preparation, Assignment of Configuration andHydrolysis to Enolones. Carbohydr. Res. 1977, 59, 47–61.
39. Lichtenthaler, F. W.; Kraska, U.; Ogawa, S. Sugar Enolones, VIII. A Facile Preparationof Deoxy-Hexosiduloses and Deoxy-Hexosides. Tetrahedron Lett. 1978, 19, 1323–1326.
40. Lichtenthaler, F. W. Sugar Enolones, IX. Synthesis, Reactions of Preparative Interestand γ-Pyrone Formation. Pure Appl. Chem. 1978, 50, 1343–1362.
41. Lichtenthaler, F. W.; Nishiyama, S.; Jarglis, P. Zuckerenolone, X. Neuartige,hochstereoselektive Umlagerungen chiraler Dihydropyranone. Angew. Chem. 1979,91, 1001–1002; Angew. Chem., Int. Ed. Engl. 1979, 18, 936–938.
42. Lichtenthaler, F. W.; Jarglis, P. Sugar Enolones, XII. Peroxidation of Pyranose-DerivedEnolesters: An Efficacious Synthesis of Peracetyl-hexosuloses and Their Conversion Intoγ-Pyrones via 3,2-Enolones. Chem. Ber. 1980, 113, 489–510.
43. Lichtenthaler, F. W.; Jarglis, P. Sugar Enolones, XIII. Selective Deacylation of EnolEsters With Hydroxylamine. Tetrahedron Lett. 1980, 21, 1425–1428.
44. Lichtenthaler, F. W.; El Ashry, E. S. H.; G€ockel, V. H. Sugar Enolones, XIV, XIV.A Convenient Access to 1,5-Anhydroketoses. Tetrahedron Lett. 1980, 21, 1429–1432.
45. Jarglis, P.; Lichtenthaler, F. W. Zuckerenolone, XV. Eine stereospezifische Synthesevon S,S-Palythazin aus D-Glucose. Angew. Chem. 1982, 94, 140–141; Angew. Chem.,Int. Ed. Engl. 1982, 21, 141–142.
146 Franz Dietrich Klingler
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46. Brehm,M.; Dauben,W.G.; K€ohler, P.; Lichtenthaler, F.W. Enantioreine Bausteine ausZuckern, 5. Beweis der S,S-Konfiguration von (�)-Bisseton durch Synthese ausD-Glucose. Angew. Chem. 1987, 99, 1318–1319; Angew. Chem., Int. Ed. Engl. 1987,26, 1271–1273.
47. Jarglis, P.; Lichtenthaler, F. W. Zuckerenolone, XVII. Boron Trifluoride-CatalyzedOxidation of Glycal Esters: An Effective and Mild Method for Their ConversionInto α, β-Unsaturated Lactones. Tetrahedron Lett. 1982, 23, 3781–3784.
48. Lichtenthaler, F. W.; R€onninger, S.; Jarglis, P. Enantiopure Building Blocks FromSugars, 9. An Expedient Approach to Pyranoid Ene and Enol Lactones by BF3-Catalyzed Peroxidation of Glycal and Hydroxyglycal Esters. Liebigs Ann. Chem. 1989,1989, 1153–1161.
49. Lichtenthaler, F. W.; Klingler, F. D.; Jarglis, P. Enantiopure Building Blocks FromSugars, 2. Simple Synthesis of (S)-Parasorbic Acid and Other (5S)-Hydroxy Six-Carbon Synthons From L-Rhamnose. Carbohydr. Res. 1984, 132, C1–C5.
50. Lichtenthaler, F.W. Enantiopure Building Blocks from Sugars: Efficient Preparation andUtilization in Natural Product Synthesis. In: New Aspects in Organic Chemistry I;Yoshida, Z., Shiba, T., Ohshiro, Y., Eds.; Wiley-VCH: Weinheim, NY, 1989;pp 351–384.
51. Klingler, F.D. Doctoral Dissertation, Technische Universit€at Darmstadt, Germany, 1985.52. Neff, K.H. Doctoral Dissertation, Technische Universit€at Darmstadt, Germany, 1988.53. Lichtenthaler, F. W.; Lorenz, K.; Ma, W. Y. Enantiomerically Pure Building Blocks
From Sugars, 4. A Convergent Total Synthesis of (�)-Anamarine. Tetrahedron Lett.1987, 27, 47–50.
54. Lorenz, K.; Lichtenthaler, F. W. Enantiopure Building Blocks From Sugars, 6.A Convergent Total Synthesis of (+)-Anamarine from (R,R)-Tartrate andL-Gulonolactone. Tetrahedron Lett. 1987, 28, 6437–6440.
55. Lichtenthaler, F. W.; Dinges, J.; Fukuda, Y. Enantioreine Bausteine aus Zuckern,13. ACRL Toxin I: Konvergente Totalsynthese des 3-Methylenolethers ausD-Glucose. Angew. Chem. 1991, 103, 1385–1389; Angew. Chem., Int. Ed. Engl. 1991,30, 1339–1343.
56. Lichtenthaler, F. W.; Nakamura, K.; Klotz, J. (�)-Daucic Acid: Revision ofConfiguration, Synthesis and Biosynthetic Implications. Angew. Chem. 2003, 115,6019–6023; Angew. Chem., Int. Ed. 2003, 42, 5838–5843.
57. Lichtenthaler, F. W.; Klotz, J.; Nakamura, K. Sugar-Derived Building Blocks,31. � (�)-Daucic Acid: Proof of D-lyxo Configuration, Synthesis of D-ribo, D-xylo,L-arabino, and L-lyxo Analogs, and Biosynthetic Implications. Tetrahedron: Asymmetry2003, 14, 3973–3986.
58. Lichtenthaler, F. W.; Jarglis, P. Zuckerenolone, XVI. Funktionalisierung proanomererZentren durch Photobromierung. Ein neuer Zugang zu Oxo- und Oximino-glycosyl-bromiden. Angew. Chem 1982, 94, 643; Angew. Chem., Int. Ed. Engl. 1982, 21, 625;Angew. Chem. Suppl., 1982, 21, 1449–1459.
59. Lichtenthaler, F. W.; Jarglis, P.; Hempe, W. Sugar Enolones, XVIII. StereocontrolledFunctionalization at Proanomeric Centres by Photobromination. A Novel EfficientAccess to Oxo- and Oximinoglycosyl Bromides. Liebigs Ann. Chem. 1983, 1983(11),1959–1972.
60. Lichtenthaler, F. W.; Cuny, E.; Weprek, S. Zuckerenolone, XX. Eine einfache undleistungsf€ahige Synthese acylierter Glyculosylbromide aus Hydroxylglycal-estern.Angew. Chem. 1983, 95, 906; Angew. Chem., Int. Ed. Engl. 1983, 22, 891.
61. Lichtenthaler, F. W. 2-Oxoglycosyl (“Ulosyl”) and 2-Oximinoglycosyl Bromides:Versatile Donors for the Expedient Assembly of Oligosaccharides with β-D-Mannose,β-L-Rhamnose, N-Acetyl-β-D-Mannosamine, and N-Acetyl-β-D-MannosaminuronicAcid Units. Chem. Rev. 2011, 111, 5569–5609.
147The scientific legacy of Frieder W. Lichtenthaler
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62. Cuny, E.; Lichtenthaler, F. W.; Lindner, H. J. Sugar-Derived Building Blocks, 35—Pyrano-Dioxanes via vic-Acetalic Annulation of 2-Ketosugars to Vicinal Diols. Eur.J. Org. Chem. 2004, 4901–4910.
63. Lichtenthaler, F. W.; Cuny, E. Sugar-Derived Building Blocks, 36.—Linear FusedPyran-Dioxane-Cyclohexane Tricycles: Synthesis of Five Linkage Isomers andEnsuing Reactions. Eur. J. Org. Chem. 2004, 4911–4920.
64. Cuny, E.; Lichtenthaler, F. W. Sugar-Derived Building Blocks, 39.—A ConciseStereocontrolled Synthesis of Spectinomycin.Tetrahedron: Asymmetry 2006, 17, 1120–1124.
65. Lichtenthaler, F. W.; Cuny, E.; Sakanaka, O. Sugar-Derived Building Blocks, 37.—AnEfficient and General Method for Doubly Attaching 2-Ketosugars to Aglycon Diols:Synthesis of the Gomphosides and of Spectinomycin. Angew. Chem. 2005, 117,5024–5028; Angew. Chem., Int. Ed. 2005, 44, 4944–4948.
66. Kaji, E.; Lichtenthaler, F. W. Expedient Conversion of Lactose Into VersatileDerivatives of Lactosamine and Galactosyl-β-(1-4)-mannosamine. J. Carbohydr. Chem.1995, 14, 791–803.
67. Lichtenthaler, F. W.; Immel, S.; Martin, D.; M€uller, V. Some Disaccharide-DerivedBuilding Blocks of Potential Industrial Utility. Starch/Staerke 1992, 44, 445–456.
68. Lichtenthaler, F. W.; Immel, S.; Martin, D.; M€uller, V. Some Disaccharide-derivedBuilding Blocks of Potential Industrial Utility. In: Carbohydrates as Organic RawMaterials II; Descotes, G. Ed.; Wiley-VCH: Weinheim/New York, 1993; pp 59–98.
69. Lichtenthaler, F. W.; Immel, S.; Kreis, U. Molecular Modeling of Saccharides,1. The Structural Representation of Sucrose. Starch/Staerke 1991, 43, 121–132;Republished (in Japanese): Shokuhin Kogyo (The Food Industry) 1992, 35, 65–85.
70. Lichtenthaler, F. W.; Immel, S. Molecular Modeling of Saccharides, 5.Computersimulation of Chemical and Biological Properties of Sucrose, theCyclodextrins, and Amylose. Int. Sugar J. 1995, 97, 12–22.
71. Lichtenthaler, F. W. Molecular Modeling of Saccharides, 2. Perspektiven in derNutzung niedermolekularer Kohlenhydrate als Rohstoffe f€ur die ChemischeIndustrie. Zuckerindustrie (Berlin) 1991, 116, 701–712.
72. Lichtenthaler, F. W.; Immel, S. Molecular Modeling of Saccharides, 4. Cyclodextrins,Cyclomannins and Cyclogalactins With Five and Six (1-4)-Linked Sugar Units:Comparative Assessment of Their Conformations and Hydrophobicity PotentialProfiles. Tetrahedron: Asymmetry 1994, 5, 2045–2060.
73. Immel, S.; Brickmann, J.; Lichtenthaler, F. W. Molecular Modeling of Saccharides, 6.Small Ring Cyclodextrins: Their Geometries and Hydrophobic Topographies. LiebigsAnn. 1995, 1995, 929–942.
74. Immel, S.; Lichtenthaler, F. W. Molecular Modeling of Saccharides, 9. On theHydrophobic Characteristics of Cyclodextrins: Computer-Aided Visualization ofMolecular Lipophilicity Patterns. Liebigs Ann. 1996, 1996, 27–37.
75. Lichtenthaler, F. W.; Immel, S. Molecular Modeling of Saccharides, 11. TowardsUnderstanding Formation and Stability of Cyclodextrin-Inclusion Complexes:Computation and Visualization of the Lipophilicity Patterns. Starch/Staerke 1996, 48,145–154.
76. Nakagawa, T.; Immel, S.; Lichtenthaler, F. W.; Lindner, H. J. Molecular Modeling ofSaccharides, 23.—Topography of a 1:1 α-Cyclodextrin–Nitromethane InclusionComplex. Carbohydr. Res. 2000, 324, 141–146.
77. Lichtenthaler, F. W.; Klotz, J.; Flath, F. J. Studies on Ketoses, 10. Acylation andCarbamoylation of D-Fructose: Acyclic, Furanoid and Pyranoid Derivatives and TheirConformational Features. Liebigs Ann. 1995, 1995, 2069–2080.
78. Lichtenthaler, F. W.; Hahn, S.; Flath, F. J. Studies on Ketoses, 11. Enantiopure BuildingBlocks From Sugars, 19, Pyranoid endo- and exo-Glycals from D-Fructose andL-Sorbose: Practical Routes for Their Acquisition and Ensuing Reactions. LiebigsAnn. 1995, 1995, 2081–2088.
148 Franz Dietrich Klingler
http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0305http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0305http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0305http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0310http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0310http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0310http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0315http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0315http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0320http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0320http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0320http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0320http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0325http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0325http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0325http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0325http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0330http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0330http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0330http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0335http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0335http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0335http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0335http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0340http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0340http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0340http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0345http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0345http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0345http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0350http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0350http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0350http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0350http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0355http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0355http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0355http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0355http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0360http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0360http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0360http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0365http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0365http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0365http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0370http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0370http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0370http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0370http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0375http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0375http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0375http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0375http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0380http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0380http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0380http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0385http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0385http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0385http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0385
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79. Boettcher, A.; Lichtenthaler, F. W. Sugar-Derived Building Blocks, 33.—D-Fructose-and L-Sorbose-Derived Endo- and Exo-Hydroxyglycal Esters and Some of TheirChemistry. Tetrahedron: Asymmetry 2004, 15, 2693–2701.
80. Lichtenthaler, F. W. Enantiopure Building Blocks From Sugars, 24.—TowardsImproving the Utility of Ketoses as Organic Raw Materials. Carbohydr. Res. 1998,313, 69–90.
81. Lichtenthaler, F. W. Emil Fischer, His Personality, His Achievements, and His ScientificProgeny. Eur. J. Org. Chem. 2002, 4095–4122.
82. Lichtenthaler, F. W. Emil Fischer’s Establishment of the Configuration of Sugars:A Centennial Tribute. Angew. Chem. 1992, 104, 1577–1593; Angew. Chem., Int. Ed.Engl. 1992, 31, 1541–1556.
83. Lichtenthaler, F.W. Emil Fischer: 100 Years of Carbohydrate Chemistry. InAbstr. 203rdAm. Chem. Soc. Natl. Mtg, 1992, San Francisco.
149The scientific legacy of Frieder W. Lichtenthaler
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The scientific legacy of Frieder W. LichtenthalerReferences