the scientific legacy of frieder w. lichtenthaler · 2021. 1. 20. · chapter three the scientific...

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

121

https://doi.org/10.1016/bs.accb.2020.05.001

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

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

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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.”


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.


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.


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


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.


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.


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.


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.


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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.


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

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.


http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0135http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0135http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0140http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0140http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0140http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0145http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0145http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0145http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0150http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0150http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0150http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0155http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0155http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0155http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0160http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0160http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0160http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0160http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0165http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0165http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0170http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0170http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0170http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0170http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0170http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0175http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0175http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0175http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0175http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0175http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0175http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0180http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0180http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0185http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0185http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0185http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0185http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0190http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0190http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0195http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0195http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0195http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0200http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0200http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0205http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0205http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0205http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0210http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0210http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0210http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0215http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0215http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0215http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0220http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0220http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0225http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0225http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0225http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0230http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0230http://refhub.elsevier.com/S0065-2318(20)30001-9/rf0230

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.


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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.


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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.


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