Sabine Köpper

Rare sugars and sugar-based synthons by chemo-enzymatic synthesis.

The unique catalytic potential of the fungal enzyme pyranose oxidase was demonstrated by preparative conversions of a variety of carbohydrates, and by extensive chemical characterization of the reaction products with NMR spectroscopy. The studies revealed that POx not only oxidizes most substrates very efficiently but also that POx possesses a glycosyl-transfer potential, producing disaccharides from beta-glycosides of higher alcohols. Although most substrates are oxidized by POx at the C-2 position, several substrates are converted into the 3-keto-derivatives. On the basis of these products, strategies are developed for the convenient production of sugar-derived synthons, rare sugars and fine chemicals by combining biotechnical and chemical methods.

CONVENIENT CHEMO-ENZYMATIC SYNTHESIS OF D-TAGATOSE

Abstract The ketohexose d-tagatose is a rare sugar that is of interest as a potent noncaloric sweetener. The synthesis of d-tagatose has been accomplished by microbiological conversion of dulcitol1,2 as well as by chemical syntheses in low yields originating from d-galactose3 or d-fructose.4 Recently, some patents concerning the synthesis of d-tagatose have been published.5,6,7 We here present an alternative approach to the preparation of d-tagatose by a combined chemoenzymatic synthesis starting from d-galactose. Enzymatic oxidation of d-galactose (1) leads to the 2-oxidised product, d-galactosone, which in turn is reduced chemically to d-tagatose (2). The target sugar is thus available in a one-pot / two-step procedure in a yield of 30 %.

Silver Zeolite as Promoter in Glycoside Synthesis. The Synthesis of 2-Deoxy-β-D-Glycopyranosides

Abstract The use of silver zeolite as a promoter for the preparation of β-linked 2-deoxygtycosides and disaccharides of biological relevance has been explored. Starting from benzoylated glycosyl bromides, the total yield of glycosides varies from 54 to 84% and the α:β ratio from 0.25 to 1.18.

Syntheses of kijanimicin oligosaccharides

Abstract Various di- and trisaccharide precursors of the kijanimicin tetrasaccharide were prepared by the N-iodosuccinimide glycosylation procedure employing regioselectively blocked L-digitoxosides and L-digitoxals. Assumed 13-neighboring group participations were studied in acid- and silver or mercury salt-promoted glycosylations with selectively functionalized digitoxoses or their glycosyl chlorides. No evidence for enhanced β:α-ratios exceeding that of previous glycosylations in 2-deoxy-ribo components could be observed. A straightforward sequential synthetic approach applied both the studied glycosylation methods and thus a synthesis of the blocked DC B-A tetrasaccharide of kijanimicin was achieved. Throughout structures and conformations of the oligosaccharides were assigned by extensive 1H NMR spectroscopy.

Reaktionen Mit Trimethylsilylhalogeniden an Derivaten Der Digitoxose

Abstract Treatment of methyl 3,4-di-O-acyl-2,6-dideoxy-α-D-ribo-hexo-pyranoside 1 or 2 with trimethylsilyl halide leads to the formation of a complex mixture of α-D-ribo-hexopyranosyl halides 3 or 5 together with the educts 1 or 2 as well as their β-anomers 8 or 9. The bromides 3 and 5, suitable for glycosidations, are preferably obtained by reaction of the digitoxose acetate derivatives 6 and 7, respectively, which in turn are prepared from 1 and 2 by mild acetolysis. Further reaction of the halides 3 to 5 with trimethylsilyl halides gives rise to a quantitative formation of the 2,3,6-trideoxy-4-0-acyl-3-halo-α-D -arabino-hexopyranosyl halides 10 to 12. In another reaction sequence starting with the olivose triacetate 20 the formation of 10 via the halide 13 is demonstrated. Structural evidence for the halides 10 to 12 is given by 1H NMR data as well as by analyses of their glycosides 14 to 19. The results support a mechanistic interpretation for the formation of 10 to 12 via a 3,4-acetoxonium ion as the...

Die anlagerung von mercaptocarbonsäuren an 3-thiazoline und anschließende lactamisierung

Zusammenfassung The reaction of 3-thiazolines 1a–c with α- or β-mercaptocarboxylic acids leads to bicyclic lactams 2–4. Depending on the reaction conditions diastereomeric mixtures 2b, 3, 4a, b are formed. The synthesis of the latter can be explained by a two-step mechanism. The configuration and conformation of the diastereomers is deducted by 1H, 13C-NMR spectroscopy and NOE experiments.

Vorteilhafte Darstellungen Selektiv Acylierter und Alkylierter L-Digitoxoside

Abstract Acid catalyzed glycosylations of L-digitoxose or its derivatives lead to anomeric mixtures 3 or 4. By 1,4-addition of certain alcohols to the hex-1-en-3-ulose 8 a selective preparation of alkyl-α-L-ervthro-hexopyranoside-β-uloses 10 or 12 is achieved. The ulosides are stereoselectively reduced to give alkyl α-L-digitoxo-sides 13 or 14. By use of phase transfer catalyzed benzylation the latter is regioselectively transformed into the monobenzyl ethers 17 and 18. respectively. The 3,4-carbonate 19 can be opened with N-methylamine or ammonia to give predominantly the 3-carbamoyl derivatives 20 (or 22) together with the regioisomers 21 (or 23) as side products. Methylation of the mixture 20 plus 21 uniformly lead to the 4-O-methyl ether 28, the reaction mechanism of which is outlined. The 3-N-methy1-carbaraoyl derivatives 29 and the corresponding 3-O-p-methoxybenzoate compound 32, obtained straightforwardly from the epoxide 25 or from 28 represent L-digitoxose building units useful for further glycos...

One-pot-synthesis of α-linked deoxy sugar trisaccharides

Abstract Various α-linked 2,6-dideoxy- ribo -trisaccharides, models for part of the antibiotic kijanimicin, were synthesised by the N -iodosuccinimide method employing different pathways. The efficiency of a sequential synthesis suffered from side reactions of the axial HO-3, which are typical of digitoxosides. These problems did not arise in a straightforward polymerisation, performed as a one-pot-procedure. It afforded the trisaccharide directly from the monosaccharide precursor in 30% yield. A combination of the oligomerisation pathway and the sequential synthesis led to trisaccharides with different protecting group patterns. In these reactions different glycal and alcohol components were used and allowed to define the optimal partners in a sequential synthesis: the two components should ideally be of comparable reactivity.

Unusual Formation of a β-linked Disaccharide in a Nis Glycosylation

Abstract The N-halosuccinimide glycosylation is a highly selective reaction that leads to trans-configured 1-alkoxy-2-halo-glycosides (halo = bromo, iodo).23 As an exception to the generally observed exclusive formation of α-linked glycosides in such reactions,2 we obtained a 3 / 1 mixture of α- and β-disaccharide 6 and 7, when we treated the silylated glycal 4 with NIS (N-iodosuccinimide) and the glycoside 5.4 The similarly protected arabino glycal 9, on the other hand, gave exclusively the expected α-linked saccharide 11, when treated with NIS and the alcohol component 10.5 Silylated glycals 4 and 9 were obtained from L-digitoxal 1 6 and L-rhamnal 8 7 by treatment with tert-butyldiphenylchlorosilane8 and tert-butyldimethylchlorosilane,9 respectively. In both cases the 3-O-silylated derivatives formed in high yields. Only in case of the ribo-configuration minor amounts of a 4-O-silylated product 3 were identified.

Rigid gt conformation of the C5/C6 bond in a gluco derivative

Abstract The rotational freedom of the C5/C6 bond of hexopyranosides very often governs the conformation of oligosaccharides, especially when 1→6 linkages are present in the saccharide. Conformational analysis may be complicated by the existence of a dynamic equilibrium between three staggered rotamers in the C5/C6 fragment.1 The population of the individual rotamers can be deduced from J5,6s and J5,6R coupling constants by ap- plying an equation that connects the experimentally derived time-averaged coupling constants to the populational equilibrium. A prerequisite for this approach is the assign- ment of the prochiral protons H-6R and H-6S2 and a correct evaluation of the effects of substituents on the coupling constant.