Nucleosides having acyclic 2-deoxy-1-thio- -arabino-hexitol and 2-deoxy-1-thio- -erythro-pentitol chains

Aspects of the pyrolysis of 1-deoxy-1-glycino-d-fructose and 1-β-alanino-1-deoxy-d-fructose are reported. Thermal analysis and parallel chemical investigations demonstrate that formation of these Amadori compounds provides a low-energy route to the thermal degradation of their amino acid and sugar moieties. Furthermore, the pathway leads to the production of increased quantities of various aroma compounds as compared with controls. Pyrolysis of the 1-amino-l-deoxyketoses also produces the toxic compound protoanemonin; a degradation pathway leading to its formation is proposed.     

Synthesis of 1-deoxy-3-C-methyl-d-fructose and 1-deoxy-3-C-methyl-d-sorbose

Hydroxylation of trans-1,3,4-trideoxy-5,6-O-isopropylidene-3-C-methyl-d-glycero-hex-3-enulose with osmium tetraoxide gave a mixture of 1-deoxy-5,6-O-isopropylidene-3-C-methyl-d-arabino- and -d-xylo-hexulose that was partially resolved by acetonation to give 1-deoxy-2,3:4,5-di-O-isopropylidene-3-C-methyl-β-d-fructopyranose (4), 1-deoxy-3,4:5,6-di-O-isopropylidene-3-C-methyl-keto-d-fructose (5), and 1-deoxy-2,3:4,6-di-O-isopropylidene-3-C-methyl-α-d-sorbofuranose (6). Treatment of a mixture of 4 and 5 with sodium borohydride gave, after column chromatography, 4 and 1-deoxy-3,4:5,6-di-O-isopropylidene-3-C-methyl-d-manno- and -d-gluco-hexitol. Deuterated derivatives corresponding to 4–6 were obtained when isopropylidenation was carried out with acetone-d₆. Deacetonation of 4 and 5 yielded 1-deoxy-3-C-methyl-d-fructose, and 6 similarly afforded 1-deoxy-3-C-methyl-d-sorbose.     

Access to tetrachlorophthalimide-protected ethyl 2-amino-2-deoxy-1-thio-beta-D-glucopyranosides.

Ethyl 2-deoxy-2-tetrachlorophthalimido-1-thio-beta-D-glucopyranoside (7) was prepared from glucosamine hydrochloride in four steps with a 20-25% overall yield. Formation of 1,3,4,6-tetra-O-acetyl-2-deoxy-2-tetrachlorophthalimido-beta-D- glucopyranoside (5) was found to be crucial for this reaction sequence since the corresponding alpha-1-acetate did not react in Lewis-acid-catalyzed ethylthio glycosidations. Formation of the beta-1-acetate (5) was achieved by treatment of 3,4,6-tri-O-acetyl-2-deoxy-2-tetrachlorophthalimido-alpha-D-glucop yranosyl bromide (4) with acetic acid under silver zeolite promotion. This was necessary because conditions normally used for beta-1-acetate formation were not tolerated by the tetrachlorophthalimido (TCP) group.     

Synthesis of aryl-2-deoxy-D-lyxo/arabino-hexopyranosides from 2-deoxy-1-thioglycosides

The synthesis of either anomers of aryl 2-deoxy-D-glycopyranosides from 2-deoxy-1-thioglycosides is reported. The alpha-anomers form as the major product when thioglycosides react with differently substituted phenols and naphthols, in the presence of N-iodosuccinimide/triflic acid. On the other hand, reaction of the thioglycosides with bromine initially, followed by reaction with aryloxy anions lead to aryl 2-deoxy-beta-D-glycosides with high specificities.     

Preparation of glycosides of 2-deoxy-2-methylamino-D-mannose, 2-deoxy-2-methylamino-D-glucose,and 2-deoxy-2-methylamino-D-galactose: observations on N-methylation of amides

Benzyl 2-[(benzyloxycarbonyl)methylamino]-2-deoxy-α-D-mannopyranoside (10) and its furanose isomer (9), the derived N-methyloxazolidinones 11 and 6, benzyl 2-[(benzyloxycarbonyl)methylamino]-2-deoxy-β-D-glucofuranoside (15) and methyl 2-deoxy-2-methylacetamido-β-D-galactofuranoside (20), were prepared from appropriate diethyl dithioacetals. They were considered the most suitable starting materials for synthesis of O-methyl-2-deoxy-2-methylamino-hexoses because of their ease of preparation and the presence of suitable blocking groups. Oxazolidinones were prepared from N-benzyloxycarbonyl derivatives of 2-amino-2-deoxy-D-mannose by using methanolic sodium methoxide. Their use in preparation of 2-deoxy-2-methyl-amino derivatives is discussed. The Kuhn reagent was used in these syntheses for N-methylating amides. However, certain amides containing comparatively bulky substituents in the vicinity of the NH group are resistant to methylation.     

Synthesis of 2-deoxy-2-(4-nitroimidazol-1-yl)-D-alditols

Small molecules possessing defined configuration at centres of chirality provide a valuable chiral pool. Among different strategies applied for modification of chiral compounds, the most common is to begin with a single stereoisomer and use a synthesis that does not affect the chiral centres. The ANRORC type reaction has been applied for conversion of unprotected 2-amino-2-deoxy-D-hexopyranoses into 2-deoxy-2-(4-nitroimidazol-1-yl)-D-hexopyranoses in a reaction of some 2-aminosugars with 1,4-dinitroimidazoles. The reaction occurs with retention of configuration at C-2 of sugar ring. The products of the reaction were obtained as anomeric mixtures and separated into anomers after acetylation followed by column chromatography. 2-Deoxy-2-(4-nitroimidazol-1-yl)-D-hexopyranoses treated with sodium borohydride in methanolic solution gave the corresponding 2-deoxy-2-(4-nitroimidazol-1-yl)-D-hexitols, characterised as per-O-acetylated derivatives.     

5-deoxy-5-fluoro-L-sorbose originating from 2-deoxy-2-fluoro-D-glucitol by fermentation withAcetomonas oxydans

Using fermentation with a selected strain ofAcetomonas oxydans it was possible to convert 2-deoxy-2-fluoro-D-glucitol to 5-deoxy-5-fluoro-L-sorbose, in agreement with Bertrand’s and Hudson’s rule. The last-named compound was isolated in a yield of 88%. Both compounds were little toxic againstAcetomonas oxydans. Part VIII of the serios Biochemical Dehydrogenation of Saccharides.     

Catalytic ceric ammonium nitrate mediated synthesis of 2-deoxy-1-thioglycosides

Synthesis of 2-deoxy-1-thioglycosides from glycals, mediated by catalytic amounts of ceric ammonium nitrate is reported. Apart from the 2-deoxy-1-thioglycosides, formation of the 2,3-unsaturated enose, corresponding to the Ferrier product, is also observed, especially for the glucal substrates. A radical oxocarbenium ion and a thiolate intermediates are most likely to mediate the reaction. Upon synthesis of 2-deoxy-1-thioglycosides, few representative glycosylation reactions with both aglycosyl and glycosyl acceptors were performed and alpha-anomeric 2-deoxy glycosides were obtained exclusively.     

Synthesis of enantiomerically pure, sn-1 modified sn-2-deoxy-2-amido-glycero-3-phospholipids

The synthesis of two types of enantiomerically pure sn-2-deoxy-2-amido-glycero-phospholipids differing in the connection of the alkyl chain at the sn-1-position is described. Both types of lipids were prepared from L-serine-methylester as the chiral starting material.