Synthesis of eight glycosides of hexasaccharide fragments representing the terminus of the O-polysaccharide of Vibrio cholerae O:1, serotype Inaba and Ogawa, bearing aglycons suitable for linking to proteins.

The title substances were prepared from intermediate, fully acetylated alpha-trimethylsilylethyl (SE) glycosides. The latter were assembled in a blockwise manner, using as the glycosyl donor the alpha-glycosyl chloride of a disaccharide bearing two 4-azido-4-deoxy functions. Next, the azido groups in the assembled hexasaccharides were converted to the corresponding amines, and these were acylated with 4-O-benzyl-3-deoxy-L-glycero-tetronic acid in the presence of a water-soluble carbodiimide. The SE glycosides were then transformed to glycosyl imidates, and these were coupled with methyl 6-hydroxyhexanoate or methyl 2-(2-hydroxyethylthio) propionate. The aglycons in the glycosides thus obtained were then converted to the corresponding carboxylic acids or acyl hydrazides. Such compounds are suitable for linking to proteins to obtain neoglycoproteins.

Syntheses of three interglycosidic isomers of N-acetyl-beta-D-mannosaminyl-L-rhamnoses associated with O-antigens of several gram-negative opportunistic pathogens.

We achieved practical, highly stereoselective syntheses of three interglycosidic isomers of N-acetyl-beta-D-mannosaminyl-L-rhamnoses, among which a beta(1-->4)-isomer corresponds to the repeating unit of the O-antigen of lipopolysaccharide (LPS) from the opportunistic pathogens Pseudomonas cepacia O5 and Pseudomonas aeruginosa X (Meitert). The other isomers are a beta(1-->2)-disaccharide, a constituent of LPS from Escherichia coli O1A, and an artificial beta(1-->3)-isomer. The disaccharides were obtained by simple three-step reaction sequences from 2-(benzoyloxyimino)-2-deoxyglycosyl halides (mannosamine progenitor). beta-Selective glycosylations of appropriately protected L-rhamnosyl acceptors were performed. Subsequent reduction of the 2-acyloxyimino function to an amino group, N-acetylation, and removal of the protecting groups provided the target disaccharides. 13C-NMR and nuclear Overhauser effect spectra proved to be useful for structural determination of the positional isomers of the disaccharides.