Synthesis of the methyl α-glycosides of a di-, tri-, and a tetra-saccharide fragment mimicking the terminus of the O-polysaccharide of Vibrio cholerae 0:1, serotype Ogawa

Methyl 4-(3-deoxy-l-glycero-tetronamido)-4,6-dideoxy-2-O-methyl-α-d-mannopyranoside was acetylated, and the fully protected methyl glycoside was treated with dichloromethyl methyl ether-ZnCl2 (DCMME-ZnCl2) reagent to give 3-O-acetyl-4-(2,4-di-O-acetyl-3-deoxy-l-glycero-tetronamido)-4,6-dideoxy-2-O-methyl-α-d-mannopyranosyl chloride (3). Condensation of 3 with methyl 3-O-acetyl-4-(2,4-di-O-acetyl-3-deoxy-l-glycero-tetronamido)-4,6-dideoxy-α-d-mannopyranoside (4) gave the fully acetylated disaccharide 5, which was deacetylated yielding the methyl α-glycoside of title disaccharide. The disaccharide glycosyl donor required for the blockwise synthesis of the title tri- and the tetra-saccharide, 3-O-acetyl-4-(2,4-di-O-acetyl-3-deoxy-l-glycero-tetronamido)-4,6-dideoxy-2-O-methyl-α-d-mannopyranosyl-(1 → 2)-3-O-acetyl-4- (2,4-di-O-acetyl-3-deoxy-l-glycero-tetronamido)-4,6-dideoxy-α-d-mannopyranosyl chloride (12), was obtained by condensation of 3 with the 1-O-acetyl analog of 4, followed by treatment of the disaccharide formed with DCMME-ZnCl2. The synthesis of the methyl α-glycoside of the title trisaccharide involved a condensation of 12 with 4, followed by deacetylation. Similarly, the condensation of 12 with 15, the latter being the analog of 5 having a free HO-2, followed by deacetylation, gave the methyl α-glycoside of the title tetrasaccharide. All glycosylation reactions were mediated by silver trifluoromethanesulfonate in the presence of 2,4,6-trimethylpyridine. 4-(3-Deoxy-l-glycero-tetronamido)-4,6-dideoxy-2-O-methyl-α,β-d-mannopyranose was prepared for the first time. It was characterized by NMR spectroscopy, and via its crystalline per-O-acetyl derivative. It is the saccharide whose α-form constitutes the terminal, non-reducing end-group of the O-PS of V. cholerea O:1, serotype Ogawa.