Synthesis of the methyl α-glycoside of a trisaccharide mimicking the terminus of the O antigen of Vibrio cholerae O:1, serotype Inaba

Coupling of methyl 4-amino-4,6-dideoxy-2-O-4-methoxybenzyl-α-d-mannopyranoside, obtained from the corresponding 4-azido derivative by treatment with H2S, with 3-deoxy-l-glycero-tetronolactone gave the crystalline methyl 4-(3-deoxy-l-glycero-tetronamido)-4,6-dideoxy-2-O-4-methoxybenzyl-α-d-mannopyranoside (7). Subsequent acetylation of 7, followed by O-demethoxybenzylation of the 8 formed gave the crystalline methyl 3-O-acetyl-4,6-dideoxy-4-(2,4-di-O-acetyl-3-deoxy-l-glycero-tetronamido)-α-d-mannopyranoside (9), which was used as the key intermediate in the construction of the title trisaccharide. To make a glycosyl donor allowing the extension of the oligosaccharide chain at O-2, compound 9 was converted, via conventional transformations, into 3-O-acetyl-2-O-bromoacetyl-4,6-dideoxy-4-(2,4-di-O-acetyl-3-deoxy-l-glycero-tetronamido)-α-d- mannopyranosyl chloride (12). Condensation of 12 with 9 afforded the disaccharide 20 having a selectively removable protecting group at O-22. The latter was O-debromoacetylated, and the disaccharide nucleophile thus obtained was treated with 2,3-di-O-acetyl-4,6-dideoxy-4-(2,4-di-O-acetyl-3-deoxy-l-glycero-tetronamido)-α-d-mannopyranosyl chloride to give, after O-deacetylation, the target, title trisaccharide. The constituent monosaccharide of the O-specific polysaccharide antigen of Vibrio cholerae serotype Inaba, 4-(3-deoxy-l-glycero-tetronamido)-4,6-dideoxy-d-mannopyranose (18), was obtained from the peracetate of its methyl α-glycoside by acetolysis, followed by O-deacetylation. The amorphous compound 18 was characterized by 1H and 13C NMR spectroscopy and through its crystalline α-per-O-acetyl derivative.