Synthesis of the Methyl α-Glycoside of the Intracatenary Disaccharide Repeating Unit of the O-Polysaccharide of Vibrio Cholerae O:1. A Comparison of two Assembly Strategies

Abstract

The two strategies engaged in the construction of the title disaccharide 17 comprise: 1. assembly of a diamino disaccharide and its N-acylation using chiral reagents to introduce the 4-(3-deoxy-l-glycero-tetronyl) group, followed by deprotection, and 2. preparation of a glycosyl acceptor and a glycosyl donor both having the chiral 3-deoxy-l-glycero-tetronamido group already in place, their condensation to give a fully substituted disaccharide, and deprotection. Accordingly, the crystalline diamino disaccharide methyl 2-O-(4-amino-3-O-benzyl-4, 6-dideoxy-α-d-mannopyranosyl)-4-amino-3-O-benzyl-4, 6-dideoxy-α-d-mannopyranoside, (14), was prepared from the known [Bundle, D. R. et al., Carbohydr. Res. 174, 239 (1988)] diazido disaccharide 12, and treated with the lactone 30, or its acetylated or benzylated analogs 31 and 32, respectively, as the N-acylating reagents. Subsequent deprotection of the respective products applying standard chemistry gave 17. Alternatively, the methyl α-glycoside of the monomeric intracatenary repeating unit of Vibrio cholerae 0:1 (2) was converted to the fully benzoylated glycosyl chloride 26, and the latter glycosyl donor was condensed with methyl 3-O-benzyl-4,6-dideoxy-4-(2,4-di-O-benzoyl-3-deoxy- l-glycero-tetronamido)-α-d-mannopyranoside (24), to give the corresponding, fully protected derivative 27. Deprotection then readily gave 17. It appears that the title disaccharide can be most efficiently synthesized using synthons 24 and 26. The lactones 30 and 32 appear to be promising acylating reagents for the introduction of the 3-deoxy-l-glycero-tetronamido group when higher oligosaccharides in this series will be synthesized via their (poly)amino precursors.