Synthesis and two-dimensional nuclear magnetic resonance analysis of a tetra- and a hexa-saccharide fragment of the O-specific polysaccharide of Shigella dysenteriae type 1

Abstract

The synthesis of the tetra- and hexa-saccharide methyl glycosides α- d-Gal p-(1 → 3)α- d-Glc pNAc-(1 → 3)-α- l-Rha p-(1 → 3)-α- l-Rha p-OMe ( 1), and α- l-Rha p-(1 → 3)-α- l-Rha p-(1 → 2)-α- d-Gal p-(1 → 3)-α- d-Glc pNAc-(1 → 3)-α- l-Rha p-(1 → 3)α- l-Rha p-OMe ( 3) is described, which represent various epitopes of the O-specific polysaccharide of Shigella dysenteriae type 1. The following monosaccharide intermediates were used: 1,3-di- O-acetyl-2- O-benzoyl-4- O-benzyl-α- l-rhamnopyranose ( 6α), methyl 2,4-di- O-benzyl-α- l-rhamnopyranoside ( 7), methyl 2,4-di- O-benzoyl-1-thio-α- l-rhamnopyranoside ( 8), 2,3,4-tri- O-benzoyl-α- l-rhamnopyranosyl bromide ( 9), methyl 3,4,6-tri- O-benzyl-2- O-(4-methoxybenzyl)-1-thio-β- d-galactopyranoside ( 13), methyl 2,3,4,6-tetra- O-benzyl-1-thio-β- d-galactopyranoside ( 16), and 2-azido-4,6- O-benzylidene-3- O-bromoacetyl-2-deoxy-β- d-glucopyranosyl chloride ( 19). A detailed analysis of the 1H and 13C NMR spectra of oligosaccharides 1 and 3 confirmed that the hexasaccharide 3 better approaches the conformation of the native polysaccharide, than either 1 or the homologous pentasaccharide 41.