Artificial carbohydrate antigens. Synthesis and conformation of a Shigella flexneri trisaccharide hapten

Abstract

The trisaccharide 8-methoxycarbonyloctyl 2-O-[2′-acetamido-2′-deoxy-3′-O-(α-L-rhamnopyranosyl)-β-D-glucopyranogyl]-α-L-rhamnopyranoside has been synthesised in good yield utilising silver trifluoromethanesulphonatepromoted Königs–Knorr reactions. 3,4-Di-O-benzyl-β-L-rhamnopyranose 1,2-(methyl orthoacetate) provided access to the 2-O-substituted rhamnoside, 2-O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-α-L-rhamnopyranoside. Introduction of the amino-sugar was achieved with tri-O-acetyl-2-deoxy-2-phthalimido-D-glucopyranosyl bromide in conjunction with silver trifluoromethanesulphonate and 2,4,6-trimethylpyridine. Selective conversion of the 2-deoxy-2-phthalimido glucoside to a 2-acetamido-2-deoxy glucoside blocked at positions C-4 and,-6 of the pyranose ring by a benzylidene acetal gave the trisaccharide, following reaction with tri-O-acetyl-α-L-rhamnopyranosyl bromide. Proton and ¹³C n.m.r. evidence indicated that, despite a sterically crowded environment, the orientation of both the 2-acetamido-2-deoxy-glucose and terminal rhamnose residues is dictated by the exo-anomeric effect.