Synthesis of oligosaccharides corresponding to the antigenic determinants of the β-haemolytic Streptococci Group A. Part 1. Overall strategy and synthesis of a linear trisaccharide

Abstract

The overall strategy for the synthesis of higher-order oligosaccharides corresponding to the repeating unit of the cell-wall polysaccharide of the β-haemolytic Streptococci Group A is described. The trisaccharide, β-D-GlcpNAc-(1→3)-α-L-Rhap-(1→3)-α-L-Rhap has been synthesized by a series of Königs-Knorr reactions. The selectively protected rhamnose derivative, allyl 2-O-benzoyl-4-O-benzyl-α-L-rhamnopyranoside, reacted with 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-β-D-glucopyranosyl bromide to give the blocked disaccharide. Deallylation, followed by treatment with N,N-dimethyl(chloromethylene)ammonium chloride then gave the corresponding disaccharide chloride. In conjunction with the same rhamnose monosaccharide unit or 8-methoxycarbonyloctyl 2,4-di-O-benzoyl-α-L-rhamnopyranoside, the synthesis of the blocked trisaccharide, as its allyl glycoside or its 8-methoxycarbonyloctyl glycoside, respectively, was accomplished. Transesterification, followed by hydrazinolysis, selective N-acetylation, and hydrogenolysis afforded the pure trisaccharide, as its propyl glycoside or 8-methoxycarbonyloctyl glycoside, for use as a hapten in binding studies and n.m.r. studies or for use in the preparation of glycoconjugates, respectively. Similar treatment of the blocked disaccharide afforded the hapten, β-D-GlcpNAc-(1→3)-α-LRhap, as its propyl glycoside.