Synthesis of ligands related to the O-specific polysaccharides of Shigella flexneri serotype 2a and Shigella flexneri serotype 5a part 5 -: Linear synthesis of the methyl glycosides of tetra and pentasaccharide fragments specific for the Shigella flexneri serotype 2a O-antigen

Starting from the known methyl 2,3,4,6-tetra-O-benzyl-alpha -D-glucopyranosyl(1-->4)-2-O-benzoyl-alpha -L-rhamnopyranoside, the stepwise linear syntheses of methyl alpha -L-rhamnopyranosyl-(1-->2)-alpha -L-rhamnopyranosyl-(1-->3)-[alpha -D-glucopyranosyl-(1-->4)]alpha -L-rhamnopyranoside (AB(E)C, 4), and methyl 2-acetamido-2-deoxy-beta -D-glucopyranosyl-(1-->2)-alpha -L-rhamnopyranosyl-(1-->2)-alpha -L-rhamnopyranosyl-(1-->3)-[alpha -D-glucopyranosyl-(1-->4)]-alpha -L-rhamnopyranoside (DAB(E)C, 5) are described; these constitute the methyl glycosides of a branched tetra- and pentasaccharide fragments of the O-specific polysaccharide of Shigella flexneri serotype 2a, respectively. The chemoselective O-deacetylation at position 2(B) and/or 2(A) of key tri- and tetrasaccharide intermediates bearing a protecting group at position 2(C) was a limiting factor. As such a step occurred once in the synthesis of 4 and twice in the synthesis of 5, the regioselective introduction of residue A on a B(E)C diol precursor (12) and that of residue D on an AB(E)C diol precursor (19) was also attempted. In all cases, a trichloroacetimidate donor was involved. The latter pathway was found satisfactory for the construction of the target 4 using the appropriate tri-O-benzoyl rhamnosyl donor. However, attempted chain elongation of 12 using 2-O-acetyl-3,4-di-O-benzyl-alpha -L-rhamnopyranosyl trichloroacetimidate (8) resulted in an inseparable mixture which needed to be benzoylated to allow the isolation of the target tetrasaccharide. Besides, condensation of the corresponding tetrasaccharide acceptor and the N-acetylglucosaminyl donor was sluggish. As the target pentasaccharide was isolated in a poor yield, this route was abandoned.