Synthesis of ligands related to the O-specific polysaccharides of Shigellaflexneri 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-glucopyranos yl(1-->4)-2-O-benzoyl-alpha -L-rhamnopyranoside, the stepwise linear synthe ses 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-rh amnopyranosyl-(1-->2)-alpha -L-rhamnopyranosyl-(1-->3)-[alpha -D-glucopyran osyl-(1-->4)]-alpha -L-rhamnopyranoside (DAB(E)C, 5) are described; these c onstitute the methyl glycosides of a branched tetra- and pentasaccharide fr agments 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 th e synthesis of 4 and twice in the synthesis of 5, the regioselective introd uction 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 trichlor oacetimidate donor was involved. The latter pathway was found satisfactory for the construction of the target 4 using the appropriate tri-O-benzoyl rh amnosyl donor. However, attempted chain elongation of 12 using 2-O-acetyl-3 ,4-di-O-benzyl-alpha -L-rhamnopyranosyl trichloroacetimidate (8) resulted i n an inseparable mixture which needed to be benzoylated to allow the isolat ion of the target tetrasaccharide. Besides, condensation of the correspondi ng tetrasaccharide acceptor and the N-acetylglucosaminyl donor was sluggish . As the target pentasaccharide was isolated in a poor yield, this route wa s abandoned.