Synthesis of ligands related to the O-specific polysaccharides of Shigella flexneri serotype 2a and Shigella flexneri serotype 5a -: Part 3 -: Linear synthesis of the methyl glycosides of tri-, tetra-, and pentasaccharide fragments of the Shigella flexneri serotype 5a O-antigen

The stepwise synthesis of methyl alpha-D-glucopyranosyl-(1-->3)-alpha-L-rhamnopyranosyl-(1-->3)-alpha-L-rhamnopyranoside (EBC-OMe, 1), methyl alpha-L-rhamnopyranosyl-(1-->2)-[alpha-D-glucopyranosyl-(1-->3)]-alpha-L-rhamnopyranosyl-(1 --> 3)-alpha-L-rhamnopyranoside (A(E)BC-OMe, 2), and methyl 2-acetamido-2-deoxy-beta-D-glucopyranosyl-(1 --> 2)-alpha-L-rhamnopyranosyl-(1-->2)-[alpha-D-glucopyranosyl-(1-->3)]-alpha-L-rhamnopyranosyl-(1-->3)-alpha-L-rhamnopyranoside (DA(E)BC-OMe, 3) is described. Compounds 1, 2 and 3 constitute the methyl glycosides of fragments of the O-specific polysaccharide of Shigella flexneri serotype 5a. Methyl 2,4-di-O-benzoyl-alpha-L-rhamnopyranosyl-(1-->3)-2,4-di-O-benzoyl-alpha-L-rhamnopyranoside was an appropriate BC precursor for the synthesis of 1. For the synthesis of the branched targets 2 and 3, a benzyl group was best suited at position 2 of rhamnose C. Thus, methyl 4-O-benzyl-alpha-L-rhamnopyranosyl-(1-->3)-2, L-rhamnopyranoside was the key intermediate to the BC portion. In all cases, 2,3,4,6-tetra-O-benzyl-alpha-D-glucopyranosyl fluoride was a convenient E precursor, when used in combination with titanium tetrafluoride. All along, attention was paid to steric hindrance as a factor of major impact on the condensation steps outcome. Therefore, based on previous experience, 2-O-acetyl-3,4-di-O-allyl-alpha-L-rhamnopyranosyl trichloroacetimidate and 3,4,6-tri-O-acetyl-2-deoxy-2-trichloroacetamid- alpha-D-glucopyranosyl trichloroacetimidate were used as donors. Both suited all requirements when used as key precursors for residues A and D in the synthesis of 3, respectively.