Synthesis of tri- and tetrasaccharide fragments of the Shigella dysenteriae type 1 O-antigen deoxygenated and fluorinated at position 3 of the methyl α-d-galactopyranoside terminus

The blockwise synthesis of methyl alpha tri- and tetrasaccharide analogs of the biochemical repeating unit of the Shigella dysenteriae type 1 O-polysaccharide is described. Modifications include deoxygenation and deoxyfluorination at position 3 of the galactopyranoside residue. Methyl 4,6-O-benzylidene-3-deoxy-α-d-xylo-hexopyranoside (8) and methyl 4,6-O-benzylidene-3-deoxy-3-fluoro-α-d-galactopyranoside (9) were condensed with (2,3,4-tri-O-benzoyl-α-l-rhamnopyranosyl)-(1→3)-2,4-di-O-benzoyl-α-l-rhamnopyranosyl chloride to give, after deprotection, the target trisaccharide methyl α-l-rhamnopyranosyl-(1→3)-α-l-rhamnopyranosyl-(1→2)-3-deoxy-α-d-xylo-hexopyranoside and the corresponding fluorinated oligosaccharide. For the tetrasaccharide synthesis, the glycosyl acceptors 8 and 9 were condensed with the temporarily protected (2,4-di-O-benzoyl-3-O-chloroacetyl-α-l-rhamnopyranosyl)-(1→3)-2,4-di-O-benzoyl-α-l-rhamnopyranosyl chloride. Removal of the chloroacetyl group was followed by condensation of the resulting selectively deblocked trisaccharides with 3,4,6-tri-O-acetyl-2-azido-2-deoxy-α-d-glucopyranosyl chloride. Reduction and deprotection then gave the free methyl 2-acetamido-2-deoxy-α-d-glucopyranosyl-(1→3)-α-l-rhamnopyranosyl-(1→3)-α-l-rhamnopyranosyl-(1→2)-3-deoxy-α-d-xylo-hexopyranoside and the fluorinated analog.