Stereoselective syntheses of a di-, tri-, and tetra-saccharide fragment of Shigella dysenteriae type 1 O-antigen using 3,4,6-tri-O-acetyl-2-azido-2-deoxy-alpha-D-glucopyranosyl chloride as a glycosyl donor.

Methyl 2,4-di-O-benzoyl-alpha-L-rhamnopyranoside (1) furnished a crystalline 3-O-bromoacetyl derivative that was treated with the dichloromethyl methyl ether-ZnCl2 reagent to give 2,4-di-O-benzoyl-3-O-bromoacetyl-alpha-L-rhamnopyranosyl chloride (3). Compounds 1 and 3 were condensed under the conditions of base-deficient, silver trifluoromethanesulfonate-mediated glycosylation to give a fully protected rhamnobioside, which on O-debromoacetylation afforded the disaccharide nucleophile 10. Similar condensation of 3 with methyl 3-O-benzoyl-4,6-O-benzylidene-alpha-D-galactopyranoside, followed by O-debromoacetylation and condensation of the thus formed methyl O-(2,4-di-O-benzoyl-alpha-L-rhamnopyranosyl)-(1----2)-4,6-O-benzylidene- 3-O-benzoyl-alpha-D-galactopyranoside again with 3, gave the trisaccharide glycoside. Subsequent O-debromoacetylation gave 17, having only HO-3(3) unsubstituted. Silver perchlorate-mediated glycosylations of 1, 10, and 17 with 3,4,6-tri-O-acetyl-2-azido-2-deoxy-alpha-D-glucopyranosyl chloride afforded, with high alpha stereoselectivity, protected di-, tri-, and tetra-saccharide glycosides. Subsequent hydrogenation, followed by N-acetylation and O-deacylation, afforded three oligosaccharide glycosides having nonreducing terminal 2-acetamido-2-deoxy-alpha-D-glucopyranosyl residues and comprising successively larger portions of the repeating unit of Shigella dysenteriae type 1 O-antigen.