THE SYNTHESIS OF CHEMICALLY MODIFIED DISACCHARIDE DERIVATIVES OF THE SHIGELLA-FLEXNERI Y POLYSACCHARIDE ANTIGEN

Disaccharide analogs related to the 2-acetamido-2-deoxy-3-O-(alpha-L-rhamnopyranosyl)-beta-D-gluco-pyranose element of the Shigella flexneri Y polysaccharide antigen have been synthesized and used to map the binding site of murine monoclonal antibodies GC-4 and SYA/J6 by solid-phase inhibition assays. N-Acetyl, N-trifluoroacetyl and N-benzyloxycarbonyl derivatives of methyl 2-amino-4,6-O-benzylidene-2-deoxy-beta-D-glucopyranoside 1, 3, and 4 were glycosylated by rhamnopyranosyl bromide and thioglycoside donors 5 and 6. These in turn provided access to a series of alpha-L-Rhap-(1 --> 3)-beta-D-GlcNp-(1 --> O)-Me disaccharide glycosides with amino 13, N-acetyl 10, N-propionyl 14, N-pivaloyl 15, and N-trifluoroacetyl 11 functionalities. Congeners of the disaccharide 10 were synthesized with monodeoxy groups introduced at the C-4 and C-6 positions of the GlcNAc residues and at the C-4' position of the rhamnose unit. Chlorosulfation of the selectively protected disaccharide 24, followed by reduction of the 4-chloro-4-deoxy compound 25, was used to prepare the 4-deoxy congener 27, while the C-6 and C-4' deoxy derivatives 31 and 23 were assembled from their respective pre-functionalized monosaccharide building blocks 29 and 19.