Synthesis of antigenic determinants of the Brucella a antigen, utilizing methyl 4-azido-4,6-dideoxy-α-d-mannopyranoside efficiently derived from d-mannose

A strategy for the synthesis of Brucella O-antigenic determinants containing 2-linked 4,6-dideoxy-4-formamido-α-d-mannopyranosyl residues is described. The approach adopted also permits the N-acyl moiety to be varied. A high-yield synthesis of methyl 4-azido-4,6-dideoxy-α-d-mannopyranoside (7) from d-mannose on the 10-20-g scale provided the key intermediate. Regioselective acetylation of 7 gave the 2-acetate 8, which, on treatment with benzyl trichloroacetimidate, provided methyl 2-O-acetyl-4-azido-3-O-benzyl-4,6-dideoxy-α-d-mannopyranoside (9). This compound served as a common precursor to the glycosyl donor 12 and acceptor 10 molecules. Silver trifluoromethanesulphonate-promoted glycosylation of 10 by 12 gave a disaccharide derivative (13), hydrogenolysis of which gave methyl 4-amino-2-O-(4-amino-4,6-dideoxy-α-d-mannopyranosyl)-4,6-dideoxy-α-d-mannopyranoside (16) from which the N-formyl (17) and N-acetyl (18) derivatives were obtained. Deacetylation of 13 followed by glycosylation with 12 gave a trisaccharide derivative. The N-formylated disaccharide 17 inhibited the binding of Brucella O-polysaccharide to Brucella-specific monoclonal antibodies.