Synthesis of antigenic determinants of the Brucella A antigen, utilizing methyl 4-azido-4,6-dideoxy-alpha-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-alpha-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-alpha-D-mannopyranoside 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-alpha-D-mannopyranoside. 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, hydrogenolysis of which gave methyl 4-amino-2-O-(4-amino-4,6-dideoxy-alpha-D-mannopyranosyl)-4,6-dideoxy- alpha-D-mannopyranoside from which the N-formyl and N-acetyl 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.
Bundle
D R
DR
Division of Biological Sciences, National Research Council of Canada, Ottawa, Ontario.
Gerken
M
M
Peters
T
T
D000942:Antigens, Bacterial; D002002:Brucella / Q000276:immunology*; D004187:Disaccharides / Q000138:chemical synthesis* / Q000276:immunology; D000939:Epitopes; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008358:Mannose / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D009904:Optical Rotation
D000942:Antigens, Bacterial; D004187:Disaccharides; D000939:Epitopes; D007202:Indicators and Reagents; C056092:methyl 4-azido-4,6-dideoxymannopyranoside; D008358:Mannose