Synthetic antigenic determinants of the Brucella A polysaccharide: A disaccharide thioglycoside for block synthesis of pentasaccharide and lower homologues of α1,2-linked 4,6-dideoxy-4-formamido-α-D-mannose

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Abstract
Methyl glycosides 13, 18, and 22, which represent potential antigenic determinants of the Brucella A polysaccharide, are the first synthetic analogues of this antigen. Their synthesis was necessitated by crystallographic studies of a Fab combining site obtained from a monoclonal antibody that binds the Brucella A antigen and synthetic pentasaccharide. Monosaccharide synthon 3 and disaccharide 7, S-ethyl glycoside derivatives of 4-azido-4,6-dideoxy-D-mannose, have been used successfully as key intermediates in a convergent strategy to synthesize α1,2-linked homo-oligosaccharides of 4,6-dideoxy-4-formamido-D-mannose. The disaccharide thioglycoside 7 was activated by methyl triflate in the presence of selectively protected mono- or trisaccharide alcohols 1, 6, or 10 to give α1,2-linked tri- and pentasaccharides 8, 9, and 19. Despite the non-participating glycosyl substituent at position two of the thioglycoside, 1,2-trans glycosidic products appeared to be formed exclusively. Conversion of 3 to the glycosyl bromide 5 by bromine under mild conditions provided routes to both the disaccharide building block 7 and a tetrasaccharide 15 using conventional silver triflate promoted glycosylation reactions. Deprotection was accomplished by transesterification, hydrogen sulphide reduction of azido groups, followed by N-formylation and finally hydro-genolysis of benzyl ethers. Keywords: Brucella A antigen, pentasaccharide synthesis, thioglycosides, oligosaccharide building units, 4,6-dideoxy-4-formamido-D-mannose, antibody combining sites.