Block synthesis of two pentasaccharide determinants of the Brucella M antigen using thioglycoside methodologies

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Abstract
Two frame shifted pentasaccharides containing a 4,6-dideoxy-4-formamido-D-mannose (4-deoxy-4-formamido-D-rhamnose) have been synthesized by applicatin of a strategy utilizing S-ethyl disaccaharide glycosie building blocks 16 and 25. The target molecules contain a single .alpha.1,3 linkage as either the first or last inter-residue linkage in an otherwise .alpha.1,2-linked homo-pentameric structure: .alpha.-D-Rha4NFo(1 .fwdarw. 3)-7a-D-Rha4NFo(1 .fwdarw. 2)-.alpha.-D-Rha4NFo(1 .fwdarw. 2)-.alpha.-D-Rha4NFo(1 .fwdarw. 2)-.alpha.-D-Rha4NFo-1 .fwdarw. OCH3 and .alpha.-D-Rha4NFo(1 .fwdarw. 2)-.alpha.-D-Rha4NFo(1 .fwdarw. 2)-.alpha.-D-Rha4NFo(1 .fwdarw. 3)-.alpha.-D-Rha4NFo-1 .fwdarw. OCH3. These structures represent possible biological repeating units of the Brucella M antigen and their synthesis is designed to facilitate the identification of the structural element that is polymerized to provide the intact polysaccharide antigen. The .alpha.1,2-linked tetrasaccharide component of each pentasaccharide was constructed by methyl triflate promoted activation of the .alpha.1,2-linked S-ethyl disaccharide glycoside 16. Glycosylation of methyl 4-azido-2-O-benzyl-4,6-dideoxy-.alpha.-D-mannopyranoside 3 by 16, followed by a second block extension, gave the pentasaccharide 22 with an .alpha.1,3 linkage at the reducing terminus. In analogous fashion the .alpha.1,3-linked S-ethyl derivative 25 was used in conjunction with methyl triflate to glycosylate the .alpha.1,2-linked trisaccharide 26, and provided the pentasaccharide 27 that possesses a 1,3 linkage at its non-reducing end. The synthesis of an .alpha.1,3-linked disaccharide and a trisaccharide are also reported.