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Along with the application of the S-benzoxazolyl glycosides to the high-yielding synthesis of disaccharides of the 2-amino-2-deoxy series, chemoselective assembly of oligosaccharides containing multiple residues of 2-amino-2-deoxyglycoses is reported. This modified armed-disarmed approach is relying on the observation that 2-N-trichloroethoxycarbonyl derivatives of Sbenzoxazolyl glycosides are significantly more reactive than their 2-N-phthaloyl counterparts in MeOTf-promoted glycosylations. This allowed efficient chemoselective synthesis of 1,2-translinked oligosaccharides, the disarmed reducing end of which can be activated for immediate second step glycosidation in the presence of a more powerful activator AgOTf. As a result of this two-step activation, trans-trans-patterned trisaccharides could be assembled in a highly efficient manner. This result differs from the classic armed-disarmed technique, according to which usually cis-transpatterned oligosaccharides are generated. Keywords 2; amino; 2; deoxy sugars; glycosylation; carbohydrates; thioimidates The involvement of complex glycostructures in the pathogenesis of deadly diseases such as AIDS, cancer, pneumonia, meningitis, and hepatitis is now well recognized. This knowledge has been translated into an appreciation of carbohydrates as targets for modern therapeutics. 1,2 Amongst a variety of biologically important carbohydrates are the prokaryotic and eukaryotic glycoconjugates which comprise mainly of residues of the 2-amino-2-deoxy-β-Dglucopyranosyl (D-glucosamino) series. Most representative examples include, but are not limited to chitin, a linear homopolymer of 2-acetamido-D-glucosamine (GlcNAc) that is a component of fungal cell wall and arthropod integuments; 3 heparin, a linear sulfated polysaccharide consisting of alternating GlcNAc and L-iduronic acid units that is a major factor in diverse biological processes including blood coagulation, viral infections, cell growth, inflammation, etc.; 4,5 and the lipid-A region of antigenic lipopolysaccharides, an amphiphilic macromolecule composed of two D-glucosamine residues that has been shown to effect a variety of inflammatory processes. 6,7 Multiple glycosamino residues have been also found in a variety of tumor-associated glycosphingolipids. 8 Although it is now possible to selectively cleave, isolate, purify, and characterize certain classes of natural glycostructures, their accessibility in pure form is still limited. As a result, methods for the synthesis of glycosides and oligosaccharides containing 2-deoxy-2-amino residues have been the focus of a considerable amount of research. 9-11 A vast majority of naturally-occurring glycosamine residues are N-acetylated and linked via 1,2-trans (β-D-gluco/galacto) linkage. However, it has been shown that glycosylation of complex aglycones with glycosyl donors bearing a 2-acetamido-2-deoxy functionality is usually impractical. 9,11 Unlike the reactive acyloxonium intermediate formed via these glycosylations, the yields achieved in these glycosyla...

Using recombinant tetanus toxin H(C) fragment (rTT-H(C)) as carrier, we prepared multimeric bivalent immunogens featuring the synthetic hexasaccharide fragment of O-PS of Vibrio cholerae O:1, serotype Ogawa, in combination with either the synthetic hexasaccharide fragment of O-PS of Vibrio cholerae O:1, serotype Inaba, or a synthetic disaccharide tetrapeptide peptidoglycan fragment as adjuvant. The conjugation reaction was effected by squaric acid chemistry and monitored in virtually real time by SELDI-TOF MS. In this way, we could prepare well-defined immunogens with predictable carbohydrate-carrier ratio, whose molecular mass and the amount of each saccharide attached could be independently determined. The ability to prepare such neoglycoconjugates opens unprecedented possibilities for preparation of conjugate vaccines for bacterial diseases from synthetic carbohydrates.

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