Synthesis of di- to hexasaccharide 1,2-linked beta-mannopyranan oligomers, a terminal S-linked tetrasaccharide congener and the corresponding BSA glycoconjugates

Abstract

Homo oligomers of (1-->2)-beta-D-mannopyranosyl residues have been synthesized in order to study the unique immunological properties of the cell wall mannan of C. albicans. p-Chlorobenzyl-protected ulosyl bromide (2) in combination with the sterically hindered, participating solvent, pivaloyl nitrile, facilitated a new approach for the synthesis of these unique homooligomers ranging from disaccharide up to hexasaccharide. The glycosyl donor 2 demonstrates high diastereoselectivity over both the glycosylation and subsequent reduction step and minimizes the number of protecting group manipulations necessary for the synthesis. Congeners of the (1-->2)-beta-D-mannotetraose were synthesized containing a terminal S-linked (1-->2)-beta-D-mannopyranosyl residue. Deprotection of these compounds afforded the propyl glycosides as well as oligomers with amino terminated aglyconic tethers. The tethers were generated from the oligosaccharide allyl glycosides by photoaddition with 2-aminoethanethiol. The functionalized haptens were coupled to BSA via squarate conjugation, and the degree of incorporation was established by TOF mass spectrometry.