No abstract

Mannosylations of various acceptors with donors possessing an electron-withdrawing o-trifluoromethylbenzenesulfonyl, benzylsulfonyl, p-nitrobenzoyl, benzoyl, or acetyl group at O-3, O-4, or O-6 positions were found to be beta-selective except when donors had 3-O-acyl and 6-O-acetyl groups, which afforded alpha-mannosides as major products. The alpha-directing effect of 3-O-acyl and 6-O-acetyl groups was attributed to their remote participation, and the isolation of a stable bicyclic trichlorooxazine ring resulting from the intramolecular trapping of the anomeric oxocarbenium ion by 3-O-trichloroacetimidoyl group provided evidence for this remote participation. The triflate anion, counteranion of the mannosyl oxocarbenium ion, was essential for the beta-selectivity, and covalent alpha-mannosyl triflates with an electron-withdrawing group at O-3, O-4, or O-6 were detected by low-temperature NMR. The strongly electron-withdrawing sulfonyl groups, which exhibited a higher beta-directing effect in the mannosylation, made the alpha-mannosyl triflates more stable than the weakly electron-withdrawing acyl groups. We therefore proposed the mechanism for the beta-mannosylation and the origin of the beta-directing effect: the electron-withdrawing groups would stabilize the alpha-mannosyl triflate intermediate, and the subsequent reaction of the alpha-triflate (or its contact ion pair) with the acceptor would afford the beta-mannoside. The beta-selective mannosylation of a sterically demanding acceptor was achieved by employing a donor possessing two strongly electron-withdrawing benzylsulfonyl groups at O-4 and O-6 positions.

No abstract

Synthetic cell-surface glycans are promising vaccine candidates against Clostridium difficile. The complexity of large, highly antigenic and immunogenic glycans is a synthetic challenge. Less complex antigens providing similar immune responses are desirable for vaccine development. Based on molecular-level glycan–antibody interaction analyses, we here demonstrate that the C. difficile surface polysaccharide-I (PS-I) can be resembled by multivalent display of minimal disaccharide epitopes on a synthetic scaffold that does not participate in binding. We show that antibody avidity as a measure of antigenicity increases by about five orders of magnitude when disaccharides are compared with constructs containing five disaccharides. The synthetic, pentavalent vaccine candidate containing a peptide T-cell epitope elicits weak but highly specific antibody responses to larger PS-I glycans in mice. This study highlights the potential of multivalently displaying small oligosaccharides to achieve antigenicity characteristic of larger glycans. The approach may result in more cost-efficient carbohydrate vaccines with reduced synthetic effort.