Stereoselective Synthesis of the O‐antigen of A. baumannii ATCC 17961 Using Long‐Range Levulinoyl Group Participation

Herein, we described the first synthesis of the pentasaccharide and decasaccharide of the A. baumannii ATCC 17961 O‐antigen for developing a synthetic carbohydrate‐based vaccine against A. baumannii infection. The efficient synthesis of the rare sugar 2,3‐diacetamido‐glucuronate was achieved using our recently introduced organocatalytic glycosylation method. We found, for the first time, that long‐range levulinoyl group participation via a hydrogen bond can result in a significantly improved β‐selectivity in glycosylations. This solves the stereoselectivity problem of highly branched galactose acceptors. The proposed mechanism was supported by control experiments and DFT computations. Benefiting from the long‐range levulinoyl group participation strategy, the pentasaccharide donor and acceptor were obtained via an efficient [2+1+2] one‐pot glycosylation method and were used for the target decasaccharide synthesis. We described the first synthesis of the pentasaccharide and decasaccharide of the A. baumannii ATCC 17961 O‐antigen for the development of a synthetic carbohydrate‐based vaccine against A. baumannii infection. We found that long‐range levulinoyl group assistance via hydrogen bonding strikingly improves the β‐selectivity of the glycosylation. The proposed mechanism was investigated experimentally and via DFT calculations.