Chiral-auxiliary-mediated 1,2-cis-glycosylations for the solid-supported synthesis of a biologically important branched α-glucan

Abstract

Solid phase oligosaccharide synthesis (SPOS) offers the promise to provide libraries of oligosaccharides for glycomics research. A major stumbling block to SPOS has been a lack of general methods to stereoselectively install 1,2-cis-glycosides, and intractable mixtures of compounds will be obtained if several of such glycosides need to be installed. We have prepared on-resin a biologically important glucoside containing multiple 1,2-cis-glycosidic linkages with complete anomeric control by using glycosyl donors having a participating (S)-(phenylthiomethyl)benzyl chiral auxiliary at C-2. A branching point could be installed by employing 9-fluorenylmethyloxycarbonyl (Fmoc) and allyloxycarbonyl (Alloc) as a versatile set of orthogonal protecting groups. The synthetic strategy made it possible for partial on-resin deprotection of the completed oligosaccharide thereby increasing the overall efficiency of the synthesis. The combination of classical and auxiliary mediated neighboring group participation for controlling anomeric selectivity is bringing the promise of routine automated solid supported oligosaccharides synthesis closer.