Catalytic Stereoselective Synthesis of Glycosides

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The power of carbohydrate synthesis has been highlighted by the development of vaccines and anticoagulants for human use and the recent chemical synthesis of glycoproteins. Thus, expedient chemical methods to streamline the synthesis of these complex molecules will be an important development not only in synthetic chemistry but also in glycobiology research, with long term impact in the area of glycomedicine. The stereoselective synthesis of glycosides is one of the biggest challenges in oligosaccharide synthesis. The chemical synthesis of complex carbohydrates generally involves the coupling of a fully protected glycosyl donor bearing a leaving group at its anomeric centre with a suitably protected glycosyl acceptor containing a nucleophile (R-OH). In most instances, these reactions lead to a mixture of two stereoisomers. The most reliable method for stereoselective glycosylations is based on neighbouring group participation (NGP), which requires the introduction of specific groups at the C-2 position to direct nucleophilic attack. However, the incorporation of NGP groups is often troublesome, impractical and not applicable to every type of monosaccharide i.e. N-2, 2-deoxy glycosides, etc. Our team have recently reported a mild organocatalytic method for the synthesis of 2-deoxygalactosides, with excellent yields and alpha-selectivity. (Angew. Chem. Int. Ed. (2012), 51, 36, 9152-9155). The proposed project aims to develop general and catalytic methods for the stereoselective synthesis of glycosides.