Stereoselective glycosylation using oxathiane glycosyl donors

A bicyclic glycosyl donor is activated as an arylsulfonium ion and used to synthesise α-glycosides with high stereoselectivity. Carbohydrates form the most abundant class of biological molecules on Earth.1 They play essential roles in energy storage, as structural materials and for molecular recognition to control processes as diverse as protein folding, fertilisation, inflammation and cancer metastasis.2 Often synthetic chemistry provides the only source of pure oligosaccharides for biological studies. Both solid phase synthesis3 and multi-component one-pot solution synthesis4 can provide rapid access to complex oligosaccharides. However, if several glycosylation reactions are to be performed in sequence without separating the intermediate products, it is essential that each glycosylation reaction is highly stereoselective,5 or complex mixtures of oligosaccharides will result. While 1,2-trans-glycosides can be formed easily through neighbouring group participation by an ester protecting group adjacent to the anomeric centre (Scheme 1a),6stereoselective synthesis of cis-1,2-glycosidic linkages remains a significant challenge.7 Although the anomeric effect favours the formation of α-glycosides, in reality, mixtures of α- and β-glycosides are often obtained when using glycosyl donors bearing non-participating ether protecting groups (Scheme 1b). Therefore, the precise control of anomeric stereochemistry remains a major challenge to be overcome.