A broadly applicable stereospecific glycosylation.

Abstract

The development of a general strategy for stereospecific construction of every type of glycosidic linkage remains a much sought-after yet unrealized goal. Such a strategy would be particularly useful in the context of complex glycan syntheses. Glycosylations involving an S_N2 mechanism are ideal to ensure stereospecificity but have been challenging to implement in a manner conferring generality across a range of sugars. Here we disclose a stereospecific glycosylation method that accommodates a broad range of monosaccharides, including hexopyranoses (for example, glucose, galactose, mannose, fucose, alluronate, 2-azido-2-deoxyglucose and 2-azido-2-deoxygalactose) and pentofuranoses (for example, arabinose, ribose, xylose and lyxose). Mild activation with an electrophilic bromine reagent results in complete inversion of the anomeric configuration and excellent yields for many glycosylations. The method proved reliable in multistep oligosaccharide syntheses and automated glycan assembly.