Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

Abstract

Most glycosylation reactions are performed by mixing the glycosyl donor and acceptor together followed by the addition of a promoter. While many oligosaccharides have been synthesized successfully using this premixed strategy, extensive protective group manipulation and aglycon adjustment often need to be performed on oligosaccharide intermediates, which lower the overall synthetic efficiency. Preactivation-based glycosylation refers to strategies where the glycosyl donor is activated by a promoter in the absence of an acceptor. The subsequent acceptor addition then leads to the formation of the glycoside product. As donor activation and glycosylation are carried out in two distinct steps, unique chemoselectivities can be obtained. Successful glycosylation can be performed independent of anomeric reactivities of the building blocks. In addition, one-pot protocols have been developed that have enabled multiple-step glycosylations in the same reaction flask without the need for intermediate purification. Complex glycans containing both 1,2-cis and 1,2-trans linkages, branched oligosaccharides, uronic acids, sialic acids, modifications such as sulfate esters and deoxy glycosides have been successfully synthesized. The preactivation-based chemoselective glycosylation is a powerful strategy for oligosaccharide assembly complementing the more traditional premixed method.