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

Bo Yang,Xuefei Huang,Weizhun Yang,Sherif Ramadan

doi:10.3762/bjoc.13.207

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.

Highlights

Carbohydrates are widely present in nature and many of them are involved in important physiological and pathological events, such as anticoagulation, inflammation and pathogen infection [1,2]
In order to explore their biological functions, oligosaccharides with high purity are needed [3]. This is hampered by the limited availability of complex glycans from nature
To test the applicability to iterative synthesis, donor 143 was preactivated with p-TolSCl and AgOTf at −78 °C followed by the addition of acceptor to afford disaccharide in 70% yield with complete α selectivity (Scheme 21b)

Summary

Introduction

Carbohydrates are widely present in nature and many of them are involved in important physiological and pathological events, such as anticoagulation, inflammation and pathogen infection [1,2]. Upon the addition of a promoter to the reaction mixture, the donor is activated to glycosylate the acceptor yielding a disaccharide, which is subsequently deprotected to expose a free hydroxy group (Scheme 1a). The preactivation of 2-pyridyl glycoside was performed using Tf2O as the promoter, which was followed by the addition of acceptor generating disaccharide in 96% yield (Scheme 5a).

Results

Conclusion