Glycosylation of Thioglycosides with Bromodiethylsulfonium bromopentachloroantimonate as novel activator

Abstract

Glycosylation is an important reaction in carbohydrate synthesis of complex molecules such as oligosaccharides, glycoproteins, and glycolipids. Thioglycosides are widely used as precursors in oligosaccharide synthesis due to their ease of preparation, high stability towards protecting group manipulations and variety of activation methods. Recently, bromodiethylsulfonium bromopentachloroantimonate (BDSB) was reported as a novel source of highly electrophilic bromine. It was used to efficiently initiate cation-π cyclizations of polyene at low temperature. Herein, we report a chemical glycosylation of thioglycosides activated by BDSB. Firstly, armed and disarmed glycosyl donors and glycosyl acceptors were synthesized by using modified previous method. Next, several reaction conditions and parameters are investigated. It is found that treatment of reaction mixture with only BDSB in acetonitrile at –35 oC to room temperature gives the desired O-linked disaccharide in 41% yield and selectivity. However, applying BDSB in combination with stoichiometric silver triflate (AgOTf) provides the disaccharide in 79% yield and exclusive β selectivity without using neighboring participation group at C2. Moreover, glycosylation of disarmed thioglycosides are performed under the optimal conditions to give disaccharides in 27-85% yield. Next, glycosylation with several alcohols are performed and gave the desired products in 20-85% yield. The glycosyl chloride intermediate in this glycosylation activated with BDSB is isolated and identified by NMR spectroscopy.