Thioperoxide-Mediated Activation Of Thioglycosides And Application In Oligosaccharide Synthesis

This dissertation focuses on a new thioperoxide that could be used as thioglycoside promoter. Thioglycosides could be readily activated by this new promoter in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf). Eight disaccharides and six trisaccharides were synthesized effectively with thioglycosides as glycosyl donors under the action of the new promoter. Of them, the trisaccharides were synthesized in one-pot manner. The ease of the synthesis demonstrated that the new promoter system could be applied to synthesize larger oligosaccharides. This project has laid down a solid basis for further study of thioglycoside activation and would facilitate carbohydrate synthesis.Three chapters are included in this thesis:Chapter one is the introduction, consisting of three parts. The first part describes the importance of carbohydrate-derived drug research. The second part gives an overview of common promoters which have been widely used for thioglycosides activation. The third part describes the versatility of thioglycoside donors in the glycosylation reaction.Chapter two covers the extensive investigation of thioperoxides as promoter for thioglycoside activation. Experimental results showed thioperoxide I was the most effective promoter among the investigated. The new promoter, together with TMSOTf, was employed to activate a series of ethyl thioglycoside donors, and most reactions gave very positive results. A large number of glycosyl donors and acceptors were prepared in this work in order to carry out the above study. It should be noted here that this new promoter system has been used previously in the activation of benzyl thioglycosides, including both "armed" and "disarmed" thioglycosides. The experimental results reported in this thesis show that ethyl thioglycoside donors could also been activated effectively with the current new promoter system.Chapter three present "one-pot" glycosylation. The new promoter system was applied to one-pot chemistry in order to synthesize oligosaccharides in a more efficient way. Glycosidation conditions were carefully optimized to attain one-pot synthesis. "Armed" thioglycosides protected with ether protecting groups were chosen as the donor. "Disarmed" thioglycoside protected with ester protecting groups were chosen as the acceptor, which could also act as glycosyl donors in the following step. Methyl glucoside was used as the second acceptor. Experimental results show that this new promoter system can complete the "one-pot" glycosidations efficiently.