Stereospecific Synthesis Of Thioglycosides Based On Pyranones

Carbohydrates are an essential and vital component of life activities.O-Glycosides are in turn an important composition of carbohydrates,but thioglycosides have received extensive attention and been studied as biologically active analogues of natural O-glycosides,because S-glycosides are more stable to chemical degradation and enzymatic hydrolysis than Oglycosides.In addition,thioglycopeptides/proteins have shown critical biological activity in living systems.However,strategies for the general and stereoselective synthesis of Sglycosides remain extremely challenging.In this paper,pyranosides were prepared by a three-step reaction of asymmetric reduction of the carbonyl group,Achmatowicz rearrangement reaction and Boc protection using furanone as a starting material.Then,a stereospecific S-glycosylation method was established by using pyranosides as glycosyl donors to form α-and β-thioglycosides via palladium-catalyzed decarboxylative allylation with thiol compounds under mild conditions.22 aryl thioglycosides and 17 alkyl thioglycosides were synthesized by using this method.The experimental results show that the method has good substrate compatibility and a wide range of substrates were tolerated.The results of 4 competitive reactions showcased that the thiols possessed exclusive chemoselectivities and were not affected by the other reactive groups such as amine,hydroxyl and amide moieties.In addition,2 S-linked disaccharides,6thioglycopeptides and 5 functionalized products were synthesised,which demonstrating the practicality of the method and paving the way for the synthesis and study of thiopolysaccharides,S-linked glycoproteins and different types of thioglycosides.The generation of four diastereoselective products further illustrates the stereospecificity of the method.This indicates that this method has a wide range of applications,can tolerate multiple substrates,and high yield thioglycosides with excellent diastereoselectivity could be prepared.Finally,we also investigated the activity of α-glucosidase in some synthesized compounds,and the results showed that compound 7c has a weak inhibitory activity,which still need further investigated.