Improved Synthesis Of Thioglycosides By Inhibition Of Acyl Group Migration

Thioglycosides have a very important role in the synthesis of sugar chemistry,carbohydrates,oligosaccharides,and the interaction of sugar and protein.Considering that the sulfur-glycosidic bond has similar properties to the oxygen-glycosidic bond,and the nucleophilic ability of the sulfur atom is stronger than that of the oxygen atom,SN2 reaction is more likely to occur.Therefore,it is possible to find an efficient means for synthesizing thioglycoside.In the current thioglycoside synthesis process,the main choice of acetyl,benzoyl acyl as a protecting group.Since such protecting groups are readily deprotected,they tend to cause the participation of the adjacent groups and the acyl groups.The purpose of this study is to improve the synthesis of thioglycosides and the main aspects of this research were showing as the following:1.Based on the double transformation strategy to synthesize 4-thio mannoside,by trying multiple sets of experiments,the optimal conditions were obtained through multi-group experiments:solvent was acetic anhydride when equivalents of acetyl potassium reacted 24h at 75?,and 4-thio mannoside were successfully synthesized.Using the optimal conditions to expand to different configurations of glycosides,the yield of the product was 53%-70%.2.By controlling the acidity of the reaction system to improve the synthesis of thioglycosides,(1)synthesis of 6 thioglycosides improved by multiple sets of experiments.The optimal conditions were obtained through multi-group experiments:0.5 equivalents of p-toluenesulfonic acid and solvent was DMF when KSAc reacted 6h at 60?.Using the optimal conditions to expand to different configurations of glycosides,the yield of the product was 76%-85%.The experiment showed that this method can be used to inhibit the migration of six groups of acyl groups.(2)Synthesis of 2,4-dithioglycosides was improved by multiple sets of experiments,the optimal conditions were obtained through multi-group experiments:conjugate acid was thioacetic acid and solvent was MeCN when 5 equivalent potassium thiosulfate reacted 24h at 40 ?,Using the optimal conditions to expand to different configurations of glycosides,the yield of the product was 46%-85%.3.Substitution reaction of thiobutylammonium nitrite to activated thioacetyl groups.If the substitution reaction of the thioacetyl group without any activator,it need a very long reaction time.And we have recently found that tetrabutyl nitrite can activate the sulfonyl group,can make SN2 reaction quickly.The optimal equivalent of tetrabutylammonite was obtained by multiple experiments.Using the optimal equivalent to expand to different configurations of glycosides,the product of the isolated yield more than 85%.And the reaction time is about 30 seconds.