Direct Oxidation Of S-Acetyl And Photochemical Desulfurization Reaction In Thio-containing Glycosides

Carbohydrate chemistry is an ancient discipline whose origin can be traced back to ancient civilization.In recent years,with the advancement of modern separation and analysis techniques,as well as the continuous deepening of biological research,more and more people are aware of the biological activities of carbohydrate compounds.Carbohydrate compounds plays an important role in signal transduction,biorecognition,immunoregulation,viral replication,cancer cell metastasis,and protein regulatory folding in vivo,which has stimulated human interest in carbohydrate.Thio-containing glycosides are a class of interesting compounds,in many cases,it has an anti-metabolic effect,is well adapted to the environment in the living body and can inhibit the hydrolysis of glycosidases.In addition,thioglycosides plays an important role in the synthesis of oligosaccharides.Based on these characteristics,thioglycosides have become one of the hot spots in the field of carbohydrate chemistry.In this article,we will begin our work by reviewing the application of thio-containing glycosides in organic chemistry and research progress.This paper focuses on the efficient synthesis of deoxy sugars,glycosyl disulfides,glycosyl thiols and glycosyl donors via thioglycosides.1.We have developed a new method for the preparation of deoxyglycosides.By introducing a thiol group into a sugar molecule,trialkyl phosphine is added to perform a desulfurization reaction under the irradiation of ultraviolet light for 0.5 h,deoxyglycosides were prepared in high yields.At the same time,we found that glycosyl disulfide can also react to generate deoxyglycosides under this condition.We believe that this reaction takes place in two steps.First,the disulfide bonds break down under the action of trialkylphosphine to generate glycosyl thiol,and glycosyl thiol continue to react with the trialkyl phosphine under ultraviolet light conditions to generate deoxyglycosides.Moreover,we verified through NMR that a small amount of water in the air participates in the reduction of disulfide bonds.The theoretical calculations support the view that triethylphosphine is more active than Triethyl phosphite in the photochemical desulfurization reaction.This method may provide a new approach to synthesize 2-deoxyglycosides via the stereoselective control of C-2 thioacetate groups.2.Glycosyl disulfides have been reported to be formed via the oxidation of the corresponding glycosyl thiols,However,acquiring glycosyl thiols from glycosyl precursors commonly requires extra steps and special means,Great improvement in reaction rate,yield,and general convenience was demonstrated in the presence of NIS.Furthermore,these per-O-acetylated glycosyl disulfides were efficiently reduced with TCEP in polar solvents,Our method supplied an efficient way to obtain both per-O-acetylated glycosyl disulfides and per-O-acetylated glycosyl thiols in which the sulfur group can be located at any position.3.Nitrite is often used in our lab to generate carbohydrate structure of inverse configuration through the nitrite-mediated epimerization.Accidentally,we observed that1-S-acetyl per-O-acetylated glycoside produced glycosyl disulfide in the presence of tetrabutylammonium nitrite?TBANO₂?in DMF.The disulfide can be readily separated by the extraction using dicholoromethane.after optimization,we chose the less inexpensive and more readily available reagent,potassium nitrite as the oxidant.During ¹H NMR studies,it can be observed that the signal of O-acetyl formed with the disappearance of the signal of S-acetyl.At the same time,we used a special method detecting the generated gas,and combined with previous literature reports,demonstrating NO generated during the reaction.By this method,per-O-acetylated glycosyl disulfides were synthesized in very high yields.The disulfides were further reduced by TCEP to form selectively deacetylated glycosyl thiols in high yields in a one-pot reaction.Furthermore,by making use of the S-arylation between thiol group and aryl-iodide catalyzed by Xantphos Pd-G3,thio-glycosyl donors were efficiently synthesized in high yields at very mild conditions in a one-pot reaction starting from per-acetylated 1-thio-glycosides,so as to avoid the use of toxic aryl-thiols.In summary,this paper developed a new method for preparing deoxyglycosides,glycosyl disulfides,glycosyl thios and glycosyl donors based on the specific properties of thioglycosides,simplified the synthesis of these compounds,achieved some valuable research results.