Reports on large-scale syntheses of rare deoxy sugars are notably limited,which poses a significant obstacle to the identification of glycans containing these rare sugars as potential therapeutic agents in the treatme...Reports on large-scale syntheses of rare deoxy sugars are notably limited,which poses a significant obstacle to the identification of glycans containing these rare sugars as potential therapeutic agents in the treatment of infectious diseases.In this manuscript,we present a hectogram-scale synthesis of the rare 3-amino sugar,saccharosamine,which is an essential component of the heptadecasaccharide saccharomicins,demonstrating considerable potential for the development of a novel class of antibiotics.The synthesis was initiated from the naturally abundant mannose and involved three batch processes in conjunction with five continuous flow processes,representing the most efficient synthetic pathway established to date.A total of five purification steps were conducted,and the process was meticulously designed to obviate the necessity for column chromatography.The effectiveness of these streamlined procedures,along with straightforward manipulation and purification protocols,effectively addresses the challenges associated with scaling up and provides a viable and environmentally sustainable solution for the rapid synthesis of related rare deoxy sugars.展开更多
Highly stereoselective synthesis of 2-azido-2-deoxyglucosides and 2-azido-2-deoxygalactosides is achieved via a gold-catalyzed S_(N)2 glycosylation.The glycosyl donors feature a designed 1-naphthoate leaving group con...Highly stereoselective synthesis of 2-azido-2-deoxyglucosides and 2-azido-2-deoxygalactosides is achieved via a gold-catalyzed S_(N)2 glycosylation.The glycosyl donors feature a designed 1-naphthoate leaving group containing an amide group.Upon gold activation of the leaving group,the amide group is optimally positioned to direct an S_(N)2 attack by an acceptor via H-bonding interaction.Both 2-azido-2-deoxyglucosyl/galactosyl donor anomers can undergo stereoinversion at the anomeric position,affording the opposite anomeric glycoside products with excellent levels of stereoselectivity or stereospecificity and in mostly excellent yields.This S_(N)2 glycosylation accommodates a broad range of acceptors.The utility of this chemistry is demonstrated in the synthesis of a trisaccharide featuring three 1,2-cis-2-azido-2-deoxyglycosidic linkages.展开更多
基金Supported by National Natural Science Foundation of China(No.30870506,No.31070724)Qingdao Science and Technology Project(No.11-2-2-1-hy)Public Science and Technology Research Funds Projects of Ocean(No.201005024)~~
基金supports from STI2030-Major Projects-2022ZD0211800the National Natural Science Foundation of China(22277033,22477033,22025102).
文摘Reports on large-scale syntheses of rare deoxy sugars are notably limited,which poses a significant obstacle to the identification of glycans containing these rare sugars as potential therapeutic agents in the treatment of infectious diseases.In this manuscript,we present a hectogram-scale synthesis of the rare 3-amino sugar,saccharosamine,which is an essential component of the heptadecasaccharide saccharomicins,demonstrating considerable potential for the development of a novel class of antibiotics.The synthesis was initiated from the naturally abundant mannose and involved three batch processes in conjunction with five continuous flow processes,representing the most efficient synthetic pathway established to date.A total of five purification steps were conducted,and the process was meticulously designed to obviate the necessity for column chromatography.The effectiveness of these streamlined procedures,along with straightforward manipulation and purification protocols,effectively addresses the challenges associated with scaling up and provides a viable and environmentally sustainable solution for the rapid synthesis of related rare deoxy sugars.
基金the National Institutes of Health(grant nos.U01GM125289 and R35GM139640)for financial supportthe National Science Foundation(grant no.MRI-1920299)for the acquisition of two Bruker NMR instruments.
文摘Highly stereoselective synthesis of 2-azido-2-deoxyglucosides and 2-azido-2-deoxygalactosides is achieved via a gold-catalyzed S_(N)2 glycosylation.The glycosyl donors feature a designed 1-naphthoate leaving group containing an amide group.Upon gold activation of the leaving group,the amide group is optimally positioned to direct an S_(N)2 attack by an acceptor via H-bonding interaction.Both 2-azido-2-deoxyglucosyl/galactosyl donor anomers can undergo stereoinversion at the anomeric position,affording the opposite anomeric glycoside products with excellent levels of stereoselectivity or stereospecificity and in mostly excellent yields.This S_(N)2 glycosylation accommodates a broad range of acceptors.The utility of this chemistry is demonstrated in the synthesis of a trisaccharide featuring three 1,2-cis-2-azido-2-deoxyglycosidic linkages.
