Total synthesis of the aminopropyl functionalized ganglioside GM_1  

作　　者：SUN Bin YANG Bo HUANG XueFei 

机构地区：[1]Department of Chemistry,Michigan State University,East Lansing,Michigan 48824,USA [2]Research Center of Medicinal Chemistry and Chemobiology,Chongqing Technology and Business University,Chongqing 400067,China

出　　处：《Science China Chemistry》2012年第1期31-35,共5页中国科学（化学英文版）

基　　金：supported by NIH (R01-GM72667 and R01-CA149451)

摘　　要：GM1 is a common ganglioside pentasaccharide present on mammalian cell surface.It has been shown to play important roles in cellular communications and initiation of β-amyloid aggregation.In order to synthesize GM1,an efficient synthetic route was developed via a [3+2] strategy.The GM3 trisaccharide acceptor bearing an azido propyl group at the reducing end was prepared using the traditional acetamide protected sialyl thioglycosyl donor,which gave better stereoselectivity than sialyl donors protected with trichloroacetamide or oxazolidinone.The glycosylation of the axial 4-hydroxyl group of GM3 by the disaccharide donor was found to be highly dependent on donor protective groups.Donor bearing the more rigid benzylidene group gave low glycosylation yield.Replacing the benzylidene with acetates led to productive coupling and formation of the fully protected GM1 pentasaccharide.Deprotection of the pentasaccharide produced GM1 functionalized with the aminopropyl side chain,which will be a valuable probe for biological studies.GM1 is a common ganglioside pentasaccharide present on mammalian cell surface.It has been shown to play important roles in cellular communications and initiation of β-amyloid aggregation.In order to synthesize GM1,an efficient synthetic route was developed via a [3＋2] strategy.The GM3 trisaccharide acceptor bearing an azido propyl group at the reducing end was prepared using the traditional acetamide protected sialyl thioglycosyl donor,which gave better stereoselectivity than sialyl donors protected with trichloroacetamide or oxazolidinone.The glycosylation of the axial 4-hydroxyl group of GM3 by the disaccharide donor was found to be highly dependent on donor protective groups.Donor bearing the more rigid benzylidene group gave low glycosylation yield.Replacing the benzylidene with acetates led to productive coupling and formation of the fully protected GM1 pentasaccharide.Deprotection of the pentasaccharide produced GM1 functionalized with the aminopropyl side chain,which will be a valuable probe for biological studies.

关 键 词：CARBOHYDRATE chemical synthesis GANGLIOSIDES GM1 

分 类 号：Q546[生物学—生物化学] O629.9[理学—有机化学]