Total synthesis of the aminopropyl functionalized ganglioside GM1

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 ??-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.