Gangliosides, sialic acid containing glycosphingolipids, are a class of structurally diverse molecules commonly present in vertebrate plasma membranes and especially enriched in nerve tissues*. These membrane components are thought to be responsible for important physiological activities, and it is hypothesized that the oligosaccharide moiety of these molecules is exposed as a ligand to the external environment, capable of expressing biological functions congruent to the chemical structure of the ganglioside2.3. An approach toward a systematic understanding of the structural and functional intricacies of the gangliosides necessitates efficient regio-and stereo-selective synthetic routes, affording various gangliosides and their analogs.
The focal point in the synthesis of gangliosides has been the stereoselective cr-glycosidation of sialic acid with various sugar residues. Recently, we reported an abridged version4a of a versatile procedure for a-glycosidation with thioglycosides of sialic acid, using dimethyl(methylthio)sulfonium triflate (DMTST)' as the promoter for reactions with suitably protected galactose and lactose acceptors in acetonitrile4b. From the application of this procedure we have reported' the total synthesis of several gangliosides and their analogs, to be used in pursuit of our objective of elucidating the function of sialoglycoconjugates.
Ganglioside GMlb was first isolated by Yip' from rat brain and, in a recent reportx, it is described to be associated with GMla in extremely minor quantities. A total synthesis of this ganglioside was first achieved by Ogawa et a1.9. Here we describe a facile total synthesis of ganglioside GM 1 b (18) and its positional analog 22, involving high-yielding glycosidation reactions performed according to our methods4'6.
Compounds 4 and 5 were used as the glycosyl donors while intermediate 3 was selected as the glycosyl acceptor for the synthesis of the core oligosaccharide chains of GMlb and its analog. The stereoselective synthesis of the glycosyl donors has been reported elsewhere'@.