Synthesis and function analysis of Gangliosides

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Sialic acids are well known as constituents of glycoprotein and glycolipids of cell membranes, and they play a role in biological recognition and many other biological functions. It is also known that naturally occurring sialo compounds contain sialic acids in alpha-glycosidic linkage, except for CMP-N-acetylneuraminic acid. Therefore, a facile regio- and alpha-selective glycoside synthesis of N-acetylneuraminic acid is critically important, in order to investigate the structure-function relationships of such sialoglycoconjugates as glycoproteins and gangliosides. Glycosidation of methyl (5-acetamido-4,7,8,9-tetra-0-acetyl-3,5-dideoxy-D-glycero-beta-D-galacto-2-nonulopyranosyl chloride)onate as the glycosyl donor with sugar derivatives usually gives a mixture of alpha- and beta- glycoside. When reacting with secondary hydroxyl groups of sugar derivatives, this donor affords the expected a-glycosides in very low yields. We demonstrated that the methyl alpha-thioglycoside of Neu5Ac derivative are useful glycosyl donor to afford alpha-glycosides of Neu5Ac by use of dimethyl(methylthio)sulfonium triflate (DMTST) and the suitably protected glycosyl acceptors, in acetonitrile under kinetically controlled conditions. We have achieved to synthesize a variety of gangliosides and the analogs by using this methodology.