Synthesis and function analysis of Gangliosides

唾液酸是细胞膜糖蛋白和糖脂的组成成分，在生物识别和许多其他生物学功能中发挥重要作用。除了cmp - n -乙酰神经氨酸外，天然存在的唾液酸化合物含有α -糖苷键的唾液酸。因此，为了研究诸如糖蛋白和神经节苷类唾液糖缀合物的结构-功能关系，一个易于区域和α选择性的n -乙酰神经氨酸的糖苷合成是至关重要的。作为糖基供体的甲基（5-乙酰氨基-4,7,8,9-四-0-乙酰基-3,5-二脱氧-d -甘油- β -d -半乳糖-2-non - ulopyranoyl chloride）酸酯与糖衍生物糖化通常得到α -糖苷和β -糖苷的混合物。当与糖衍生物的仲羟基反应时，该供体以极低的产率提供预期的a-糖苷。在动力学控制条件下，利用三氟化二甲基（甲基硫）磺酸（DMTST）和适当保护的糖基受体，在乙腈中证明了Neu5Ac衍生物的甲基α -巯基糖苷是提供Neu5Ac α -糖苷的有效糖基供体。我们利用这种方法合成了多种神经节苷脂及其类似物。

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.