【作者】 刘运鹏；

【导师】 耿美玉；

【作者基本信息】 中国海洋大学 ， 药物化学， 2009， 博士

【摘要】 N-乙酰神经氨酸(Neu5Ac)是一类自然界中分布最广的唾液酸类化合物,它位于哺乳动物细胞表面糖蛋白和糖脂的末端。在人体内,N-乙酰神经氨酸往往以α(2→3)或者α(2→6)唾液酸苷键与半乳糖和N-乙酰半乳糖连接。细胞表面的Neu5Ac在细胞间的相互作用中起到了重要的作用,例如病原体-宿主的识别、肿瘤的转移、毒素-受体的相互作用、细胞的分化和增殖。为了进一步研究它们的生物功能,发展有效和区域选择性的合成α(2→3)和α(2→6)-Neu5Ac-Gal单元的路线是非常必要的。一以唾液酸三氟乙酰亚胺酯为给体高效合成　Neu5Acα(2→3)-Gal模块,并将其应用于神经节苷脂GM3的合成本文对以唾液酸三氟乙酰亚胺酯为给体,设计合成了不同的半乳糖受体,进行糖苷化反应研究。获得了一条有效合成Neu5Acα(2→3)-Gal单元的路线,用2,3,4-羟基裸露的半乳糖为受体,TBSOTf作为催化剂进行糖苷化反应,并找到了最佳的一个半乳糖受体2-(trimethylsilyl)ethyl 6-O-tert-butyldiphenylsilyl-β-D- galactopyranoside(75g),以73%的收率和89%的立体选择性合成了Neu5Acα(2→3)-Gal糖苷键,并将得到的二糖模块成功的应用于GM3的合成。二唾液酸苯基炔酸酯为给体的糖苷化研究一种新的以唾液酸炔基苯甲酸酯为给体,以Au(I)为催化剂,四氢呋喃为溶剂的唾液酸苷化方法被发现,并将其应用于唾液酸糖苷的合成中得到了比较理想的效果。合成的炔酯给体可以直接使用,而且稳定性好;糖苷化的产率较高;促进剂是催化量的,催化体系是中性的,可以有效抑制消除产物的生成。更多还原

【Abstract】 N-Acetylneuraminic acid (Neu5Ac), the most abundant sialic acid congener in nature, is found at the termini of glycoproteins and glycolipids on mammalian cell surfaces. In humans, Neu5Ac occurs frequently via aα(2→3) glycosidic linkage to galactose orα(2→6) linkages to galactose and N-acetylgalactosamine. Since Neu5Ac on the cell surfaces plays diverse and important roles in cell-cell interaction processes, such as pathogen-host recognition, tumor metastasis, toxin-receptor interaction, malignant alteration, cell differentiation and proliferation, much effort has been devoted to the efficient and stereoselective synthesis ofα(2→3) andα(2→6)-Neu5Ac-Gal units in order to further investigate their biological functions.1. Efficient Synthesis of a Sialic Acidα(2→3) Galactose Building Block using N-phenyltrifluoroacetimidate as leaving group and Its Application to the Synthesis of Ganglioside GM3.Glycosylation of various galactose derivatives with O-acetylated sialic acid N-phenyltrifluoroacetimidate as the donor was investigated. Efficientα(2→3) sialylation of galactose, with up to 73% yield and 8.4:1 stereoselectivity, was realized when 2,3,4-unprotected galactose derivatives and TBSOTf were used as acceptors and promoter, respectively. Sialylation of 2-(trimethylsilyl)ethyl 6-O-tert -butyldiphenylsilyl-β-D-galactopyranoside gave the best result, and the resultant Neu5Acα(2→3) Gal disaccharide was successfully used to synthesize ganglioside GM3. 2. Study on sialylation using ortho-alkynylbenzoate as donorsA novel sialylation method was investigated, which using ortho-alkynylbenzoates as the donor, Au(I) as promoter and THF as the solvent, showed favorability compared with previous protocols for direct sialylation. The donors are readily available and stable; the glycosidic coupling yields are generally excellent; the promotion system is catalytic, neutral, and orthogonal to the known glycosylation conditions.更多还原