具有自由胺基肝素三醣體的合成研究

Synthesis of Heparin Trisaccharide With a Free Amino group

黃琳絹(Lin-Chuan Huang)

指導教授 ： 廖文峯 ； 洪上程

國立清華大學/理學院/化學系/碩士(2009年)

https://doi.org/10.6843/NTHU.2009.00294

摘要

肝素與硫酸乙醯肝素是屬於葡胺巨醣的一種生物巨分子，在許多生物機制中扮演重要的角色。研究發現具有自由氨基的葡萄胺醣片段在肝素或硫酸乙醯肝素中的含量都很少，卻是與蛋白質作用的特殊活性位置，例如，皰疹病毒醣蛋白gD及白血球細胞膜上的蛋白質。
利用實驗室已開發的方法，以D式葡萄胺醣為起始物，經八步反應得醣予體29，進一步與以雙丙酮α-D葡萄糖為起始物經六步合成所得醣受體28偶合得單一α位向的雙醣體27，接著經三步驟將對溴苯甲基轉換為苯甲醯基，再經五步驟官能基修飾得醣受體24，隨即與醣予體26進行醣鏈結反應，建立起三醣體骨架。三醣體23經去酯類保護後，接著氧化成內酯化合物，再進一步去掉矽烷基並打開內酯環，而後只需再經磺化反應與氫解反應，便可得目標三醣體22。

關鍵字

肝素三醣體 ； 自由胺基 ； 醣鏈結

並列摘要

Heparin (HP) and heparin sulfate (HS) are both members of glycosaminoglycans and play significant roles in biological processes. There are traces of HP and HS with free amino group, which are important for interaction with L-selectin of leukocyte and the key position combined with protein gD of Herpes Simplex Virus type-1.
The glycosyl acceptor 28 and glycosyl donor 29 were prepared by known strategy developed by our laboratory. Coupling of the acceptor 28 with the donor 29 to form the α-linked only disaccharide. Disaccharide 27 changes to acceptor 24 in 8 steps, and then coupled with donor 26 to construct trisaccharide skeleton. Removed ester groups of trisaccharide 23 and underwent oxidation to get lactone-derivative. Opening the lactone ring and desilylation in 1 step, followed by sulfation and hydrogenation to afford target trisaccharide 22.

並列關鍵字

Heparin Trisaccharide ； glycosylation

參考文獻

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