摘要

肝素/硫酸乙醯肝素是屬於葡胺巨醣（GAGs）中的一類分子。硫酸乙醯肝素分布在細胞表面及細胞外纖維組織裡，在生物系統扮演非常重要的角色，包括病毒感染、細胞成長調控、血液凝結及癌細胞轉移等；而肝素為一結構與硫酸乙醯肝素類似的葡胺巨醣，只存在於巨細胞及造血細胞中，被廣泛的使用作為抗血栓藥物。由於缺乏分離及純化硫酸乙醯肝素的適合方法，而較易取得並被用來模擬硫酸乙醯肝素功能的肝素分子又無法妥切代表硫酸乙醯肝素在生物系統中的角色，所以為了深入探究肝素/硫酸乙醯肝素醣體與生物巨分子辨識間的關係，我們實驗室投入大量人力來進行肝素/硫酸乙醯肝素醣體分子的合成工作，本論文即是著重在其中12個肝素/硫酸乙醯肝素雙醣體的合成研究工作上。

利用實驗室已開發的方法，以D式五乙醯葡萄醣為起始物，經八步反應可取得醣受體分子，進一步與以D式葡萄胺醣為起始物經八步反應所得的醣予體進行醣鏈結反應、官能基轉換，即可得到合成12個肝素/硫酸乙醯肝素雙醣體所需的共同中間體1、2。以這兩個共同中間體為基礎，經過不同位置羥基保護基的移除以及自由羥基的磺化反應，最終可得到12個肝素/硫酸乙醯肝素雙醣體。

Abstract

Heparan sulfate (HS) and its structurally related heparin (HP) belong to the family of glycosaminoglycans. HS, distributed on the cell surface as well as the extracellular matrix, plays significant roles in a diverse set of biological processes, including virus infection, cell growth and tumor metastasis. HP is found only in mast cells and some hematopoietic cells and is widely used as an anticoagulant drug. There is a rapid growing interest in the structure and function of heparin sulfate whose heterogeneity enables these molecules to participate in various processes in the body. Although HP and HS have similar structural skeletons, their biological roles in vivo are quite different. To tackle this problem, we have made a lot of efforts to synthesize the whole set of HP/HS disaccharides and trisaccharides. This dissertation focuses on the synthesis of twelve HP/HS disaccharides.

The glycosyl acceptor was successfully synthesized in an eight-step procedure which is successfully developed in our laboratory. Coupling of the acceptor with the donor gave the α-linked disaccharide. The common intermediate disaccharide 1 and 2 could be afforded through functional group transformation. With the common intermediate disaccharide 1 and 2 in hand, the final twelve HP/HS disaccharides could be generated by the subsequent deprotection and sulfonation in several steps.

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