博碩士論文 91223035 詳細資訊


姓名 潘冠榮(Guan-Rong Pan)  查詢紙本館藏   畢業系所 化學學系
論文名稱 硫酸乙醯肝素雙醣體之合成研究
(Synthesis of Heparan Sulfate Disaccharides)
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摘要(中) 摘要
硫酸乙醯肝素為葡胺巨醣的生物分子,其廣佈於細胞表面與胞外的纖維組織之中,在生物系統中扮演重要的角色,包括病毒感染、細胞成長調控、血液凝結及癌細胞轉移等。在其組成單元裡,雙醣體1和2的含量很少,但在葡萄胺醣第三號碳上氧原子位置接有硫酸脂基時,對皰疹病毒入侵人體細胞的機制及與抗血症的作用機制等有重要的影響。我們實驗室為了模擬雙醣1和2在生物體內的作用,已合成了雙醣體4,本論文即研究雙醣體5的前驅合成。
我們利用實驗室已開發的方法,以D式雙丙酮葡萄醣為起始物,經五項反應步驟可取得1,6–無水L式艾杜醣9,進一步與醣予體34做醣鏈結反應可得到高產率且高選擇性的雙醣體35?,接著成功克服了乙醯化開環反應,並選擇性的在艾杜醣酸部分的變旋異構中心引進?式的甲氧基,得到化合物37?,最後,根據實驗室已經開發的方法,我們確信再經過?步官能基的轉換,可成功合成目標分子?。
摘要(英) Abstract
Heparan sulfate, a complex polysaccharide belonging to the family of glycosaminoglycan, is ubiquitously distributed on the cell surface and in the extracellular matrix. It play significant roles in a diverse set of biological processes, including viral invasion, cell growth, blood coagulation, and tumor metastasis. The disaccharides 1 and 2, having a 3-O-sulfated D-glucosamine unit, are minor but very important components in heparan sulfate and are known to play a crucial role in Herpes Simplex virus entry as well as blood coagulation. The preparation of compound 4 has been carried out in our laboratory. In this thesis, we report a formal synthesis of the disaccharide 5.
An efficient and novel preparation of the 1,6-anhydro-?-L-idopyranose 9 from comically available diacetone ?-D-glucose in five steps was successfully developed in our laboratory. Coupling of 9 with the D-glucosamine-derived donor 34 gave the ?-linked disaccharide 35? in high yield and selectivity. Subsequent anomeric deprotection, imidation and concomitant glycosylation using methanol as an acceptor successfully furnishes the requisite ?-methyl glycoside 37?. We believe that the target molecule 5 could be generated via functional group transformation of disaccharide 37? in seven steps, according to the developed method in our laboratory.
關鍵字(中) ★ 硫酸乙醯肝素 關鍵字(英) ★ Heparan Sulfate
論文目次 目錄
中文摘要----------------------------------------------------------------i
英文摘要----------------------------------------------------------------ii
謝誌--------------------------------------------------------------------iii
縮寫對照表---------------------------------------------------------------iv
目錄---------------------------------------------------------------------vi
壹、緒言----------------------------------------------------------------- 1
貳、反合成分析-----------------------------------------------------------9
參、結果與討論-----------------------------------------------------------11
(一)、D式葡萄胺醣衍生物22的合成------------------------------------------11
(二)、雙醣體21?的合成----------------------------------------------13
(三)、對化合物21?醋酸酐開環反應的探討----------------------------------- 16
(四)、D式葡萄胺醣衍生物34的合成------------------------------------------ 18
(五)、雙醣體36的合成---------------------------------------------- 19
(六)、目標雙醣體5的合成------------------------------------------ 20
肆、結論----------------------------------------------------------------- 24
伍、實驗部分------------------------------------------------------------- 25
陸、參考文獻------------------------------------------------------------- 51
柒、光譜附錄------------------------------------------------------------ 56
參考文獻 伍、參考文獻
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50. 國立清華大學,李靜琪,細胞表面硫酸乙醯肝素寡醣的合成研究,2003年。
指導教授 洪上程、李文仁
(Shang-Cheng Hung、Wen-Ren Li)
審核日期 2004-7-14
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