本篇論文目的是 (1) 合成醣苷鞘胺醇酯以模擬免疫球蛋白A1 (immunoglobulin A1：IgA1) 絞鍊區結構以及 (2) 修飾硼色胺酸衍生物以提升其水溶性。
第一部分醣苷鞘胺醇的醣基化受體 (親核基) 以D-半乳糖作為起始物，經過典型的乙醯化反應及硫代乙醯的引入，得到95%產率。予體部分的植物鞘胺醇通過疊氮的引入、丙酮化的保護、對甲苯磺醯化及碘化，經過四步合成得到產率37 %。嘗試以Williamson反應耦合已上保護的一級植物鞘胺醇衍生物與一級植物鞘胺醇碘化物，但薄弱的光譜證據宣告無法合成出目標對稱型化合物。
第二部分論文透過去保護反應及聚乙二醇化，從四種硼頻那醇色胺酸衍生物中得到聚乙二醇化產物，分別為聚乙二醇化的tri-Boc 5-boronotryptophan、tri-Boc 6-boronotryptophan、N-acetyl 5-boronotryptophan與N-acetyl diBoc 5-boronotryptophan。其中色胺酸的去保護反應得到58-96% 的產率而聚乙二醇化反應純化是透過透析法，這並不是一個好的方法，產率61-88% 之中包含產物及未反應的PEG。

The thesis is aimed to 1) generate glycosphingolipid conjugates to mimic the hinge structural features of immunoglobulin A1 (IgA1) and 2) to modify the boronotryptophan derivatives to improve their aqueous solubility.
The first part of glycolsphingosine was obtained from D-galactose as the starting material of acceptor (a nucleophile). Through a typical acetylation and thioacyl introduction, the galactosyl thio acetate was obtained in 95 % yield. The donor moieties of phytosphingosine comprise azide introduction, acetonide protection, tosylation and iodination in 37% yield via 4-step procedure. Attempt to conjugate the sphingosine analogs through Williamson synthesis mediated by the protected primary alcohol sphingosine and the 1-iodo sphingosine failed to provide the desired dimers as evidenced from only poor spectroscopic data.
The second part of the thesis started from the four 5- and 6-boronopinacotryptophan derivatives via deprotection and pegylation to provide two pegylated tri-Boc 5- and 6- tryptophans and pegylated N-acetyl 5-boronotryptophan as well as pegylated N-acetyl diBoc 5-boronotryptophan. Although deprotection performed well and the yield was 58-96%, pegylation using dialysis was a fair method because the yield of 61-88% was calculated based on the product and the remaind PEG.

摘要-----------------------------------1
Abstract-----------------------------------2
誌謝-----------------------------------3
全名縮寫對照表-----------------------------------4
1.緒論-----------------------------------7
1.1台灣腎病及洗腎人口之現況-----------------------------------7
1.2 IgA腎病變 (IgA Nephropathy)-----------------------------------7
1.3 IgAN發病機制-----------------------------------7
1.4聚乙二醇性質概述-----------------------------------9
1.5聚乙二醇化之藥物傳遞策略-----------------------------------11
1.5.1聚乙二醇化蛋白質-----------------------------------12
1.5.2小分子藥物-----------------------------------13
1.6聚乙二醇化之化學-----------------------------------16
1.6.1胺基酸側鏈官能基-----------------------------------16
1.6.2聚乙二醇化小分子藥物-----------------------------------17
1.7研究動機-----------------------------------19
2.結果與討論-----------------------------------21
2.1 S-link醣酯質類似物合成路徑-----------------------------------21
2.1.1受體製備-----------------------------------23
2.1.2予體製備-----------------------------------23
2.1.3醣基化反應-----------------------------------25
2.2 IgA1分子模型建構之嘗試-----------------------------------25
2.3色胺酸衍生物之酯基去保護-----------------------------------26
2.4聚乙二醇化色胺酸衍生物之化學-----------------------------------29
2.5色胺酸衍生物與聚乙二醇耦合之光譜分析-----------------------------------29
3.實驗部分-----------------------------------30
3.1儀器設備、溶劑與試藥前處理-----------------------------------30
3.2化學合成步驟-----------------------------------31
4.結論-----------------------------------48
5.附錄-----------------------------------50
6.參考文獻-----------------------------------84

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