論文摘要
本篇論文主要分五部分測試可溶性高分子支持物( Soluble Polymer-Supports )在有機合成上的應用，並著重於
piperidine及piperazine系列衍生物之合成。
第一部份:測試可溶性高分子支持物在有機溶劑中的溶解度及其反應性，首先尋找適當條件,將可溶性高分子支持物接上連接物 ( linker )，並利用親核性試劑與其進行SN2反應，測試其反應性，並將其與?C啶及?C?D等具有生物活性的模板( templates )反應。
第二部分:將具有生物活性的可溶性高分子支持物模板與各種親電性試劑反應，利用其在各溶劑中溶解度的不同，以沈澱及過濾等簡單步驟達到純化之效果，再使用適當的條件將產物由可溶性高分子支持物上切下(cleavage)，建立一小型有機分子庫( small organic molecule libraries )。
第三部分:可溶性高分子支持物模板與胍啶試劑（guanylating agents）進行guanidinylation反應後，以此為起始物，做不同反應之測試，如與不同的親核試劑反應。
第四部分: 將Di-Boc-Guanidine-PEG去保護後進行環化反應，而建立另一多樣化的小型分子庫。
第五部分：可溶性高分子支持物在不對稱合成上的應用。利用接上具有掌性分子之可溶性高分子支持物為催化劑，測試其在不對稱合成上之可行性。
由結果可知，將組合式化學（Combinatorial Chemistry的概念運用於可溶性高分子支持物在液相（liquid phase）中的合成，可以得到高產率及高純度的產物。

Abstract
Combinatorial synthesis of chemistry libraries is undergoing rapid examination as a tool to enhance drug research and development. While it appears obvious that combinatorial chemistry strategies offer the potential to enhance drug development by shortening the time to optimize a new lead by structure-activity relationship (SAR) studies, it is often less appreciated that the greatest value of combinatorial chemistry strategies lies in its potential to enhance discovery of novel leads or pharma- cophores.
The development of both soluble and insoluble functionalized polymer is current of tremendous interest in fields of combinatorial chemistry. The conversion of reactions in solution to either soluble or insoluble or insoluble polymer-supported chemistry methodologies, minimization of side-reactions and the ability to use an excess of reagent to drive a reaction to completion, is an on-going challenge.
A novel method for soluble, inexpensive polymer-supported synthesis of piperidine and piperazine scaffolds has been development. The use of soluble supports offers a method to overcome the difficulties while maintaining the ease of solid-phase synthesis. PEG is soluble in most organic solvents and has a strong propensity to precipitate. Inclusion due to gelatinous precipitation are avoided. The products were liberated from the polymer supports in excellent yields and good purity by simple precipitation and washing.

目錄
頁次
第一章 緒論
一、簡介…………………………………………………………... 1
二、組合式有機合成與傳統有機合成…………………………... 1
三、固相合成……………………………………………………... 4
四、溶液相合成…………………………………………………... 6
五、液相合成……………………………………………………... 7
六、研究方向……………………………………………………... 8
第二章 結果與討論
一、醯化反應…………………………………………………...… 12
二、胺類醯化反應………………………………………………... 15
三、呱啶及其衍生物……………………………………………... 18
四、環化反應……………………………………………………... 24
五、不對稱合成…………………………………………………... 26
第三章 儀器與步驟
一、使用儀器……………………………………………………... 28
二、藥品與溶劑…………………………………………………... 29
三、實驗步驟……………………………………………………... 29
第一部份、醯化反應……………………………………………... 29
第二部份、胺類醯化反應………………………………………... 30
第三部份、呱啶及其衍生物之合成……………………………... 43
(i) 呱啶試劑之製備……………………………………………….. 43
(ii) 實驗步驟………...…………………………………………….. 45
第四部份、環化反應……………………………………………... 66
第五部份、不對稱合成………………………………………...… 67
參考文獻………………………………………………….. 69
附錄、核磁共振(NMR)光譜圖…………………..………. 72
圖目錄
頁次
圖一、傳統有機合成……………………………………………... 2
圖二、組合式化學合成…………………………………………... 2
圖三、組合式化學之發展………………………………………... 3
圖四、醯化反應之1H-NMR 圖譜………………………………… 13
圖五、反應1H-NMR圖譜………………………………………… 15
圖六、可溶性高分支持物純化圖………………………………... 20
圖七、切斷(cleavage) 1H-NMR圖譜…………………………….. 21
表目錄
頁次
表一、PEG-4000 在溶濟的溶解度…………………………….… 7
表二、可溶性高分子支持物在生化合成上的應用例子………... 8
表三、環狀胺類行 SN2反應之結果……………………………... 16
表四、胺醯化反應之結果………………………………………... 19
表五、胺類高分子支持物進行Guanidinylation之結果………… 24
表六、呱啶行胺類醯化反應之結果……………………………... 27

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