臺灣博碩士論文加值系統

本篇論文是利用一個tetrazole的結構來作為固相合成上所使用的安全閥鍵鏈劑(safety-catch linker)，一邊接上我們的固相載體(Merrifield Resin)而另一邊則接上我們想要的substrate接著進行一系列的反應包括Alkylation、Mitsunobu reaction、Amino Coupling、Oxidation，最後經由Julia Olefination的斷裂機制將各種衍生物從固相載體上斷裂下來形成具有雙鍵特性的結構，並且嘗試去控制其立體位相的選擇性 (Selective E-Z form) 並且探討其斷裂過程中Substrate、Base (LDA、LiHMDS、NaHMDS、KHMDS) 、Solvent (Toluene、THF、DME) Aldehyde (alkyl or benzaldehyde) 、Lewis acid(Bu3SnCl、ZnBr2)對其E-Z form選擇性的影響。

We have known many natural product with double bone maybe have bio-activity in natural world. In order to develop a method of synthesizing quickly various compounds with double bond in organic chemistry. We think the combinatorial chemistry is very good tools in our study. Now We also have known safety-catch linker playing a important role in solid phase. A useful safety-catch linker must have many advantages in synthesis process include easy to take, low cost, stable in any condition and so on. That is a key point we develop a novel safety-catch linker to use in solid phase chemistry. Our safety-catch linker have made a various kinds of alkene because it made double bone in the end of synthesis. We also try our best to study how to control the E-Z form selectivity by base, solvent, Lewis acid and aldehyde. We did not to control the selectivity but have a interesting result. These results will make us more clear and know more detail of the transformation in reaction process. I believe we will succeed in this study.

目錄
中文摘要………………………………………………………………I
英文摘要(Abstract)…………………………………………………II
謝誌…………………………………………………………………III
目錄……………………………………………………………………V
圖目錄………………………………………………………………VIII
表目錄………………………………………………………………IX

開發可應用於組合式合成烯類化合物之新型具安全閥鍵鏈劑
一、導論………………………………………………………2
1-1 何謂組合化學……………………………………………2
1-2 組合式化學的概念………………………………………2
1-3 組合式化學合成法………………………………………2
1-4 研究動機…………………………………………………4
1-5 藥物開發…………………………………………………4
1-6 固相合成法………………………………………………5
二、鍵鏈劑……………………………………………………7
2-1 何為鍵鏈劑……………………………………………7
2-2 鍵鏈劑的種類……………………………………………7
2-3 使用Tetrazole Sulfide 作為安全閥鍵鏈劑的想法……8
2-4 Modified Julia Olefination的斷裂機制………………9
2-5 Tetrazole Sulfide 鍵鏈劑的設計………………………10
2-6 保護基…………………………………………………11
2-6-1 何為保護基(Protecting Group)………………………………11
2-6-2 保護基的選擇…………………………………………………11
三、 結果與討論……………………………………………………12
3-1 此安全閥鍵鏈劑的合成流程…………………………………12
3-1-1 液相合成流程…………………………………………………12
3-1-2 固相合成流程…………………………………………………13
3-2 將硫基接上不同的基質R(substrate)…………………………16
3-3 使用Base、Solvent、Aldehyde、Lewis acid 來控制位相選擇性……………………………………………………………………18
3-3-1 Base的測試…………………………………………………19
3-3-2 溶劑的測試…………………………………………………20
3-3-3 Lewis acid的測試…………………………………………21
3-3-4 Aldehyde的測試……………………………………………22
3-3-5 E-Z form的推論……………………………………………25
3-3-6 苯醛與基質的相互影響探討………………………………31
3-4 此安全閥鍵鏈劑應用於固相合成……………………………34
3-5 結論……………………………………………………………36
3-6 研究後記………………………………………………………36
3-6-1 利用sulfide和sulfoxide來進行Julia-Lythgoe Olefination…………36
3-6-2 下圖為使用sulfoxide來進行反應的Scheme…………………………37
3-6-3 在5、6號位置上無法作用……………………………………………39
3-6-4 Tetrazole Sulfide Linker氧化限制………………………………40
四、實驗流程及光譜數據……………………………………41
4-1 實驗儀器………………………………………………41
4-2 實驗藥品………………………………………………41
4-3 一般的實驗方法………………………………………42
4-4 實驗流程與光譜資料…………………………………43
4-4-1 液相實驗步驟………………………………………43
4-4-2 固相實驗步驟………………………………………54
五. 參考文獻…………………………………………………66
六、 光譜資料附圖…………………………………………68

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