臺灣博碩士論文加值系統

摘要
本論文主要設計並合成一系列潛在的對羥基苯丙酮雙氧?(4-HPPD)抑制劑並探討其抑制結果。我們設計並合成4-HPPD催化反應之可能中間產物類似物1,6-epoxy-4-methoxy-2,5-dioxo -cyclohex -3-eneacetic acid methyl ester (37)，其抑制結果顯示 epoxyquinone 的官能基並不是抑制此?活性所需的結構。此外設計並合成具有2-oxyimino2-oxyimino-cyclohexane-1,3-dione 和 oxyphenoxypropionic結構的潛在抑制劑，抑制結果顯示前者2-oxyimine 的取代基並不是抑制對羥基苯丙酮雙氧活性所需的結構，而後者以4-hydroxyphenoxyacetic acid (51) 抑制能力最強，其IC50值為6μM。另外我們也合成具有3-cyclopropane-carbonyloxy -2-cyclohexen-1-one (21) 結構的潛在抑制劑，抑制結果顯示 3-cyclopropane-carbonyloxy-5-oxo-cyclohex-3-enecarboxylic acid ethyl ester (64) 抑制能力最強，其IC50值為0.1μM。由以上研究結果我們找到了引導方向，希望能應用醫療用途及除草劑開發。

Abstract
In this thesis, various potential 4-hydroxyphenylpyruvate dioxygenase (4-HPPD) inhibitors have been designed, synthesized, and tested as inhibitors of 4-HPPD by the enol borate-tautomerase method. 1.6-Epoxy-4-methoxy-2,5-dioxo-cyclohex-3-eneacetic acid methyl ester 37 was prepared since it possessed the similar structure to the proposed arene oxide intermediate for this 4-HPPD catalyzed reaction. The inhibition result indicated that epoxyquinone moiety of 37 was not a required functionality for potent 4-HPPD inhibition. 2-Oxyimino-cyclohexane-1,3-dione and oxyphenoxypropionic acid derivatives have also been synthesized and tested as inhibitors of 4-HPPD. Inhibition results suggested that 2-oxyimino substituent in 56a-d was again not a required functionality for 4-HPPD inhibition. The most potent inhibitor tested was 4-hydroxyphenoxyacetic acid 51 with IC50 value of 6μM. Furthermore, a serious of 3-cyclopropanecarbonyloxy -2-cyclohexen-1-one 21 derivatives have been prepared. The inhibition results indicated that 3-cyclopropane-carbonyloxy-5-oxo-cyclohex -3-enecarboxylic acid ethyl ester 64 was the best inhibitor with IC50 of 100 nM. This information is important for future design of novel inhibitors to serve as a new therapeutic agent for tyrosinemia type I and control of weeds in broadleaf crops.

目錄
誌謝……………………………………………………………………..I
中文摘要……………………………………………………………….II
英文摘要………………………………………………………………III
目錄
誌謝………………………………………………………………………I
中文摘要…………………………………………………………………II
英文摘要…………………………………………………………………III
目錄………………………………………………………………………IV
附圖目錄…………………………………………………………………V
壹、緒論…………………………………………………………………2
貳、結果討論……………………………………………………………18
一、化合物的合成…………………………………………………18
二、酵素活性的分與抑制劑的測定方法…………………………26
三、各化合物之酵素動力學的結果及討論………………………28
參、結論…………………………………………………………………33
肆、實驗部份……………………………………………………………34
一﹑儀器設備及試藥來源…………………………………………34
二、化合物的合成…………………………………………………36
伍、參考文獻…………………………………………………………… 63
陸、光譜資料……………………………………………………………66

伍、參考文獻
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