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研究生:馬基淵
研究生(外文):MA. JI YUAN
論文名稱:合成二肟二酯化合物作為具嵌合功能的光引導之核酸切割劑
論文名稱(外文):Synthesis of Dioxime Diesters as Intercalative Photo-Induced DNA-Cleaving Agents
指導教授:周善行周善行引用關係
指導教授(外文):Shang-Shing P. Chou
學位類別:碩士
校院名稱:輔仁大學
系所名稱:化學系
學門:自然科學學門
學類:化學學類
論文種類:學術論文
論文出版年:2001
畢業學年度:89
語文別:中文
論文頁數:31
中文關鍵詞:二肟二酯光引導之核酸切割劑
外文關鍵詞:Dioxime DiestersDNA-Cleaving AgentsPhoto-Induced
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由於之前劉志奮學長所合成的anthraquinone 肟酯有良好的切割效果,尤其是以para位置接CN, NO2, F的衍生物有最好的切割效果,可切雙股DNA,因此,本論文以anthraquinone為主體來合成二肟二酯 7,另外,亦合成二肟二酯8,9,以期能得到更好的切割效果。
合成方法主要是利用氫化鈉拔除2、6兩個肟化合物中羥基質子,再將其與不同對位取代的苯甲醯氯衍生物及1-或2-醯氯進行親核性取代反應。另外,肟化合物4 則是以DMAP和不同對位取代的苯甲醯氯衍生物及1-或2-醯氯進行反應。共合成十九個二肟二酯化合物7-9。目前十三個二肟二酯化合物7a-g、8a-f經清大胡紀如教授實驗室測試其切割DNA之效果,顯示7c-e具有最好的切割效果,且肟酯化合物之結構與切割DNA之效能有密切的關係。
本論文亦探討二肟二酯化合物7a於氮氣下,在二氯甲烷/異丙醇中之光解產物及反應機構。由實驗之結果推測二肟二酯化合物7a於紫外光照射下,其鍵能較弱之氮-氧鍵會均解,形成亞胺自由基及苯甲酸根自由基。亞胺自由基除可自異丙醇中獲得兩個氫原子,而形成anthraquinone 二亞胺 11,另外,亦可水解形成anthraquinone 1﹔而苯甲酸根自由基除可捕捉氫原子形成苯甲酸,亦會脫去二氧化碳形成苯自由基,再捕捉氫原子而形成苯。

Abstract
Our laboratory reported earlier that anthraquinone oxime esters have good photo-induced DNA-cleaving efficiency. This thesis will synthesize dioxime diesters derived from anthraquinone and other diketones with the hope to get better DNA-cleaving agents.
Deprotonation of oximes 2 and 6 with sodium hydride followed by treatment with para-substituted benzoyl chlorides (p-YC6H4COCl; Y = H, CH3, F, NO2, CN), 1- or 2-naphthoyl chloride gave the nucleophilic substitution products 7 and 9. Direct reaction of oxime 4 with DMAP and aroyl chlorides gave the corresponding dioxime diesters 8. Thirteen of these dioxime diesters (7a-g, 8a-f) have been tested for their DNA-cleaving efficiency by Professor J. R. Hwu’s laboratory in National Tsing Hua University. Compounds 7c-e exhibited the best cleaving efficiency among these thirteen compounds. These results also demonstrated that the structures of the dioxime diesters have important effect on the DNA-cleaving efficiency.
The second part of the thesis studies the photocleavage of dioxime diester 7a in CH2Cl2 /i-PrOH under nitrogen. The structures of the products were proven by GC/MS. It is proposed that the weak N-O bond first undergoes a homolytic fission under the UV irradiation to give an iminyl radical and a benzoyloxy radical. The iminyl radical can abstract two hydrogen atoms from isopropanol to form anthraquinone diimine 11, which may be hydrolyzed to anthraquinone 1. The benzoyloxy radical could either capture a hydrogen atom to give benzoic acid, or decarboxylate to give a phenyl radical, which then abstracts a hydrogen atom to give benzene.

中文摘要………………………………………………………i
英文摘要………………………………………………………ii
緒 論……………………….…………………………….. 1
本論文研究目標……………..………………………………..8
結果與討論…………………………………………..……….10
結 論………………………………………………….…..16
使用之儀器、藥品和溶劑………………………………………..17
實驗步驟與光譜數據…………………………………….…..19
參考文獻……………………………………………….….….30

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