我們設計了一系列新型烯雙炔化合物及其衍生物，並評估化合物對於人類腫瘤細胞株抑制的活性。本論文共分成兩部份。第一部份，以化合物6c、6e、6g和7g對於A549(non-small-cell lung cancer)非微小型細胞肺癌、AGS(human stomach adenocarcinoma)人類胃腺癌、PC-3(prostate cancer)攝護腺癌、BT483(breast carcinomas)乳癌、HeLa(human cervical epithelioid carcinoma)子宮頸癌、OVCA(ovarian cancer cell line)卵巢癌、SKHep(hepatocellular carcinoma)肝癌、H460 (human lung cancer cell line)肺癌和SW620(Human Colorectal Cancer Cell Line)結腸癌等這九種腫瘤細胞株有較好的抑制效果，特別是化合物7g活性最好，平均IC50為8.79μM。第二部份，以化合物25a跟化合物26的活性最好，平均IC50分別為10.82和11.08 μM，對於HeLa子宮頸癌癌細胞株、OVCA卵巢癌癌細胞株、AGS胃腺癌和 H460肺癌癌細胞株皆有不錯的活性。

We designed a new series of enediyne and their derivatives, and evaluating for their growth inhibition activity against human tumor cell lines. This dissertation is composed of two parts. First, compounds 6c, 6e, 6g and 7g displayed good growth inhibition activity against A549 (non-small-cell lung cancer), AGS (human stomach adenocarcinoma), PC-3 (prostate cancer), BT483 (breast carcinomas), HeLa (human cervical epithelioid carcinoma), OVCA (ovarian cancer cell line), SKHep (hepatocellular carcinoma), H460 (human lung cancer cell line) and SW620 (Human Colorectal Cancer Cell Line), especially compound 7g is better, and its average IC50 is 8.79μM. Second, compounds 25a and 26 displayed better growth inhibition activity against HeLa (human cervical epithelioid carcinoma),
OVCA (ovarian cancer cell line), AGS (human stomach adenocarcinoma) and H460 (human lung cancer cell line), and their average IC50 are10.82 and 11.08 μM.

第一章 緒論
1-1. 前言………...……………………………………………………….1
1-2. 細胞週期…………...……………………………………………….2
1-3. 有絲分裂抑制劑…………………...……………………………….5
1-4. Combretastatin A-4…………………………………...……………..9
1-5. 新型烯雙炔………………………………………………………..11

第二章 合成具有烯雙炔結構之Combretastatin A-4衍生物(I)
2-1. 研究動機…………………...……………………………………...21
2-2. 化學合成……………………...…………………………………...23
2-3. 生物活性探討………………………...…………………………...26
2-4. 結論………………………...……………………………………...29

第三章 合成具有烯雙炔結構之Combretastatin A-4衍生物(II)
3-1. 前言…………………………………………...…………………...30
3-2. 研究動機……………………………………...…………………...34
3-3. 化學合成……………………………………...…………………...36
3-4. 生物活性探討………………………………...…………………...41
3-5. 結論……………………………...………………………………...44

第四章 參考文獻……………………...……………………………….45

第五章 化合物的製備方法
5-1. 儀器部分……………………….………………………………….48
5-2. 實驗部分…………………………………………………………..50
方法A. 甲基化反應……………………………………………………50方法B. Sonogashira偶合反應………………………………………….51
方法C. 去矽反應………………………………………………………52
方法D. 去矽偶合反應…………………………………………………55
(Z)-5-(6-(2-Aminophenyl)hexa-3-en-1,5-diynyl)-2-methoxybenzenamine
(6a)…………………...…………………………………………………55
(Z)-2-Methoxy-5-(6-(pyridin-2-yl)hexa-3-en-1,5-diynyl)benzenamine
(6b)……………………………………………………………………...56
(Z)-2-Methoxy-5-(6-(2-methoxyphenyl)hexa-3-en-1,5-diynyl)
benzenamine (6c)..……………….………………………….…….……57
(Z)-2-Methoxy-5-(6-(pyrazin-2-yl)hexa-3-en-1,5-diynyl)benzenamine
(6d)……………………………………………………………………...58
(Z)-2-Methoxy-5-(6-(2-(methylthio)phenyl)hexa-3-en-1,5-diynyl)
benzenamine (6e).………………………..……………………………..59
(Z)-2-Methoxy-5-(6-(2-(trifluoromethyl)phenyl)hexa-3-en-1,5-diynyl)
benzenamine (6f)…………………………………..…………...………60
(Z)-2-Methoxy-5-(6-(2-nitrophenyl)hexa-3-en-1,5-diynyl)benzenamine
(6g)……………………………………………………………………...61
(Z)-2-(6-(3-Amino-4-methoxyphenyl)hexa-3-en-1,5-diynyl)
benzonitrile (6h)…………..……………………..……………………..62
(Z)-5-(6-(2-Aminophenyl)hexa-3-en-1,5-diynyl)-2-methoxy-N,N-dimethylbenzenamine (7a)…………......…………………………………..……62
(Z)-2-Methoxy-N,N-dimethyl-5-(6-(pyridin-2-yl)hexa-3-en-1,5-diynyl)
benzenamine (7b)…………………………..…………………………..63
(Z)-2-Methoxy-5-(6-(2-methoxyphenyl)hexa-3-en-1,5-diynyl)-N,N-
dimethylbenzenamine (7c)……...…………………..………………….64
(Z)-2-Methoxy-N,N-dimethyl-5-(6-(pyrazin-2-yl)hexa-3-en-1,5-diynyl)
Benzenamine (7d)……………………..………………………………..65
(Z)-2-Methoxy-N,N-dimethyl-5-(6-(2-(methylthio)phenyl)hexa-3-en-1,5-
diynyl)benzenamine (7e)…………………….………………………….65
(Z)-2-Methoxy-N,N-dimethyl-5-(6-(2-(trifluoromethyl)phenyl)hexa-3-en-1,5-diynyl)benzenamine (7f)……………………………...…………….66
(Z)-2-Methoxy-N,N-dimethyl-5-(6-(2-nitrophenyl)hexa-3-en-1,5-diynyl)
benzenamine (7g)..……………………………………………..………67
(Z)-2-(6-(3-(Dimethylamino)-4-methoxyphenyl)hexa-3-en-1,5-diynyl)
benzonitrile (7h)…………………………………………..……………68
(Z)-2-(6-(3,5-Dimethoxyphenyl)hexa-3-en-1,5-diynyl)benzenamine
(25a)……………………...……………………………………………..75
(Z)-2-(6-(3,5-Dimethoxyphenyl)hexa-3-en-1,5-diynyl)pyridine (25b)...76
(Z)-1,3-Dimethoxy-5-(6-(2-methoxyphenyl)hexa-3-en-1,5-diynyl)benzene (25c)………………….………………………………………………..77
(Z)-2-(6-(2,5-Dimethoxyphenyl)hexa-3-en-1,5-diynyl)benzenamine
(25d)…………………………………………………………………….77
(Z)-2-(6-(2,5-Dimethoxyphenyl)hexa-3-en-1,5-diynyl)pyridine (25e)....78
(Z)-1,4-Dimethoxy-2-(6-(2-methoxyphenyl)hexa-3-en-1,5-diynyl)benzene (25f)….………………………………………………………………..79
(Z)-2-(6-(2,6-Dimethoxyphenyl)hexa-3-en-1,5-diynyl)benzenamine
(25g)……………………………………………………..……………...80
(Z)-2-(6-(2,6-Dimethoxyphenyl)hexa-3-en-1,5-diynyl)pyridine (25h)....80
(Z)-1,3-Dimethoxy-2-(6-(2-methoxyphenyl)hexa-3-en-1,5-diynyl)benzene (25i)…………………..………………………………………………..81
(Z)-3-(6-(3,4,5-Trimethoxyphenyl)hexa-3-en-1,5-diynyl)pyridin-2-amine
(26)……………………………………………………………………...82
(Z)-N,N-Dimethyl-2-(6-(3,4,5-trimethoxyphenyl)hexa-3-en-1,5-diynyl)
benzenamine (28)…………………………...…………………………..83
(Z)-2-Methoxy-6-(6-(3,4,5-trimethoxyphenyl)hexa-3-en-1,5-diynyl)
pyridine (27)……………………...…………………………………..…87

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