合成醯胺鍵結苯并咪唑與香豆素之化合物並探討其構形

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姓名

邱柏銘(Bo-Ming Ciou) 查詢紙本館藏

畢業系所

化學學系

論文名稱

合成醯胺鍵結苯并咪唑與香豆素之化合物並探討其構形
(Synthesis of Benzimidazole–Coumarin Conjugates withAmide Linkers and Study on Their Conformation)

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摘要(中)

依據世界衛生組織(WHO)統計，全球約有1 億7 千萬人口感染C 型肝
炎病毒(Hepatitis C Virus, HCV)，台灣亦有92 萬人口為C 型肝炎病患，HCV造成日益嚴重的肝臟疾病。故我們希望合成出具有抗C 型肝炎病毒潛力的化合物，並進一步討論其合成條件與立體結構。我們合成出化合物coumarin carboxylic acids 與benzoimidazol-2-amines 後利用耦合試劑進行醯胺鍵結的合成。使用不同的耦合試劑與活化試劑如：carbodiimide 類型的DCC 與EDCI（WSCI）和Aminium-base reagent 的HBTU 加上活化試劑1-Hydroxybenzotriazole（HOBt）與N-Hydroxysuccinimide（NHS or HOSu）合成所需的醯胺官能基。並藉由核磁共振之氫譜（1H NMR）、質譜儀（FAB Mass）與紅外線光譜（FTIR）判定我們所合成出化合物的結構。並使用核磁共振之氫譜（1H NMR）與分子模擬軟體討論其立體結構而得知化合物的構型。此結果可幫助我們討論結構與活性關係（SAR）時的參考依據。

摘要(英)

According to the World Health Organization (WHO) statistics, about 170 million people infected with hepatitis C virus (HCV), and in Taiwan is also a population of 920,000 patients with hepatitis C, HCV causes more serious liver disease. So we hope that synthesis has the potential of anti-hepatitis C compounds, and further more discuss the synthesis conditions and
stereo structure. First, we synthesized coumarin carboxylic acid and benzoimidazol-2-amine
then using coupling reagents for amide bond formation. Using different coupling reagents
and activation reagents, such as carbodiimide type of DCC and EDCI (WSCI) and Aminium-base reagent HBTU with activated reagents, 1-hydroxybenzotriazole (HOBt) and
N-hydroxysuccinimide (NHS or HOSu) to prepare the required amide functional groups.We used nuclear magnetic resonance spectra of hydrogen (1H NMR), mass spectrometry
(FAB Mass) and infrared spectroscopy (FTIR) to confirm our compounds. Then we used 1H NMR and molecular simulation to discuss the stereo structure and conformation. The results
can help us to discuss the structure and activity relationship (SAR).

關鍵字(中)

★ 苯并咪唑

關鍵字(英)

★ Benzimidazole

論文目次

中文摘要 ……………………………………………………………………..i
英文摘要 …………………………………………………………………….ii
謝誌 …………………………………………………………………………iii
目錄 …………………………………………………………………………iv
圖目錄 ………………………………………………………………………vi
表目錄 ………………………………………………………………………vii
一、緒論 ………………………………………………………………….1
二、結果 ………………………………………………………………….5
2-1 合成具有不同官能基之coumarin-3-carboxylic acid (4a–4e)….5
2-2 合成Coumarin carboxamide 前驅物…………………………...6
2-3 合成1H-Benzimidazol-2-amine化合…………………………...6
2-4 合成2-[(Coumarin-3'-carbonyl)amino]benzimidazole..…………7
2-5 合成2-[(Coumarin-3'-carbonyl)amino]benzimidazole
不同反應試劑與當量數的控制 .……………………………...10
三、討論 …………………………………………………………………13
3-1 利用NMR光譜判定產物8a–8h之結構 ……………………..14
3-2 利用FT-IR判定產物8a–8h之結構 ………………………….15
3-3 利用分子模擬預測產物8a–8h之結構 ……………………….17
3-4 利用分子模擬討論不同Linker與立體結構關係………………19
3-5 探討合成2-[(Coumarin-3'-carbonyl)amino]benzimidazole
之最佳化條件………..…………………………………………..21
四、結論 …………………………………………………………………..25
五、實驗部分 …………………………………………………………...26
2-[(Coumarin-3'-carbonyl)amino]benzimidazole (8a) …...…………......27
2-[(Coumarin-3'-carbonyl)amino]-5,6-dimethylbenzimidazole (8b)……28
2-[(6'-Methylcoumarin-3'-carbonyl)amino]benzimidazole (8c)……..….28
2-[(6'-Methylcoumarin-3'-carbonyl)amino]-5,6-dimethyl
benzimidazole (8d)……………………………………….……………...29
2-[(6'-Methoxycoumarin-3'-carbonyl)amino]benzimidazole (8e)……….29
2-[(6'-Methoxycoumarin-3'-carbonyl)amino]-5,6-dimethyl
benzimidazole (8f)…………………………………………………….…30
2-([7-(diethylamino)coumarin-3'-carbonyl]amino)benzimidazole(8g).....30
2-([7-(diethylamino)coumarin-3'-carbonyl]amino)-5,6-dimethyl
benzimidazole (8h)……………………………………………….……...31
六、參考文獻 …………………………………………………………...32
七、光譜 …………………………………………………………………...37

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指導教授

胡紀如(Jih-Ru Hwu)

審核日期

2010-7-16

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