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中文論文名稱 含硼之胜肽衍生物合成與其生物活性之評估(I); 含硼之異腈衍生物之合成(II)
英文論文名稱 Synthesis and Biological Evaluation of Boron-Containing Peptide-Based Analogues(I); Synthesis of Boron-Containing Isocyanide Analogues(II)
校院名稱 淡江大學
系所名稱(中) 化學學系碩士班
系所名稱(英) Department of Chemistry
學年度 100
學期 2
出版年 101
研究生中文姓名 蔡佳驊
研究生英文姓名 Chia-Hua Tsai
學號 699160411
學位類別 碩士
語文別 中文
口試日期 2012-07-02
論文頁數 186頁
口試委員 指導教授-潘伯申
委員-王三郎
委員-黃俊誠
中文關鍵字 硼酸  硼酯  三氟硼酸  蛋白酶  胜肽  抗癌  異腈 
英文關鍵字 boronic acid  boronic ester  trifluoroborate  protease  proteasome  peptide  anti-cancer  isocyanide 
學科別分類 學科別自然科學化學
中文摘要 含硼之胜肽衍生物合成與其生物活性之評估(I)
本論文設計與合成了一系列含硼胜肽化合物。此類化合物可以以簡單的合成方法製備與純化。並且成功合成出系列A 與系列B 之含硼胜肽化合物。
本研究使用了HepG2(肝癌)和MDA-MB231(乳癌)兩種癌細胞,來評估所合成之化合物的抗癌能力。藉由改變含硼化合物之結構來探討分子結構與生物活性之關係。由實驗結果發現,化合物A-07、A-08、A-09、A-11、A-12 對於HepG2 癌細胞具有抑制的效果。
B-38、B-41、B-42 對MDA-MB231 細胞具有抑制效果,其中B-41、B-42 對HepG2 細胞亦具有抑制效果。含硼胜肽化合物之活性測試中,發現(a)取代基對於抑制效果具有重要的影響;(b)在對照組與三種含硼官能基比較中,又以三氟硼酸的抑制效果最好。

含硼之異腈衍生物之合成(II)
本論文設計與合成了含硼異腈化合物。經由一系列合成步驟後,可得到最終產率為
58%。
英文摘要 Synthesis and Biological Evaluation of Boron-Containing
Peptide-Based Analogues(I)
In this research, we have designed and synthesized two series of boron-containing analogues. These compounds could be easily synthesized and purified via simple synthetic operations. In addition, MTT assay was applied to evaluate their biological potencies against HepG2 (liver cancer), and MDA-MB231 (drug resistant breast cancer).
Compounds A-07, A-08, A-09, A-11 and A-12 potent against HepG2(liver cancer) cell line. B-38, B-41, B-42 are active against MDA-MB231(drug resistant breast cancer) cell line and B-41, B-42 are potent against HepG2 cancer cell line. The structure-activity relationship (SAR)indicated that compounds possess lager side chain were generally more potent against either HepG2 or MDA-MB231 cell lines. In addition, inclusion of a potassium trifluoroborate was essential to the compound’s biological activity. In summery, inclusion of a phenylalanine at position 2, a benzyl-protected serine at position 3 and a potassium trifluoroborate generated the most potent compound (B41) against HepG2 and MDA-MB231 cell lines.

Synthesis of Boron-Containing Isocyanide Analogues(II)
In the second project, we have designed and synthesized boron-containing isocyanide. The overall yield was 58% over 9 steps synthetic operations. More boron-containing isocyanide derivatives were being synthesized and their biological evaluation will be reported in due course.
論文目次 謝誌 I
中文摘要 II
英文摘要 IV
目錄 VI
圖表目錄 IX
附圖目錄 XIV
含硼之胜肽衍生物合成與其生物活性之評估(I) ...................... 1
Chapter 1 前言 ........................................... 1
1–1 硼化學簡介 ............................................ 2
1–2 含硼化合物在有機合成上的應用 ............................. 6
1–3 含硼化合物在藥物化學上的應用 ............................. 7
1–4 含硼化合物在酵素抑制上之運用 ............................. 8
1–5 三氟硼酸化合物抑制機制介紹 .............................. 17
Chapter 2 結果與討論 ..................................... 19
2–1 硼胜肽合成策略 ....................................... 19
2–2 胜肽骨架的合成 ........................................ 20
2–3 系列A 的合成 ......................................... 23
2–4 系列B 的合成 ......................................... 26
2–5 生物活性測試 .......................................... 31
2–5–1 含硼胺基酸化合物 ..................................... 32
2–5–2 含硼雙胜肽化合物 ..................................... 34
2–5–3 含硼參胜肽化合物 ..................................... 35
2–6 結論 ................................................ 38
含硼之異腈衍生物之合成(II) .................................. 39
Chapter 3 前言 .......................................... 39
3–1 異腈化學探討........................................... 41
3–2 異腈合成 ............................................. 44
3–3 多組成反應簡介 ........................................ 48
3–4 多組成反應的歷史回顧 ................................... 49
3–5 含硼異腈介紹 .......................................... 52
Chapter 4 結果與討論 ..................................... 54
4–1 合成策略 ............................................ 54
4–2 含硼異腈之合成 ........................................ 54
4–3 結論 ................................................ 61
Chapter 5 藥品、實驗步驟與儀器 ............................. 62
5–1 反應試劑介紹 .......................................... 62
5–2 使用藥品 ............................................. 64
5–3 實驗儀器與測試方法 ..................................... 66
5–4 含硼胜肽實驗步驟 ....................................... 68
5–5 含硼胜肽光譜部分 ....................................... 73
5–6 生物活性評估使用之細胞介紹 .............................. 92
5–7 含硼異腈實驗步驟 ....................................... 93
附錄一 參考資料 ........................................... 98
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