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博碩士論文 etd-0823110-165622 詳細資訊
Title page for etd-0823110-165622
論文名稱
Title
設計具有吡嗪基[2,1-b]喹唑啉-3,6-雙酮和四氫異喹啉結構之抗癌藥物
Design of Anticancer Agents Based on the Tetrahydroisoquinoline Alkaloids Containing a Pyrazino[2,1-b]quinazoline-3,6-diones structure
系所名稱
Department
畢業學年期
Year, semester
語文別
Language
學位類別
Degree
頁數
Number of pages
117
研究生
Author
指導教授
Advisor
召集委員
Convenor
口試委員
Advisory Committee
口試日期
Date of Exam
2010-05-26
繳交日期
Date of Submission
2010-08-23
關鍵字
Keywords
吡嗪基、四氫異喹啉生物鹼、比特-史賓格勒環化反應、喹唑啉、抗癌活性、生物活性、喹唑酮
Tetrahydroisoquinoline alkaloids, pyrazino, quinazoline, Pictet-Spengler cyclization, biological activity, quinazolinone, anti-tumor activity
統計
Statistics
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中文摘要
四氫異喹啉生物鹼是一類結構複雜且數量龐大的天然物,其天然
物廣存於自然界當中,從發現至今已超過了一個世紀,因此類化合物
具有很好的抗腫瘤活性、抗菌和其他生理活性,也因為其結構特殊,
與其低濃度的生物活性,但是此類生物鹼卻無法在市面上販售,主要
原因來是自然界萃取量少,且以化學合成方式步驟多、產率低。因此
我們建構了結合四氫異喹啉生物鹼及吡嗪基[2,1-b]喹唑啉-3,6-雙
酮結構的新型化合物,而這些具有喹唑酮結構的化合物在於藥物合成
和藥物鍵結活性上,亦為一種獨特又廣泛使用的藥物結構,引起了很
多科學家及藥物研究上的興趣與討論,成為我們所開發的動機。
Abstract
Tetrahydroisoquinoline alkaloids are a class of structurally complex natural products and a huge number of its natural product widely exist in nature which, from the discovery has been more than a century, it compounds with high anti-tumor activity, antibacterial and other physical activity, but also because of its special structure, with low oncentration of biological activity, but these alkaloids are not sold in the market mainly due to a less natural extraction, chemical synthesis method and multi-step, low yield.
Therefore, we constructed a combination of tetrahydroisoquinoline alkaloids and the pyrazino [2,1-b] quinazoline-3,6-diones structure of the new compounds, which have the quinazolinone compounds which is the drug synthesis and drug activity on the bond, is also a kind of unique and widely
used drug structure, and causes a lot of scientists and drug research interest and discussion, as we develop the motivation.
目次 Table of Contents
第一章: 具四氫異喹啉結構之天然物……………………………………1
1.0 前言……………………………………………………………………..1
1.1 具有四氫異喹啉結構之天然物………………………………………2
1.2 生物活性…………………………………………………………………6
1.3 藥物作用機轉…………………………………………………………..16
1.4 四氫異喹啉生物鹼之合成研究………………………………………18
1.4.1 The Saframycins…………………………………………………...19
1.4.1.1 Fukuyama 對於(±)-Saframycin B 的全合成研究…………..19
1.4.1.2. Kubo 對於(±)-Saframycin B 的全合成研究…………….…23
1.4.1.3. Fukuyama 對於(±)-Saframycin A 的全合成研究…………26
1.4.1.4. William 對於Saframycins 的合成探討……………..…..…28
1.4.1.5. Corey 對於(-)Saframycin A 鏡向選擇性的合成研究……31
1.4.2 The Renieramycins………………………………………………..33
1.4.3 Danishefsky 對於Cribrostatin IV (Renieramycin H)的
合成研究…………………………………………………………….35
1.5 結論……………………………………………………………………39
1.6 參考文獻………………………………………………………...……..40
第二章: 具有喹唑酮及吡嗪基[2,1-b]喹唑啉-3,6-雙酮結構之
天然物…………………………………………………………..……..42
2.0 前言……………………………………………………………..………42
2.1 具有喹唑酮和吡嗪基[2,1-b]喹唑啉-3,6-雙酮結構之天然
物及其類似物……………………………………………………..….44
2.2 具有喹唑酮和吡嗪基[2,1-b]喹唑啉-3,6-雙酮化合物的合
成研究……………………………………………………………….…48
2.2.1 Fumiquinazolines 的合成研究………………………………...48
2.2.2 N-acetylardeemin 的合成研究…………………………………52
2.2.3 具苯二氮焯(benzodiazepine)骨架之生物鹼………………...54
2.3 生物活性……………………………………………….………………61
2.3.1 N-acetylardeemin 可做為抗藥性調控劑…………………….61
2.3.2 Evodiamine 的生物活性…………………………………………63
2.3.3 Fiscalins A, B, C可作為物質P 的拮抗劑…………………64
2.3.4 Asperlicin可用來治癒腸胃道疾病及中樞神經失調……….65
2.3.5 具喹唑酮結構相關化合物的生物活性研究…………………..67
2.4 結論……………………………………………………………………72
2.5 參考文獻………………………………………………………………73
第三章: 設計具有吡嗪基[2,1-b]喹唑啉-3,6-雙酮和四氫異
喹啉結構之抗癌藥物…………………………………………..76
3.0 合成動機……………………………………………………………….76
3.1 合成策略……………………………………………………………….79
3.2 合成與討論…………………………………………………………….81
3.3 生物活性……………………………………………………………….87
3.4 結論…………………………………………………………………….89
第四章:實驗部份…………………………………………………………..90
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