設計及合成含藥物之新穎鉑錯合物

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姓名

葉子聖(Tzu-sheng Yeh) 查詢紙本館藏

畢業系所

化學學系

論文名稱

設計及合成含藥物之新穎鉑錯合物
(Design and Synthesis of New Drug-Containing PlatinumComplexes)

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摘要(中)

於本篇論文中，本人發展一系列具有雙重功效的抗癌前驅藥物之新型有機鉑錯合物的合成路徑。此外，本人亦藉由核磁共振光譜儀(NMR)、傅立葉轉換紅外線光譜儀(FTIR)、紫外光光譜儀(UV)之技術來討論Vorinostat (5)、Acetohydroxamic acid (7)、Bufexamac (9) and Hydroxyurea (12)這些抗癌藥物與鉑金屬之間的鍵結，首先Vorinostat (5)經由實驗及光譜證明是以Hydroxamic acid官能基中的N原子與Sulfoplatin (4)之鉑金屬鍵結，Acetohydroxamic acid (7)、Bufexamac (9)這兩個一樣含有Hydroxamic acid官能基的藥物於更進一步的實驗也被證明是以Hydroxamic acid官能基中的N原子與Sulfoplatin (4)之鉑金屬鍵結，Hydroxyurea (12)和前述Vorinostat (5)、Acetohydroxamic acid (7) and Bufexamac (9)三種藥物一樣具有Hydroxamic acid官能基，但是此藥物卻無法和Sulfoplatin (4)反應，而無法得到我們所預期的產物。最後我們合成出新穎鉑錯合物6, 8, 10且發展出以Hydroxamic acid官能基與鉑金屬鍵結的方法，也確定了其鍵結的形式，此類含Hydroxamic acid官能基的藥物預期於將來會有更多更深入的研究與發展。

摘要(英)

A synthetic pathway of novel organoplatinum complex as anti-cancer prodrugs with dual functions was developed. On the other hand, we investigated the binding mod of drugs “Vorinostat (5)、Acetohydroxamic acid (7)、Bufexamac (9) and Hydroxyurea (12)” to platinum metal by NMR(Nuclear magnetic resonance), FTIR(Fourier transform infrared), UV (Ultraviolet) spectroscopy. First the binding mod between Vorinostat (5) and Sulfoplatin (4) was proved by experiments and spectroscopy, Vorinostat (5) binding to Sulfoplatin (4) with nitrogen atom in hydroxamic acid functional group. Acetohydroxamic acid (7) and Bufexamac (9) with hydroxamic acid functional group also show the same binding mod with Sulfoplatin (4) just like Vorinostat (5). Hydroxyurea (12) and the aforementioned drugs “Vorinostat (5), Acetohydroxamic acid (7) and Bufexamac (9)” has the same hydroxamic acid functional group, but it did not work in the same experimental conditions as aforementioned drugs “Vorinostat (5), Acetohydroxamic acid (7) and Bufexamac (9)”, it will be discussed in this contents of my thesis. Furthermore, the platinum complex 6, 8, 10 with hydroxamic acid functional group was expected for more study and investigation in the future.

關鍵字(中)

★ 鉑
★ 藥物

關鍵字(英)

★ drug
★ platinum

論文目次

中文摘要 ..............................................................................................................i
英文摘要 .............................................................................................................ii
謝誌 ....................................................................................................................iii
目錄 ....................................................................................................................iv
圖目錄 ................................................................................................................vi
一、緒論 .........................................................................................................1
二、結果 .........................................................................................................7
2-1 合成具有雙重功效之新穎鉑錯合物 (6)、(8)、(10) ..............................7
2-2 Vorinostat (5)和Sulfoplatin (4)間之鍵結測試 ......................................9
2-3 反應條件測試 .....................................................................................10
三、討論 .......................................................................................................12
3-1 Vorinostat (5)和Sulfoplatin (4)之間鍵結之探討 ................................12
3-2 Hydroxyurea (12)和Sulfoplatin (4)反應之探討 .................................12
3-3 進一步探討Hydroxamic acid官能基和Sulfoplatin (4)之鍵結 ........13
3-4高效能液相層析儀之純度探討............................................................18
四、結論 .......................................................................................................22
五、實驗部份 ...........................................................................................23
(Dimethylsulfoxide-S)(N1-hydroxy-N8-phenyloctane-1,8-diamido-N1)(η2-2-mercaptopyridine N-oxido-O,S)platinum(II) (6)之合成 ..........................24
(Dimethylsulfoxide-S)(N-hydroxyacetamido-N)(η2-2-mercaptopyridine N-oxido-O,S)platinum(II) (8)之合成 ........................................................25
(Dimethylsulfoxide-S)(4-butoxy-N-hydroxybenzeneacetamido-N)(η2-2-mercaptopyridine N-oxido-O,S)platinum(II) (10)之合成 ...............................26
六、參考文獻 ...........................................................................................28
七、光譜 .......................................................................................................31

參考文獻

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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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