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博碩士論文 etd-0707105-101449 詳細資訊
Title page for etd-0707105-101449
論文名稱
Title
抹香鯨(Physeter macrocephalus L.)龍涎香素之化學轉變與生物活性研究
Studies on Chemical Transformation and Biological Activities of Ambrein from Sperm Whale Physeter macrocephalus L.
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
140
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
2005-06-29
繳交日期
Date of Submission
2005-07-07
關鍵字
Keywords
龍涎香素、化學轉變、生物活性
Chemical Transformation, Biological Activities, Ambrein
統計
Statistics
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The thesis/dissertation has been browsed 5645 times, has been downloaded 2268 times.
中文摘要
龍涎香-來自於抹香鯨大腸的一種分泌物,是極重要的動物香水之一。龍涎香內富含一個主要的類固醇脂質成份,其結構為具有三個環的
Abstract
Ambergris, a secretion from the large intestine of the sperm whale, is one of the most important animal perfumes. It is abundant in steroid lipids, the tricyclic triterpene ambrein, a fatty compound bearing some resemblance to cholesterin on considered as one of the main constituents. Ambrein has been used as a stimulant to the circulatory and nervous systems. It has likewise been employed in low grades of fevers and the folk use of this drug as an aphrodisiac is well known. It is more generally used in the preparation of perfumes.

(E)-Ambrein (1) was used as starting material for allylic oxidation with SeO2 / dioxane to yield 15α-hydroxy-(E)-ambrein (2), 15β-hydroxy-(E)-ambrein (3), 27-
hydroxy-(E)-ambrein (4) and 15-oxo-(E)-ambrein (5). Compounds 2, 3 and 4 were modified by benzoylation with benzoyl chloride / pyridine to afford 15α-benzoyl-
(E)-ambrein (6), 15β-benzoyl-(E)-ambrein (7) and 27-benzoyl-(E)-ambrein (8). On the other hand, compound 3 was modified by cyclization with PPTS to give 8α,13-
epoxy-(E)-ambrein (9) and 8α,15-epoxy-(E)-ambrein (10) which were crystallized from CH2Cl2 / MeOH ( 1:10 ). A mixture of compounds 3 and 4 was subjected to oxidation by PCC to produce compound 5. In addition, the absolute configurations of compounds 3 and 4 were determined by Mosher’s method. Moreover, 8β,13-
Epoxy-14-hydroxy-(E)-ambrein (11) and 4-(2,2-dimethyl-6-methylene-cyclohexyl)
-butan-2-one (12) were obtained from photoreaction of 1.

The structures of these modified compounds were determined on the basis of 1D and 2D NMR techniques including 1H-NMR, 13C-NMR, DEPT, COSY, HMQC, HMBC and NOESY experiments and single-crystal X-ray structural analysis. The cytotoxic activities of all the synthetic compounds were determined against Hepa59T / VGH, WiDr, A-549 and MCF-7 cells using the MTT assay. Among the tested compounds, 2 and 5 showed moderate cytotoxic activity against tumor cells. Compound 3 exhibited moderate cytotoxicity against A-549 cells selectively.
目次 Table of Contents
目錄 頁次
臺、緒論
一、前言…………………………………………………………………1
二、抹香鯨之基本資料…………………………………………………3
三、龍涎香研究之文獻回顧……………………………………………5
四、研究動機與展望…………………………………………………11
貳、材料與儀器
一、樣品之來源………………………………………………………12
二、龍涎香素(ambrein)之分離與純化………………………………12
三、結構鑑定之方法與器材
(一)儀器部分…………………………………………………………12
(二)矽膠、溶劑與試劑部分…………………………………………13
參、龍涎香素之修飾反應
一、Allylic位置之氧化反應…………………………………………15
二、醯化反應…………………………………………………………19
三、醚化反應…………………………………………………………22
四、二級醇之氧化反應………………………………………………25
五、照光反應…………………………………………………………27
六、立體結構鑑定之Mosher酯化反應………………………………30
肆、結果與討論
一、結構解析…………………………………………………………33
(一)、(E)-Ambrein (1)之結構解析…………………………………33
(二)、15α-Hydroxy-(E)-ambrein (2)之結構解析…………………37
(三)、15β-Hydroxy-(E)-ambrein (3)之結構解析…………………46
(四)、27α-Hydroxy-(E)-ambrein (4)之結構解析…………………53
(五)、15-Oxo-(E)-ambrein (5)之結構解析………………………60
(六)、15α-Benzoyl-(E)-ambrein (6)之結構解析…………………64
(七)、15β-Benzoyl-(E)-ambrein (7)之結構解析…………………71
(八)、27-Benzoyl-(E)-ambrein (8)之結構解析…………………78
(九)、8α、13-Epoxy-(E)-ambrein (9)之結構解析………………85
(十)、8α、15-Epoxy-(E)-ambrein (10)之結構解析………………93
(十一)、8β、13-Epoxy-14-hydroxy-(E)-ambrein (11)之結構解析………………………………………………………………………101
(十二)、4-(2,2-Dimethyl-6-methylene-cyclohexyl)-butan-2-one (12)之結構解析…………………………………………………109
二、細胞毒殺活性測試………………………………………………112
伍、結論………………………………………………………………115
陸、附錄………………………………………………………………116
柒、參考文獻…………………………………………………………132
參考文獻 References
1. 中國科譜博覽網頁 http://science.yam.com/

2. Mookherjee, B. D.; Patel, R. R., Paper No.137. Kyoto, Japan, 1977, 479-481.

3. http://www.ndcnc.gov.cn/

4. http://hk.geocities.com/

5. 馬蓉池,《海洋世界》-「海洋中的灰色金子:龍涎香」1997年第5期

6. Kovatcheva, A.; Golbraikh, A.; Oloff, S.; Xiao, Y.-D.; Zheng, W.; Wolschann,
P.; Buchbauer, G.; Tropsha, A., J. Chem. Inf. Comput. Sci.2004, 44, 582-595.

7. Stoll, M.; Hinder, M., Helv. Chim. Acta, 1950, 33, 1251-1261.

8. Barco, A.; Benetti, S.; Bianchi, A.; Casolari, A.; Guarneri, M.; Pollini, G. P., Tetrahedron, 1995, 51, 8333-8338.

9. Tanimoto, H.; Oritani, T., Tetrahedron: Asymmetry, 1996, 7, 1695-1704.

10. Hanson, J. R.; Truneh, A., Phytochemistry, 1996, 42, 1021-1023.

11. Akita, H.; Nozawa, M.; Shimizu, H., Tetrahedron: Asymmetry, 1998, 9, 1789-
1799.

12. Akita, H.; Nozawa, M.; Mitsuda, A.; Ohsawa, H., Tetrahedron: Asymmetry, 2000, 11, 1375-1388.

13. Bolster, M. G.; Jansen, B. J. M.; de Groot, A., Tetrahedron, 2001, 57, 5657-
5662.
14. Castro, J. M.; Salido, S.; Altarejos, J.; Nogueras, M.; Sanchez, A., Tetrahedron, 2002, 58, 5941-5949.

15. Horiuchi, S.; Takikawa, H.; Mori, K., Bioorganic & Medicinal Chemistry, 1999, 7, 723-726.

16. Bolster, M. G.; Jansen, B. J. M.; de Groot, A., Tetrahedron, 2001, 57, 5663-
5679.

17. Bolster, M. G.; Lagnel, B. M. F.; Jansen, B. J. M.; Morin, C.; de Groot, A., Tetrahedron, 2001, 57, 8369-8379.

18. de la Torre, M. C.; Garcia, I.; Sierra, M. A., Tetrahedron Letters, 2002, 43, 6351-6353.

19. Dannenfeldt, K. H., Isis, 1982, 73, 382-397.

20. Taha, S. A., J. Pharmaceutical Science, 1989, 2, 105-110.

21. Tanimoto, H.; Oritani, T., Tetrahedron, 1997, 53, 3527-3536.

22. Garcia-Granados, A.; Martinez, A.; Quiros, R., Tetrahedron, 1999, 55, 8567-
8578

23. Taha, S. A.; Ginawi, O. T., Bulletin Faculty of Pharmacy Cairo University, 1993, 31, 113-115.

24. Taha, S. A., Medical Science Research, 1994, 22(2), 97-98.

25. Taha, S. A.; Raza, M.; Gader, A. G. M. A.; Hafeez, M. A., J. Pharmacology, 1995, 67, 205-209.

26. Taha, S. A.; Raza, M.; EI-Khawad, I. E., J. Pharmacology, 1998, 60, 19-26.

27. Rabjohn, N., Org. React, 1976, 24, 261-415.

28. Katsuyama, I.; Fahmy, H.; Zjawiony, J. K.; Khalifa, S. I.; Kilada, W. R.; Konoshima, T.; Takasaki, M.; Tokuda, H., J. Nat. Prod, 2002, 65, 1809-1814.

29. Dale, J. A.; Mosher, H. S., J. Am. Chem. Soc, 1973, 95, 512.

30. Ohtani, I,; Kusumi, T.; Kashman, Y.; Kakisawa, H., J. Am. Chem. Soc, 1991, 113, 4092-4096.
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