中文摘要

本論文主要之研究目的在於分析採集自綠島的竹珊瑚Isis hippuris及採集自澎湖的海筆珊瑚Virgularia ncea的有機粗萃物的化學組成成分，從竹珊瑚I. hippuris中分離出2個新的固醇類化合物，分別是hippuristerone A (1) 及hippuristerone E (2)，和其他3個已知的固醇類化合物3β-hydroxy-5α-pregnan-20-one (3)、prenga-4-ene-3,20-dione (4) 與prenga-1,4-diene-3,20-dione (5)、以及1個已知的sesquiterpene類化合物subergorgic acid (6)，另外在海筆珊瑚V. juncea中分離出1個新的sesquiterpene類化合物junceol A (7)，2個已知的diterpene類化合物 sclerophytin A (8)、cladiellisin (9)，及1個固醇類化合物24-methylenecholesterol (10)。化合物1-10的結構均是經由物理資料(熔點、旋光度)以及各類型的圖譜測試之後加以整合解析，再配合相關文獻資料的比對之後而建立；此外，hippuristerone A (1)的結構及相對立體構型經由X-ray單晶繞射解析做進一步的印證，hippuristerone B (2)的相對立體構型則是經由化學動力計算(chemical dynamics calculations)的方法做了進一步的確認。

Abstract

In our continuing studies on the chemical constituents of Taiwanese octocorals, the gorgonian coral Isis hippuris and the sea pen coral Virgularia juncea, which were collected from the coast of Green Island and Peng-Hung Islands, respectively, have been the subjects of our investigations. Six compounds, including two new steroids, hippuristerones A and E (1 and 2), along with three known steroids 3β-hydroxy-5α-pregnan -20-one (3), prenga-4-ene-3,20-dione (4), prenga-1,4-diene-3,20-dione (5) and a known sesquiterpene subergorgic acid (6) were isolated from I. hippuris. Four compounds, incoulding a new sesquterpene, junceol A (7) and two known diterpenoids, sclerophytin A (8), cladiellisin (9) and a known steroid 24-methylenecholesterol (10) were isolated from V. juncea.
The structures of above isolates were determined by physical (mp and optical rotation) and extensive spectral (UV, IR, MS, HRMS, 1D and 2D NMR) analysis and by comparison with the related physical and spectral data from other known compounds. The structure, including the relative configuration of hippuristerone A (1) was further confirmed by a single-crystal X-ray analysis.Furthermore, the relative configuration of hippuristerone E (2) was supported by the chemical dynamics calculations.

目錄

目錄 I
圖目錄 III
表目錄 V
中文摘要 1
英文摘要 2

壹、緒論
一、研究之重要性及目的 4
二、竹珊瑚Isis hippuris天然物化學研究概況 7
三、海筆珊瑚Virgularia juncea天然物化學研究概況 13
貳、結果與討論
一、竹珊瑚Isis hippuris的成分研究
2-1-1化合物hippuristerone A (1) 15
2-1-2化合物hippuristerone B (2) 24
2-1-3化合物3β-hydroxy-5α-pregnan-20-one (3) 34
2-1-4化合物prenga-4-ene-3,20-dione (4) 39
2-1-5化合物prenga-1,4-diene-3,20-dione (5) 43
2-1-6化合物subergorgic acid (6) 47
二、海筆珊瑚Virgularia juncea 的成分研究
2-2-1化合物junceol A (7) 51
2-2-2化合物sclerophytin A (8) 60
2-2-3化合物cladiellisin (9) 68
2-2-4化合物24-methylenecholesterol (10) 71
參、生物材料與分離方法 77
一、竹珊瑚Isis hippuris部份 77
3-1-1 生物樣品材料採集時間與地點
3-1-2生物樣品的型態與分類
3-1-3萃取與純化分離步驟
二、海筆珊瑚Virgularia juncea部份
3-2-1生物樣品材料採集時間與地點 80
3-2-2生物樣品的型態與分類
3-2-3 萃取與純化分離步驟
肆、癌細胞毒殺活性測試
4-1測試採用之癌細胞株 82
4-2培養基及試劑
4-3活性測定實驗程序
伍、結論 83
陸、參考文獻 87
附錄一 竹珊瑚Isis hippuris 分離流程圖 附錄二 海筆珊瑚Virgularia juncea 分離流程圖 9192

陸、參考文獻
1. Ruggieri, G. D.; Science, 1976, 194, 491-497.
2. Faulkner, D. J.; Nat. Prod. Rep, 2000, 18, 1-49.
3. 方力行；“珊瑚學”，教育部大學聯合出版委員會，1989，34-37。
4. 戴昌鳳；“台灣的軟珊瑚”；台灣省政府教育廳，1989。戴昌鳳；“我國珊瑚生物學研究發展”；生命科學簡訊，1993，2-6。
5. Groweissz, A.; Fenical, W.; Cun-heng, H.; Clardy, J.; Zhongde, W.; and Kanghpu, L.; Tetrahedron Lett, 1985, 26, 2379-2382.
6. Sheu, J. H.; Sung, P. J.; Cheng, M. C.; Liu, H.Y.; Fang, L. S.; Duh, C. Y. and Chiag, M. Y.; J. Nat. Prod, 1998, 61, 602-608.
7. Sung, P. J.; Su, J. H.; Wang, G. H.; Lin, S. F.; Duh, C. Y. and Sheu, J. H.; J. Nat. Prod, 1999, 62, 457-463.
8. Sheu, J. H.; Sung, P. J.; Su, J. H.; Wang, G. H.; Duh, C. Y.; Shen, Y. C.; Chiag, M. Y.; Chen, I. T.; J. Chem. Soc. Perkin Trans.1,1998, 1959-1965.
9. Sheu, J. H.; Sung, P. J.; Huang, L. H.; Lee, S. F.; Wu, T.; Chang, B. Y.; Duh, C. Y.; Fang, L.S. K. Soong and. Lee, J.J.; J. Nat. Prod, 1996, 59, 935-938.
10. Schmitz, F. J.; Schulz, M. M.; Siripitayananon, J.; Hossain, M. B.; and Helm, D. V.; J. Nat. Prod, 1993, 56, 1339-1349.
11. Coval, S. J.; Cross, S.; Bernardinelli, G. And Jefford, C. W.; J. Nat. Prod, 1988, 51, 981-984.
12. Pordesimo, E. O.; Schmitz, F. J.; Ciereszko, L. S.; Hossain, M. B.; Helm, D.V.; J. Org. Chem, 1991, 56, 2344-2357.
13. Kobayashi, J.; Cheng, J. F.; Nakamura, H.; Ohizumi, Y.; Timitake, Y.; Matsuzaki, T.; Grace, K. L. S.; Jacos, R. S.; Kato, Y.; Brinre, L.; Experientia, 1991, 47, 501-502.
14. Hamann, M. T.; Harrison, K. N.; Carroll, A. R.; Scheuer, P. J.; Heterocycles, 1996, 42, 325-331.
15. Keifer, P. A.; Rinehart, K. L.; Hooper, I. R.; J. Org. Chem, 1986, 51, 4450-4454.
16. Grode, S. H.; James, T. R.; Cardellina, J. H.; J. Org. Chem, 1983, 48, 5203-5207.
17. Hendrickson,R. L.; Cardellina, J. H.; Tetrahedron, 1986, 42, 6565-6570.
18. 戴昌鳳；“墾丁國家公園-珊瑚之美”； 墾丁國家公園管理處員工消費合作社出板，屏東，中華民國，1987, p9-16
19. Kazlauskas, R.; Murphy, P. T.; Qumn, R. J.; Wells, R. T.; Trtrahedron Lett, 1977, 50, 4439-4442.
20. Ling, N. C.; Hole, R. L.; Djerassi, C.; J. Am. Chem. Soc, 1970, 92, 5281-5283.
21. Higa, T.; Tachibana, K.; Tanaka, J.; Tetrahedron Lett, 1981, 22, 2777-2780.
22. Van Antwerp, C. L.; Eggert, H.; Meakins, G. D.; Miners, J. O.; Djerassi, C.; J. Org. Chem, 1977, 42, 789-791.
23. Rao, C. B.; Rao, D. V.; Ramana, K. V.; Fahy, E.; Faulkner, D. J.; J. Nat. Prod, 1988, 22, 2777-2780.
24. Higa, T.; Kikuchi, H.; Tanaka, J.; Tsukitani, Y.; Chemistry Lett, 1981, 11, 1647-1650.
25. Tanaka, J.; Higa, T.; Iwashita, T.; Tachibana, K.; Chemistry Lett, 1982, 8, 1295-1296.
26. Kobayashi, M.; Hayashi, T.; Nakajima, F.; Mitsuhashi, H.; Steroids, 1979, 34, 285-290.
27. Sheu, J. H.; Hung, K. C.; Sung, P. J.; Chiang, M. Y.; Dai, C. F.;
J. Nat. Prod, 2000, 63, 1603-1607.
28. Anjaneyulu, A. S. R.; Prakash, C. V. S.; Mallavadhani, U. V. S.; J. Indian Chem. Soc, 1992, 69, 150-152.
29. Anjaneyulu, A. S. R.; Prakash, C. V. S.; J. Indian Chem. Soc, 1994, 33B, 55-58.
30. Costantino, V.; Aversano,; Helv, 1946, 29, 33.
31. Plattner, Pl. A.; Heusser, H.; Angliker, E.; Helv,1946, 29, 468.
32. Kubota, T.; yoshiha, K .; Hay, C. D.; Fattorusso, E.; Mangoin, A .; Steroids, 2000, 65, 138-142.
33. Meystre, Ch.; Miescher, H.; Hshi, F.; Takeda, K.; Chem. Pharm. Bull, 1965, 13, 50-57.
34. Sondheimer, F.; Velasco, M.; Rosenkranz, G.; J. Am. Chem. Soc, 1955, 77, 5673-5676.
35. Barton, D. H. R.; Boivin, J.; Hill, C. H.; J. Chem. Soc. Perkin Trans. I, 1986, 1797-1804.
36. Parameswaran, P. S.; Naik, C. G.; Kamat, S. Y.; Puar, M. S.; Das, P.; Hegde, V. R.; J. Nat. Prod, 1998, 61, 832-834,1074.
37. For significant activity of pure compounds, an ED50 value of ≦4.0
μg / mL is required. Geran, R. I.; Greenberg, N. H.; MacDonald, M. M.; Schumacher, A. M.; Abbott, B.; J. Carcer Chemother. Rep, 1972, 3, 1-91.
38. Alley, M. C.; Acudiero, D. A.; Monks, A.; Huresy, M. L.;
Czerwinski, M. J.; Fine, D. L.; Abbott, B. J.; Mayo, J. G.;
Shoemark, R. H.; Boyd, M. R.; Cancer Res, 1988, 48, 589-601.
39. Sheu, J. H.; Liaw, C. C.; Duh, C. Y.; J. Nat. Prod, 1995, 58,
1521-1526.
40. Sharma, P.; Alam, M. J.; Chem. Soc. Perkin. Trans.1, 1988, 2537-
2540.
41. Alam, M.; Sharma, P.; Zektzer, A. S.; Martin, G. E.; Ji, X.;
van der Helm, D.; J. Org . chem, 1989, 54, 1896-1900.
42. Liu, J.; Zeng, L.; Wu, D.; Chin. Sci. Bull., 1992, 37, 1627-1630.
43. Yamada, K.; Ogata, N.; Ryu, K.; Miyamoto, T.; Komori, T.;
Higuchi, R.; J. Nat. Prod, 1997, 60, 393-396.
44. Idler, D. R.; Fagerlund, U. H. M.; J. Am. Chem. Soc, 1955, 77,
4142.
45. Duh, C. Y;. Wang, S. K.; Chu, M. J.; Dai, C. F.; Sheu, J. H.;
J. fish Soc. Taiwan, 1997, 24, 127.
46. Goad, L. J . in marine Natural Products-chemical and biological Perspectives, Vol II; Scheuer, P. J. Ed.; academic Press; London, 1981; Chapter 2.
47. Sheu, J. H.; Chang, K. C.; Sung, P. J.; Duh, C.Y.; Shen, Y. C.;
J. Chin. Chem. Soc, 1999, 46, 253-257.
48. Gonzalez, N.; Barral, M. A.; Rodriguez, J.; Jimenez, J.; Tetrahedron,
2001, 57, 3487-3497.