在過去的研究中，從軟珊瑚Sinularia和Clavularia屬中發現過許多不同骨架和具有生物活性的二次代謝物，因此我們主要針對軟珊瑚Sinularia erecta和Clavularia viridis中所包含的化學成分進行研究。在我們研究海洋生物二次代謝物的過程中，從採集自澎湖的指形軟珊瑚(Sinularia erecta)之丙酮萃取物，分離到一個新的cyclic peroxide-containing sesquiterpene類化合物，並命名為sinularioperoxide F (1) 、一個nor-monoterpene類化合物(2)，命名為sinuladione、兩個新骨架化合物sinulariatricyclo A 和 B (3和4)和三個已知的cyclic peroxide-containing sesquiterpenes類化合物，sinularioperoxide A (5)、sinularioperoxide C (6)和sinularioperoxide D (7)；此外，我們還從採集自綠島踺形羽軟軟珊瑚(Clavularia viridis)之乙酸乙酯萃取物中，分離到兩個新骨架化合物viridisolide A 和 B (8和9)及一個已知nardosinane類化合物lemnal-1(10)-ene-2,12-dione (10)。這些二次代謝物的結構鑑定，主要是透過有機光譜的鑑定分析(包含了一維和二維NMR、質譜、紫外線光譜、紅外線光譜和比旋光)以及與已知化合物比對光譜文獻而決定的。此外將化合物1－4, 8和9進行老鼠血癌細胞(P-388)、人類直腸癌細胞(HT-29)人類肺癌細胞(A-549)之毒殺活性測試，以及進行抗人類巨細胞病毒(HCMV)測試，發現化合物1和2對老鼠血癌細胞(P-388)有顯著的活性(ED50 ≦ 4 μg/mL)，化合物1對於人類肺癌細胞(A-549)也有顯著的活性(ED50 = 2.2 μg/mL)。

Soft corals of the genus Sinularia and Clavularia were found to rich sources for secondary metabolites of different skeletons and biological activity. In the course of our studies on secondary metabolites from marine organisms, the acetone-solubles of the Formosan octocoral Sinularia erecta collected at Penghu has led to the isolation of a new cyclic peroxide-containing sesquiterpene, sinularioperoxide F (1), a new nor-monoterpene, sinuladione (2), two novel compounds, sinulariatricyclo A and B (3 and 4) along with three known cyclic peroxide-containing sesquiterpenes namely, sinularioperoxide A (5), sinularioperoxide C (6), and sinularioperoxide D (7). In addition, the EtOAc extract of Clavularia viridis, collected at the Green Island, yielded two novel compounds, viridisolide A and B (8 and 9), along with one known compound, lemnal-1(10)-ene-2,12-dione (10). The structures of these compounds were determined on the basis of their spectroscopic analyses (1H NMR, 13C NMR, 1H-1H COSY, HSQC, HMBC, NOESY, HRESIMS, UV and IR) and by comparison of the physical and spectral data with those of the related known compounds.
The cytotoxicity against P-388 (murine lymphocytic leukemia), HT-29 (human colon adenocarcinoma), and A-549 (human lung epithelial carcinoma) cells as well as the anti-HCMV (human cytomegalovirus) activities of new metabolites 1–4, 8 and 9, were evaluated in vitro. Metabolites 1 and 2 exhibited significant cytotoxic activity against P-388 cell in vitro (ED50 ≦ 4 μg/mL), metabolites 1 also exhibited significant cytotoxic activity against P-388 cell in vitro (ED50 = 2.2 μg/mL).

論文審定書 i
謝辭 ii
中文摘要 iii
英文摘要 iv
化合物1–10之化學結構 v
目錄 vi
表次 ix
圖次 xi
縮寫對照表 xvi

壹、緒論 1
一、前言及研究動機與目的 1
二、指形軟珊瑚Sinularia erecta二次代謝物研究回顧 3
三、葉形軟珊瑚Clavularia viridis二次代謝物研究回顧 10
貳、材料與研究方法 21
一、Sinularia erecta樣品採集、分類地位及分離流程 21
1. 樣品採集時間、地點與鑑定 21
2. 樣品之分類地位 21
3. 萃取與分離流程 22
4. 指形軟珊瑚S. erecta之分離純化 23
(1) 化合物1之純化分離 23
(2) 化合物2之純化分離 24
(3) 化合物3和4之純化分離 25
(4) 化合物5之純化分離 26
(5) 化合物6和7之純化分離 27
二、Clavularia viridis樣品採集、分類地位及分離流程 28
1. 樣品採集時間、地點與鑑定 28
2. 樣品之分類地位 28
3. 萃取與分離流程 29
4. 葉形軟珊瑚C. viridis之分離純化 31
(1) 化合物8–10之純化分離 31
参、化合物之結構解析 33
一、指形軟珊瑚Sinularia erecta之化學成分 33
1. 化合物1之結構解析 33
2. 化合物2之結構解析 49
3. 化合物3之結構解析 61
4. 化合物4之結構解析 75
5. 化合物5之結構判定 89
6. 化合物6之結構判定 101
7. 化合物7之結構判定 113
二、踺形羽軟珊瑚Clavularia viridis之化學成分 125
1. 化合物8之結構解析 125
2. 化合物9之結構解析 143
3. 化合物10之結構判定 161
肆、生物活性之測試 166
一、細胞毒殺活性測試方法 166
二、MTT分析原理 166
三、抗HCMV病毒的測試方法 167
四、活性測試結果 167
伍、結論 168
陸、參考文獻 170
柒、附錄 174
一、實驗設備儀器及材料 174
1.實驗設備儀器 174
2.實驗材料 175

1. 吳永昌、蘇燦隆，抗癌天然藥物的研發，中國化學年會季刊，2004，62，173–186。
2. 戴昌鳳，台灣珊瑚礁地圖(上)-台灣本島篇，天下遠見出版，2011。
3. Callum M. R.; Colin J. M.; John E. N. V.; Julie P. H.; Gerald R. A.; Don E. M.; Cristina G. M.; Frederick W. S.; Mark S.; Fred W.; Carly V.; Timothy B. W., Science 2002, 295, 1280–1284.
4. Shen, Y. C.; Ahmed, A. F.; Shiue, R. T.; Dai, C. F.; Kuo, Y. H., Scabrolides A-D, Four New Norditerpenoids Isolated from the Soft Coral Sinularia scabra. J. Nat. Prod. 2002, 65, 1904–1908.
5. Rashid, M. A.; Gustafson, K. R.; Boyd, M. R., Scabrolides A-D, HIV-Inhibitory Cembrane Derivatives from a Philippines Collection of the Soft Coral Lobophytum Species. J. Nat. Prod. 2000, 63, 531–533.
6. Lu, Y.; Huang, C. Y.; Lin, Y. F.; Wen, Z. H.; Su, J. H.; Kuo, Y. H. ; Chiang, M. Y. ; Sheu, J. H., Anti-inflammatory Cembranoids from the Soft Corals Sinularia querciformis and Sinularia granosa. J. Nat. Prod. 2008, 71, 1754–1759.
7. Lai, D.; Geng, Z.; Deng, z.; van Ofwegen, L.; Proksch, P.; Lin, W., Cembranoids from the Soft Coral Sinularia rigida with Antifouling Activities. J. Agric. Food Chem. 2013, 61, 4585–4592.
8. Ahmed, A. F.; Su, J. H.; Kuo, Y. H.; Sheu, J. H., Scabrolides E-G, Three New Norditerpenoids from the Soft Coral Sinularia scabra. J. Nat. Prod. 2004, 67, 2079–2082.
9. Su, J. H.; Ahmed, A. F.; Sung, P. J.; Chao, C. H.; Kuo, Y. H.;Sheu, J. H., Manaarenolides A-I, Diterpenoids from the Soft Coral Sinularia manaarensis. J. Nat. Prod. 2006, 69, 1134–1139.
10. Kamel, H. N.; Ferreira, D.; Garcia-Fernandez, L. F.; Slattery, M., Cytotoxic Diterpenoids from the Hybrid Soft Coral Sinularia maxima × Sinularia polydactyla. J. Nat. Prod. 2007, 70, 1223–1227.
11. Ahmed, A. F.; Wen, Z. H.; Su, J. H.; Hsieh, Y. T.; Wu, Y. C.; Hu, W. P.; Sheu, J. H., Oxygenated Cembranoids from a Formosan Soft Coral Sinularia gibberosa. J. Nat. Prod. 2008, 71, 179–185.
12. Su, J. H.; Wen, Z. H., Bioactive Cembrane-Based Diterpenoids from the Soft Coral Sinularia triangular. Mar. Drugs. 2011, 9, 944–951.
13. Chao, C. H.; Chou, K. J.; Huang, C. Y.; Wen, Z. H.; Hsu, C. H.; Wu, Y. C.; Dai, C. F.; Sheu, J. H., Bioactive Cembranoids from the Soft Coral Sinularia crassa. Mar. Drugs. 2011, 9, 1955–1968.
14. Thao, N. P.; Nam, N. H.; Cuong, N. X.; Quang, T. H.; Tung, P. T.; Dat, L. D.; Chae, D.; Kim, S.; Koh, Y. S.; Kiem, P. V.; Minh, C. V.; Kim, Y. H., Anti-inflammatory norditerpenoids from the soft coral Sinularia maxima. Bioorg. Med. Chem. Lett. 2013, 23, 228–231
15. Kitagawa, I.; Kobayashi, M.; Yasuzawa, T.; Son, B. W.; Yoshihara, M.; Kyogoku, Y., New Prostanoids from Soft Coral. Tetrahedron. 1985, 41, 995–1005.
16. Chang, C. H.; Wen, Z. H.; Wang, S. K.; Duh, C. Y., New Anti-inflammatory Steroids from the Formosan Soft Coral Clavularia viridis. Steroids 2008, 73, 562–567.
17. Lei, J.; Zhou, J., A Marine Natural Product Database. J. Chem. Inf. Comput. Sci. 2002, 42, 742–748.
18. Kikuchi, H.; Tsukitani, Y.; Iguchi, K.; Yamada, Y., Clavulones, New Type of Prostanoids from the Stolonifer Clavularia viridis Quoy and Gaimard. Tetrahedron Lett. 1982, 23, 5171–5174.
19. Honda, A.; Yamamoto, Y.; Mori, Y.; Yamada, Y.; Kikuchi, H., Antileukemic Effect of Coral Prostanoids Clavulones from the Stolonifer Clavularia viridis on Human Myeloid Leukemia (HL-60) Cells. Biochem Bioph Res Co. 1985, 130, 515–523.
20. Kobayashi, M.; Yasuzawa, T.; Yoshihar, M.; Akutsu, H.; Kyogoku, Y.; Kitagawa, I., Four New Prostanoids: Claviridenone-A, -B, -C, and -D from the Okinawan Soft Coral Clavularia viridis. Tetrahedron Lett. 1982, 23, 5331–5334

21. Iguchi, K.; Yamada, Y.; Kikuchi, H.; Tsukitani, Y., Novel C-20 Oxygenated Prostanoids, 20-Acetoxyclavulones, from the Stolonifer Clavularia viridis Quoy and Gaimard. Tetrahedron Lett. 1983, 24, 4433–4434.
22. Iguchi, K.; Kaneta, S.; Mori, K.; Yamada, Y.; Honda, A.; Mori, Y., Bromovulone I and Iodovulone I, Unprecedented Brominated and Iodinated Marine Prostanoids with Antitumor Activity Isolated from the Japanese Stolonifer Clavularia viridis Quoy and Gaimard. J. Chem. Soc. Chem. Commun. 1986, 981–982.
23. Iguchi, K.; Kaneta, S.; Mori, K.;Yamada, Y., A New Marine Epoxy Prostanoid with an Antiproliferative Activity from the Stolonifer Clavularia viridis Quoy and Gaimard. Chem. Pharm. Bull. 1987, 35, 4375–4376.
24. Iwashima, M.; Okamoto, K.; Iguchi, K., Clavirins, A New Type of Marine Oxylipins with Growth-inhibitory Activity from the Okinawan Soft Coral, Clavularia viridis. Tetrahedron Lett. 1999, 40, 6455–6459.
25. Watanabe, M.; Sekine, M.; Takahashi, H.; Iguchi, K., New Halogenated Marine Prostanoids with Cytotoxic Activity from the Okinawan Soft Coral Clavularia viridis. J. Nat. Prod. 2001, 64, 1421–1425.
26. Duh, C. Y.; El-Gamal, A. A. H.; Chu, C. J.; Wang, S. K.; Dai, C. F., New Cytotoxic Constituents from the Formosan Soft Corals Clavularia viridis and Clavularia violacea. J. Nat. Prod. 2002, 65, 1535–1539.
27. Shen, Y. C.; Cheng, Y. B.; Lin, Y. C.; Guh, J. H.; Teng, C. M.; Ko, C. L., New Prostanoids with Cytotoxic Activity from Taiwanese Octocoral Clavularia viridis. J. Nat. Prod. 2004, 67, 542–546.
28. Lin, Y. S.; Khalil, A. T.; Chiou, S. H.; Kuo, Y. C.; Cheng, Y. B.; Liaw, C. C.; Shen, Y. C., Bioactive Marine Prostanoids from Octocoral Clavularia viridis. Chem Biodivers. 2008, 5, 784–792.
29. Shen, Y. C.; Lo, K. L.; Chang, J. Y.; Lin, Y. S.; Mendbayar, K.; Kuo, Y. H.; Lin, Y. C., New Cytotoxic Prostanoids from Taiwanese Soft Coral Clavularia viridis. Chem Biodivers. 2010, 7, 2702–2708.
30. Watanabe, K.; Iwashima, M.; Iguchi, K., New Bioactive Marine Steroids from the Okinawan Soft Coral Clavularia viridis. Steroids. 1996, 61, 439–446.
31. Duh, C. Y.; Lo, I. W.; Wang, S. K.; Dai, C. F., New Cytotoxic Steroids from the Soft Coral Clavularia viridis. Steroids 2007, 72, 573–579.
32. Su, J. H.; Hsieh, C. H.; Lo, C. L.; Huang, C. Y.; Dai, C. F.; Kuo, Y. H.; Sheu, J. H., Sesquiterpenoids-related Metabolites from the Soft Coral Sinularia sp.. J. Chin. Chem. Soc. 2008, 55, 1286–1289.
33. Chao, C. H.; Hsieh, C. H.; Chen, S. P.; Lu, C. K.; Dai, C. F.; Wue, Y. C.; Sheu, J. H., Novel Cyclic Sesquiterpene Peroxides from the Formosan Soft Coral Sinularia sp.. Tetrahedron Lett. 2006, 47, 2175–2178.