過去在海洋領域的天然物學者們發現從軟珊瑚 Sinularia spp.、Sacrophyton spp.以及Lobophytum spp.分離出具有許多不同骨架的二次代謝物，其中包含sesquiterpenoids與cembranoids等相關骨架，並進一步尋找具有生物活性的新化合物。本篇主要針對綠島、龜山島以及東沙島海域之葇夷指形軟珊瑚、花環肉質軟珊瑚、葉形軟珊瑚屬Lobophytum michaelae以及柔指形軟珊瑚進行海洋天然物萃取與分離研究，藉由多種層析技術之純化，本篇分離出13個化合物，其中包含1個新的倍半萜類化合物 (1)、4個新的西柏烯類化合物 (2−5)以及8個已知化合物，epoxycembrene (6)、diepoxycembrene B (7)、diepoxycembrene A (8)、5-dehydrosinulariolide (9)、(1R,13S,12S,9S,8R,5S,4R)-9-acetoxy-5,8:12,13-diepoxy-cembr-15(17)-en-16,4-olide (10)、querciformolide A (11)、sinulariolide (12)與sinulariolone (13)。二次代謝物1−13的結構鑑定主要由有機光譜分析，包括一維、二維 NMR、質譜、紅外線光譜、紫外線光譜及旋光)以及和已知化合物文獻比對光譜資料(氫、碳及質譜)所決定。此外並針對化合物1−13進行人類肺癌細胞 (A-549)、人類直腸癌細胞(HT-29)及老鼠血癌細胞進行毒殺活性測試。發現化合物2、4、6及9對HT-29細胞具毒殺活性 (範圍：1.29−1.76 μg/ mL)。

Natural product scientists have reported many secondary metabolites containing sesquiterpenoids and cembranoids from soft corals Lobophytum spp., Sacrophyton spp., and Sinularia spp., and further search for new compounds with biological activity. In this report, we focused on marine natural product extraction and separation studies, purified by various chromatographic techniques, isolating thirteen compounds from the soft corals Sinularia leptoclados, Sacrophyton trocheliophorum, Lobophytum michaelae and Sinularia flexibilis of Green Island, Gueishan Island and Pratas Island. Thirteen compounds (1−13), including one new sesquiterpene compound (1) and four new cembrenes (2−5), along with eight known compounds, epoxycembrene (6), diepoxycembrene B (7), diepoxycembrene A (8), 5-dehydrosinulariolide (9), (1R, 13S, 12S, 9S, 8R, 5S, 4R)-9-Acetoxy-5, 8: 12, 13-diepoxy-cembra-15(17)-en-16,4-olide (10), querciformolide A (11), sinulariolide (12), and sinulariolone (13), have been isolated from organic extracts of soft corals Lobophytum michaelae, Sacrophyton trocheliophorum and Sinularia Leptoclados. The structures of isolates 1-13 were elucidated by spectroscopic evidences (1D, 2D NMR, Mass, IR, UV, and optical rotation) and compared with the spectral data of known compounds. The cytotoxicity of these isolates against A-549 (human lung epithelial carcinoma) and HT-29 (human colon adenocarcinoma), and were found compound 2, 4, 6 and 9 had cell activity (1.29−1.76 μg/ mL) .

謝辭 ii
中文摘要 iii
英文摘要 iv
化合物1-13之化學結構 v
目錄 vi
表次 ix
圖次 xi
縮寫對照表 xvii
壹、緒論 1
一、前言及研究動機與目的 1
二、葇夷指形軟珊瑚Sinularia leptoclados二次代謝物研究回顧 2
1. Sesquiterpenes類二次代謝物研究回顧 2
2. Norcembranes類二次代謝物研究回顧 5
3. Steroids類二次代謝物研究回顧 8
4. Lipids和guaianes類文獻回顧 11
三、花環肉質軟珊瑚Sarcophyton trocheliophorum二次代謝物研究回顧 13
1. Fatty acids類二次代謝物研究回顧 13
3. Cembranes類二次代謝物研究回顧 19
四、葉形軟珊瑚Lobophytum michaelae二次代謝物研究回顧 29
1. Cembranes類二次代謝物研究回顧 29
五、柔指形軟珊瑚Sinularia flexibilis二次代謝物研究回顧 33
1. Cladiellanes類二次代謝物研究回顧 33
2. Cinnamides類二次代謝物研究回顧 34
3. Quinones類二次代謝物研究回顧 34
4. Steroids類二次代謝物研究回顧 35
5. Cembranes類二次代謝物研究回顧 37
貳、材料與研究方法 56
一、葇夷指形軟珊瑚Sinularia leptoclados樣品採集、分類地位與分離 56
流程 56
1. S. leptoclados樣品採集時間、地點與鑑定 56
2. S. leptoclados之分類地位 56
3. S. leptoclados萃取與分離流程 57
4. S. leptoclados化學成分之分離純化 58
(1) 化合物1之純化分離 58
二、花環肉質軟珊瑚Sarcophyton trocheliophorum樣品採集、 59
分類地位及分離流程 59
1. S. trocheliophorum樣品採集時間、地點與鑑定 59
2. S. trocheliophorum之分類地位 59
3. S. trocheliophorum萃取與分離流程 60
4. S. trocheliophorum 化學成分之分離純化 61
(1) 化合物2之分離純化 61
三、葉形軟珊瑚Lobophytum michaelae 樣品採集、分類地位及分離 63
流程 63
1. L. michaelae樣品採集時間、地點與鑑定 63
2. L. michaelae之分類地位 63
3. L. michaelae萃取與分離流程 64
4. L. michaelae化學成分之分離純化 65
(1) 化合物3之分離純化 65
四、Sinularia flexibilis樣品採集、分類地位及分離流程 67
1. S. flexibilis樣品採集時間、地點與鑑定 67
2. S. flexibilis樣品之分類地位 67
3. S. flexibilis萃取與分離流程 68
4. S. flexibilis各化學成分之分離純化 70
(1) 化合物6之分離純化 70
(2) 化合物7分離純化 70
(3) 化合物8之分離純化 71
(4) 化合物9和10之分離純化 71
(5) 化合物11和4之分離純化 72
(6) 化合物12之分離純化 74
(7) 化合物13之分離純化 74
(8) 化合物5之分離純化 75
參、化合物之結構證明 76
一、指形軟珊瑚Sinularia leptoclados 之化學成分 76
1. 化合物1之結構解析 76
二、花環肉質軟珊瑚Sarcophyton trocheliophorum之化學成分 93
1. 化合物2之結構解析 93
三、葉形軟珊瑚Lobophytum michaelae之化學成分 107
1. 化合物3之結構解析 107
四、柔指形軟珊瑚Sinularia flexibilis之化學成分 126
1. 化合物4之結構解析 126
2. 化合物5之結構解析 145
3. 化合物6之結構判定 158
4. 化合物7之結構判定 170
6. 化合物8之結構判定 175
7. 化合物9之結構判定 186
8. 化合物10之結構判定 191
9. 化合物11之結構判定 196
11. 化合物12之結構判定 200
12. 化合物13之結構判定 210
肆、生物活性之測試 216
一、細胞毒殺活性測試步驟 216
二、MTT分析原理 216
三、活性測試結果 217
伍、結論 219
陸、參考文獻 221
柒、附錄 233
一、實驗設備儀器及材料 233
1. 實驗設備儀器 233
2. 實驗材料 234

1. 吳全安，海洋資源管理，五南出版，2007/3/6，台北，台灣。
2. 戴昌鳳，台灣珊瑚圖鑑（全新美耐版），貓頭鷹出版，2009/2/26，台北，台灣。
3. 國立海洋生物博物館，海洋生物科技特展專輯，國立海洋生物博物館出版，2006/11/1，車城，台灣。
4. Wright, A.D.; Nielson, J.L.; Tapiolas, D.M.; Liptrot, C.H.; Motti C.A. A Great Barrier Reef Sinularia sp. Yields Two New Cytotoxic Diterpenes. Mar. Drugs12012, 10, 1619-1630.
5. Su, T.-R.; Tsai, F.-J.; Lin, J.-J.; Huang, H.-H.; Chiu, C.-C.; Su, J.-H.; Yang, Y.-T.; Chen, J.Y.-F.; Wong, B.-S.; Wu, Y.-J. Induction of Apoptosis by 11-Dehydrosinulariolide via Mitochondrial Dysregulation and ER Stress Pathways
in Human Melanoma Cells. Mar. Drugs 2012, 10, 1883-1898.
6. Su, J.-H.; Wen, Z.-H. Bioactive Cembrane-Based Diterpenoids from the Soft
Coral Sinularia triangular. Mar. Drugs 2011, 9, 944-951.
7. Huang, T.-C.; Lee, J.-F.; Chen, J.-Y. Pardaxin, an Antimicrobial Peptide, Triggers Caspase-Dependent and ROS-Mediated Apoptosis in HT-1080 Cells. Mar. Drugs 2011, 9, 1995-2009.
8. Cheng, S.-Y.; Huang, K.-J.; Wang, S.-K.; Wen, Z.-H.; Chen, P.-W.; C.-Y. Duh. Antiviral and Anti-inflammatory Metabolites from the Soft Coral Sinularia capillosa. J. Nat. Prod. 2010, 73, 771-775.
9. Shi, H.-Y.; Yu, S.-J.; Liu, D.; van Ofwegen, L.; Proksch, P.; Lin, W.-H. Sinularones A-I, New Cyclopentenone and Butenolide Derivatives from a Marine Soft Coral Sinularia sp. and Their Antifouling Activity. Mar. Drugs 2012, 10,
1331-1344.
10. Su,J.-H.; Chiang, M.Y.; Wen, Z.-H.; Dai, C.-F.; Hsu, C.-H.; Sheu, J.-H. Sesquiterpenoids from the Formosan Soft Coral Sinularia leptoclados. Chem. Pharm. Bull. 2010, 58, 250-253.
11. Tsai, T.-C.; Wu, Y.-J.; Su, J.-H.; Lin, W.-T.; Lin, Y.-S. A New Spatane Diterpenoid from the Cultured Soft Coral Sinularia leptoclados. Mar. Drugs 2013, 11, 114-123.
12. Liang, C.-H.; Wang, G.-H.; Chou, T.-H.; Wang, S.-H.; Lin, R.-J.; Chan, L.-P.; So, E.-C.; Sheu, J.-H. 5-epi-Sinuleptolide induces cell cycle arrest and apoptosis through tumor necrosis factor/mitochondria-mediated caspase signaling pathway in human skin cancer cells.Biochem. Biophys. Acta. 2012, 1820, 1149-1157.
13. Bowden, B.F.; Coll, J.C.; Mitchell, S.J.; Mulder, J.; Stokie, J.G. Studies of Australian Soft Corals. IX A Novel Nor-Diterpene from the Soft Coral Sinularia leptoclados. Aust. J. Chem. 1978, 31, 2049-2056.
14. Lakshmi, V.; Schmitz, F.J. Metabolites from Two Soft Corals from Guam: Sinularia leptoclados and Sinularia gyrosa. J. Nat. Prod. 1986, 49, 728-730.
15. Ahmed, A.F.; Shiue, R.-T.; Wang, G.-H.; Dai, C.-F.; Kuo, Y.-H.; Sheu, J.-H. Five Novel Norcembranoids from Sinularia leptoclados and S. parva. Tetrahedron 2003, 59, 7337-7344.
16. Shoji, N.; Umeyama, A.; Arihara, S. A Novel Norditerpenoid from the Okinawan Soft Coral Sinularia sp. J. Nat. Prod. 1993, 56, 1651-1653.
17. Duh, C.-Y.; Wang, S.-K.; Chia, M.-C.; Chiang,M.Y. A Novel Cytotoxic Norditerpenoid from the Formosan Soft Coral Sinularia inelegans. Tetrahedron Lett. 1999, 40, 6033-6035.
18. Sheu, J.-H.; 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.
19. Takaki, H.; Koganemaru, R.; Iwakawa, Y.; Higuchi, R.; Miyamoto, T. Inhibitory Effect of Norditerpenes on LPS-Induced TNF-α Production from the Okinawan Soft Coral, Sinularia sp. Biol. Pharm. Bull. 2003, 26, 380-382.
20. Su, J.-H.; Tseng, Y.-J.; Huang, H.-H.; Ahmed, A. F.; Lu, C.-K.; Wu, Y.-C.; Sheu, J.-H. 9,11-Secosterols from the Soft Corals Sinularia lochmodes and Sinularia leptoclados. J. Nat. Prod. 2006, 69, 850-852.
21. Kazlauskas, R.; Murphy, P.T.; Ravi, B.N.; Sanders, R.L.; Wells, R.J. Spermidine Derivatives and 9,11-Secosteroids from a Soft Coral Sinularia sp. Aust. J. Chem. 1982, 35, 69-75.
22. Bonini, C.; Cooper C.B.; Kazlauskas, R.; Wells, R. J.; Djerassi, C. Minor and Trace Sterols in Marine Invertebrates. 41. Structure and Stereochemistry of Naturally Occurring 9,11-Seco Sterols. J. Org. Chem. 1983, 48, 2108-2111.
23. Cheng, S.-Y.; Chen, H.-P.; Wang, S.-K.; Duh, C.-Y. Three New 9,11-Secosterols from the Formosan Soft Coral Sinularia leptoclados. Bull. Chem. Soc. Jpn. 2011, 84, 648-652.
24. Berg, J. M.; Tymockzo, J. L.; Stryer, L. Biochemistry 7th Edition .
25. Reddy, B.S.; Rao, B. S. Dhananjaya, N.; Kuttan, R.; Babu, T.D. Isolation and Structural Determination of New Sphingolipids and Pharmacological Activity of Africanene and Other Metabolites from Sinularia leptoclados. Chem. Pharm. Bull. 1999, 47, 1214-1220.
26. Huang, C.-Y.; Su, J.-H.; Liu, Y.-C.; Wen, Z.-H.; Hsu,C.-H. Chiang, M.; Sheu, J.-H. Oppositane-Type Sesquiterpenoids from the Formosan Soft Coral Sinularia leptoclados. Bull. Chem. Soc. Jpn. 2010, 83, 678-682.
27. Rezanka, T.; Dembitsky, V.M. γ-Lactones from the Soft Coral Sarcophyton trocheliophorum and Lithophyton arboreum. Tetrahedron 2001, 57,　8743-8749.
28. Liu, Z.; Cheng, W.; Liu, D.; van Ofwegen, L.; Proksch, P.; Lin, W.-H. Capnosane-type cembranoids from the soft coral Sarcophyton trocheliophorum with antibacterial effects. Tetrahedron 2014, 70, 8703-8713.
29. Chen, W.-T.; Yao, L.-G.; Li, X.-W.; Guo, Y.-W. Sarcophytrols A–C, new capnosane diterpenoids from the South China Sea soft coral Sarcophyton trocheliophorum. TetrahedronQLett. 2015, 56, 1348-1352.
30. Venkateswarlu, Y.; Chavakula, R.; Biabani, M.A.F.; Rao, T.P. A new diterpene from a soft coral Sarcophyton trocheliphorum. Nat. Prod. Lett. 1994, 5, 131-134.
31. Duh, C.-Y.; Hou, R.-S. Cytotoxic Cembranoids from the Soft Corals Sinularia gibberosa and Sarcophyton trocheliophorum. J. Nat. Prod., 1996, 59, 595-598.
32. Grote, D.; Soliman, H.S.M.; Shaker, K.H.; Hamza, M.; Seifert, K. Cembranoid diterpenes and a briarane diterpene from corals. Nat. Prod. Res. 2006, 20, 285-291.
33. Yao, L.-G.; Zhang, H.-Y.; Liang, L.-F.; Guo, X.-J.; Mao, S.-C.; Guo, Y.-W. Yalongenes A and B, Two New Cembranoids with Cytoprotective Effects from the Hainan Soft Coral Sarcophyton trocheliophorum. Helv. Chim. Acta 2012, 95, 235-239.
34. Liang, L.-F.; Gao, L.-X.; Li, J.; Taglialatela-Scafati, O.; Guo, Y.-W. Cembrane diterpenoids from the soft coral Sarcophyton trocheliophorum Marenzeller as a new class of PTP1B inhibitors. Bioorgan. Med. Chem. 2013, 21, 5076-5080.
35. Liang, L.-F.; Lan, L.-F.; Taglialatela-Scafati, O.; Guo, Y.-W. Sartrolides AG and bissartrolide, new cembranolides from the South China Sea soft coral Sarcophyton trocheliophorum Marenzeller. Tetrahedron 2013, 69, 7381-7386.
36. Liang, L.-F.; Kurtan, T.; Mandi, A.; Yao, L.-G.; Li, J.; Zhang, W.; Guo, Y.-W. Unprecedented Diterpenoids as a PTP1B Inhibitor from the Hainan Soft Coral Sarcophyton trocheliophorum Marenzeller. Org. Lett. 2013, 15, 274-277.
37. Hegazy, M.E.F.; Mohamed, T.A.; Abdel-Latif, F.F.; Alsaid, M.S.; Shahat, A.A.; Pare, P.W. Trochelioid A and B, new cembranoid diterpenes from the Red Sea soft coral Sarcophyton trocheliophorum. Phytochem. lett. 2013, 6, 383-386.
38. Liang, L.-F.; Kurtan, T.; Mandi, A.; Gao, L.-X.; Li, J.; Zhang, W.; Guo, Y.-W. Sarsolenane and Capnosane Diterpenes from the Hainan Soft Coral Sarcophyton trocheliophorum Marenzeller as PTP1B Inhibitors. Eur. J. Org. Chem. 2014, 2014, 1841-1847.
39. Khaled, A.S.; Mohamed, A.G.; Mohamed, S. New Cembranoid Diterpenes from Sarcophyton trocheliophorum. Brit. J. Pharm. Res. 2015, 5, 192-201.
40. Al-Footy,K.; Alarif, W.; Asiri, F.; Aly, M.; Ayyad, S. -E. Rare pyrene-based cembranoids from the Red Sea soft coral Sarcophyton trocheliophorum as potential antimicrobial-antitumor agents. Med. Chem. Res. 2015, 24, 505-512.
41. Chen, W.-T.; Liang, L.-F.; Li, X.-W.; Xiao, W.; Guo, Y.-W. Further New Highly Oxidative Cembranoids from the Hainan Soft Coral Sarcophyton trocheliophorum. Nat. Prod. Bioprospect 2016, 6, 97-102.
42. Dong, H.; Gou, Y.-L.; Kini, R. M.; Xu, H.-X.; Chen, S.-X.; Teo, S.L.; But, P.P. A New Cytotoxic Polyhydroxysterol from Soft Coral Sarcophyton trocheliophorum. Chem. Pharm. Bull. 2000, 48, 1087-1089.
43. Shaaban, M.; Ghani, M.A.; Shaaban, K.A. Zahramycins AB, two new steroids from the coral Sarcophyton trocheliophorum. J. Chem. Sci. 2013, 68, 939-945.
44. Coll, J.C.; Mitchell, S. J.; Stokie, G.J. Studies of Australian Soft Corals. II. A Novel Cembranoid Diterpene from Lobophytum michaelae. Aust. J. Chem. 1977, 30, 1859-1863.
45. Wang, S.-K.; Duh, C.-Y.; Wu, Y.-C.; Wang, Y.; Cheng, M.-C.; Soong, K.-Y.; Fang, L.-S. Studies on Formosan Soft Corals. II. Cytotoxic Cembranolides from the Soft Coral Lobophytum michaelae. J. Nat. Prod. 1992, 55, 1430-1435.
46. Wang, L.-T.; Wang, S.-K.; Soong, K.-Y.; Duh, C.-Y. New Cytotoxic Cembranolides from the Soft Coral Lobophytum michaelae. Chem. Pharm. Bull. 2007, 55, 766-770.
47 Wang, S.-K.; Duh, C.-Y. New Cytotoxic Cembranolides from the Soft Coral Lobophytum michaelae. Mar. Drugs12012, 10, 306-318.
48. Kusumi, T.; Uchida, H.; Ishitsuka, M.O.; Yamamoto, H.; Kakisawa, H. Alcyonin, a New Cladiellane Diterpene from the Soft Coral Sinularia flexibilis. Chem. Lett. 1988, 17, 1077-1078.
49. Anjaneyulu, A.S.R.; Sagar, K.S.; Rao, N.S.K. A novel cinnamide dimer from the Indian Ocean soft coral Sinularia flexibilis. Nat. Prod. Lett. 1997, 11, 5-11.
50. Lin, Y.-F.; Kuo, C.-Y.; Wen, Z.-H.; Lin, Y.-Y.; Wang, W.-H.; Su, J.-H.; Sheu, J.-H.; Sung,P.-J. Flexibilisquinone, a New Anti-Inflammatory Quinone from the Cultured Soft Coral Sinularia flexibilis. Molecules 2013, 18, 8160-8167.
51. Yu, S.-J.; Deng, Z.-W.; van Ofwegen, L.; Proksch, P.; Lin, W.-H. 5, 8-epidioxysterols and related derivatives from a Chinese Soft Coral Sinularia flexibilis. Steroids 2006, 71, 955-959.
52. Chen, W.-T., Liu, H.-L.; Yao, L.-G.; Guo, Y.-W. 9, 11-Secosteroids and polyhydroxylated steroids from two South China Sea soft corals Sarcophyton trocheliophorum and Sinularia flexibilis. Steroids 2014, 92, 56-61.
53. Tursch, B.; Braekman, J. C.; Daloze, D.; Herin, M.; Karlsson, R.; Losman, D. Chemical Studies of Marine Invertebrates-XI. Sinulariolide, a New Cembranolide Diterpene from the Soft Coral Sinularia flexibilis. Tetrahedron 1975, 31, 129-133.
54. Weinheimer, A.J.; Matson, J.A.; Hossain, M.B.; van der Helm, D. Marine anticancer agents: sinularin and dihydrosinularin, new cembranolides from the soft coral, Sinularia flexibilis. TetrahedronQLett. 1977, 34, 2923-2926.
55. Mori, K.; Sukeji, S.; Iguchi, K.; Yamada, Y. 8, 11-Epoxy Bridged Cembranolide Diterpene from the Soft Coral Sinularia flexibilis. Chem. Lett. 1983, 10, 1515-1516.
56. Li, H.-H.; Su, J.-H.; Chiu, C.-C.; Lin, J.-J.; Yang, Z.-Y.; Hwang, W.-I.; Chen, Y.-K.; Lo, Y. -H.; Wu, Y.-J. Proteomic Investigation of the Sinulariolide-Treated Melanoma Cells A375: Effects on the Cell Apoptosis through Mitochondrial-Related Pathway and Activation of Caspase Cascade. Mar. Drugs 2013, 11, 2625-2642.
57. Chen, Y.-J.; Su, J.-H.; Tsao, C.-Y.; Hung, C.-T.; Chao, H.-H.; Lin, J.-J.; Liao, M.-H.; Yang, Z.-Y.; Huang, H.-H.; Tsai, F.-J.; Weng, S.-H.; Wu, Y.-J. Sinulariolide Induced Hepatocellular Carcinoma Apoptosis through Activation of Mitochondrial-Related Apoptotic and PERK/eIF2α/ATF4/CHOP Pathway. Molecules 2013, 18, 10146-10161.
58. Duh, C.-Y.; Wang, S.-K.; Tseng, H.-K.; Sheu, J.-H. A Novel Cytotoxic Biscembranoid from the Formosan Soft Coral Sinularia flexibilis. Tetrahedron Lett. 1998, 39, 7121-7122.
59. Duh, C.-Y.; Wang, S.-K.; Tseng, H.-K.; Sheu, J.-H.; Chiang, M.Y.1Novel Cytotoxic Cembranoids from the Soft Coral Sinularia flexibilis.1J. Nat. Prod. 1998, 61, 844-847.
60. Aceret, T.L.; Coll, J.H.; Uchio, Y.; Sammarco, P.W. Antimicrobial activity of the diterpenes flexibilide and sinulariolide derived from Sinularia flexibilis Quoy and Gaimard 1833(Coelenterata: Alcyonacea, Octocorallia). Comp. Biochem. Phys. A. 1998, 120, 121-126.
61. Chen, N.-F.; Huang, S.-Y.; Lu, C.-H.; Chen, C.-L.; Feng, C.-W.; Chen, C.-H.; Hung, H.-C.; Lin, Y.-Y.; Sung, P.-J.; Sung, C.-S.; Yang, S.-N.; Wang, D.H.-M.; Chang, Y.-C.; Sheu, J.-H.; Chen, W.-F.; Wen, Z.-H. Flexibilide Obtained from Cultured Soft Coral Has Anti-Neuroinflammatory and Analgesic Effects through the Upregulation of Spinal Transforming Growth Factor-β1 in Neuropathic Rats. Mar. Drugs 2014, 12, 3792-3817.
62. Hsieh, P.-W.; Chang, F.-R.; Mcphail, A.T.; Lee, K.-H.; Wu, Y.-C. New cembranolide analogues from the formosan soft coral Sinularia flexibilis and their cytotoxicity.1Nat. Prod. Res. 2003, 17, 409-418.
63. Liu, C.-I.; Chen, C.-C.; Chen, J.-C.; Su, J.-H.; Huang, H.-H.; Chen, J. Y.-F.; Wu, Y.-J. Proteomic Analysis of Anti-Tumor Effects of 11-Dehydrosinulariolide on CAL-27 Cells. Mar. Drugs12011, 9, 1254-1272.
64. Su, T.-R.; Tsai, F.-J.; Lin, J.-J.; Huang, H.-H.; Chiu, C.-C.; Su, J.-H.; Yang, Y.-T.; Chen, J.Y.-F.; Wong, B.-S.; Wu, Y.-J. Induction of Apoptosis by 11-Dehydrosinulariolide via Mitochondrial Dysregulation and ER Stress Pathways
in Human Melanoma Cells. Mar. Drugs12012, 10, 1883-1898.
65. Liu, C.-I.; Wang, R.Y.-L.; Lin, J.-J.; Su, J.-H.; Chiu, C.-C.; Chen, J.-C.; Chen, J. Y.-F.; Wu, Y.-J. Proteomic profiling of the 11-dehydrosinulariolide-treated oral carcinoma cells Ca9–22: Effects on the cell apoptosis through mitochondrial-related and ER stress pathway. J. Proteomics, 2012, 75, 5578-5589.
66. Lin, J.-J.; Su, J.-H.; Tsai, C.-C.; Chen, Y.-J.; Liao, M.-H.; Wu, Y.-J. 11-epi-Sinulariolide Acetate Reduces Cell Migration and Invasion of Human Hepatocellular Carcinoma by Reducing the Activation of ERK1/2, p38MAPK and FAK/PI3K/AKT/mTOR Signaling Pathways. Mar. Drugs 2014, 12, 4783-4798.
67. Hsu, W.-L.; Chiu, S.-J.; Tsai, Y.-T.; Chang, C.-M.; Wang, J.-Y.; Wang, E.-T.; Hou, M.-F.; Huang, C.-Y.; Sheu, J.-H.; Chang, W.-C. A Soft Coral Natural Product, 11-episinulariolide Acetate, Inhibits Gene Expression of Cyclooxygenase-2 and Interleukin-8 through Attenuation of Calcium Signaling. Molecules 2013, 18, 7023-7034.
68. Chen, W.-F.; Chakraborty, C.; Sung, C.-S.; Feng, C.-W.; Jean, Y.-H.; Lin, Y.-Y.; Hung, H.-C.; Huang, T.-Y.; Huang, S.-Y.; Su, T.-M.; Sung, P.-J.; Sheu, J.-H.; Wen, Z.-H. Neuroprotection by marine-derived compound, 11-dehydrosinulariolide, in an in vitro Parkinson ’ s model:a promising candidate for the treatment of Parkinson’ s
disease. N-S. Arch. Pharmacol. 2012, 385, 265-275.
69. Wen, T.; Ding, Y.; Deng, Z.-W.; van Ofwegen, L.; Proksch, P.; Lin, W.-H. Sinulaflexiolides AK, Cembrane-Type Diterpenoids from the Chinese Soft Coral Sinularia flexibilis. J. Nat. Prod. 2008, 71, 1133-1140.
70. Lin, Y.-S.; Chen, C.-H.; Liaw, C.-C.; Chen, Y.-C.; Kuo, Y.-H.; Shen, Y.-C. Cembrane diterpenoids from the Taiwanese soft coral Sinularia flexibilis. Tetrahedron 2009, 65, 9157-9164.
71. Lo, K.-L.; Khalil, A.T.; Kuo, Y.-H.; Shen, Y.-C. Sinuladiterpenes AF, New Cembrane Diterpenes from Sinularia flexibilis. Chem. Biodivers 2009, 6, 2227-2235.
72. Su, J.-H.; Lin, Y.-F.; Lu, Y.; Heh, H.-C.; Wang, W.-H.; Fan, T.-Y.; Sheu, J.-H. Oxygenated Cembranoids from the Cultured and Wild-Type Soft Corals Sinularia flexibilis. Chem. Pharm. Bull. 2009, 57, 1189-1192.
73. Wang, D.-X.; Liu, P.; Ren, H.-Y.; Lin, W.-H.; Yang, Y.-Q.; Ma, X.-F.; Wen, T. Liao, H.-B. Effects of cembrene-type diterpenes on proliferation of PC12 cells and their antagonistic effects on neurotoxicity induced by glutamate. J. Chinese Integr. Med. 2009, 7, 1061-1066
74. Chen, B.-W.; Liao, C.-C.; Su, J.-H.; Huang, C.-Y.; Dai, C.-F.; Wen, Z.-H.; Sheu, J.-H. A novel symmetric sulfur-containing biscembranoid from the Formosan soft coral Sinularia flexibilis. Tetrahedron Lett. 2010, 51, 5764-5766.
75. Lo, K.-L.; Khalil, A.T.; Chen, M.-H.; Shen, Y.-C. New Cembrane Diterpenes from Taiwanese Soft Coral Sinularia flexibilis. Helv. Chim. Acta 2010, 93, 1329-1335.
76. Shih, H.-J.; Tseng, Y.-J.; Huang, C.-Y.; Wen, Z.-H.; Dai, C.-F.; Sheu, J.-H. Cytotoxic and anti-inflammatory diterpenoids from the Dongsha Atoll soft coral Sinularia flexibilis. Tetrahedron 2012, 68, 244-249.
77. Hu, L.-C.; Yen, W.-H.; Su, J.-H.; Chiang, M.Y.-N.; Wen, Z.-H.; Chen, W.-F.; Lu, T.-J.; Chang, Y.-W.; Chen, Y.-H.; Wang, W.-H.; Wu, Y.-C.; P.-J. Sung. Cembrane Derivatives from the Soft Corals, Sinularia gaweli and Sinularia flexibilis. Mar. Drugs 2013, 11, 2154-2167.
78. Su, C.-C.; Wong, B.-S.; Chin, C.; Wu, Y.-J. Su, J.-H. Oxygenated Cembranoids from the Soft Coral Sinularia flexibilis. Int. J. Mol. Sci. 2013, 14, 4317-4325.
79. Tsai, T.-C.; Chen, H.-Y.; Sheu, J.-H.; Chiang, M.Y.; Wen, Z.-H.; Dai, C.-F.; Su, J.-H. Structural Elucidation and Structure-Anti-inflammatory Activity Relationships of Cembranoids from Cultured Soft Corals Sinularia sandensis and
Sinularia flexibilis. J. Agric. Food Chem. 2015, 63, 7211-7218.
80. Chen, W.-T.; Li, J.; Wang, J.-R.; Li, X.-W.; Guo, Y.-W. Structural diversity of terpenoids in the soft coral Sinularia flexibilis, evidenced by a collection from the South China Sea. Roy. Soc. Chem. Adv. 2015, 5, 23973-23980.
81. Ohtani, I.; Kusumi, T.; Kashman, Y. High-Field FT NMR Application of Mosher’s Method. The Absolute Configurations of Marine Terpenoids. J. Am. Chem. Soc. 1991, 113, 4092-409.
82. Ampofo, S.A.; Roussis, V.; Wiemer, D.F. New Prenylated Phenolics from Piper auritum. Phytochemistry 1987, 26, 2367-2370.
83. Bowden, B.F.; Coll, J.C.; Mitchell, S.J.; Kazlauskas, R. Two Cembranoids Diterpenes from the Soft Coral Sinularia facile. Aust. J. Chem. 1981, 34, 1551-1556.
84. Groweiss, A.; Kashman, Y.; Vanderah, D.J.; Tursch, B.; Cornet, P.; Braekman, J.C.; Daloze, D. The Structure of Trocheliophorol, a Cembranoid Diterpene from Soft Coral of the Genus Sarcophyton. Bull. Soc. Chim. Belg. 1978, 87, 277-283.
85. Kusumi, T.; Yamada, K.; Ishitsuka, M.; Fujita, Y.; Kakisawa, H. New Cembranoids from the Okinawan Soft Coral Sinularia mayi. Chem. Lett. 1990, 19, 1315-1318.
86. Guerrero, P.P.; Read, R.W.; Batley, M.; Janairo, G. C. The Structure of a Novel Cembranoid Diterpene fron a Philippine Collection of the Soft Coral Sinularia flexibilis. J. Nat. Prod. 1995,58, 1185-1191.
87. 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.
88. Anjaneyulu, A.S.R.; Sagar, K.S.; Venugopal, M.J.R.V. Terpenoid and Steroid Constituents of the Indian Ocen Soft Coral Sinularia maxima. Tetrahedron 1995, 51, 10997-11010.
89. Duh, C.-Y.; Wang, S.-K.; Weng, Y.-L.; Chiang, M.Y.; Dai, C.-F. Cytotoxic Terpenoids from the Formosan Soft Coral Nephthea brassica. J. Nat. Prod. 1999, 62, 1518-1521.
90. Fattorusso, E.; Romano, A.; Taglialatela-Scafati, O.; Maffettone, C.I.C.; Bavestrello, G.; Cerrano, C. Oxygenated cembranoids of the decaryiol type from the Indonesian soft coral Lobophytum sp. Terahedron 2009, 65, 2898-2904.
91. Bowden, B.F.; Coll, J. C.; Tapiolas, D.M. Studies of Australian Soft Corals. XXXIII New Cembranoid Diterpenes From a Lobophytum Species. Aust. J. Chem. 1983, 36, 2289-2295.
92. Qin, S.; Huang, H.; Guo,Y.-W. A new cembranoid from the Hainan soft coral Sinularia sp. J. Asian Nat. Prod. Res. 2008, 10, 1075-1079.
93. Su, J.-Y.; Yang, R.-L.; Kuang, Y.-Y.; Zeng, L.-M. A New Cembranolide from the Soft Coral Sinularia capillosa. J. Nat. Prod. 2000, 63, 1543-1545.
94. Tursch, B.; Braekman, J.C.; Daloze, D.; Herin, M.; Karlsson, R.; Losman, D. Sinulariolide, A New Cembranolide Diterpene from The Soft Coral Sinularia flexibilis. Tetrahedron 1975, 31, 129-133.
95. Liu, Z.-S.; Li, W.-D.Z.; Li, Y.-L. Enantioselective Total Synthesis of (+)-3,4-epoxycembrene-A. Tetrahedron Asymmetr. 2001, 12, 95-100.
96. Mosmann, T. Rapid Colorimetric Assay for Cellular Growth and Survival: Application to Proliferation and Cytotoxicity Assays. J. Immunol. Methods 1983, 65, 55-63.
97. Cory, A.H.; Owen, T.C.; Barltrop, J.A.; Cory, J. G. Use of an Aqueous Soluble tetrazolium/ formazan Assay for Cell Growth Assays in Culture. Cancer Commun. 1991, 3, 207-212.
98. Berridge, M.V.; Herst, P.M.; Tan, A.-S. Tetrazolium Dyes as Tools in Cell Biology: New Insights into Their Cellular Reduction. Biotech. Annu. Rev. 2005, 11, 127-152.