本研究主要是從柔軟冠形軟珊瑚 Klyxum molle 的乙酸乙酯溶劑萃取物中尋找具有生物活性的化學成分。本研究總共分離得到16個eunicellin類的天然化合物1–16，其中klymollin A–J (1–10) 為新化合物，11–16為已知的化合物。所有化合物的化學構造均由光譜數據的分析 (IR, MS, 1D、2D NMR) 和比對文獻上已知化合物的光譜資料而確定。而化合物1–10是eunicellin型態骨架的化合物中，首次發現在C-11/C-17具有epoxy官能基的化合物。化合物4的絕對立體結構，則可經由Mosher’s酯化反應加以確定。
本研究中，將所獲得的化合物1–8和11–16進行人類肺腺癌細胞(A549)、肝癌細胞(HepG2)和(Hep3B)、乳癌細胞(MCF-7)和(MDA-MB231) 的細胞毒殺活性測試與抗發炎活性測試。化合物11對A549有細胞毒殺活性 (IC50值為3.14 μg/mL)，化合物15和16對HepG2有細胞毒殺活性 (IC50值為3.82和2.50 μg/mL)。而化合物6、7對於在濃度為1 µM下可有效的抑制發炎蛋白質iNOS和COX-2的表現，其中化合物4、5、8對於iNOS也具有良好的抑制效果。

In order to discover for bioactive compounds, we have studied the chemical constituents from the organic extracts of soft coral Klyxum molle. This study had led to the isolation of 16 eunicellin-type diterpenoids, including ten new compounds, klymollins A–J (1–10), along with six know compounds 11–16. The structures of compounds 1–16 were established by spectroscopic methods and by comparison of the spectral data with those of the related known compounds. It is noteworthy to mention that compounds 1–10 represent the first example of eunicellins possessing a C-11/C-17 epoxide. The absolute configuration of 4 was determined using a modified Mosher’s method.
The cytotoxicity of compounds 1–8 and 11–16 against the A549 (human lung epithelial cells), HepG2 (human hepatocellular carcinoma), Hep3B (human hepatocellular carcinoma), MCF-7 (human breast adenocarcinoma)、MDA-MB231 (human breast adenocarcinoma) tumor cell lines were determined. Compound 11 showed cytotoxicity toward A549 tumor cells (IC50 value of 3.14 μg/mL) and compounds 15 and 16 were found to exhibit cytotoxicity toward HepG2 tumor cell (IC50 values of 3.82 and 2.50 μg/mL). Compounds 6 and 7 were found to show significant activity against the accumulation of the pro-inflammatory iNOS and COX-2 protein at 1 μM.

目 錄 頁 次
中文摘要 IX
英文摘要 X
化合物1-10化學結構 XI
化合物11-16化學結構 XII
第一章、緒論 1
第一節、前言 1
第二節、研究動機 2
第三節、文獻回顧 3
第二章、生物材料與研究方法 33
第一節、研究流程 33
第二節、Klyxum molle 樣品採集時間、地點、分類地位 35
第三節、Klyxum molle 分離流程 36
第四節、實驗設備儀器及材料 38
第三章、化合物之結構證明 41
第一節：軟珊瑚Klyxum molle 所分離出之化合物的結構證明 41
(一)、Klymollin A (1) 化合物構造之解析 41
(二)、Klymollin B (2) 化合物構造之解析 52
(三)、Klymollin C (3) 化合物構造之解析 62
(四)、Klymollin D (4) 化合物構造之解析 72
(五)、Klymollin E (5) 化合物構造之解析 84
(六)、Klymollin F (6) 化合物構造之解析 94
(七)、Klymollin G (7) 化合物構造之解析 104
(八)、Klymollin H (8) 化合物構造之解析 114
(九)、Klymollin I (9) 化合物構造之解析 124
(十)、Klymollin J (10) 化合物構造之解析 134
(十一)、6-Acetoxy analog of litophynin E (11) 化合物構造之解析 144
(十二)、(1R*, 2R*, 3R*, 6S*, 9R*, 10R*, 14R*)-3- acetoxycladiell
-7(16), 11 (17)-dien-6-ol (12) 化合物構造之解析 148
(十三)、Litophynin F (13) 化合物構造之解析 152
(十四)、Cladiellisin (14) 化合物構造之解析 156
(十五)、Sclerophytin E (15) 化合物構造之解析 160
(十六)、(1R*, 2R*, 3R*, 6S*, 7S*, 9R*, 10R*, 14R*) -3-butanoyloxycladiell-11(17)-en-6,7-diol (16) 化合物構造之解析 164
第二節:化學反應步驟 168
第三節:化合物物理性質及圖譜數據整理
169
第四章、生物活性試驗 173
第一節、生物活性試驗方法 173
(一)、細胞毒殺活性試驗方法 173
(二)、抗發炎活性試驗方法 175
第二節、生物活性試驗結果 178
(一)、細胞毒殺活性試驗結果 178
(二)、抗發炎活性試驗結果 179
第五章、結論 182
第六章、參考文獻 186
圖 目 錄

Figure 2-1. Klyxum molle 圖 35
Figure 2-2. Klyxum molle 軟珊瑚的分離流程 37
Figure 3-1-1. 1H–1H COSY and selective HMBC correlations of 1 43
Figure 3-1-2. Selected NOESY correlations of 1 44
Figure 3-1-3. IR spectrum of 1 46
Figure 3-1-4. ESIMS spectrum of 1 46
Figure 3-1-5. HRESIMS spectrum of 1 47
Figure 3-1-6. 1H NMR spectrum of 1 47
Figure 3-1-7. 1H NMR (2.4~5.4 ppm) spectrum of 1 48
Figure 3-1-8. 13C NMR spectrum of 1 48
Figure 3-1-9. DEPT spectra of 1 49
Figure 3-1-10. HMQC spectrum of 1 49
Figure 3-1-11. COSY spectrum of 1 50
Figure 3-1-12. HMBC spectrum of 1 50
Figure 3-1-13. NOESY spectrum of 1 51
Figure 3-2-1. 1H–1H COSY and selective HMBC correlations of 2 53
Figure 3-2-2. Selected NOESY correlations of 2 54
Figure 3-2-3. IR spectrum of 2 56
Figure 3-2-4. ESIMS spectrum of 2 56
Figure 3-2-5. HRESIMS spectrum of 2 57
Figure 3-2-6. 1H NMR spectrum of 2 57
Figure 3-2-7. 1H NMR (2.0~5.4 ppm) spectrum of 2 58
Figure 3-2-8. 13C NMR spectrum of 2 58
Figure 3-2-9. DEPT spectra of 2 59
Figure 3-2-10. HMQC spectrum of 2 59
Figure 3-2-11. COSY spectrum of 2 60
Figure 3-2-12. HMBC spectrum of 2 60
Figure 3-2-13. NOESY spectrum of 2 61
Figure 3-3-1. 1H–1H COSY and selective HMBC correlations of 3 63
Figure 3-3-2. Selected NOESY correlations of 3 64
Figure 3-3-3. IR spectrum of 3 66
Figure 3-3-4. ESIMS spectrum of 3 66
Figure 3-3-5. HRESIMS spectrum of 3 67
Figure 3-3-6. 1H NMR spectrum of 3 67
Figure 3-3-7. 1H NMR (1.4~5.0 ppm) spectrum of 3 68
Figure 3-3-8. 13C NMR spectrum of 3 68
Figure 3-3-9. DEPT spectra of 3 69
Figure 3-3-10. HMQC spectrum of 3 69
Figure 3-3-11. COSY spectrum of 3 70
Figure 3-3-12. HMBC spectrum of 3 70
Figure 3-3-13. NOESY spectrum of 3 71
Figure 3-4-1. 1H–1H COSY and selective HMBC correlations of 4 73
Figure 3-4-2. Selected NOESY correlations of 4 74
Figure 3-4-3. 1H NMR chemical shift differences (Δδ) for the MTPA esters of 4 75
Figure 3-4-4. IR spectrum of 4 77
Figure 3-4-5. ESIMS spectrum of 4 77
Figure 3-4-6. HRESIMS spectrum of 4 78
Figure 3-4-7. 1H NMR spectrum of 4 78
Figure 3-4-8. 1H NMR (2.0~5.0 ppm) spectrum of 4 79
Figure 3-4-9. 13C NMR spectrum of 4 79
Figure 3-4-10. DEPT spectra of 4 80
Figure 3-4-11. HMQC spectrum of 4 80
Figure 3-4-12. COSY spectrum of 4 81
Figure 3-4-13. HMBC spectrum of 4 81
Figure 3-4-14. NOESY spectrum of 4 82
Figure 3-4-15. 1H-NMR (1.6~5.5 ppm) spectrum of 4a 82
Figure 3-4-16. 1H-NMR (1.6~5.5 ppm) spectrum of 4b 83
Figure 3-5-1. 1H–1H COSY and selective HMBC correlations of 5 85
Figure 3-5-2. Selected NOESY correlations of 5 86
Figure 3-5-3. IR spectrum of 5 88
Figure 3-5-4. ESIMS spectrum of 5 88
Figure 3-5-5. HRESIMS spectrum of 5 89
Figure 3-5-6. 1H NMR spectrum of 5 89
Figure 3-5-7. 1H NMR (2.2~5.6 ppm) spectrum of 5 90
Figure 3-5-8. 13C NMR spectrum of 5 90
Figure 3-5-9. DEPT spectra of 5 91
Figure 3-5-10. HMQC spectrum of 5 91
Figure 3-5-11. COSY spectrum of 5 92
Figure 3-5-12. HMBC spectrum of 5 92
Figure 3-5-13. NOESY spectrum of 5 93
Figure 3-6-1. 1H–1H COSY and selective HMBC correlations of 6 95
Figure 3-6-2. Selected NOESY correlations of 6 96
Figure 3-6-3. IR spectrum of 6 98
Figure 3-6-4. ESIMS spectrum of 6 98
Figure 3-6-5. HRESIMS spectrum of 6 99
Figure 3-6-6. 1H NMR spectrum of 6 99
Figure 3-6-7. 1H NMR (2.3~5.7 ppm) spectrum of 6 100
Figure 3-6-8. 13C NMR spectrum of 6 100
Figure 3-6-9. DEPT spectra of 6 101
Figure 3-6-10. HMQC spectrum of 6 101
Figure 3-6-11. COSY spectrum of 6 102
Figure 3-6-12. HMBC spectrum of 6 102
Figure 3-6-13. NOESY spectrum of 6 103
Figure 3-7-1. 1H–1H COSY and selective HMBC correlations of 7 105
Figure 3-7-2. Selected NOESY correlations of 7 106
Figure 3-7-3. IR spectrum of 7 108
Figure 3-7-4. ESIMS spectrum of 7 108
Figure 3-7-5. HRESIMS spectrum of 7 109
Figure 3-7-6. 1H NMR spectrum of 7 109
Figure 3-7-7. 1H NMR (2.3~5.7 ppm) spectrum of 7 110
Figure 3-7-8. 13C NMR spectrum of 7 110
Figure 3-7-9. DEPT spectra of 7 111
Figure 3-7-10. HMQC spectrum of 7 111
Figure 3-7-11. COSY spectrum of 7 112
Figure 3-7-12. HMBC spectrum of 7 112
Figure 3-7-13. NOESY spectrum of 7 113
Figure 3-8-1. 1H–1H COSY and selective HMBC correlations of 8 115
Figure 3-8-2. Selected NOESY correlations of 8 116
Figure 3-8-3. IR spectrum of 8 118
Figure 3-8-4. ESIMS spectrum of 8 118
Figure 3-8-5. HRESIMS spectrum of 8 119
Figure 3-8-6. 1H NMR spectrum of 8 119
Figure 3-8-7. 1H NMR (2.8~8.2 ppm) spectrum of 8 120
Figure 3-8-8. 13C NMR spectrum of 8 120
Figure 3-8-9. DEPT spectra of 8 121
Figure 3-8-10. HMQC spectrum of 8 121
Figure 3-8-11. COSY spectrum of 8 122
Figure 3-8-12. HMBC spectrum of 8 122
Figure 3-8-13. NOESY spectrum of 8 123
Figure 3-9-1. 1H–1H COSY and selective HMBC correlations of 9 125
Figure 3-9-2. Selected NOESY correlations of 9 126
Figure 3-9-3. IR spectrum of 9 128
Figure 3-9-4. ESIMS spectrum of 9 128
Figure 3-9-5. HRESIMS spectrum of 9 129
Figure 3-9-6. 1H NMR spectrum of 9 129
Figure 3-9-7. 1H NMR (1.9~5.3 ppm) spectrum of 9 130
Figure 3-9-8. 13C NMR spectrum of 9 130
Figure 3-9-9. DEPT spectra of 9 131
Figure 3-9-10. HMQC spectrum of 9 131
Figure 3-9-11. COSY spectrum of 9 132
Figure 3-9-12. HMBC spectrum of 9 132
Figure 3-9-13. NOESY spectrum of 9 133
Figure 3-10-1. 1H–1H COSY and selective HMBC correlations of 10 135
Figure 3-10-2. Selected NOESY correlations of 10 136
Figure 3-10-3. IR spectrum of 10 138
Figure 3-10-4. ESIMS spectrum of 10 138
Figure 3-10-5. HRESIMS spectrum of 10 139
Figure 3-10-6. 1H NMR spectrum of 10 139
Figure 3-10-7. 1H NMR (1.8~5.0 ppm) spectrum of 10 140
Figure 3-10-8. 13C NMR spectrum of 10 140
Figure 3-10-9. DEPT spectra of 10 141
Figure 3-10-10. HMQC spectrum of 10 141
Figure 3-10-11. COSY spectrum of 10 142
Figure 3-10-12. HMBC spectrum of 10 142
Figure 3-10-13. NOESY spectrum of 10 143
Figure 3-11-1. ESIMS spectrum of 11 146
Figure 3-11-2. 1H NMR spectrum of 11 146
Figure 3-11-3. 13C NMR spectrum of 11 147
Figure 3-12-1. ESIMS spectrum of 12 150
Figure 3-12-2. 1H NMR spectrum of 12 150
Figure 3-12-3. 13C NMR spectrum of 12 151
Figure 3-13-1. ESIMS spectrum of 13 154
Figure 3-13-2. 1H NMR spectrum of 13 154
Figure 3-13-3. 13C NMR spectrum of 13 155
Figure 3-14-1. ESIMS spectrum of 14 158
Figure 3-14-2. 1H NMR spectrum of 14 158
Figure 3-14-3. 13C NMR spectrum of 14 159
Figure 3-15-1. ESIMS spectrum of 15 162
Figure 3-15-2. 1H NMR spectrum of 15 162
Figure 3-15-3. 13C NMR spectrum of 15 163
Figure 3-16-1. ESIMS spectrum of 16 166
Figure 3-16-2. 1H NMR spectrum of 16 166
Figure 3-16-3. 13C NMR spectrum of 16 167
Figure 4-1. 化合物 1–5、8、11–16之濃度為10 µM，6、7 為1 µM抑制LPS誘發老鼠巨噬細胞 (macrophage, RAW264.7) 產生iNOS (inducible nitric oxide synthase) 之抗發炎活性篩檢結果 179
Figure 4-2. 化合物 1–5、8、11–16之濃度為10 µM，6、7 為1 µM抑制LPS誘發老鼠巨噬細胞 (macrophage, RAW264.7) 產生COX-2 (cyclooygenase-II) 之抗發炎活性篩檢結果 180
Figure 4-3. 化合物 1–5、8、11–16之濃度為10 µM，6、7 為1 µM抑制LPS誘發老鼠巨噬細胞 (macrophage, RAW264.7) 產生iNOS與COX-2實驗之內標準β-actin蛋白質之表現 181
表 目 錄 頁次
Table 1-1. Klyxum屬所含天然物的文獻回顧 4
Table 1-2. Eunicellin骨架之相關的的文獻回顧 11
Table 3-1. 1H and 13C NMR Data, 1H–1H COSY, and HMBC correlations of 1 45
Table 3-2. 1H and 13C NMR Data, 1H–1H COSY, and HMBC correlations of 2 55
Table 3-3. 1H and 13C NMR Data, 1H–1H COSY, and HMBC correlations of 3 65
Table 3-4. 1H and 13C NMR Data, 1H–1H COSY, and HMBC correlations of 4 76
Table 3-5. 1H and 13C NMR Data, 1H–1H COSY, and HMBC correlations of 5 87
Table 3-6. 1H and 13C NMR Data, 1H–1H COSY, and HMBC correlations of 6 97
Table 3-7. 1H and 13C NMR Data, 1H–1H COSY, and HMBC correlations of 7 107
Table 3-8. 1H and 13C NMR Data, 1H–1H COSY, and HMBC correlations of 8 117
Table 3-9. 1H and 13C NMR Data, 1H–1H COSY, and HMBC correlations of 9 127
Table 3-10. 1H and 13C NMR Data, 1H–1H COSY, and HMBC correlations of 10 137
Table 3-11. 1H and 13C NMR Data of 11 145
Table 3-12. 1H and 13C NMR Data of 12 149
Table 3-13. 1H and 13C NMR Data of 13 153
Table 3-14. 1H and 13C NMR Data of 14 157
Table 3-15. 1H and 13C NMR Data of 15 161
Table 3-16. 1H and 13C NMR Data of 16 165
Table 4-1. Cytotoxicity (IC50 μg/mL) of compounds 1–8 and 11–16 178
Table 4-2. Figure 4-1之數據整理 179
Table 4-3. Figure 4-2之數據整理 180
Table 4-4. Figure 4-3之數據整理 181

1. Ruggieri, G. D. “Drugs from the sea” Science 1976, 194, 491–497.
2. Simmons, T. L.; Andrianasolo, E.; McPhail, K.; Flatt, P.; Gerwick, W. H. “Marine natural products as anticancer drugs” Mol. Cancer. Ther. 2005, 4, 333–342.
3. Blunt, J. W.; Copp, B. R.; Munro, M. H. G.; Northcote, P. T.; Prinsep, M. R. “Marine natural products” Nat. Prod. Rep. 2010, 27, 165–237.
4. Bowden, B. F.; Coll, J. C.; Patalinghug, W.; Skelton, B. W.; Vasilescu, I.; White, A. H. Aust. J. Chem. 1987, 40, 2085–2096.
5. Coval, S. J.; Cross, S.; Bernardinelli, G.; Jefford, C. W. “Brianthein V, a New Cytotoxic and Antiviral Diterpene Isolated from Briareum asbestinum” J. Nat. Prod. 1988, 51, 981–984.
6. Neve, J. E.; McCool, B. J.; Bowden, B. F. “Excavatolides N－T, New Briarane Diterpenes from the Western Australian Gorgonian Briareum excavatum” Aust. J. Chem. 1999, 52, 359–366.
7. Shin, J.; Park, M.; Fenical, W. “The junceellolides new anti- inflammatory diterpenoids of the briarane class from the Chinese gorgonian Junceella fragilis” Tetrahedron 1989, 45, 1633–1638.
8. Wratten, S. J.; Fenical, W.; Faulkner, D. J. “Ptilosarcone, the toxin from the sea pen Ptilosarcus gurneyi” Tetrahedron Lett. 1977, 18, 1559–1562.
9. Kobayashi, J.; Cheng, J.-F.; Nakamura, H.; Ohizumi, Y.; Tomotake, Y.; Matsuzaki, T.; Grace, K. J. S.; Jacobs, R. S.; Kato, Y.; Brinen, L. S.; Clardy, J. “Structure and stereochemistry of brianolide, a new antiinflammatory diterpenoid from the Okinawan gorgonian Briareum sp.” Cell. Mol. Life. Sci. 1991, 47, 501–502.
10. Grode, S. H.; James, T. R., Jr; Cardellina, J. H.,II.; Onan, K.D. “Molecular Structures of the Briantheins, New Insecticidal Diterpenes from Briareum polyanthes” J. Org. Chem. 1983, 48, 5203–5207.
11. Chill, L.; Berrer, N.; Benayahu, Y.; Kashman, Y. “Eunicellin Diterpenes from two Kenyan Soft Corals” J. Nat. Prod. 2005, 68, 19–25.
12. Rodriguez, A. D.; Cobar, O. M. “The Briarellins, New Eunicellin-Based Diterpenoids from A Caribbean Gorgonian, Briareum asbestinum” Tetrahedron, 1995, 51, 6869–6880.
13. 陳威錚 “台灣產軟珊瑚Klyxum simplex和印尼產海綿Halichondria sp. 所含化學成份之研究” 國立中山大學海洋資源學系碩士論文，2005年。
14. Wu, S-L; Su, J-H; Wen, Z-H; Hsu, C-H; Chen, B-W; Dai, C-F; Kuo, Y-H; Sheu, J-H; “Simplexins A－I, Eunicellin-Based Diterpenoids from the Soft Coral Klyxum simplex” J. Nat. Prod. 2009, 72, 994–1000.
15. Chen, B-W; Wu, Y-C; Chiang, Michael Y.; Su, J-H; Wang, W-H; Fan, T-Y; Sheu, J-H; “Eunicellin-based diterpenoids from the cultured soft coral Klyxum simplex” Tetrahedron 2009, 65, 7016–7022.
16. Hassan, H. M.; Khanfar, M. A.; Elnagar, A. Y.; Mohammed, R.; Shaala, L. A.; Youssef, D. T. A.; Hifnawy, M. S.; Sayed, K. A. El “Pachycladins A－E, Prostate Cancer Invasion and Migration Inhibitory Eunicellin-Based Diterpenoids from the Red Sea Soft Coral Cladiella pachyclados” J. Nat. Prod. 2010, 73, 848–853.
17. Bowden, B. F.; Coll, J. C.; Dai, M. C.; “Studies of Australian Soft Corals. XLIII. The Structure Elucidation of a New Diterpene from Alcyonium molle” Australian J. Chem. 1989, 42, 665–673.
18. Su, J.; Zheng, Y.; Zeng, L.; Pordesimo, Eva O.; Schmitz, F. J.; Hossain, M. B.; Helm, D. V. D. “Patagonicol: A Diterpenoid from the Chinese Soft Coral Alcyonium patagonicum” J. Nat. Prod. 1993, 56, 1601–1604.
19. Kyeremeh, K.; Baddeley, T. C.; Stein, B. K.; Jaspars, M. “A Homologous Series of Eunicellin-Based Diterpenes from Acalycigorgia sp. Characterised by tandem mass spectrometry” Tetrahedron 2006, 62, 8770–8778.
20. Lin, Y.; Bewely, C. A.; Faulkner, D. J. “The Valdivones, Antiinammatory Diterpene Esters from the South African Soft Coral Alcyonium valdivae ” Tetrahedron 1993, 49, 7977–7984.
21. Fusetani, N.; Nagata, H.; Hirota, H.; Tsuyuki, T. “Astrogorgiadiol and Astrogorgin, Inhibitors of Cell Division in Fertilized starfish Eggs, from a Gorgonian Astrogorgia sp.” Tetrahedron Lett. 1989, 50, 7079–7082.
22. Seo, Y.; Rho, J.-R.; Cho, K. W.; Shin, J. “Isolation of Diterpenoids of Cladiellane Class from Gorgonians of the Genus Muricella” J. Nat. Prod. 1997, 60, 171–174.
23. Mancini, I.; Guella, G.; Zibrowius, H.; Pietra, F. “Configuration, Conformation, and Reactivity of Highly Functionalized Eunicellane Diterpenes Isolated from the Gorgonians Eunicella cavolinii and Eunicella singularis from Marseille” Helv. Chim. Acta. 2000, 83, 1561–1575.
24. De Rosa, S. ; Cimino, G.; De Giulio, A.; Milone, A.; Crispino, A.; Iodice, C. “A New Bioactive Eunicellin-Type Ditepene from the Gorgonian Eunicella cavolini” Nat. Prod. Lett. 1995, 7, 259–265.
25. Ochi, M.; Yamada, K.; Futatsugi, K.; Kotsuki, H.; Shibata, K. “Litophynin D and E, Two new Diterpenoids from a soft coral Litophyton sp.” Chem. Lett. 1990, 12, 2183–2186.
26. Rodriguez, A. D.; Cobar, O. M. “Studies on the Minor Constituents of the Caribbean Gorgonian Octocoral Briareum asbestinum Pallas. Isolation and Structure Determination of the Eunicellin-Based Diterpenoids Briarellins E－I” Chem. Pharm. Bull. 1995, 43, 1853–1858.
27. Ospina, C. A.; Rodriguez, A. D.; Ortega-Barria, E.; Capson, T. L. “Briarellins J－P and Polyanthellin A: New Eunicellin-Based Diterpenes from the Gorgonian Coral Briareum polyanthrs and Their Antimalarial Activity” J. Nat. Prod. 2003, 66, 357–363.
28. Ospina, C. A.; Rodriguez, A. D. “Bioactive Compounds from the Gorgonian Briareum polyanthes. Correction of the structures of Four Asbestinane-Type Diterpenes” J. Nat. Prod. 2006, 69, 1721–1727.
29. Ahmed, A. F.; Wu, M.-H.; Wang, G.-H.; Wu, Y.-C.; Sheu, J.-H. “Eunicellin-Based Diterpenoids, Australins A－D, Isolated from the Soft Coral Cladiella australis” J. Nat. Prod. 2005, 68, 1051–1055.
30. Kennard, O.; Watson, D. G.; Sanseverino, L. R. D. “The Crystal and Molecular Structure of Eunicellin Dibromide, C28H42O9Br2” Acta Cryst. 1970, B26, 1038.
31. Rao, C. B.; Rao, D. S.; Satyanarayana, C.; Rao, D. V.; Kassuhlke, K. E.; Faulkner, D. J. “New Cladlellane Diterpenes from the Soft Coral Cladiella Australis of the Andaman and Nicobar Islands” J. Nat. Prod. 1994, 57, 574–580.
32. Sarma, N. S.; Chavakula, R.; Rao, I. N.; Kadirvelraj, R.; Row, T. N. G.; Saito, I. “Crystal and Molecular structure of Sclerophytin F methyl ether from the Soft Coral Cladiella krempfi” J. Nat. Prod. 1993, 56, 1977–1980.
33. Yamada, K.; Ogata, N.; Ryu, K.; Miyamoto, T.; Komori, T.; Higuchi, R. “Bioactive Terpenoids from Octocorallia. 3. A New Eunicellin-Based Diterpenoid from the Soft Coral Cladiella sphaeroides” J. Nat. Prod. 1997, 60, 393–396.
34. Chen, S.-P.; Sung, P.-J.; Duh, C.-Y.; Dai, C. F.; Sheu, J.-H. “Junceol A, a New Sesquiterpenoid from the Sea Pen Virgularia juncea” J. Nat. Prod. 2001, 64, 1241–1242.
35. Ketzinel, S.; Rudi, A.; Schleyer, M.; Benayahu, Y.; Kashman, Y. “Sarcodictyin A and Two Novel Diterpenoid Glycosides, Eleuthosides A and B, from the Soft Coral Eleutherobia aurea” J. Nat. Prod. 1996, 59, 873–875.
36. Ortega, M. J.; Zubia, E.; Salva, J. “A New Cladiellane Diterpenoid from Eunicella labiata” J. Nat. Prod. 1997, 60, 485–487.
37. Roussis, V.; Fenical, W.; Vagias, C.; Kornprobst, J.-M.; Miralles, J. “Labiatamides A, B, and other Eunicellan Diterpenoids from the Senegalese Gorgonian Eunicella labiata” Tetrahedron 1996, 52, 2735–2742.
38. Kakonikos, C.; Vagias, C.; Roussis, V.; Roussakis, C.; Kornprobst, J.-M. “New Eunicellin Type Diterpenoids from the Gorgonian Coral Eunicella labiata” Nat. Prod. Lett. 1999, 13, 89–95.
39. Ortega, M. J.; Zubia, E.; Salva, J. “Structure and Absolute Configuration of Palmonine F, A New Eunicellin-Based Diterpene from the Gorgonian Eunicella verrucosa” J. Nat. Prod. 1994, 57, 1584–1586.
40. Ortega, M. J.; Zubia, E.; He, H.-Y.; Salva, J. “New Eunicellin-Based Diterpene from the Gorgonian Eunicella verrucosa” Tetrahedron 1993, 49, 7823–7828.
41. Miyamoto, T.; Yamada, K.; Ikeda, N.; Komori, T.; Higuchi, R. “Bioactive Terpenoids from Octocorallia, I. Bioactive Diterpenoids: Litophynols A and B from the Mucus of the Soft Coral Litophyton sp.” J. Nat. Prod. 1994, 57, 1212–1219.
42. Ochi, M.; Yamada, K.; Futatsugi, K.; Kotsuji, H.; “Litophynin F, G and H, Three new Diterpenoids from a soft coral Litophyton sp.” Heterocycles, 1991, 1, 29–31
43. Wang, G.-H.; Sheu, J.-H.; Chiang, M. Y.; Lee, T.-J. “Pachyclavulariaenines A－C, Three Novel Diterpenoids from the Soft Coral Pachyclavularia violacea” Tetrahedron Lett. 2001, 42, 2333–2336.
44. Wang, G.-H.; Sheu, J.-H.; Duh, C.-Y.; Chiang, M. Y. “Pachyaclavulariaenones D－G, New Diterpenoids from the Soft Coral Pachyclavlaria violacea” J. Nat. Prod. 2002, 65, 1475–1478.
45. Sharma, P.; Alam, M. “Sclerophytin A and B. Isolation and Structures of Novel Cytotoxic Diterpenes from the Marine Coral Sclerophytum capitalis” J. Chem. Soc., Perkin Trans. 1 1988, 2537–2540.
46. Alam, M.; Sharma, P.; Zektzer, A. S.; Martin, G. E.; Ji, X.; Helm, D. V. D. “Sclerophytin C－F: Isolation and Structures of Four New Diterpenes from the Soft Coral Sclerophytum capitalis” J. Org. Chem. 1989, 54, 1896–1900.
47. 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, 6, 1077–1078.
48. Bloor, S. J.; Schmitz, F. J.; Hossain, M. B.; Helm, D. V. D. “Diterpenoids from the Gorgonian Solenopodium stechei” J. Org. Chem. 1992, 57, 1205–1216.
49. Su, J.-H.; Huang, H.-C.; Chao, C.-H.; Yan, L.-Y.; Wu, Y.-C.; Wu, C.-C.; Sheu, J.-H. “Vigulariol, a New Metabolite from the Sea Pen Vigularia juncea” Bull. Chem. Soc. Jpn. 2005, 78, 877–879.
50. Dale, J. A.; Mosher, H. S. “Nuclear Magnetic Resonance Enantiomer Regents. Configurational Correlations via Nuclear Magnetic Resonance Chemical Shifts of Diastereomeric Mandelate, O-methylmandelate, and a-Methoxy-a-trifluoromethylphenylacetate (MTPA) esters” J. Am. Chem. Soc. 1973, 95, 512–519.
51. Ohtani, I.; Kusumi, T.; Kashman, Y.; Kakisawa, H. “High-Field FT NMR Application of Mosher’s Mehod. The Absolute Configurations of Marine Terpenoids” J. Am. Chem. Soc. 1991, 113, 4092–4096.
52. Alley, M.-C.; Scudiero, D. A.; Monks, A.; Hursey, M. L.; Czerwinski, M. J.; Fine, D. L.; Abbott, B. J.; Mayo, J. G.; Shoemaker, R. H.; Boyd, M. R. “Feasibility of drug screening with panels of human tumor cell lines using a microculture tetraxolium assay” Cancer Res. 1988, 48, 589–601.
53. Scudiero, D. A.; Shoemaker, R. H.; Paull, K. D.; Monks, A.; Tierney,
S.; Nofziger, T. H.; Currens, M. J.; Seniff, D.; Boyd, M. R. “Evalution of a soluble with tetrazolium/ formazan assay for cell growth and drug sensitivity in culture using human and other tumor cell lines” Cancer Res. 1988, 48, 4827–4833.
54. Findlay, J. A.; Patil, A. D. “Novel sterols from the finger spong Haliclona oculata” Can. J. Chem., 1985, 63, 2406–2410.
55. Ho, F.-M.; Lai, C.-C.; Huang, L.-J.; Kuo, T.-C.; Chao, C.-M.; Lin, W.-W. “The anti-inflammatory carbazole, LCY-2-CHO, inhibits lipopolysaccharide-induced inflammatory mediator expression through inhibition of the p38 mitogen-activated protein kinase signaling pathway in macrophages” Br. J. Pharmacol. 2004, 141, 1037–1047.
56. Chen, B-W; Chao, C-H; Su, J-H; Wen, Z-H; Sung, P-J; Sheu, J-H; ”Anti-inflammatory eunicellin-based diterpenoids from the cultured soft coral Klyxum simplex” Org & Biomol Chem. 2010, 8, 2363–2366.