臺灣博碩士論文加值系統

本論文主要研究一種海綿（Ircinia formosana）與三種軟珊瑚（Sinularia flexibilis、Cespitularia hypotentaculata、Clavularia viridis），對這些海洋生物以化學方式分析其乙酸乙酯萃取層中所含的成分，一共獲得四十個海洋天然化合物，其中有二十三個新天然化合物。並對分離出之化合物做抗癌活性分析。
在海綿Ircinia formosana中共分離出四個C22-sesterterpenoids天然化合物，皆為新的C22-sesterterpenoids天然化合物，命名為Irciformonins A-D (1-4)；在軟珊瑚Sinularia flexibilis中共分離出十二個cembrane類的天然化合物，其中有九個新的cembrane類的天然化合物，命名為Sinuladiterpenes A-I (5-13) 以及三個已知的cembrane類的天然化合物，分別為11-epi-sinulariolide acetate（24）、sinulariolide（25）、11-dehydrosinulariolide（26）。在軟珊瑚Cespitularia hypotentaculata中共分離出十三個雙萜類化合物，其中有六個新的雙萜類化合物，命名為Cespihypotins Q-V (14-19)，以及七個已知的雙萜類化合物，分別為Cespitularin E（27）、Cespihypotin D（28）、Cespihypotin C（29）、Cespitulacton A（30）、Cespitulacton B（31）、Cespitularin D（32）、Cespitularin F（33）。在軟珊瑚Clavularia viridis中共分離出十一個類前列腺素的天然化合物，其中分離出四個新的類前列腺素的天然化合物，命名為Claviridic esters A-D (20-23)，以及七個已知的類前列腺素天然化合物，分別為Clavulones I-III（34-36）、Claviridic acids A-E（37-40）。
上述化合物之結構鑑定主要是由一維及二維核磁共振圖譜資料(1H NMR, 13C NMR, DEPT, HMQC, HMBC, COSY, NOESY)，加上質譜(ESIMS)、光譜資料(UV, IR, optical rotation)分析，並與文獻比對後所訂定的。活性部分則委託國立中國醫藥研究所郭曜豪老師實驗室幫忙測試，其中海綿Ircinia formosana中的化合物irciformonins C (3)及D (4)對人類結腸癌細胞(WiDr)有毒殺活性，其ED50分別為6.7及4.9 μg/mL；軟珊瑚Cespitularia hypotentaculata中所分離出的化合物Cespihypotin T (17)對於人類髓母細胞瘤癌細胞(Daoy)及人類結腸癌細胞(WiDr)有中等的毒殺活性其ED50分別為9.3及7.5 μg/mL；而羽珊瑚Clavularia viridis所分離出的化合物claviridic esters A (20)及B (21) 對人類肝癌細胞(Hep2)有顯著毒殺活性，其ED50分別為0.19及0.16 μg/mL，claviridic ester B (21)對人類髓母細胞瘤癌細胞(Daoy) 有顯著毒殺活性，其ED50為0.18 μg/mL。

This dissertation mainly investigates the constituents of one species of sponge (Ircinia formosana) and three species of soft corals（Sinularia flexibilis、Cespitularia hypotentaculata and Clavularia viridis）. These organisms were extracted with EtOAc and analyzed them with chemical methods. Twenty three new natural products were isolated and the cytotoxicity of these copounds was tested and evaluated.
Four new C22-sesterterpenoids were isolated from the sponge Ircinia formosana, and designated as irciformonins A-D (1-4). In the investigation of the soft coral Sinularia flexibilis, nine new cembranes were purified, and they were called sinuladiterpenes A-I (5-13). Six new diterpenes, cespihypotins Q-V (14-19) were obtained from the soft coral Cespitularia hypotentaculata. In addition, the soft coral Clavularia viridis afforded four new prostanoids, designated claviridic esters A-D (20-23).
The structures of these metabolites including their stereochemistries have been established by detailed spectroscopic analyses, particularly 2D NMR (1H–1H COSY, HMQC, HMBC, and NOESY) spectroscopy and mass and by comparison with the related physical and spectral data of known compounds. Cytotoxicity of the isolated compounds was measured by Dr. Kuo Yao-Haur, Institute of Chinese Medicine. Irciformonins C (3) and D (4) from sponge Ircinia formosana showed the cytotoxicity against WiDr (Human colon adenocarcinoma) with ED50 at 6.7 and 4.9 μg/mL, respectively. Cespihypotin T (17) was found to exhibit the inhibition against Daoy (Human medulloblastoma) and WiDr (Human colon adenocarcinoma) at ED50 9.3 and 7.5 μg/mL. Claviridic esters A (20) and B (21) exhibited significant cytotoxicity against the growth of Hep2 (Human hepatoma) at ED50 0.19 nad 0.16 μg/mL, respectively. Claviridic ester B (21) also showed significant cytotoxicity against Daoy (Human medulloblastoma) tumor cells at ED50 0.18 μg/mL.

第一章、緒論
第一節 前言……………………………………………………1
第二節 研究動機………………………………………………2
第二章、文獻回顧
第一節 Ircinia屬………………………………………………3
第二節 Sinularia屬…………………………………………11
第三節 Cespitularia屬………………………………………17
第四節 Clavularia屬…………………………………………25
第三章、材料與方法
第一節 樣品採集與分類地位…………………………………34
第二節 實驗程序與方法………………………………………46
第三節 實驗設備儀器…………………………………………47
第四節 矽膠與溶劑部分………………………………………48
第五節 結構之鑑定……………………………………………49
第四章、結果與討論
第一節 海綿Ircinia formosana部分……………………………..…………50
Irciformonin A (1)之結構解析………………………….50
Irciformonin B (2)之結構解析………………………….59
Irciformonin C (3)之結構解析………………………….67
Irciformonin D (4)之結構解析………………………….75
第二節 軟珊瑚Sinularia flexibilis部分………………………………….…83
Sinuladiterpene A (5)之結構解析……………………….85
Sinuladiterpene B (6)之結構解析……………………….94
Sinuladiterpene C (7)之結構解析……………………….102
Sinuladiterpene D (8)之結構解析……………………….111
Sinuladiterpene E (9)之結構解析……………………….119
Sinuladiterpene F (10)之結構解析……………………….127
Sinuladiterpene G (11)之結構解析……………………….135
Sinuladiterpene H (12)之結構解析……………………….143
Sinuladiterpene I (13)之結構解析……………………….152
第三節 軟珊瑚Cespitularia hypotentaculata部分………………….……159
Cespihypotin Q (14)之結構解析…..…………………………161
Cespihypotin R (15)之結構解析………..…………………168
Cespihypotin S (16)之結構解析………..…………………176
Cespihypotin T (17)之結構解析………..…………………184
Cespihypotin U (18)之結構解析……..……………………192
Cespihypotin V (19)之結構解析……..……………………200
第四節 軟珊瑚Clavularia viridis部份……………………....……………208
Clavuridic ester A (20)之結構解析………………….………210
Clavuridic ester B (21)之結構解析……………..…..………217
Clavuridic ester C (22)之結構解析……………..…..………224
Clavuridic ester D (23)之結構解析……………..…..………231
第五章 活性測試結果
第一節 海綿Ircinia formosana部分…………………………....…………239
第二節 軟珊瑚Sinularia flexibilis部分………………………….……..…240
第三節 軟珊瑚Cespitularia hypotentaculata部分………………..………241
第四節 軟珊瑚Clavularia viridis部份……………………………………242
第六章 結論………………………………………………………….………….243
參考文獻…………………………………………………………….……………244
個人成果…………………………………………………………….……………249

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