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研究生:陳佩文
研究生(外文):Pei-wen Chen
論文名稱:指形軟珊瑚Sinularialeptoclados與Sinulariasandensis所含二次代謝物之研究
論文名稱(外文):Studies on the Secondary Metabolites from the Soft Corals Sinularia leptoclados and Sinularia sandensis
指導教授:杜昌益杜昌益引用關係
指導教授(外文):Chang-yih Duh
學位類別:碩士
校院名稱:國立中山大學
系所名稱:海洋生物科技暨資源學系研究所
學門:自然科學學門
學類:海洋科學學類
論文種類:學術論文
論文出版年:2010
畢業學年度:98
語文別:中文
論文頁數:251
中文關鍵詞:二次代謝物指形軟珊瑚
外文關鍵詞:Sinularia leptocladossoft corals11-secosteroids9Sinularia sandensis
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在過去的研究中,發現Sinularia 屬之軟珊瑚具有許多不同骨架的二次代謝物,並且許多都具有特殊的生物活性,為了尋找具有生物活性的新化合物,我們主要針對東沙環礁海域之指形軟珊瑚(Sinularia leptoclados)和小琉球海域之指形軟珊瑚(Sinularia sandensis)的二次代謝物進行分析研究。從軟珊瑚S. leptoclados 之有機萃取物中分離得到四個新的固醇類化合物(1-3 和11)、一個人工的固醇類化合物(5)以及六個已知的9,11-seco 固醇類化合物(4 和6-10)。另外,從軟珊瑚S. sandensis 的有機萃取物中純化出三個sesquiterpenoids 類的新骨架化合物(12-14)。這些二次代謝物的結構鑑定,主要是透過其有機光譜的分析(包含紅外線光譜、紫外線光譜、質譜、旋光、圓二色分光光譜、一維及二維NMR)以及與已知化合物之文獻比對光譜資料而決定的,而化合物12 之絕對立體位向的決定是運用Mosher 的方法加以證明。此外並針對化合物1-4 和6-14 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(P-388)毒殺活性測試,以及化合物4、10、11 和13 進行抗人類巨細胞病毒(HCMV)測試,發現化合物2、4 及6-10 對老鼠血癌細胞(P-388)有顯著的活性(ED50≦4 mg/mL)。
Soft corals of the genus Sinularia have been proved to yield a wide variety of secondary metabolites. In order to search for novel bioactive substances from marine organisms, we have investigated the secondary metabolites of the soft corals Sinularia leptoclados and Sinularia sandensis. Chromatographic separation of the organic extracts of the
Formosan soft coral Sinularia leptoclados, collected at Dongsha Atoll of the South China Sea, led to the isolation of four new steroids (1-3 and 11), along with an unexpected artificial sterol (5) and six known 9,11-secosteroids (4 and 6-10). In addition, the acetone extract of the soft coral, Sinularia sandensis, collected at the Tsau-Lou-Cho Island off the southwestern coast of Taiwan, yielded three novel sesquiterpenoids (12-14). The structures of the isolated metabolites were elucidated by extensive spectroscopic analyses (IR, UV, mass, optical rotations, CD, 1D and 2D NMR) and by comparison of the spectral data with those of the related known compounds. Moreover, the absolute configuration of 12 was established by application of modified Mosher’s method. The cytotoxicity against of P-388 (mouse lymphocytic leukemia), HT-29 (human colon adenocarcinoma), and A-549 (human lung epithelial carcinoma) cells of metabolites 1-4 and 6-14 as well as the anti-HCMV (human cytomegalovirus) activities of metabolites 4, 10, 11, and 13 were evaluated. Metabolites 2, 4 and 6-10 exhibited significant activity against P-388 cell in vitro (IC50≦4 mg/mL).
壹、緒論 1
一、前言 1
二、軟珊瑚Sinularia leptoclados之二次代謝物研究回顧 3
三、軟珊瑚Sinularia sandensis 之二次代謝物研究回顧 15
四、研究動機與目的 17
貳、材料與研究方法 18
一、Sinularia leptoclados 樣品採集及分離流程 18
1. Sinularia leptoclados 樣品採集時間、地點與鑑定 18
2. Sinularia leptoclados 之分類地位 18
3. Sinularia leptoclados 之萃取與分離流程 19
二、Sinularia sandensis 樣品採集及分離流程 23
1. Sinularia sandensis 樣品採集時間、地點與鑑定 23
2. Sinularia leptoclados 之分類地位 23
3. Sinularia sandensis 之萃取與分離流程 24
参、化學成分之結構證明 26
一、軟珊瑚Sinularia leptoclados 之化學成分的結構證明 26
1. Leptosecosterol A (1)之結構解析 26
2. Leptosecosterol B (2)之結構解析 56
3. Leptosecosterol C (3)之結構解析 90
4.化合物4 之結構鑑定 108
5.化合物5 之結構解析 113
6.化合物6 之結構鑑定 129
7.化合物7 之結構鑑定 134
8.化合物8 之結構鑑定 140
9.化合物9 之結構鑑定 145
10.化合物10 之結構鑑定 150
11.化合物11 之結構解析 155
二、軟珊瑚Sinularia sandensis 之化學成分的結構證明 173
1.化合物12 之結構解析 173
2.化合物13 之結構解析 190
3.化合物14 之結構解析 203
肆、生物活性之測試 216
一、細胞毒殺活性測試方法 216
二、MTT 分析原理 217
三、抗HCMV 病毒的測試方法 218
四、活性測試結果 219
伍、結論 221
陸、參考文獻 224
柒、附錄 229
一、Mosher 醯化反應的原理與製備 229
二、實驗設備儀器及材料 231
1.實驗設備儀器 231
2.實驗材料 232
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