穗軟珊瑚屬和叢軟珊瑚屬中有許多具生物活性的固醇與萜類化合物，因此我們針對自小琉球所採集的白穗軟珊瑚(Nephthea chabroli)及綠島採集的綠叢軟珊瑚 (Cespitularia caerulea)進行研究。從白穗軟珊瑚中分離出3個新固醇類化合物 (1‒3)及1個已知固醇類 (4)，分別為1個19-oxygenated sterol (1)、1個polyoxygenated sterol (2)、1個3β-oxygenated sterol (3)及1個已知的3β-oxygenated sterol (4)。從綠叢軟珊瑚中分離出1個已知的eudesmane 類倍半萜(5)、4個已知的verticillene類二萜(6‒9)及1個已知cespitularin類化合物(10)。
上述化合物的平面結構是根據光譜分析(IR, UV, MS, 1D NMR, 2D NMR)及比對已發表之文獻中的化學位移所決定，而其立體相對位向是根據NOESY圖譜的關聯訊號、耦合常數及電腦模擬所定出。將化合物1‒10針對B16­F10 (老鼠皮膚黑色素瘤細胞)及MDA-MB-231 (人類乳腺癌細胞)以MTT試驗法進行毒殺測試。

Soft corals belonging to the genera Nephthea and Cespitularia have proven to be a rich source of bioactive steroids and terpenoids. N. chabroli collected from Hsiao Liouciou and C. caerulea collected from Green island were studied in this thesis. Three new steroids (1‒3) and one known steroid (4) were isolated from Nephthea chabroli, including one 19-oxygenated sterol (1), one polyoxygenated sterol (2), one 3β-oxygenated sterol (3) and one known 3β-oxygenated sterol (4). One known eudesmane-type sesquiterpene (5), four known verticillene-type diterpenes (6‒9) and one known cespitularin (10) were isolated from C. caerulea.
The structures of these compounds were determined on the basis of spectroscopic analysis (IR, UV, MS, 1D NMR and 2D NMR) and by comparison the chemical shift from reported literatures. The relative stereochemistry was determined by NOESY correlation, coupling constants and computer simulation. Compounds 1‒10 were tested against B16-­F10 (Mus musculus skin melanoma) and MDA-MB-231 (human breast cancer) by MTT method.

論文審定書 i
謝辭 ii
中文摘要 iii
英文摘要 iv
化合物1‒10化學結構 v
目錄 vi
表次 ix
圖次 x
縮寫對照表 xvii
壹、 緒論 1
一、 前言與研究動機 1
二、 Nephthea屬軟珊瑚之二次代謝物研究回顧 2
1. 19-Oxygenated sterols固醇類文獻回顧 2
2. Polyoxygenated sterols固醇類文獻回顧 10
3. 4α-Methylated sterols固醇類文獻回顧 16
4. 19-Norergosterol固醇類文獻回顧 19
三、 Cespitularia屬之二次代謝物研究回顧 22
1. Sesquiterpene類化合物之文獻回顧 22
2. Verticillene 與norverticillene類化合物之文獻回顧 25
3. Cespitularane類化合物之文獻回顧 34
4. Nitrogen-containing verticillene類化合物之文獻回顧 36
5. Steroid與ceramide類化合物之文獻回顧 40
貳、 材料與研究方法 42
一、 白穗軟珊瑚Nephthea chabroli樣品採集、分類地位與分離流程 42
1. Nephthea chabroli 樣品採集時間、地點與鑑定 42
2. Nephthea chabroli之分類地位 42
3. Nephthea chabroli之萃取與分離流程 42
4. Nephthea chabroli軟珊瑚代謝物之分離純化 45
(1) 化合物1‒4之分離純化 45
二、 綠叢軟珊瑚Cespitularia caerulea樣品採集、分類地位與分離流程 47
1. Cespitularia caerulea樣品採集時間、地點與鑑定 47
2. Cespitularia caerulea之分類地位 48
3. Cespitularia caerulea之萃取與分離流程 48
4. Cespitularia caerulea軟珊瑚代謝物之分離純化 51
(1) 化合物5、7和9之分離純化 51
(2) 化合物6之分離純化 51
(3) 化合物8和10之分離純化 52
參、化合物之結構鑑定 54
一、 白穗軟珊瑚Nephthea chabroli之二次代謝物 54
1. 化合物1之結構解析(CDCl3) 54
2. 化合物2之結構解析(CDCl3) 84
3. 化合物3之結構解析(CDCl3) 109
4. 化合物4之結構判定(CDCl3) 134
二、 綠叢軟珊瑚Cespitularia caerulea之二次代謝物 139
1. 化合物5之結構判定(CDCl3) 139
2. 化合物6之結構判定(CDCl3) 159
3. 化合物7之結構判定(CDCl3) 176
4. 化合物8之結構判定(CDCl3) 194
5. 化合物9之結構判定(CDCl3) 199
6. 化合物10之結構判定(CDCl3) 204
肆、生物活性之測試 222
一、 老鼠黑色素瘤(B16­-F10)細胞毒殺活性測試方法 222
二、 人類乳腺癌(MDA-MB-231)細胞毒殺活性測試方法 222
三、 WST-1與MTT分析原理 223
四、 活性測試結果 223
伍、結論 225
陸、參考文獻 227
柒、附錄 234
一、 實驗設備儀器及材料 234
1. 實驗設備儀器 234
2. 實驗材料 234

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