摘要

由台灣綠島海域所採集的柳珊瑚Isis hippuris已往曾分離出具有顯著活性的萜類物質，同時粗萃取物乙酸乙酯層以及正己烷層對於數種癌細胞P-388, A-549, HT-29皆有極佳的毒殺活性,可是在歷經各位學長的分離之後，發現有良好活性的化合物並不多，於是促使我們更進一步尋找其他未被發現的活性物質，我們再進一步分析柳珊瑚I. hippuris的化學成分。於是分離到11個新發現的固醇類天然物。分別為A-nor-2-carboxy-22-epi-hippurin-1 (1)、2a-acetoxy-3a-hydroxy-11b- hydroxy-24-methyl-22,25-epoxy-5a-furostan-18,20b-lactone (2)、2a,3 a-dihydroxy-11b-hydroxy-24-methyl-22,25-epoxy-5a-furostan-18,20b-lactone (3)、2a-hydroxy-3a-acetoxy-11b-hydroxy-24-methyl-22,25- epoxy-5a-furostan-18,20b-lactone (4)、2a-hydroxy-3a-acetoxy-24- methyl-11b,18;18,20b;22,25-triepoxy-5a-furostane (5)、2a-acetoxy- 3a-hydroxy-24-methyl-11b,18;18,20b;22,25-triepoxy-5a-furostane (6)、hippuristerone K (7)、hippuristerone L (8)、 hippuristerol F (9)、1a,3b,5b,11a-tetrahydroxygorgostan-6-one (10)、22-epi-hippuristan- 11-one (11)。此外還分離到兩個已知化和物22-epi-hippuristanol (19)、2-desacetyl-22-epi-hippurin-1 (25)。
所有化合物的結構解析均由2D NMR，及文獻的比對來解析。其中化合物1是一具有新骨架的固醇類化合物，其相對立體位向已由X-ray單晶繞射分析來確立。由於所分離出之化合物產率太低，不夠進行活性測試，目前正朝半合成方向來進行。

Several terpenoids isolated from a Formosan gorgonian coral Isis hippuris have shown significant cytotoxic activity against various cancer cell lines. In our studies, the EtOAc and n-Hexane extracts showed potent cytotoxic response toward P-388, A549 and HT-29 cancer cell lines. In order to search other active components, we have studied the chemical constituents of I. hippuris from a Green Island specimen. Thus, the investigation on the chemical content of this extract was carried out.
After our hard working, we haved isolated eleven new steroids (1- 11) , A-nor-2-carboxy-22-epi-hippurin-1 (1)、2a-acetoxy-3a-hydroxy- 11b-hydroxy-24-methyl-22,25-epoxy-5a-furostan-18,20b-lactone (2)、2a,3a-dihydroxy-11b-hydroxy-24-methyl-22,25-epoxy-5a-furostan-18,20b-lactone (3)、2a-hydroxy-3a-acetoxy-11b-hydroxy-24-methyl-22, 25-epoxy-5a-furostan-18,20b-lactone (4)、2a-hydroxy-3a-acetoxy-24- methyl-11b,18;18,20b;22,25-triepoxy-5a-furostane (5)、2a-acetoxy- 3a-hydroxy-24-methyl-11b,18;18,20b;22,25-triepoxy-5a-furostane (6)、hippuristerone K (7)、hippuristerone L (8)、 hippuristerol F (9)、1a, 3b,5b,11a-tetrahydroxy gorgostan-6-one (10)、22-epi-hippuristan-11-one (11). We also isolated two known compounds, 22-epi- hippuristanol (19)、 2-desacetyl-22-epi-hippurin-1 (25).
The structures of new compounds (1-11) were elucidated by spectroscopic evidences (IR, MS, 1D NMR, 2D NMR) and the comparison of literature. Among those, the stereochemistry of compound 1, with a new skeleton, were confirmed by single-crystal X-ray diffraction analyses. Unfortunately, because of the poor yield, the cytotoxicity test can not be carry out. But now, we try to get enough by semisynthesis.

頁次
中文摘要 1
Abstract 2
化合物結構 3
壹、 緒論 4
一、 前言 4
二、 研究動機 5
三、 文獻回顧 9
四、 hippurins類型結構特徵分析 28

貳、 生物材料與分離方法
一、 生物樣品材料採集時間與地點 31
二、 生物樣品的分類 31
三、 萃取與純化分離步驟 32

參、 器材與實驗 34
一、 儀器 34
二、 試劑藥品 35
肆、 結果與討論 36
一、 化合物結構鑑定 37
(一)、化合物A-nor-2-carboxy-22-epi- hippurin-1 (1) 37
(二)、化合物(22S)-2a-acetoxy-3a-hydroxy-11b-hydroxy-24
-methyl-22,25-epoxy-5a-furostan-18,20b-lactone (2) 45
(三)、化合物(22S)-2a,3a-dihydroxy-11b-hydroxy-24-methyl -22 ,25-epoxy-5a-furostan-18,20b-lactone (3) 55
(四)、化合物(22S)-2a-hydroxy-3a-acetoxy-11b-hydroxy-24
-methyl-22,25-epoxy-5a-furostan-18,20b-lactone (4) 64
(五)、化合物2a-hydroxy-3a-acetoxy-24-methyl-11b,18
18,20b; 22,25-triepoxy-5a-furostane (5) 69
(六)、化合物2a-acetoxy-3a-hydroxy-24-methyl-11b,18;
18,20b; 22,25-triepoxy-5a-furostane (6) 78
(七)、化合物hippuristerone K (7) 86
(八)、化合物hippuristerone L (8) 94
(九)、化合物hippuristerol F (9) 101
(十)、化合物1a,3b,5b,11a-tetrahydroxygorgostan-6-one (10) 110
(十一)、化合物22-epi-hippuristan-11-one (11) 120
(十二)、化合物 2-desacetyl-22-epi-hippurin-1 (25) 128
(十三)、化合物 22-epi-hippuristanol (19) 133

伍、 結論 138
陸、 參考文獻 140
附錄一、化合物1之X-ray實驗數據 143

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