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研究生:王智欣
研究生(外文):Chih-Hsin Wang
論文名稱:台灣產薄葉嘉賜木活性雙萜類成分研究
論文名稱(外文):Chemical and Cytotoxic Constituents from the Formosan Casearia membranacea Hance
指導教授:沈雅敬沈雅敬引用關係
指導教授(外文):YA-CHING SHEN
學位類別:碩士
校院名稱:國立中山大學
系所名稱:海洋資源學系研究所
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:2003
畢業學年度:91
語文別:中文
論文頁數:82
中文關鍵詞:薄葉嘉賜木雙萜類成分
外文關鍵詞:Casearia membranacea
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薄葉嘉賜木 (Casearia membranacea Hance) 為大風子科 (Flacourtiaceae) 嘉賜木屬 (Casearia) 之常綠喬木,採集於台灣北部山區。以生物活性為導向對其甲醇層進行分離純化,共得到六個新的雙萜類化合物,Caseambrins A-F (1-6) 以及一個已知的化合物rel-(2S,5R,6R,8S,9S,10R,18S,19R)-diacetoxy-18,19-epoxy-6-hydroxy-2-
(2-methylbutanoyloxy)cleroda-3,13(16),14-triene (7)。化合物1-6的結構鑑定是利用物理資料 (紅外線光譜、質譜、旋光度) 以及一維、二維核磁共振光譜分析,再加上相關文獻資料比對所建立的。
從薄葉嘉賜木分離得到的化合物其基本骨架為clerodane diterpenes,而化合物1-6 亦具有其相同骨架;主要結構皆為兩個六圓環,在第9位上接了具有六個碳的共軛雙鍵側鏈,以及在C-2位置和C-18上接有兩個酯基官能基。
化合物1在C-18位上接有酯基烷類側鏈,且在C-6、19位上分別有烃基及乙醯基取代,其化學結構為rel-(2S,5R,6R,8S,9S,10R,18S,19R)-18-butanoyloxy-19-acetoxy-18,19-
epoxy-6-hydroxy-2-(2-methylbutanoyloxy)cleroda-3,13(16),14-triene (Caseamembrin A)。化合物2在C-18位上接有OMe 之取代基,化學結構為rel-(2S,5R,6R,8S,9S,10R,18S,19R)-18-methoxy-19-acetoxy-18,19
-epoxy-6-hydroxy-2-(2-methylbutanoyloxy)cleroda-3,13(16),14-triene (Caseamembrin B)。化合物3在C-19位上有乙醯基之取代基,以及在C-6、7位上為OH,鑑定為rel-(2S,5R,6R,7R,8S,9S,10R,18S,19R)
-18-butanoyloxy-19-acetoxy-18,19-epoxy-6,7-dihydroxy-2-(2-methylbutanoyloxy)cleroda-3,13(16),14- triene (Caseamembrin C)。化合物4 其6位上接了OH,而C-7、19位上分別為乙醯基取代,化學結構為rel-(2S,5R,6S,7R,8S,9S,10R,18S,19R)-18-butanoyloxy-19-acetoxy-18,19
-epoxy-6-hydroxy-7-acetoxy-2-(2-methylbutanoyloxy)cleroda-3,13(16),14- triene (Caseamembrin D)。化合物5在18、19位上皆為乙醯基取代,6位上則為OH,鑑定為rel-(2S,5R,6R,8S,9S,10R,18S,19R)-18,19-
diacetoxy-18,19-epoxy-6-hydroxy-2-(2-methylbutanoyloxy)cleroda-3,13(16),14-triene (Caseamembrin E)。化合物6 在C-6 位上接了OH,在C-18、19位上則開環取代的是兩個醛基,化學結構為rel-(2S,5R,6R,7R
,8S,9S,10R,18S,19R)-6-hydroxy-2-(2-methylbutanoyloy)cleroda-3,13(16),14-triene-18,19-dicarboxyaldehyde (Caseamembrin F)。
化合物1-6為首次發現新的天然物結構,在細胞毒殺活性方面,對於人類胃癌細胞及人類鼻咽癌細胞,化合物1-6在濃度20mg/ml毒殺活性達到0~1﹪。
Casearia membranacea Hance (Flacourtiaceae) is a tree found in the northern region of Taiwan. Bioassay-directed fractionation of the MeOH-layer has resulted in the isolation of six new clerodane diterpenes, Caseamembrins A-F (1-6) along with a known compound, rel-(2S,5R,6R,
8S,9S,10R,18S,19R)-diacetoxy-18,19-epoxy-6-hydroxy-2-(2-methylbut-
anoyloxy)cleroda-3,13(16),14-triene (7).

The structures of compounds 1-6 were determined by the physical methods such as IR、mass、optical rotation, 1D、2D NMR spectral analysis, and the published reports about the data of related compounds .

The spectral data of 1-6 are in conformity with the basic skeleton of clerodane diterpenes previously isolated from Casearia membranacea Hance.. The basic structures of 1-6 contain two 6-membred ring linked with six carbon diene side chain at C-9 and two ester carbonyl functional groups at C-2 and C-18 respetirely.

Compound 1 had an ester carbonyl at C-2 position, with an acetoxyl and a hydroxyl group at C-19/6 position, the structure of 1 was assigned as rel-(2S,5R,6R,8S,9S,10R,18S,19R)-18-butanoyloxy-19-acetoxy-18,19
-epoxy-6-hydroxy-2-(2-methylbutanoyloxy)cleroda-3,13(16),14-triene (Caseamembrin A). Compound 2 had a methoxyl group at C-18 position, that 2 has the structure of rel-(2S,5R,6R,8S,9S,10R,18S,19R)-18-methoxy
-19-acetoxy-18,19-epoxy-6-hydroxy-2-(2-methylbutanoyloxy)cleroda-3,13(16),14-triene (Caseambrin B). Compound 3 had an acetoxyl at C-19 position, and two hydroxyl group at C-6/7. Compound 3 was assigned the structure of rel-(2S,5R,6R,7R,8S,9S,10R,18S,19R)-18-butanoyloxy-19-
acetoxy-18,19-epoxy-6,7-dihydroxy-2-(2-methylbutanoyloxy)cleroda-3,
13(16),14- triene (Caseamembrin C). Compound 4 had two acetoxyl at C-7/19 and hydroxyl group at C-6, the assignment of its structure as rel-(2S,5R,6S,7R,8S,9S,10R,18S,19R)-18-butanoyloxy-19-acetoxy
-18,19-epoxy-6-hydroxy-7-acetoxy-2-(2-methylbutanoyloxy)cleroda-3,13(16),14- triene (Caseamembrin D). Compound 5 had two acetoxyl at C-18/19 position, and a hydroxyl group at C-6 position. 5 was established as rel-(2S,5R,6R,8S,9S,10R,18S,19R)-18,19-diacetoxy-18,19-epoxy-6-
hydroxy-2-(2-methylbutanoyloxy)cleroda-3,13(16),14-triene (Caseamembrin E). Compound 6 had a hydroxyl group at C-6 position and it was deduced that the C-18/19 acetal ring was opened thus forming the two aldehydic units. The structure of 6 was established as rel-(2S,5R,6R,7R,8S,9S,10R,18S,19R)-6-hydroxy-2-(2-methylbutanoyloy)
cleroda-3,13(16),14-triene-18,19-dicarboxyaldehyde (Caseamembrin F).

It is worthy to mention that this is the first report of the isolation of 1-6 from a natural source. In a preliminary pharmacological aporach (cytotoxicity), compounds 1-6 exhibited moderate cytotoxicity against (NUGC-3) and (HONE-1) cancer cells with IC50 0~1﹪values at 20mg/ml.
目 錄
頁次
壹 緒論
第一章 前言…………………………………………………………1
第二章 過去成分研究相關文獻回顧………………………………3
第三章 研究動機與目的……………………………………………12

貳 材料與方法
第一章 樣品的採集…………………………………………………13
第二章 分離與純化…………………………………………………14
第三章 結構之鑑定…………………………………………………19
第一節 儀器部分
第二節 矽膠與溶劑部分
第四章 衍生物之製備………………………………………………21
第一節 乙醯基化反應 (Acetylation)
第二節 酯化反應 (Esterification)
第五章 生物活性之篩選……………………………………………23

參 結果與討論…………………………………………..…………25
肆 結論…………………………………………………..…………75
伍 參考文獻……………………………………………..…………81
伍 參考文獻
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