臺灣博碩士論文加值系統

台灣梭羅木（Reevesia formosana Sprague）為梧桐科（Sterculiaceae）的落葉性喬木，台灣固有種，主要分布於台灣島南部的低海拔森林。高雄醫學大學 藥用植物學研究室對超過1,400 種台灣產植物進行一系列之細胞毒篩選，發現台灣梭羅木的莖部甲醇抽出物對MCF-7（乳癌細胞株）、NCI-H460（肺癌細胞株）和 HepG2（肝癌細胞株）等細胞株有細胞毒殺作用。過去本研究室曾對台灣梭羅木根部進行化學成分與活性之研究，發現了13 個新的化合物，且所有新化合物對MCF-7、NCI-H460 和HepG2 三種細胞株都表現出強之細胞毒殺效果。然而本植物的莖部之化學成分以及生物活性尚未被研究。因此，本研究的目的為針對台灣梭羅木莖部之化學成分之分離以及細胞毒活性之探討。台灣梭羅木莖部之甲醇抽出物利用乙酸乙酯與水分配得到乙酸乙酯層與水層。利用生物活性導向試驗，台灣梭羅木莖部乙酸乙酯層經由管柱層析法與製備型薄層層析法共分離得到21 個化合物，包含了1 個新的coumarinolignan 類化合物： reevesiacoumarin (1)，1 個天然物首次分離之neolignan 類化合物：(±)-trans-5-O-demethylbilagrewin (2) ， 1 個新的triterpenoid 類化合物： 3α,27-di-Ocaffeoylbetulinic acid (3) ，以及18 個已知的化合物： (±)-simplidin (4) 、3β-(E)-caffeoylbetulinic acid (5) 、3β-(E)-caffeoylbetulin (6) 、27-O-transcaffeoylcylicodisic acid (7)、3-epi-betulinic acid (8)、3-epi-betulinic acid acetate (9)、betulonic acid (10)、lupeol (11)、oleanolic acid (12)、reevesioside A (13)、混合物 reevesioside G (14) 與epi-reevesioside G (15)、(±)-syringaresinol (16)、scopoletin (17)、混合物β-sitosterol (18) 與stigmasterol (19)、3β-hydroxysitost-5-en-7-one (20)以及ergosterol peroxide (21)。所有化合物之構造均經過各種光譜分析予以確定。在分離之化合物中：化合物13 及混合物14 與15 對於MCF-7、NCI-H460及HepG2癌細胞株有強之細胞毒殺活性，其IC50 值分別為63、19、368以及2071、486、8900 nM。

Reevesia formosana Sprague (Sterculiaceae) is a deciduous tree, endemic to Taiwan, distributed in low altitude forests of sourthern Taiwan. In a cytotoxicity screening program on Formosan plants, over 1,400 species were screened against MCF-7, NCI-H460, and HepG2 cancer cell lines in vitro, and the methanolic extract of the stem of R. formosana has been shown cytotoxicity. Previously, 13 new compounds were isolated from the root of R. formosana by our laboratory, and all of them showed potent cytotoxicity against above cancer cell lines in vitro. However, the stem of this plant has not been studied before. Thus, the aims of this study are the isolation of chemical constituents and their cytotoxicity. The methanolic extract of the stem of R. formosana was partitioned into ethyl acetate and water-soluble layers. Bioassay-guided fractionation of the active ethyl acetate layer has led to the isolation of 21 compounds, including one new coumarinolignan: reevesiacoumarin (1), one new neolignan: (±)-trans-5-Odemethylbilagrewin (2), one new triterpenoid: 3α,27-di-O-caffeoylbetulinic acid (3), and 18 known compounds: (±)-simplidin (4), 3β-(E)-caffeoylbetulinic acid (5), 3β-(E)-caffeoylbetulin (6), 27-O-trans-caffeoylcylicodisic acid (7), 3-epi-betulinic acid (8), 3-epi-betulinic acid acetate (9), betulonic acid (10), lupeol (11), oleanolic acid (12), reevesioside A (13), a mixture of reevesioside G (14) and epi-reevesioside G (15), (±)-syringaresinol (16), scopoletin (17), a mixture of β-sitosterol (18) and stigmasterol (19), 3β-hydroxysitost-5-en-7-one (20), and ergosterol peroxide (21). The structures of these isolates were elucidated by spectral analysis. Among the isolates, compound 13 and a mixture of 14 and 15 showed potent cytotoxicity against MCF-7, NCI-H460, and HepG2 cell lines with the IC50 values as 63, 19, 368 and 2071, 486, 8900 nM, respectively.

目錄........................................................................................................I
圖目錄.....................................................................................................III
表目錄.....................................................................................................VIII
中文摘要..................................................................................................IX
英文摘要..................................................................................................X
Glossary of Abbreviations..........................................................................XI
第一章、序言...........................................................................................1
第二章、研究動機與目的...........................................................................3
第三章、過去化學成分研究概要.................................................................4
第四章、萃取與分離.................................................................................8
第五章、化合物結構鑑定
第一節、reevesiacoumarin (1) 之結構鑑定..................................................12
第二節、(±)-trans-5-O-demethylbilagrewin (2) 之結構鑑定.............................20
第三節、3α,27-di-O-caffeoylbetulinic acid (3) 之結構鑑定.............................28
第四節、(±)-simplidin (4) 之結構鑑定..........................................................36
第五節、3β-(E)-caffeoylbetulinic acid (5) 之結構鑑定....................................44
第六節、3β-(E)-caffeoylbetulin (6) 之結構鑑定.............................................48
第七節、27-O-trans-caffeoylcylicodisic acid(7)之結構鑑定............................52
第八節、3-epi-betulinic acid (8) 之結構鑑定.................................................54
第九節、3-epi-betulinic acid acetate (9) 之結構鑑定.....................................57
第十節、betulonic acid (10) 之結構鑑定......................................................60
第十一節、lupeol (11) 之結構鑑定..............................................................63
第十二節、oleanolic acid (12) 之結構鑑定...................................................66
第十三節、reevesioside A (13) 之結構鑑定..................................................69
第十四節、混合物reevesioside G(14)與epi-reevesioside G(15)之結構鑑定.......73
第十五節、(±)-syringaresinol (16) 之結構鑑定..............................................77
第十六節、scopoletin (17) 之結構鑑定........................................................80
第十七節、β-sitosterol (18) 與stigmasterol (19)............................................83
第十八節、3β-hydroxysitost-5-en-7-one (20)................................................86
第十九節、ergosterol peroxide (21).............................................................89
第六章、細胞毒活性之研究........................................................................92
第七章、結果與討論..................................................................................95
第八章、實驗部分
第一節、儀器與材料..................................................................................96
第二節、萃取與分離..................................................................................98
第三節、乙酸乙酯可溶部之分離..................................................................98
第四節、化合物數據.................................................................................102
第九章、參考文獻....................................................................................113

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