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研究生:簡鈺潔
研究生(外文):Yu-Chieh Chien
論文名稱:長花厚殼樹根部化學成分及抗結核活性之研究
論文名稱(外文):Chemical Constituents and Antitubercular Activity from the Root of Ehretia longiflora
指導教授:蔡烟力
指導教授(外文):Ian-Lih Tsai
學位類別:碩士
校院名稱:高雄醫學大學
系所名稱:天然藥物研究所
學門:醫藥衛生學門
學類:藥學學類
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:220
中文關鍵詞:長花厚殼樹紫草科根部抗結核活性
外文關鍵詞:Ehretia longifloraBoragenaceaerootantitubercular activity
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長花厚殼樹(Ehretia logiflora Champ. ex Benth.)為紫草科(Boraginaceae)厚殼樹屬之落葉性小喬木。分布於中國南方以及印度支那(中南半島),在台灣則是分布在低海拔~750公尺高的森林。長花厚殼樹根部甲醇抽出物具有抗結核菌(Mycobacterium tuberculosis H37Rv)活性,其根部化學從未被研究過,本研究目的為分離長花厚殼樹根部具有抗結核菌活性之化學成分。
根部甲醇抽出物經分配萃取後,得到乙酸乙酯及水可溶部,經初步的活性篩選,其中乙酸乙酯層顯示具有抑制結核菌的活性,遂進行乙酸乙酯層的化學成分研究,共分離得到30個化合物,包括一個quinonoid類: ehretiquinone (1),一個coumarin類:ehreticoumarin (2),一個benzolactone類:ehretilactone A (3),一個butenolide類:ehretilactone B (4),一個amide類: ehretiamide (5),兩個alkaloids類:ehretine (6)、ehretiquinolone (7),三個triterpenoids類:ehretiolide (8)、O-acetyloleanolic acid (9)、oleanolic acid (10),兩個chromanoids類:(3S)-3,6-dihydroxy-2,2-dimethylchromane (11)、6-hydroxy-2,2-dimethyl-2H-chromene (12),五個bezenoids類:ehretiate (13)、prenylhydroquinone (14)、4-hydroxy-3-prenylbenzoic acid (15)、proglobeflowery acid (16)、syringaldehyde (17),四個diphenylbutanoids類:ehretidiol A (18)、ehretidiol B (19)、混合物ehretidiol C (20)與(2R,3R)-1,4-diphenylbutan-2,3-diol (21),一個hemiterpenoid類:3-methylbut-2-enoic acid (22),一個sesquiterpenoid類:(+)-(2E,6E)-methyl-10,11-dihydroxy-3,7,11-trimethyl-2,6-dodecadienoate (23),三個glycerides類:2,3-dihydroxypropyl palmitate (24)、(9Z,12Z)-2,3-dihydroxypropyl octadeca-9,12-dienoate (25)、(9Z,12Z,15Z)-2,3-dihydroxypropyl octadeca-9,12,15-trienoate (26),一個alkanoid derivative類:methyl linoleate (27),兩個steroids類:混合物β-sitosterol (28)與stigmasterol (29),一個其他類之化合物:ehretilactone C (30)。分離之化合物均由光譜分析確認其化學結構。
所有分離得到的化合物中,化合物1-6, 8, 11, 13, 30為新化合物,化合物7, 18-20為天然首次分離得到之化合物,而化合物1, 2, 12, 14, 15, 18及22具有體外抗結核菌活性,MIC值分別為25.0, 50.0, 50.0, 26.2, 43.0, 30.0及 36.0 µg/mL。


Ehretia longiflora Champ. ex Benth. (Boraginaceae) is a medium sized deciduous tree, distributed in south China, Indochina, and in forests from low elevations to 750 m of Taiwan. The methanolic extract of the root of this plant showed antitubercular activity against Mycobacterium tuberculosis H37Rv in vitro. The aim of this study is to isolate the antitubercular active constituents from the root of this plant.
Bioassay-guided fractionation of the ethyl acetate-soluble layer from the root of this species led to the isolation of thirty compounds, including one quinonoid: ehretiquinone (1); one coumarin: ehreticoumarin (2); one benzolactone: ehretilactone A (3); one butenolide: ehretilactone B (4); one amide: ehretiamide (5); two alkaloids: ehretine (6), ehretiquinolone (7); three triterpenoids: ehretiolide (8), O-acetyloleanolic acid (9), oleanolic acid (10); two chromanoids: (3S)-3,6-dihydroxy-2,2-dimethylchromane (11), 6-hydroxy-2,2-dimethyl-2H-chromene (12); five bezenoids: ehretiate (13), prenylhydroquinone (14), 4-hydroxy-3-prenylbenzoic acid (15), proglobeflowery acid (16), syringaldehyde (17); four diphenylbutanoid: ehretidiol A (18), ehretidiol B (19), a mixture of ehretidiol C (20) and (2R,3R)-1,4-diphenylbutan-2,3-diol (21); one hemiterpenoid: 3-methylbut-2-enoic acid (22); one sesquiterpenoid: (+)-(2E,6E)-methyl-10,11-dihydroxy-3,7,11-trimethyl-2,6-dodecadienoate (23); three glycerides: 2,3-dihydroxypropyl palmitate (24), (9Z,12Z)-2,3-dihydroxypropyl octadeca-9,12-dienoate (25), (9Z,12Z,15Z)-2,3-dihydroxypropyl octadeca-9,12,15-trienoate (26); one alkanoid derivative: methyl linoleate (27); two steroids: a mixture of β-sitosterol (28) and stigmasterol (29); one other skeleton: ehretilactone C (30)。The structures of these isolates were elucidated by spectral analysis.
Among these isolates, compounds 1-6, 8, 11, 13 and 30 were new compounds, and compounds 7, 18-20 were first isolated from nature. Compounds 1, 2, 12, 14, 15, 18 and 22 exhibited antitubercular activities in vitro, and showing MIC values of 25.0, 50.0, 50.0, 26.2, 43.0, 30.0 and 36.0 µg/mL, respectively.

目錄---I-XIII
圖目錄---IV-XII
表目錄---XIII
中文摘要---XIV
英文摘要---XV
Glossary of Abbreviations---XVI
第一章 緒論---1
第二章 研究動機與目的---3
第三章 厚殼樹屬植物研究之回顧
第一節 厚殼樹屬植物成分研究回顧---6
第二節 厚殼樹屬植物藥理研究回顧---18
第四章 萃取與分離---21
第五章 結果與討論
第一節 ehretiquinone (1)之結構鑑定---27
第二節 ehreticoumarin (2)之結構鑑定---37
第三節 ehretilactone A (3)之結構鑑定---44
第四節 ehretilactone B (4)之結構鑑定---50
第五節 ehretiamide (5)之結構鑑定---57
第六節 ehretine (6)之結構鑑定---64
第七節 ehretiquinolone (7)之結構鑑定---71
第八節 ehretiolide (8)之結構鑑定---78
第九節 O-acetyloleanolic acid (9)之結構鑑定---87
第十節 oleanolic acid (10)之結構鑑定---90
第十一節 (3S)-3,6-dihydroxy-2,2-dimethylchromane (11)之結構鑑定---93
第十二節 6-hydroxy-2,2-dimethyl-2H-chromene (12)之結構鑑定---99
第十三節 ehretiate (13)之結構鑑定---103
第十四節 prenylhydroquinone (14)之結構鑑定---110
第十五節 4-hydroxy-3-prenylbenzoic acid (15)之結構鑑定---114
第十六節 proglobeflowery acid (16)之結構鑑定---118
第十七節 syringaldehyde (17)之結構鑑定---121
第十八節 ehretidiol A (18)之結構鑑定---124
第十九節 ehretidiol B (19)之結構鑑定---131
第二十節 ehretidiol C (20) & (2R,3R)-1,4-diphenylbutan-2,3-diol (21)之結構鑑定---135
第二十一節 3-methylbut-2-enoic acid (22)之結構鑑定---139
第二十二節 (+)-(2E,6E)-methyl-10,11-dihydroxy-3,7,11-trimethyl-2,6-dodecadienoate (23)之結構鑑定---143
第二十三節 2,3-dihydroxypropyl palmitate (24)之結構鑑定---146
第二十四節 (9Z,12Z)-2,3-dihydroxypropyl octadeca-9,12-dienoate (25)之結構鑑定---149
第二十五節 (9Z,12Z,15Z)-2,3-dihydroxypropyl octadeca-9,12,15-trienoate(26)之結構鑑定---153
第二十六節 methyl linoleate (27)之結構鑑定---157
第二十七節 β-sitosterol (28) & stigmasterol (29)之結構鑑定---160
第二十八節 ehretilactone C (30)之結構鑑定---162
第六章 抗結核活性之研究---172
第七章 結論---173
第八章 相關實驗部份
第一節 儀器與材料---175
第二節 抗結核活性測試---177
第三節 乙酸乙酯可溶部之分離---179
第四節 化合物之實驗數據---183
參考文獻---198


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