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研究生:姜純靜
研究生(外文):Chun-Ching Chiang
論文名稱:細齒水蛇麻化學成分與抗結核活性之研究
論文名稱(外文):Chemical Constituents and Antitubercular Activity from Fatoua pilosa
指導教授:陳益昇陳益昇引用關係
指導教授(外文):Ih-Sheng Chen
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:2008
畢業學年度:96
語文別:中文
論文頁數:214
中文關鍵詞:桑科細齒水蛇麻香豆素
外文關鍵詞:MoraceaeFatoua pilosacoumarin
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細齒水蛇麻 (Fatoua pilosa Gaud.)為桑科,多年生草本植物,主要分布於台灣、菲律賓、摩鹿加群島和新幾內亞。在台灣產植物活性成分之一系列研究,發現F. pilosa植物之全草甲醇萃取物,對Mycobacterium tuberculosis H37Rv標準菌種,具有抗結核活性,而Fatoua屬植物全世界只有三種,其化學成分及生物活性均未被報告過。
將本植物之甲醇萃取物進行分配,得到乙酸乙酯及水層,針對乙酸乙酯層進行研究,迄今分離得到六個新coumarins,分別為: (+)-fatouain A (1), (-)-fatouain B (2), (+)-fatouain C (3), (-)-fatouain D (4), (+)-fatouain E (5), (-)-fatouain F (6),另外四個新bis-coumarins,分別為: (+)-fatouain G (7), (+)-fatouain H (8), fatouain I (9), fatouapilosin (10),還有18個已知化合物,其中3個為simple coumarins: umbelliferone (11), scopoletin (12), phellodenol-A (13),6個為furanocoumarins: psoralen (14), bergapten (15), S-(+)-marmesin (16), S-(+)-rutaretin methyl ether (17), S-(+)-rutaretin (18), 2’,3’-dehydromarmesin (19),1個為pyranocoumarin: xanthyletin (20),3個為chaclones: isobavachalcone (21), kanzonol C (22), (E)-1-[2,4-dihydroxy-3-(3-methyl-2-butenyl)phenyl]-3-
(2,2-dimethyl-8-hydroxy-2H-benzopyran-6-yl)-2-propen-1-one (23),1個為ben-
zenoid: syringaldehyde (24),1個為quinone: α-tocopheryl quinone (25),1個為triterpenoid: lupeol (26),2個為steroids: a mixture of β-sitosterol (27) and stigamasterol (28)。所有化合物之結構均經各種光譜分析或化學誘導,予以確認。
scopoletin (12), isobavachalcone (21) and (E)-1-[2,4-dihydroxy-3-(3-methyl-
2-butenyl)-phenyl]-3-(2,2-dimethyl-8-hydroxy-2H-benzopyran-6-yl)-2-propen-1-
one (23),對Mycobacterium tuberculosis H37Rv,呈現抑制作用,MICs值分別為: 42.1, 17.6, 30.0 μg/ mL。
Fatoua pilosa Gaud. (Moraceae) is a small perennial herb, which distributed in Taiwan, Philippine, Moluccas and New Guinea. In a series of studies on the active constituents of Formosan plants, the methanolic extract of the whole plant of this species showed antitubercular activity against Mycobacterium tuberculosis H37Rv in vitro. There are only three species of Fatoua in the world. The chemical constituents and bioactivities of Fatoua plants have never been conducted.
The methanolic extract of whole plant of this species was partitioned into EtOAc and H2O-soluble fractions. Investigation of EtOAc-soluble fraction led to the isolation of six new coumarins: (+)-fatouain A (1), (-)-fatouain B (2), (+)-fatouain C (3), (-)-fatouain D (4), (+)-fatouain E (5), (-)-fatouain F (6) and four new bis-coumarins: (+)-fatouain G (7), (+)-fatouain H (8), fatouain I (9), fatouapilosin (10), along with eighteen known compounds, including three simple coumarins: umbelliferone (11), scopoletin (12), phellodenol-A (13), six furanocoumarins: psoralen (14), bergapten (15), S-(+)-marmesin (16), S-(+)-rutaretin methy1 ether (17), S-(+)-rutaretin (18), 2’,3’-dehydromarmesin (19), one pyranocoumarin: xanthyletin (20), three chaclones: isobavachalcone (21), kanzonol C (22), (E)-1-[2,4-dihydroxy-3-(3-methyl-2-butenyl)phenyl]-3-(2,2-di-
methyl-8-hydroxy-2H-benzopyran-6-yl)-2-propen-1-one (23), one benzenoid: syringaldehyde (24), one quinone: α-tocopheryl quinone (25), one triterpenoid: lupeol (26), two steroids: a mixture of β-sitosterol (27) and stigamasterol (28). The structures of these compounds were elucidated by spectral analysis or by chemical derivation.
Scopoletin (12), isobavachalcone (21) and (E)-1-[2,4-dihydroxy-3-(3-methyl-
2-butenyl)-phenyl]-3-(2,2-dimethyl-8-hydroxy-2H-benzopyran-6-yl)-2-propen-1-
one (23) showed antituburcular acivity aganist Mycobacterium tuberculosis H37Rv in vitro with MIC values: 42.1, 17.6 and 30.0 μg/ mL, respectively.
目錄
目錄…………………………………………………………………………I-III
圖目錄……………………………………………………………………IV-X
表目錄………………………………………………………………………XI
中文摘要………………………………………………………………………1
英文摘要………………………………………………………………………2
第一章 緒論………………………………………………………………… 3
第二章 研究動機與目的…………………………………………………… 4
第三章 過去台灣產桑科植物成分研究之回顧…………………………… 6
第一節 水蛇麻屬植物過去成分之研究……………………………… 6
第二節 麵包樹屬植物過去成分之研究………………………………6
第三節 構樹屬植物過去成分之研究…………………………………7
第四節 榕屬植物過去成分之研究……………………………………14
第五節 柘樹屬植物過去成分之研究…………………………………25
第六節 葎屬植物過去成分之研究……………………………………28
第七節 盤龍木植物過去成分之研究…………………………………28
第八節 桑屬植物過去成分之研究……………………………………29
第四章 過去抗結核菌植物研究概要……………………………………34
第五章 細齒水蛇麻全草之萃取與分離…………………………………43
第六章 細齒水蛇麻全草成分之構造研究………………………………47
第一節 (+)-fatouain A (1) 之構造研究………………………………47
第二節 (-)-fatouain B (2) 之構造研究………………………………54
第三節 (+)-fatouain C (3) 之構造研究………………………………61
第四節 (-)-fatouain D (4) 之構造研究………………………………70
第五節 (+)-fatouain E (5) 之構造研究………………………………77
第六節 (-)-fatouain F (6) 之構造研究………………………………85
第七節 (+)-fatouain G (7) 之構造研究………………………………96
第八節 (+)-fatouain H (8) 之構造研究……………………………104
第九節 fatouain I (9)or (9a) 之構造研究…………………………112
第十節 fatouapilosin (10) 之構造研究……………………………117
第十一節 umbelliferone (11) 之構造研究…………………………125
第十二節 scopoletin (12) 之構造研究……………………………127
第十三節 phellodenol-A (13) 之構造研究…………………………129
第十四節 psoralen (14) 之構造研究………………………………131
第十五節 bergapten (15) 之構造研究………………………………133
第十六節 S-(+)-marmesin (16) 之構造研究………………………135
第十七節 S-(+)rutaretin methy1 ether (17) 之構造研究……………137
第十八節 S-(+)-rutaretin (18) 之構造研究…………………………139
第十九節 2’,3’-dehydromarmesin (19) 之構造研究………………141
第二十節 xanthyletin (20) 之構造研究……………………………143
第二十一節 isobavachalcone (21) 之構造研究……………………145
第二十二節 kanzonol C (22) 之構造研究…………………………147
第二十三節 (E)-1-[2,4-dihydroxy-3-(3-methyl-2-butenyl)phenyl]-3-
(2,2-dimethyl-8-hydroxy-2H-benzopyran-6-yl)-2-propen-
1-one之構造研究(23) …………………………………149
第二十四節 syringaldehyde (24) 之構造研究………………………155
第二十五節 α-tocopheryl quinone (25) 之構造研究………………157
第二十六節 lupeol (26) 之構造研究………………………………159
第二十七節 混合物β-sitosterol (27) 與 stigmasterol (28) 之構造
研究……………………………………………………161
第七章 抗結核活性之研究………………………………………………163
第八章 結果與討論………………………………………………………164
第九章 實驗部份…………………………………………………………166
化合物數據…………………………………………………………………173
參考文獻……………………………………………………………………185

















圖目錄
Scheme A. 細齒水蛇麻之全草分離流程圖…………………………………43
圖 1-1 (+)-fatouain A (1)之1H-NMR圖譜………………………………49
圖 1-2 (+)-fatouain A (1)之13C-NMR圖譜………………………………49
圖 1-3 (+)-fatouain A (1)之DEPT圖譜…………………………………50
圖 1-4 (+)-fatouain A (1)之HMQC圖譜…………………………………50
圖 1-5 (+)-fatouain A (1)之COSY圖譜…………………………………51
圖 1-6 (+)-fatouain A (1)之HMBC圖譜…………………………………51
圖 1-7 (+)-fatouain A (1)之NOESY圖譜………………………………52
圖 1-8 (+)-fatouain A (1)之IR圖譜………………………………………52
圖 1-9 (+)-fatouain A (1)之ESIMS圖譜…………………………………53
圖 1-10 (+)-fatouain A (1)之HRESIMS圖譜……………………………53
圖 2-1 (-)-fatouain B (2)之1H-NMR圖譜………………………………56
圖 2-2 (-)-fatouain B (2)之13C-NMR圖譜………………………………56
圖 2-3 (-)-fatouain B (2)之DEPT圖譜…………………………………57
圖 2-4 (-)-fatouain B (2)之HMQC圖譜…………………………………57
圖 2-5 (-)-fatouain B (2)之COSY圖譜…………………………………58
圖 2-6 (-)-fatouain B (2)之HMBC圖譜…………………………………58
圖 2-7 (-)-fatouain B (2)之NOESY圖譜………………………………59
圖 2-8 (-)-fatouain B (2)之IR圖譜………………………………………59
圖 2-9 (-)-fatouain B (2) 之ESIMS圖譜………………………………60
圖 2-10 (-)-fatouain B (2)之HRESIMS圖譜……………………………60
圖 3-1 (+)-fatouain C (3)之 1H-NMR圖譜………………………………64
圖 3-2 (+)-fatouain C (3)之13C-NMR圖譜………………………………64
圖 3-3 (+)-fatouain C (3)之DEPT圖譜…………………………………65
圖 3-4 (+)-fatouain C (3)之HMQC圖譜…………………………………65
圖 3-5 (+)-fatouain C (3)之COSY圖譜…………………………………66
圖 3-6 (+)-fatouain C (3)之HMBC圖譜…………………………………66
圖 3-7 (+)-fatouain C (3)之NOESY圖譜………………………………67
圖 3-8 (+)-fatouain C (3)之 IR圖譜……………………………………67
圖 3-9 (+)-fatouain C (3)之ESIMS圖譜…………………………………68
圖 3-10 (+)-fatouain C (3)之HRESIMS圖譜……………………………68
圖 3-11 (+)-fatouain C-acetonide (3)之 1H-NMR圖譜……………………69
圖 3-12 (+)-fatouain C (3)之NOE圖譜……………………………………69
圖 4-1 (-)-fatouain D (4)之1H-NMR圖譜………………………………72
圖 4-2 (-)-fatouain D (4)之13C-NMR圖譜………………………………72
圖 4-3 (-)-fatouain D (4)之DEPT圖譜…………………………………73
圖 4-4 (-)-fatouain D (4)之HMQC圖譜…………………………………73
圖 4-5 (-)-fatouain D (4)之COSY圖譜…………………………………74
圖 4-6 (-)-fatouain D (4)之HMBC圖譜…………………………………74
圖 4-7 (-)-fatouain D (4)之NOESY圖譜………………………………75
圖 4-8 (-)-fatouain D (4)之IR圖譜………………………………………75
圖 4-9 (-)-fatouain D (4)之ESIMS圖譜…………………………………76
圖 4-10 (-)-fatouain D (4)之HRESIMS圖譜……………………………76
圖 5-1 (+)-fatouain E (5)之1H-NMR圖譜………………………………79
圖 5-2 (+)-fatouain E (5)之13C-NMR圖譜………………………………79
圖 5-3 (+)-fatouain E (5)之DEPT圖譜…………………………………80
圖 5-4 (+)-fatouain E (5)之HMQC圖譜…………………………………80
圖 5-5 (+)-fatouain E (5)之COSY圖譜…………………………………81
圖 5-6 (+)-fatouain E (5)之HMBC圖譜…………………………………81
圖 5-7 (+)-fatouain E (5)之NOESY圖譜………………………………82
圖 5-8 (+)-fatouain E (5)之IR圖譜………………………………………82
圖 5-9 (+)-fatouain E (5)之ESIMS圖譜…………………………………83
圖 5-10 (+)-fatouain E (5)之HRESIMS圖譜……………………………83
圖 5-11 (+)-fatouain E-acetonide (5)之1H-NMR圖譜……………………84
圖 5-12 (+)-fatouain E (5)之NOE difference圖譜………………………84
圖 6-1 (-)-fatouain F (6)之1H-NMR圖譜………………………………87
圖 6-2 (-)-fatouain F (6)之13C-NMR圖譜………………………………87
圖 6-3 (-)-fatouain F (6)之DEPT圖譜…………………………………88
圖 6-4 (-)-fatouain F (6)之HMQC圖譜…………………………………88
圖 6-5 (-)-fatouain F (6)之COSY圖譜…………………………………89
圖 6-6 (-)-fatouain F (6)之HMBC圖譜…………………………………89
圖 6-7 (-)-fatouain F (6)之HMQC圖譜…………………………………90
圖 6-8 (-)-fatouain F (6)之IR圖譜………………………………………90
圖 6-9 (-)-fatouain F (6)之ESIMS圖譜…………………………………91
圖 6-10 (-)-fatouain F (6)之HRESIMS圖譜………………………………91
圖 6-11 (-)-fatouain F-acetonide (6)之1H-NMR圖譜……………………92
圖 6-12 (-)-fatouain F (6)之 NOE difference圖譜………………………92
圖 7-1 (+)-fatouain G (7)之1H-NMR圖譜………………………………99
圖 7-2 (+)-fatouain G (7)之13C-NMR圖譜………………………………99
圖 7-3 (+)-fatouain G (7)之DEPT圖譜…………………………………100
圖 7-4 (+)-fatouain G (7)之HMQC圖譜………………………………100
圖 7-5 (+)-fatouain G (7)之COSY圖譜………………………………101
圖 7-6 (+)-fatouain G (7)之HMBC圖譜………………………………101
圖 7-7 (+)-fatouain G (7)之NOESY圖譜………………………………102
圖 7-8 (+)-fatouain G (7)之IR圖譜……………………………………102
圖 7-9 (+)-fatouain G (7)之ESIMS圖譜………………………………103
圖 7-10 (+)-fatouain G (7)之HRESIMS圖譜……………………………103
圖 8-1 (+)-fatouain H (8)之1H-NMR圖譜……………………………107
圖 8-2 (+)-fatouain H (8)之13C-NMR圖譜……………………………107
圖 8-3 (+)-fatouain H (8)之DEPT圖譜…………………………………108
圖 8-4 (+)-fatouain H (8)之HMQC圖譜………………………………108
圖 8-5 (+)-fatouain H (8)之COSY圖譜………………………………109
圖 8-6 (+)-fatouain H (8)之HMBC圖譜………………………………109
圖 8-7 (+)-fatouain H (8)之NOESY圖譜………………………………110
圖 8-8 (+)-fatouain H (8)之IR圖譜……………………………………110
圖 8-9 (+)-fatouain H (8)之ESIMS圖譜………………………………111
圖 8-10 (+)-fatouain H (8)之HRESIMS圖譜……………………………111
圖 9-1 fatouain I (9)or (9a)之1H-NMR圖譜……………………………114
圖 9-2 fatouain I (9)or (9a)之COSY圖譜………………………………114
圖 9-3 fatouain I (9)or (9a)之NOESY圖譜……………………………115
圖 9-4 fatouain I (9)or (9a)之IR圖譜…………………………………115
圖 9-5 fatouain I (9)or (9a)之FABMS圖譜……………………………116
圖 10-1 fatouapilosin (10)之1H-NMR圖譜………………………………120
圖 10-2 fatouapilosin (10)之13C-NMR圖譜……………………………120
圖 10-3 fatouapilosin (10)之DEPT圖譜…………………………………121
圖 10-4 fatouapilosin (10)之HMQC圖譜………………………………121
圖 10-5 fatouapilosin (10)之COSY圖譜…………………………………122
圖 10-6 fatouapilosin (10)之HMBC圖譜………………………………122
圖 10-7 fatouapilosin (10)之NOESY圖譜………………………………123
圖 10-8 fatouapilosin (10)之IR圖譜……………………………………123
圖 10-9 fatouapilosin (10)之FABMS圖譜………………………………124
圖 11-1 umbelliferone (11)之1H-NMR圖譜……………………………126
圖 11-2 umbelliferone (11)之IR圖譜……………………………………126
圖 12-1 scopoletin (12)之1H-NMR圖譜…………………………………128
圖 12-2 scopoletin (12)之IR圖譜………………………………………128
圖 13-1 phellodenol-A (13)之1H-NMR圖譜……………………………130
圖 13-1 phellodenol-A (13)之IR圖譜……………………………………130
圖 14-1 psoralen (14)之1H-NMR圖譜…………………………………132
圖 14-2 psoralen (14)之IR圖譜…………………………………………132
圖 15-1 bergapten (15)之1H-NMR圖譜…………………………………134
圖 15-2 bergapten (15)之IR圖譜…………………………………………134
圖 16-1 S-(+)-marmesin (16)之 1H-NMR圖譜…………………………136
圖 16-2 S-(+)-marmesin (16)之 IR圖譜…………………………………136
圖 17-1 S-(+)-rutaretin methy1 ether (17)之 1H-NMR圖譜……………138
圖 17-1 S-(+)-rutaretin methy1 ether (17)之 IR圖譜……………………138
圖 18-1 S-(+)-rutaretin (18)之 1H-NMR圖譜……………………………140
圖 18-2 S-(+)-rutaretin (18)之 IR圖譜…………………………………140
圖 19-1 2’,3’-dehydromarmesin (19)之 1H-NMR圖譜…………………142
圖 19-1 2’,3’-dehydromarmesin (19)之 IR圖譜…………………………142
圖 20-1 xanthyletin (20)之 1H-NMR圖譜………………………………144
圖 20-2 xanthyletin (20)之 IR圖譜………………………………………144
圖 21-1 isobavachalcone (21)之 1H-NMR圖譜…………………………146
圖 21-2 isobavachalcone (21)之 IR圖譜………………………………146
圖 22-1 kanzonol C (22)之 1H-NMR圖譜………………………………148
圖 22-2 kanzonol C (22)之 IR圖譜……………………………………148
圖 23-1 (E)-1-[2,4-dihydroxy-3-(3-methyl-2-butenyl)phenyl]-3-(2,2-
dimethyl-8-hydroxy-2H-benzopyran-6-yl)-2-propen-1-one (23)
之 1H-NMR圖譜………………………………………………151
圖 23-2 (E)-1-[2,4-dihydroxy-3-(3-methyl-2-butenyl)phenyl]-3-(2,2-
dimethyl-8-hydroxy-2H-benzopyran-6-yl)-2-propen-1-one (23)
之 13C-NMR圖譜………………………………………………151
圖 23-3 (E)-1-[2,4-dihydroxy-3-(3-methyl-2-butenyl)phenyl]-3-(2,2-
dimethyl-8-hydroxy-2H-benzopyran-6-yl)-2-propen-1-one (23)
之 DEPT圖譜…………………………………………………152
圖 23-4 (E)-1-[2,4-dihydroxy-3-(3-methyl-2-butenyl)phenyl]-3-(2,2-
dimethyl-8-hydroxy-2H-benzopyran-6-yl)-2-propen-1-one (23)
之HMQC圖譜…………………………………………………152
圖 23-5 (E)-1-[2,4-dihydroxy-3-(3-methyl-2-butenyl)phenyl]-3-(2,2-
dimethyl-8-hydroxy-2H-benzopyran-6-yl)-2-propen-1-one (23)
之COSY圖譜……………………………………………………153
圖 23-6 (E)-1-[2,4-dihydroxy-3-(3-methyl-2-butenyl)phenyl]-3-(2,2-
dimethyl-8-hydroxy-2H-benzopyran-6-yl)-2-propen-1-one (23)
之HMBC圖譜…………………………………………………153
圖 23-7 (E)-1-[2,4-dihydroxy-3-(3-methyl-2-butenyl)phenyl]-3-(2,2-
dimethyl-8-hydroxy-2H-benzopyran-6-yl)-2-propen-1-one (23)
之NOESY圖譜…………………………………………………154
圖 23-8 (E)-1-[2,4-dihydroxy-3-(3-methyl-2-butenyl)phenyl]-3-(2,2-
dimethyl-8-hydroxy-2H-benzopyran-6-yl)-2-propen-1-one (23)
之IR圖譜………………………………………………………154
圖 24-1 syringaldehyde (24)之 1H-NMR圖譜…………………………156
圖 24-2 syringaldehyde (24)之 IR圖譜…………………………………156
圖 25-1 α-tocopheryl quinone (25)之 1H-NMR圖譜……………………158
圖 25-2 α-tocopheryl quinone (25)之 IR圖譜…………………………158
圖 26-1 lupeol (26)之 1H-NMR圖譜……………………………………160
圖 26-2 lupeol (26)之 IR圖譜……………………………………………160
圖 27-1 β-sitosterol (27) 與 stigmasterol (28)之 1H-NMR圖譜………162
圖 27-2 β-sitosterol (27) 與 stigmasterol (28)之 IR圖譜………………162

















表目錄
表一、 麵包樹屬植物過去成分之研究……………………………………6
表二、 構樹屬植物過去成分之研究………………………………………7
表三、 榕屬植物過去成分之研究…………………………………………14
表四、 柘樹屬植物過去成分之研究………………………………………25
表五、 葎屬植物過去成分之研究…………………………………………28
表六、 桑屬植物過去成分之研究…………………………………………29
表七、 台灣產桑科植物分離之coumarin…………………………………31
表八、 植物抗結核菌研究概要……………………………………………35
表九、 1H-NMR data of 1, 2, 3, 4, 5, 6 …………………………………93
表十、 13C-NMR data of 1, 2, 3, 4, 5, 6 …………………………………95
表十一、 MIC values of compounds isolated from Fatoua pilosa gainst
Mycobacterium tuberculosis H37RV……………………………163
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