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研究生:楊捷凱
研究生(外文):Chieh-kai Yang
論文名稱:狗花椒莖皮之化學成分及抗發炎活性之研究
論文名稱(外文):Studies on the Chemical Constituents and Anti-inflammatory Activities from the Stem Bark of Zanthoxylum avicennae
指導教授:陳日榮
指導教授(外文):Jih-Jung Chen
學位類別:碩士
校院名稱:大仁科技大學
系所名稱:製藥科技研究所
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:2012
畢業學年度:100
語文別:中文
論文頁數:128
中文關鍵詞:狗花椒芸香科抗發炎活性
外文關鍵詞:Rutaceaeanti-inflammatory activityZanthoxylum avicennae
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狗花椒為芸香科之常綠灌木,分佈於越南、菲律賓、中國南方及台灣。對台灣產植物進行抗發炎活性篩選,其中狗花椒為活性植物之一。
由狗花椒莖皮之EtOAc可溶部,目前已分離出三個新的coumarin derivatives: 8-formylalloxanthoxyletin (1), (E)-avicennone (2)及(Z)- avicennone (3),以及十五個已知化合物。已知化合物中包括九個coumarins: alloxanthoxyletin (4), avicennol (5), avicennol methyl ether (6), cis-avicennol methyl ether (7), avicennin (8), xanthoxyletin (9), luvangetin (10), scopoletin (11)及aesculetin dimethyl ether (12),二個benzo[c]phenanthridine derivatives: norchelerythrine (13) 及arnottiana- mide (14),一個furoquinoline: -fagarine (15),一個triterpene: -amyrin (16),以及兩個steroid混合物: -sitosterol (17)與stigmasterol (18)。上述化合物之結構,經由各種圖譜分析及文獻數據比對予以確認。
目前分離所得到的化合物中,8-formylalloxanthoxyletin (1), alloxanthoxyletin (4), xanthoxyletin (9), aesculetin dimethyl ether (12)及-fagarine (15)對於formyl-L-methionyl-L-leuckyl-L-phenylalanine/cyto- chalasin B (fMLP/CB)誘導人類嗜中性白血球產生超氧陰離子(O2•–),具有良好的抑制活性,其IC50 值 ≤ 7.65 g/mL。此外,8-formylalloxan- thoxyletin (1), (E)-avicennone (2), alloxanthoxyletin (4), avicennin (8)及xanthoxyletin (9)對於fMLP/CB誘導人類嗜中性白血球釋放彈性蛋白酶(elastase),亦有不錯的抑制效果,其IC50值 ≤ 8.17 g/mL。
Zanthoxylum avicennae (Lam.) DC. (Rutaceae) is an evergreen shrub distributed in Vietnam, Philippines, southern China, and Taiwan. In our studies on the anti-inflammatory constituents of Formosan plants, many species have been screened for in vitro anti-inflammatory activity, and Z. avicennae has been found to be one of the active species.
In our search for compounds with anti-inflammatory activities, three new coumarin derivatives, 8-formylalloxanthoxyletin (1), avicennone (2), and (Z)-avicennone (3), and 15 known compounds (4–18) have been isolated and identified from the stem bark of Z. avicennae. Fifteen known compounds include nine coumarins, alloxanthoxyletin (4), avicennol (5), avicennol methyl ether (6), cis-avicennol methyl ether (7), avicennin (8), xanthoxyletin (9), luvangetin (10), scopoletin (11), and aesculetin dimethyl ether (12), two benzo[c]phenanthridine derivatives, norchelerythrine (13) and arnottianamide (14), a furoquinoline, -fagarine (15), a triterpene, -amyrin (16), and a mixture of steroids, -sitosterol (17) and stigmasterol (18). The structures of all isolates were determined through spectral analyses and comparison of their physical and spectral data with literatures.
Among the isolated compounds, 8-formylalloxanthoxyletin (1), alloxanthoxyletin (4), xanthoxyletin (9), aesculetin dimethyl ether (12), and -fagarine (15) exhibited inhibition (IC50 values ≤ 7.65 g/mL) of superoxide anion generation by human neutrophils in response to formyl-L-methionyl-L-leuckyl-L-phenylalanine/cytochalasin B (fMLP/CB). In addition, 8-formylalloxanthoxyletin (1), (E)-avicennone (2), alloxan- thoxyletin (4), avicennin (8), and xanthoxyletin (9) inhibited fMLP/CB- induced elastase release with IC50 values ≤ 8.17 g/mL.
中文摘要 1
ABSTRACT 3
第一章 緒言 6
第二章 研究動機與目的 8
第三章 過去化學成分研究概要 10
第四章 抽出與分離 26
第五章 結果與討論 34
第一節 8-Formylalloxanthoxyletin (1)之結構研究 34
第二節 (E)-Avicennone (2)之結構研究 41
第三節 (Z)-Avicennone (3)之結構研究 48
第四節 Alloxanthoxyletin (4)之結構研究 55
第五節 Avicennol (5)之結構研究 58
第六節 Avicennol methyl ether (6)之結構研究 62
第七節 cis-Avicennol methyl ether (7)之結構研究 66
第八節 Avicennin (8)之結構研究 70
第八節 Xanthoxyletin (9)之結構研究 74
第十節 Luvangetin (10)之結構研究 77
第十一節 Scopoletin (11)之結構研究 80
第十二節 Aesculetin dimethyl ether (12)之結構研究 83
第十三節 Norchelerythrine (13)之結構研究 86
第十四節 Arnottianamide (14)之結構研究 90
第十五節 -Fagarine (15)之結構研究 94
第十六節 -Amyrin (16)之結構研究 97
第十七節 Mixture of -Sitosterol (17) and Stigmasterol (18)之 結構研究 100
第六章 抗發炎活性研究 103
第七章 結論 106
第八章 實驗部分 107
第一節 儀器與材料 107
第二節 狗花椒莖皮部之抽取與分離 109
第三節 抗發炎活性之實驗方法 113
第四節 各化合物之實驗數據 116
第九章 參考文獻 123



圖 表 目 錄
頁次
圖A:狗花椒幹刺 5
圖B:狗花椒葉 5
圖C:狗花椒莖皮部分離之流程圖 26
圖D:狗花椒莖皮部EtOAc層之成分分離 27
圖1-1:8-Formylalloxanoxyletin (1)之ESI-MS圖譜 36
圖1-2:8-Formylalloxanoxyletin (1)之HR-ESI-MS圖譜 36
圖1-3:8-Formylalloxanoxyletin (1)之IR圖譜 37
圖1-4:8-Formylalloxanoxyletin (1)之1H-NMR圖譜 37
圖1-5:8-Formylalloxanoxyletin (1)之13C-NMR圖譜 38
圖1-6:8-Formylalloxanoxyletin (1)之NOESY圖譜 38
圖1-7:8-Formylalloxanoxyletin (1)之HMBC圖譜 39
圖1-8:8-Formylalloxanoxyletin (1)之HSQC圖譜 39
圖1-9:8-Formylalloxanoxyletin (1)之DEPT圖譜 40
圖1-10:8-Formylalloxanoxyletin (1)之1H-1H COSY圖譜 40
圖2-1:(E)-Avicennone (2)之ESI-MS圖譜 43
圖2-2:(E)-Avicennone (2)之HR-ESI-MS圖譜 43
圖2-3:(E)-Avicennone (2)之IR圖譜 44
圖2-4:(E)-Avicennone (2)之13C-NMR圖譜 44
圖2-5:(E)-Avicennone (2)之1H-NMR圖譜 45
圖2-6:(E)-Avicennone (2)之NOESY圖譜 45
圖2-7:(E)-Avicennone (2)之HMBC圖譜 46
圖2-8:(E)-Avicennone (2)之HSQC圖譜 46
圖2-9:(E)-Avicennone (2)之DEPT圖譜 47
圖2-10:(E)-Avicennone (2)之1H-1H COSY圖譜 47
圖3-1:(Z)-Avicennone (3)之ESI-MS圖譜 50
圖3-2:(Z)-Avicennone (3)之HR-ESI-MS圖譜 50
圖3-3:(Z)-Avicennone (3)之IR圖譜 51
圖3-4:(Z)-Avicennone (3)之13H-NMR圖譜 51
圖3-5:(Z)-Avicennone (3)之1H-NMR圖譜 52
圖3-6:(Z)-Avicennone (3)之NOESY圖譜 52
圖3-7:(Z)-Avicennone (3)之HMBC圖譜 53
圖3-8:(Z)-Avicennone (3)之HSQC圖譜 53
圖3-9:(Z)-Avicennone (3)之DEPT圖譜 54
圖3-10:(Z)-Avicennone (3)之1H-1H COSY圖譜 54
圖4-1:Alloxanthoxyletin (4)之ESI-MS圖譜 56
圖4-2:Alloxanthoxyletin (4)之IR圖譜 56
圖4-3:Alloxanthoxyletin (4)之1H-NMR圖譜 57
圖5-1:Avicennol (5)之ESI-MS圖譜 60
圖5-2:Avicennol (5)之IR圖譜圖 60
圖5-3:Avicennol (5)之1H-NMR圖譜 61
圖6-1:Avicennol methyl ether (6)之ESI-MS圖譜 64
圖6-2:Avicennol methyl ether (6)之IR圖譜 64
圖6-3:Avicennol methyl ether (6)之1H-NMR圖譜 65
圖7-1:cis-Avicennol methyl ether (7)之ESI-MS圖譜 68
圖7-2:cis-Avicennol methyl ether (7)之IR圖譜 68
圖7-3:cis-Avicennol methyl ether (7)之1H-NMR圖譜 69
圖8-1:Avicennin (8)之ESI-MS圖譜 72
圖8-2:Avicennin (8)之IR圖譜 72
圖8-3:Avicennin (8)之1H-NMR圖譜 73
圖9-1:Xanthoxyletin (9)之ESI-MS圖譜 75
圖9-2:Xanthoxyletin (9)之IR圖譜 75
圖9-3:Xanthoxyletin (9)之1H-NMR圖譜 76
圖10-1:Luvangetin (10)之ESI-MS圖譜 78
圖10-2:Luvangetin (10)之IR圖譜 78
圖10-3:Luvangetin (10)之1H-NMR圖譜 79
圖11-1:Scopoletin (11)之ESI-MS圖譜 81
圖11-2:Scopoletin (11)之IR圖譜 81
圖11-3:Scopoletin (11)之1H-NMR圖譜 82
圖12-1:Aesculetin dimethyl ether (12)之ESI-MS圖譜 84
圖12-2:Aesculetin dimethyl ether (12)之IR圖譜 84
圖12-3:Aesculetin dimethyl ether (12)之1H-NMR圖譜 85
圖13-1:Norchelerythrine (13)之ESI-MS圖譜 88
圖13-2:Norchelerythrine (13)之IR圖譜 88
圖13-3:Norchelerythrine (13)之1H-NMR圖譜 89
圖14-1:Arnottianamide (14)之ESI-MS圖譜 92
圖14-2:Arnottianamide (14)之IR圖譜 92
圖14-3:Arnottianamide (14)之1H-NMR圖譜 93
圖15-1:-Fagarine (15)之ESI-MS圖譜 95
圖15-2:-Fagarine (15)之IR圖譜 95
圖15-3:-Fagarine (15)之1H-NMR圖譜 96
圖16-1:-Amyrin (16)之ESI-MS圖譜 98
圖16-2:-Amyrin (16)之IR圖譜 98
圖16-3:-Amyrin (16)之1H-NMR圖譜 99
圖17-1:Mixture of -Sitosterol (17) and Stigmasterol (18)之ESI-MS圖譜 101
圖17-2:Mixture of -Sitosterol (17) and Stigmasterol (18)之 IR圖譜 101
圖17-3:Mixture of -Sitosterol (17) and Stigmasterol (18)之1H-NMR圖譜 102
表1:狗花椒過去分離之化學成分及文獻 14
表2:化合物之抗發炎活性 105
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