雙面刺莖皮之化學成分及生物活性之研究

Studies on the Chemical Constituents and Biological Activities from the Stem Bark of Zanthoxylum nitidum

楊正蕙(Cheng-Hui Yang)

指導教授 ： 陳益昇

高雄醫學大學/藥學院/天然藥物研究所碩士班/碩士(2007年)

摘要

雙面刺 [Zanthoxylum nitidum (Roxb.)DC.]為芸香科(Rutaceae)之藤本灌木,因含有具細胞毒性的benzo[c]phenanthridine生物鹼, nitidine 及酚性benzo[c]phenanthridine 生物鹼, terihanine而聞名。其莖皮在民間上被用於治療毒蛇咬傷及牙痛。過去對於花椒屬材料多以酸鹼處理法進行分配，然而，這對於酸不穩定成分會造成分離的困難性。本實驗將於中性環境進行實驗以獲得這類特殊化合物。
雙面刺莖皮之甲醇萃取物分劃成正己烷、氯仿、正丁醇及水可溶部四個部分。在正己烷可溶部分及氯仿可溶部分，目前共分離得到三十二個化合物。包括五種新穎的benzo[c]phenanthridine衍生物－zanthocadinanine A (1), zanthocadinanine B (2), zanthomuurolanine (3), epi-zanthomuurolanine (4)及epi-zanthocadinanine B (5)，此等結構為dihydrochelerythrine與cadinane類sesquiterpene經亞甲基架橋相連所構成的雙聚體。其餘二十七個已知成分包含：dihydrochelerythrine (6), 6-acetonyldihydrochelerythrine (7), oxynitidine (8), oxychelerythrine (9), oxyavicine (10), norchelerythrine (11), decarine (12), arnottianamide (13), flindersine (14), 4-methoxy-1-methyl-2-quinolone (15), skimmianine (16), γ-fagarine (17), liriodenine (18), N-acetyldehydroanonaine (19), N-acetylanonaine (20), sesamin (21), epi-sesamin (22), piperitol-3,3-dimethylallyl ether (23), xanthoxylol-3,3-dimethylallyl ether (24), savinin (25), 2,3-di(3,4-methylenedioxybenzyl)-2-buten-4-olide (26), α-cadinol (27), anticopalol (28), spathulenol (29), aesculetin dimethyl ether (30), β-sitosterol (31)及 β-sitostenone (32).。其中，化合物14, 15, 17, 19, 20, 23~29等十二個化合物為本植物首次分離。所得化合物之構造均利用光譜資料來決定。
日前rhoifoline A, rhoifoline B 及 8-methoxynorchelerythrine分別被兩組研究單位以新化合物發表。經比對光譜發現，這些化合物與本研究所得之已知物oxyavicine, oxynitidine 及 oxychelerythine 是同一化合物，故其構造應予以改正。
在分離物中化合物 16, 18及24對MCF-7, NCI-H460及SF-268癌細胞株具有細胞毒殺活性。

關鍵字

雙面刺 ； 莖皮 ； 雙聚體化合物

並列摘要

Zanthoxylum nitidum (Roxb.)DC.(Rutaceae) is a scandent shrub and was famous for the cytotoxic benzo[c]phenanthridine alkaloid, nitidine and a phenolic benzo[c]phenanthridine alkaloid, terihanine. Its stem bark was used as a folk medicine to cure snake bite and to relieve toothache. Previously, conventional method was used in the separation of Zanthoxylum material by partition under acid or alkaline conditions. The acid-sensitive components might be isolated with difficulty. In this study, we try to employ the partition avoiding of acid and base and expected to obtain some unique compounds.
Investigation of n-hexane- and CHCl3- soluble fractions of the stem bark led to the isolation of thirty-two compounds, including five novel dimers－ zanthocadinanine A (1), zanthocadinanine B (2) , zanthomuurolanine (3), epi-zanthomuurolanine (4) and epi-zanthocadinanine B (5), all composed of dihydrochelerythrine and cadinane sesquiterpene linked by a methylene bridge; along with twenty-seven known compounds: dihydrochelerythrine (6), 6-acetonyldihydrochelerythrine (7), oxynitidine (8), oxychelerythrine(9), oxyavicine (10), norchelerythrine (11), decarine (12), arnottianamide (13), flindersine (14), 4-methoxy-1-methyl-2-quinolone (15), skimmianine (16), γ-fagarine (17), liriodenine (18), N-acetyldehydroanonaine (19), N-acetylanonaine (20), sesamin (21), epi-sesamin (22), piperitol-3,3-dimethylallyl ether (23) , xanthoxylol-3,3-dimethylallyl ether (24), savinin (25), 2,3-di(3,4-methylenedioxybenzyl)-2-buten-4-olide (26), α-cadinol (27), anticopalol (28), spathulenol (29), aesculetin dimethyl ether (30), β-sitosterol (31)and β-sitostenone (32). Thirteen compounds 14, 15, 17, 19, 20, 23~29 were isolated from this plant for the first time. The structures of these isolates were determined by spectroscopic analyses.
Recently, rhoifoline A, rhoifoline B and 8-methoxynorchelerythrine were reported as new compounds separately by two research groups. By comparing the spectral data, these compounds should be revised to oxyavicine (8), oxynitidine (10) and oxychelerythine (9)which was also obtained in this study, respectively.
Among the isolates, compounds 16, 18 and 24 showed cytotoxicities against MCF-7, NCI-H460 and SF-268 cell lines.

並列關鍵字

Zanthoxylum nitidum ； stem bark ； dimeric compounds

參考文獻

第九章 參考文獻

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