內苳子根部及屏東木薑子莖皮化學及生物活性成分之研究

Chemical Constituents and Biological Activities from the Root of Lindera akoensis and the Stem Bark of Litsea akoensis

張素燕(Su-Yen Chang)

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

內苳子(Lindera akoensis Hayata)為常綠灌木，屬樟科、釣樟屬之固有種植物。分佈於全臺灣低海拔闊葉樹林。其根部之甲醇萃取物呈抗結核活性，經分配，得到正己烷、乙酸乙酯及水層共三層。活性之乙酸乙酯層進行分離迄今共得到21個已知化合物,其中共13個為butanolides分別為: litsenolide A2 (1)，litsenolide B2 (2)，litseakolide C1 (3)，litseakolide C2 (4)，hamabiwalactone A (5)，hamabiwalactone B (6)，litseakolide A (7)，litseakolide B (8)，majorenolide (9)，majorynolide (10)，majoranolide (11)，isoobtusilactone (12)，obtusilactone (13)，??-sitosteryl-3-O-??-D-glucoside (16)以及stigmasteryl-3-O-??-D-glucoside (17)的混合物， 1個lignan: (±)-syringaresinol (18)，2個flavans: (–)-catechin (19)，及(–)-epicatechin (20)；1個coumarin: scopoletin (21)。從正己烷層分得??-sitosterol (14)和stigmasterol (15)之混合物。而這些化合物之構造是經由光譜分析而決定。其中化合物9–11的骨架被Ma定為δ-lactone, 在1996年Fraga等予以修訂為??-lactone，後來我們利用cigar HMBC去印證後者的結構。
其分離物中有9種butanolides: 1–5、7、9–11對Mycobacterium tuberculosis H37Rv呈現抗結核活性，其MIC值分別為50、20、25、20、15、50、50、50及50 μg/ ml。
屏東木薑子( Litsea akoensis Hayata)為樟科、木薑子屬之固有種常綠喬木。產於臺灣中南部之闊葉樹林內。過去我們對臺灣產植物約1000種進行細胞毒性之篩選, 發現該植物的莖皮之甲醇抽取物對P-388, KB16, A549, HT-29等癌細胞株具有顯著細胞毒性。進行研究其莖皮結果，分離得到14個化合物:包括5個新的butanolides，8個已知化合物及一個未知化合物LASB-1。
延續莖皮的研究，迄今再分離得到2種含有1,2-dioxane新的butanolides結構:litseadioxanin A (22)、litseadioxanin B (23)、以及4個新的butanolides: litseatrinolide A (24)、litseatrinolide B (25)、litseakolide D1 (27)、litseakolide D2 (29)，其中25、29各別和litsenolide E1 (26)以及litsenolide E2 (28)混合,還有1個已知之litsenolide B1 (30)，以及成混合物的methyl-132-hydroxy-(132-
S)-pheophorbide b (32) and methyl-132-hydroxy-(132-R)-pheophorbide b (33)。此外，先前未知化合物之LASB-1，此次亦被定為已知物之methyl asterrate (31)，其結構在此一併被解析。以上化合物之結構經由各種光譜分析予以確認。
屏東木薑子莖皮之分離物，進行細胞毒活性篩選，發現litsenolide B1 (30)對MCF-7, NCI-H460及SF-268三種癌細胞株呈現邊緣細胞毒活性。

關鍵字

內苳子 ； 屏東木薑子 ； 生物活性

並列摘要

Lindera akoensis Hayata. (Lauraceae) is an endemic evergreen shrub, distributed in broad-leaved forests in lowlands throughout the Taiwan island. The methanolic extract of the root of this species showed antitubercular activity against Mycobacterium tuberculosis H37Rv and was partitioned into n-hexane, EtOAc and H2O-soluble layers. Investigation of the active EtOAc-soluble layer led to the isolation of twenty-one known compounds, including thirteen butanolides: litsenolide A2 (1), litsenolide B2 (2), litsenolide C1 (3), litsenolide C2 (4), hamabiwalactone A (5), hamabiwalactone B (6), litseakolide A (7), litseakolide B (8), majorenolide (9), majorynolide (10), majoranolide (11), isoobtusilactone (12), and obtusilactone (13); and a mixture of ??-sitosteryl-3-O-??-D-glucoside (16) and stigmasteryl-3-O-??-D-glucoside (17); one lignan: (±)-syringaresinol (18); two flavans: (–)-catechin (19), and (–)-epicatechin (20); one coumarin: scopoletin (21). A mixture of ??-sitosterol (14) and stigmasterol (15) was also isolated from the n-hexane-soluble layer. The structures of these compounds were elucidated by speetral evidences.
Compounds 9−11 were previously assigned with a δ-lactone skeleton by Ma et al and revised to ??-lactone by Fraga et al in 1996. In this study, cigar HMBC analyses was used to substantially support the revised structures of 9−11.
Nine butanolides 1−5, 7, 9−11 showed antitubercular activities against M. tuberculosis H37Rv with MIC values : 50, 20, 25, 20, 15, 50, 50, 50 and 50 μg/ ml, respectively.
Litsea akoensis Hayata. (Lauraceae) is an evergreen medium-sized tree, endemic in Taiwan, and distributed in broad-leaved forests at low to medium altitudes throughout the Taiwan island. In a series of studies on the cytotoxic constituents of Formosan plants, we have screened ca. 1000 species for in vitro cytotoxicity and L. akoensis was one of the active species. Its stem bark showed significant cytotoxic activity against P-388, KB16, A549 and HT-29 cancer cell lines. In our previous study, fourteen compounds including five new butanolides, eight known compounds and an unknown compound, LASB-1 (31) were isolated from the stem of this species. Successive investigation of CHCl3-soluble fraction of the stem bark of this species led to the isolation of six new butanolides, two of which with 1,2-dioxane moiety: litseadioxanin A (22), litseadioxanin B (23), and litseatrinolide A (24), litseatrinolide B (25), litseakolide D1 (27), litseakolide D2 (29), along with five known compounds: litsenolide B1 (30), litsenolide E1 (26), litsenolide E2 (28), and a mixture of methyl-132-hydroxy-(132-S)-pheophorbide b (32) and methyl-132-hydroxy-(132-R)-pheophorbide b (33). An unknown LASB-1 obtained previously was also determined as a known methyl asterrate (31) this time. The structures of these compounds were elucidated through spectral analyses.
Among the isolates, litsenolide B1 (30) showed marginal cytotoxic activity against MCF-7, NCI-H460 and SF-268 cell lines.

並列關鍵字

Lindera akoensis ； Litsea akoensis ； Biological Activities

參考文獻

1. Lu SY, Yang YP. Lauraceae in Flora of Taiwan; 2 ed.; Editorial Committee of the Flora of Taiwan, Taipei, Taiwan 1996; Vol II: 458–9

2. Lu SY, Yang YP. Lauraceae in Flora of Taiwan; 2 ed.; Editorial Committee of the Flora of Taiwan, Taipei, Taiwan 1996; Vol II: 467–8

3. Chen IS. Lai-Yaun IL, Duh CY, Tsai IL. Cytotoxic butanolides from Litsea akoensis. Phytochemistry 1998; 49: 745–50

4. Tsai IL, Lai-Yaun IL, Duh CY, Jeng YF, Chen IS. A new cytotoxic butanolide from the stem bark of Litsea akoensis. Chin Pharm J 2000; 52: 235–9

5. 賴源宜倫. 屏東木薑子莖皮之化學與細胞毒活性成分之研究. 高雄醫學大學天然藥物研究所碩士論文, 1996