長花厚殼樹根部化學成分及抗結核活性之研究

Chemical Constituents and Antitubercular Activity from the Root of Ehretia longiflora

簡鈺潔(Yu-Chieh Chien)

指導教授 ： 蔡烟力

高雄醫學大學/藥學院/天然藥物研究所碩士班/碩士(2010年)

摘要

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。

關鍵字

長花厚殼樹 ； 紫草科 ； 根部 ； 抗結核活性

並列摘要

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.

並列關鍵字

Ehretia longiflora ； Boragenaceae ； root ； antitubercular activity

參考文獻

1. Yang TI, A List of Plants in Taiwan. Natural Publishing Co., LTD. Taipei, Taiwan, 1982; Vol. pp. 1096-1099

2. Hsiao JY, Liu HY, Boraginaceae in Flora of Taiwan, 2nd edition, Editorial Committee of the Flora of Taiwan, Taipei, Taiwan, 1998; Vol. IV, pp. 393-6

3. Hsiao JY, Liu HY, Boraginaceae in Flora of Taiwan, 2nd edition, Editorial Committee of the Flora of Taiwan, Taipei, Taiwan, 1998; Vol. IV, pp. 388

4. http://nidss.cdc.gov.tw/SingleDisease.aspx?dt=3&dc=1&disease=010&d=1 &i=0&s=determined_cnt&RK=W.

5. http://www.doh.gov.tw/CHT2006/DM/DM2_2.aspx?now_fod_list_no=10642 &class_no=440&level_no=3.