酪梨未熟果肉化學成分及抗結核活性之研究

Chemical Constituents and Anti-tubercular Activity from the Unripe Pulp of Persea americana

盧盈辰(Ying-Chen Lu)

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(2011年)

摘要

酪梨 (Persea americana Mill.) 為樟科之常綠喬木，在世界上主要分布於熱帶及亞熱帶氣候區。到目前為止，酪梨的根皮、葉部、果實以及種子已被研究過，並且發現了許多不同骨架的結構，例如：單萜類、倍半萜類、三萜類、黃酮類、固醇類以及類胡蘿蔔素等等，其中又以長鏈脂肪醇衍生物為主。回顧過去文獻，此植物表現出多種生物活性，包含細胞毒殺、抗黴菌、抗細菌、acetyl-CoA carboxylase酶抑制性、抑制NO及過氧化物產生、以及肝臟損傷抑制效果等等。
近年來約有1300種台灣產的植物測試體外抗結核菌 (Mycobacterium tuberculosis H37Rv) 的效果，其中酪梨未熟果肉的甲醇萃取物表現出抗結核的活性。因此，本研究的目的為針對酪梨未熟果肉進行化學及抗結核活性成分之探討。將酪梨未熟果肉之甲醇萃取物進行分配，分為乙酸乙酯可溶部及水可溶部。
利用生物活性導向，將酪梨未熟果肉之乙酸乙酯可溶部進行分離，一共獲得5個脂肪族醇類新化合物：avocadenols A-D (1-4)、avocadoin (5)，8個具有acetonide取代基的化合物：(2R,4S)-2,4-acetonide-16-heptadecene-1,2,4-triol (6)、(2R,4S,6E)-2,4-acetonide-6-en-16-heptadecene-1,2,4-triol (7)、(2R,4S)-2,4-acetonide- 16-heptadecyne-1,2,4-triol (8)、(2R,4S,6E)-2,4-acetonide-heptadec-6-en-16-yne-1,2,4- triol (9)、(2S,4S)-1,2-acetonide-16-heptadecene-1,2,4-triol (10)、(2S,4S,6E)-1,2- acetonide-heptadec-6,16-diene-1,2,4-triol (11)、(2S,4S)-1,2-acetonide-16-heptadec- yne-1,2,4-triol (12) 和 (2S,4S,6E)- 1,2-acetonide-heptadec-6-en-16-yne-1,2,4-triol (13) 以及12個已知化合物：oleic acid (14)、cedrelopsin (15)、(2R,4R)-1-acetoxy-2,4- dihydroxyheptadec-16-ene (22)、(2R,4R)-1-acetoxy-2,4- dihydroxy- heptadec-16-yne (23)、(2R,4R)-1,2,4-trihydroxyheptadec-16-ene (24)、(2R,4R)-1,2,4-trihydroxyheptadec- 16-yne (25)、1,4-diacetoxy-2-hydroxyheptadec-16-ene (30)、(2R,4R)-1,2,4- trihydroxynonadecane (53)、(2R,4R,6E)-1,2,4-trihydroxynonadec-6-ene (54)、scopoletin (77)、混合物β-sitosterol (125) 及stigmasterol (126)。根據生合成，我們推斷化合物6-13為純化過程中產生的人工產物。以上化合物之構造均以各種光譜解析決定。
Avocadenols A-B (1-2)、(2R,4S)-2,4-acetonide-16-heptadecene-1,2,4-triol (6)、(2R,4R)-1,2,4-trihydroxynonadecane (53) 、(2R,4R)-1,2,4-trihydroxyheptadec-16-ene (24) 以及(2R,4R)-1,2,4-trihydroxy-heptadec-16-yne (25) 體外抗結核菌 (Mycobacterium tuberculosis H37Rv) 所表現出的MIC數值分別為：24.0、33.8、50.0、24.9和35.7 μg/mL。

關鍵字

酪梨 ； 樟科 ； 果肉 ； 脂肪酸醇類 ； 抗結核活性

並列摘要

Persea americana Mill. (Lauraceae) is an evergreen tree, distributed in tropical and subtropical regions around the world. Until now, the bark, leaves, fruits and seeds of P. americana have been extensively studied. Previous studies on this plant identified various classes of chemical constituents, such as monoterpenoids, sesquiterpenoids, triterpenoids, flavonoids, steroids, and carotenoids, and especially long-chain fatty alcohol derivatives. From the previous investigations, this plant showed numerous bioactivities, including cytotoxicity, antifungal, antibacterial, acetyl-CoA carboxylase inhibition, nitric oxide and superoxide generation inhibition, and liver injury suppressing effects.
Approximately 1300 species of Formosan plants have been screened for antitubercular activity against Mycobacterium tuberculosis H37Rv in vitro, and the methanolic extract of the unripe pulp of P. americana was shown with antitubercular activity. The aims of this study are the isolation of chemical constituents and their antitubercular activity. The methanolic extract of the unripe pulp of P. americana was partitioned into ethyl acetate and water-soluble layers.
Bioassay-guided fractionation of the active ethyl acetate-soluble layer has led to the isolation of four new aliphatic alcohols: avocadenols A-D (1-4), avocadoin (5), and eight compounds with acetonide moiety: (2R,4S)-2,4-acetonide- 16-heptadecene-1,2,4-triol (6), (2R,4S,6E)-2,4-acetonide-6-en-16-heptadecene-1,2,4- triol (7), (2R,4S)-2,4-acetonide-16-heptadecyne-1,2,4-triol (8), (2R,4S,6E)-2,4- acetonide-heptadec-6-en-16-yne-1,2,4-triol (9), (2S,4S)-1,2-acetonide-16- heptadecene-1,2,4-triol (10), (2S,4S,6E)-1,2-acetonide-heptadec-6,16-diene-1,2,4- triol (11), (2S,4S)-1,2-acetonide-16-heptadecyne-1,2,4-triol (12) and (2S,4S,6E)-1,2- acetonide-heptadec-6-en-16-yne-1,2,4-triol (13) together with twelve known compounds: oleic acid (14), cedrelopsin (15), (2R,4R)-1-acetoxy-2,4- dihydroxyheptadec-16-ene (22), (2R,4R)-1- acetoxy-2,4-dihydroxyheptadec-16-yne (23), (2R,4R)-1,2,4-trihydroxyheptadec-16-ene (24), (2R,4R)-1,2,4-trihydroxyheptadec- 16-yne (25), 1,4-diacetoxy-2-hydroxyheptadec-16-ene (30), (2R,4R)-1,2,4- trihydroxynonadecane (53), (2R,4R,6E)-1,2,4-trihydroxynonadec-6-ene (54), scopoletin (77), mixtures of β-sitosterol (125) and stigmasterol (126). According to the biosynthesis pathway, we could presume that 6-13 are artificial products produced during purification. The structures of these isolates were elucidated by spectroscopic analysis.
Avocadenols A-B (1-2), (2R,4S)-2,4-acetonide-16-heptadecene-1,2,4-triol (6), (2R,4R)-1,2,4-trihydroxynonadecane (53), (2R,4R)-1,2,4-trihydroxyheptadec-16-ene (24), and (2R,4R)-1,2,4-trihydroxyheptadec-16-yne (25) showed antitubercular activity against M. tuberculosis H37Rv in vitro with MIC values of 24.0, 33.8, 50.0, 24.9, and 35.7 μg/mL, respectively.

並列關鍵字

Persea americana ； Avocado ； Lauraceae ； Pulp, Fatty alcohol, Anti-tubercular activity

參考文獻

第九章 參考文獻

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