Aphadilactones A–D, Four Diterpenoid Dimers with DGAT Inhibitory and Antimalarial Activities from a Meliaceae Plant

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• 作者：Jia Liu ; Xiu-Feng He ; Gai-Hong Wang ; Emilio F. Merino ; Sheng-Ping Yang ; Rong-Xiu Zhu ; Li-She Gan ; Hua Zhang ; Maria B. Cassera ; He-Yao Wang ; David G. I. Kingston ; Jian-Min Yue
• 刊名：Journal of Organic Chemistry
• 出版年：2014
• 出版时间：January 17, 2014
• 年：2014
• 卷：79
• 期：2
• 页码：599-607
• 全文大小：447K
• ISSN：1520-6904

文摘

Aphadilactones A鈥揇 (1鈥?b>4), four diastereoisomers possessing an unprecedented carbon skeleton, were isolated from the Meliaceae plant Aphanamixis grandifolia. Their challenging structures and absolute configurations were determined by a combination of spectroscopic data, chemical degradation, fragment synthesis, experimental CD spectra, and ECD calculations. Aphadilactone C (3) with the 5S,11S,5鈥?i>S,11鈥?i>S configuration showed potent and selective inhibition against the diacylglycerol O-acyltransferase-1 (DGAT-1) enzyme (IC₅₀ = 0.46 卤 0.09 渭M, selectivity index > 217) and is the strongest natural DGAT-1 inhibitor discovered to date. In addition, compounds 1鈥?b>4 showed significant antimalarial activities with IC₅₀ values of 190 卤 60, 1350 卤 150, 170 卤 10, and 120 卤 50 nM, respectively.