Liu Jia, He Xiu-Feng, Wang Gai-Hong, Merino Emilio F, Yang Sheng-Ping, Zhu Rong-Xiu, Gan Li-She, Zhang Hua, Cassera Maria B, Wang He-Yao, Kingston David G I, Yue Jian-Min
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zu Chong Zhi Road, Shanghai 201203, P. R. China.
J Org Chem. 2014 Jan 17;79(2):599-607. doi: 10.1021/jo402340h. Epub 2013 Dec 23.
Aphadilactones A-D (1-4), 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'S,11'S configuration showed potent and selective inhibition against the diacylglycerol O-acyltransferase-1 (DGAT-1) enzyme (IC50 = 0.46 ± 0.09 μM, selectivity index > 217) and is the strongest natural DGAT-1 inhibitor discovered to date. In addition, compounds 1-4 showed significant antimalarial activities with IC50 values of 190 ± 60, 1350 ± 150, 170 ± 10, and 120 ± 50 nM, respectively.
从楝科植物大叶阿芳楝中分离得到了阿法地内酯A - D（1 - 4），这四种非对映异构体具有前所未有的碳骨架。通过光谱数据、化学降解、片段合成、实验性圆二色光谱和电子圆二色计算相结合的方法确定了它们具有挑战性的结构和绝对构型。具有5S,11S,5'S,11'S构型的阿法地内酯C（3）对二酰甘油O - 酰基转移酶 - 1（DGAT - 1）表现出强效且选择性的抑制作用（IC50 = 0.46 ± 0.09 μM，选择性指数> 217），是迄今为止发现的最强效的天然DGAT - 1抑制剂。此外，化合物1 - 4表现出显著的抗疟活性，IC50值分别为190 ± 60、1350 ± 150、170 ± 10和120 ± 50 nM。
