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.