Bisabololoxide derivatives from Artemisia persica, and determination of their absolute configurations by ECD

Abstract

Five antiplasmodial bisabololoxide sesquiterpene diesters were isolated from an EtOAc extract of the aerial parts of Artemisia persica following an HPLC-time-based activity profiling of the extract. Structure elucidation was achieved by 1D and 2D NMR experiments. Relative configurations of cyclohexenone/cyclohexene and tetrahydropyran moieties of 1-5 were established on the basis of ³J(H-H) coupling constants and NOE difference spectra. Stereochemical correlation of the two rings, and assignment of absolute configuration of 1-5 were achieved by comparison of experimental ECD spectra with simulated ECD data for possible stereoisomers, by using time dependent density function theory (TDDFT). Bisaboloids 1-4 exhibited in vitro antimalarial activity against Plasmodium falciparum, with IC₅₀ values ranging from 2.8 to 20.1 μM, and selectivity indices (SI) in L-6 cells of 3.7-11.9.