Diterpenoid constituents of Euphorbia macrorrhiza.

Ten diterpenoids, named macrorilone A-B, macroripremyrsinone A, macrorilathyrone A-B, macrorieuphorone A-B and macroricasbalone A-C, together with ten known diterpenoids, jatrophalone, sikkimenoids A-D, jatrophodione A, latilagascenes F, jolkinol B, 15β-O-benzoyl-5α-hydroxyisolathyrol and jatrophalactone were isolated from the whole plant of Euphorbia macrorrhiza C.A. Mey. These diterpenoids belong to six skeleton-types, including jatropholane, premyrsinane, lathyrane, euphoractin, casbene and rhamnofolane diterpenoids. Their structures were elucidated by extensive analysis of 1D, 2D NMR and HRESIMS spectroscopic data. The absolute configurations of macrorilone B, macroripremyrsinone A and macrorilathyrone A were established by comparing their experimental and calculated electronic circular dichroism (ECD) spectra. Several of the isolated compounds exhibited weak cytotoxicity against the KB and KBv200 cell lines with IC50 values ranging from 21.19 to 47.87μM. Some also showed multidrug resistance (MDR) reversal activity, among which macrorilathyrone B exhibited a remarkable inhibitory effect on P-gp-mediated drug exclusion.