Tetrahydroxanthene-1,3(2H)-dione derivatives from Uvaria valderramensis.

Two tetrahydroxanthene-1,3(2H)-dione metabolites, valderramenols A (1) and B (2), were isolated from the Philippine endemic Annonaceous species Uvaria valderramensis. Planar structures of the rac-xanthene-1,3-(2H)-diones 1 and 2 were established by MS and NMR measurements. Their enantiomers were separated by chiral HPLC, and the absolute configurations of the separated enantiomers were determined by comparison of the HPLC-ECD spectra with computed TDDFT-generated spectra. A TDDFT-ECD study of the known grandiuvarone (3) allowed the revision of its absolute configuration as S. Compound 1 showed antitubercular activity (MIC 10 μg/mL), while 3 and 4 had weaker activities (MIC 32 μg/mL). Oxepinone 3 exhibited cytotoxic activity against KB-562, a chronic myeloid leukemia cell line.