Antimycobacterial eudesmanolides from Inula helenium and Rudbeckia subtomentosa

In a bioassay guided search for antimycobacterial compounds from higher pla nts, the root extracts of Elecampane (Inula helenium L.; Asteraceae) and Sw eet Coneflower (Rudbeckia subtomentosa Pursh.: Asteraceae) were chemically investigated for their active constituents. Chromatographic fractions of ro ot extracts of I. helenium, which exhibited significant activity against My cobacterium tuberculosis, provided the known eudesmanolides alantolactone, isoalantolactone, and 11 alpha H,13-dihydroisoalantolactone. Peracid epoxid ation of alantolactone and isoalantolactone provided 5 alpha-epoxyalantolac tone and 4(15)alpha-epoxyisoalantolactone, respectively and oxidation of al antolactone with OsO4 gave 11,13-dihydroxyalantolactone. Active fractions f rom R. subtomentosa contained the known alloalantolactone and 3-oxoalloatan tolactone. The structures of the above compounds were established by spectr oscopic methods including 1D and 2D NMR techniques as well as spectral comp arison with previously reported data. The molecular structure of 5 alpha-ep oxyalantolactone was determined by single crystal Xray diffraction. Eleven natural and semisynthetic eudesmanolides were tested in a radiorespirometri c bioassay for activity against M. tuberculosis. 5 alpha-Epoxyalantolactone and encelin from Montanoa speciosa showed minimum inhibitory concentration s (MICs) of 8 and 16 mu g ml(-1), respectively. Alantolactone, isoalantolac tone and its 4 alpha,15-epoxide, 1,2-dehydro-3-epi-isotelekin and alloalant olactone gave MICs of 32 mu g ml(-1). All other compounds showed MIC values of 128 mu g ml(-1) or higher.