The plakortones, novel bicyclic lactones from the sponge Plakortis halichondrioides: Activators of cardiac SR-Ca2+-pumping ATPase

Bioassay-guided fractionation of the EtOAc extract of sponge Plakortis halichondroides yielded four novel bicyclic lactones, plakortones A, B, C, D and a novel acid, plakortide E (3, 4, 5, 6 and 7). The structures, including stereochemistry, of these compounds were established by interpretation of spectral data. Plakortones A-D (3-6) comprise a novel class of activators of cardiac SR-Ca2+ -pumping ATPase which were found to be active at micromolar concentrations As part of an SAR study, the alpha and beta diols 9 and 10 of plakortone D were prepared using Sharpless AD procedure.