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 structu res, including stereochemistry, of these compounds were established by interpretation of spectral data. Plakortones A-D (3-6) comprise a nov el class of activators of cardiac SR-Ca2+ -pumping ATPase which were f ound 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 usin g Sharpless AD procedure.