Plakortides M and N, bioactive polyketide endoperoxides from the Caribbean marine sponge Plakortis halichondrioides

From a small specimen of the marine sponge Plakortis halichondrioides collected in Puerto Rico we have isolated the known unsaturated ester methyl (2Z,6R,8R,9E)-3,6-epoxy-4,6,8-triethyl-2,4,9-dodecatrienoate (1) along with the known cyclic peroxide plakortide F (2). In addition, the structures of two new polyketide endoperoxides, namely, plakortide M (3) and plakortide N (4), were fully characterized by spectroscopic and chemical methods. The absolute stereochemistry of plakortide M methyl ester (3a) has been determined by analysis of the (R)- and (S)-MTPA esters of the acyclic derivative 5 obtained by hydrogenolysis. Plakortide M (3) and plakortide N (4) exhibited potent cytotoxicity in the NCI human cancer screening program, whereas plakortide M methyl ester, 3a, displayed strong antimalarial activity against Plasmodium falciparum.