Metabolites from the Sponge Plakortis simplex. Part 3: Isolation and Stereostructure of Novel Bioactive Cycloperoxides and Diol Analogues

The known plakortide H (1), the novel cycloperoxide polyketides plakortide I (2) and J (3), and the diol analogues seco-plakortide H (4) and seco-plakortide I (5), have been isolated from the Caribbean marine sponge Plakortis simplex as their methyl esters 1a–5a, and their structures fully characterized by spectroscopic and chemical means. The absolute stereochemistry at the three chiral sites C-3, C-4, and C-6 of plakortide H (1) and of the novel compounds 2–5 have been determined by applying the modified Mosher method on certain reaction products. The isolated compounds exhibited good cytotoxic activity against WEHI 164, a murine fibrosarcoma cell line. Cycloperoxide esters and carboxylic acids were found considerably more active than the corresponding acyclic diol analogues.