Metabolites from the Sponge Plakortis simplex. Part 3: Isolation and Structure Determination 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 secoplakortide 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.