Configurational assignment of cyclic peroxy metabolites provides an insight into their biosynthesis: isolation of plakortolides, seco-plakortolides, and plakortones from the Australian marine sponge Plakinastrella clathrata.

Sixteen new compounds, comprising nine new plakortolides K-S (1-9), four seco-plakortolides (10-13), and three plakortones (14-16), were isolated from the Australian sponge Plakinastrella clathrata. Structural elucidation, including relative configurational assignment, was based on extensive spectroscopic analysis, while the absolute configurations of 1-4 were deduced from (1)H NMR analyses on MPA esters derived from Zn/AcOH reduction products. Diastereomeric sets of plakortolides, e.g., K and L, or M and N, differed in configuration at C-3/C-4 rather than at C-6, a stereochemical result that compromises a biosynthetic pathway involving Diels-Alder cycloaddition of molecular oxygen to a Δ(3,5)-diunsaturated fatty acid precursor. The biosynthesis may plausibly involve cyclization of a 6-hydroperoxydienoic acid intermediate following stereospecific introduction of the hydroperoxy group into a polyketide-derived precursor. Isolated seco-plakortolides converted under mild conditions into plakortones with full retention of configuration, suggesting C-6 hydroxy attack on an α,β-unsaturated lactone intermediate. The NMR data reported for the compound named plakortolide E are inconsistent with the current literature structure and are those of the corresponding seco-plakortolide (19). The reported conversion of the metabolite into a plakortone ether on storage is consistent with this structural revision.