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

Abstract

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.

Peroxy natural products

“…7 The first total synthesis of seco-plakortolide E also supported the structural revision of plakortolide E. 8 Continuing investigation of the same sponge, P. clathrata, afforded an additional set of 16 plakortolide metabolites 10-25. 9 A Jamaican collection of Plakinastrella onkodes yielded two cyclic peroxides, plakortolide F 26 and plakortolide G 27.…”

Recent Advances in Total Synthesis of Bioactive Furo[3,2‐b]furanone Natural Products

“…Plakortones A–D ( 121 – 124 ) act as a new class of activators of cardiac SR−Ca 2+ ‐pumping ATPase whereas siblings 122 – 126 also exhibit in vitro cytotoxic activity in murine fibrosarcoma cell lines . Recently, three new plakortones L, N & P ( 127 – 129 ) have been isolated from an Australian sponge Plakinastrella clathrata by Garson et al . Little is known on biogenesis of plakortones, apart from the hypothesis that dioxalane natural products, plakortides may serve as biosynthetic precursors of plakortones.…”

Chemistry and Selective Tumor Cell Growth Inhibitory Activity of Polyketides from the South China Sea Sponge Plakortis sp.

“…This family of polyketides are commonly characterized with a cyclic peroxide [2,3,4,5,6], a penta-lactone [7,8,9,10,11,12,13], or a furano ring [14,15,16] as core structure, and a flexible alkyl chain. A small number of polyketides have a simple linear structure [17,18].…”