Plakortinic acids C and D: A pair of peroxide-polyketides possessing a rare 7,8-dioxatricyclo[4.2.2.02,5]dec-9-ene core from a two-sponge association of Plakortis symbiotica–Xestospongia deweerdtae

[Display omitted] •Marine sponges constitute a source of cyclic peroxide-containing natural products.•Natural products with biological activity showcase novel molecular architectures.•The structures of the tricyclic peroxides were determined by spectroscopic analysis.•The esters of plakortinic acids constitute a mixture of inseparable diastereomers.•Polyketide endoperoxides are responsible for the cytotoxicity of the sponge extract. Plakortinic acids C (3) and D (4), two unprecedented peroxide-polyketides with 7,8-dioxatricyclo[4.2.2.02,5]dec-9-ene scaffold, as well as known biogenetically related congeners, plakortinic acids A (1) and B (2), were isolated from a two-sponge association of Plakortis symbiotica–Xestospongia deweerdtae. Upon chemical derivatization, the structures and relative configurations of 3 and 4 were characterized by analysis of HRESIMS and NMR spectroscopic data, molecular modeling studies, and chiroptical comparisons with known natural products and published values of [α]D of related synthetic analogs. A mixture of methyl ester derivatives 5 and 6 displayed negligible cytotoxicity against a panel of 60 cell lines of various human cancers at a concentration of 10 μM.