Biosynthesis of cladospirone bisepoxide, a member of the spirobisnaphthalene family

The biosynthesis of cladospirone bisepoxide (1) was investigated by feeding C-13-labeled acetate to growing cultures of the fungus Sphaeropsidales sp. (strain F-24'707). C-13 NMR spectral analysis demonstrated the polyketide origin of both naphthalene units. The origin of two epoxide oxygens was con firmed as from air by cultivation of the strain in an O-18(2)-enriched atmo sphere. The [O-18]incorporation pattern into palmarumycin C-12 (11), the pu tative precursor of 1 led to the hypothesis that the carbonyl oxygen of 1 i s derived from water by exchange of an oxygen atom. inhibition of the biosy nthesis of 1 with tricyclazole, an inhibitor of the 1,8-dihydroxynaphthalen e (DHN) melanin biosynthesis, confirmed the connection of both biosynthetic pathways.