Phomanolides A and B from the Fungus Phoma sp.: Meroterpenoids Derived from a Putative Tropolonic Sesquiterpene via Hetero-Diels-Alder Reactions

Phomanolides A (1) and B (2), unique meroterpenoids with new pentacyclic and tetracyclic skeletons, respectively, and phomanoxide (3), the double-epoxidation product of a putative biosynthetic precursor of 1 and 2, were isolated from the solid substrate fermentation cultures of the fungus Phoma sp., along with the known compound eupenifeldin (4). The structures of 1-3 were elucidated based on NMR spectroscopic data and electronic circular dichroism calculations and further secured by X-ray crystallography. Biogenetically, compounds 1 and 2 could be derived from a hypothetical monotropolonic sesquiterpene intermediate via hetero-Diels-Alder reactions. Compound 4 showed potent antiproliferative effects against three human glioma cell lines, with IC50 values of 0.08-0.13 mu M.