Phomopsolides and related compounds from the alga-associated fungus, Penicillium clavigerum

For the past fifteen years we have studied the secondary metabolites of extremophilic fungi from the Berkeley Pit, an abandoned acid mine waste lake. Fungi associated with an acid-tolerant alga have also been harvested from the Pit. Penicillium clavigerum Demelius was isolated from the green alga Chlorella vulgaris Beyerinck [Beijerinck]. In culture it produced the known compounds phomfuranone (1), patulin (2), dimethylphthalides (3 ) and (4 ), phomopsolide A (5), phomopsolide C (6), phomopsolide B (7), phomopsolide E (8), phomopsolide F (9 ), and phompyrone (10) and the new compound berkbenzofuran thioester (11 ). Compounds 5 and 6 were potent inhibitors (IC₅₀ < 10 μM) of specific and established human cancer cell lines.