Three New Derivatives of Zopfinol from Pseudorhypophila Mangenotii gen. et comb. nov.

Triangularia mangenotti was analyzed for the production of secondary metabolites, resulting in the isolation of known zopfinol ( 1 ) and its new derivatives zopfinol B-C ( 2-4 ), the 10-membered lactones 7-O-acetylmultiplolide A ( 5 ) and 8-O-acetylmultiplolide A ( 6 ), together with sordarin ( 7 ), sordarin B ( 8 ), and hypoxysordarin ( 9 ). The absolute configuration of 1 was elucidated by the synthesis of MPTA-esters. Compound 1 showed antimicrobial activity against the Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus and the fungus Mucor hiemalis . While 4 was weakly antibacterial, 3 showed stronger antibiotic activity against the Gram-positive bacteria and weak antifungal activity against M. hiemalis and Rhodotorula glutinis . We furthermore observed the cytotoxicity of 1 , 3 and 4 against the mammalian cell lines KB3.1 and L929. Moreover, the new genus Pseudorhypophila is introduced herein to accommodate Triangularia mangenotii together with several species of Zopfiella - Z. marina , Z. pilifera , and Z. submersa . These taxa formed a well-supported monophyletic clade in the recently introduced family Navicularisporaceae, located far from the type species of the respective original genera, in a phylogram based on the combined dataset sequences of the internal transcribed spacer region (ITS), the nuclear rDNA large subunit (LSU), and fragments of the ribosomal polymerase II subunit 2 ( rpb2 ) and β-tubulin ( tub2 ) genes. Zopfiella submersa is synonymized with P. marina due to the phylogenetic and morphological similarity. The isolation of zopfinols 1 - 4 and sordarins 7 - 9 confirms the potential of this fungal order as producers of bioactive compounds and suggests these compounds as potential chemotaxonomic markers.