DNA Methyltransferase Inhibitor Induced Fungal Biosynthetic Products: Diethylene Glycol Phthalate Ester Oligomers from the Marine-Derived Fungus Cochliobolus lunatus

Chemical epigenetic manipulation was applied to the marine-derived fungus Cochliobolus lunatus (TA26-46) with a DNA methyltransferase inhibitor resulting in the significant changes of the secondary metabolites. Cultivation of C. lunatus (TA26-46) with 5-azacytidine led to the isolation of seven new diethylene glycol phthalate esters, cochphthesters A -G (1-6, 10), along with four known analogues (7-9, 11). Their structures were determined by extensive NMR spectroscopic spectra as well as MS data. Compounds 2-6 and 8-11, characterized by the cross-polymerization of phthalate across diethylene glycol via ester bonds, represent the first example of naturally occurring phthalate ester oligomers.