Brominated resorcylic acid lactones from the marine-derived fungus Cochliobolus lunatus induced by histone deacetylase inhibitors

Chemical epigenetic manipulation was applied to the marine-derived fungus Cochliobolus lunatus (TA26-46) with histone deacetylase inhibitors, resulting in significant changes of the secondary metabolites. Two new 14-membered resorcylic acid lactones characterized with bromine substitution, 5-bromozeaenol (1) and 3,5-dibromozeaenol (2), together with four known analogues (3-6), were isolated from the culture treated with sodium butyrate. The absolute configurations of 1 and 2 were assigned by CD spectra and chemical conversion. Compounds 1 and 2 represent the first example of natural brominated resorcylic acid lactones. These brominated lactones were exclusively obtained from C. lunatus (TA26-46) following epigenetic modifying treatments.