Oxalactam A, a Novel Macrolactam with Potent Anti- Rhizoctonia solani Activity from the Endophytic Fungus Penicillium oxalicum .

A novel macrolactam named oxalactam A ( 1 ), three known dipeptides ( 2 - 4 ) as well as other known alkaloids ( 5 - 7 ) were obtained from the endophytic fungus Penicillium oxalicum , which was derived from the tuber of Icacina trichantha (Icacinaceae). All chemical structures were established based on spectroscopic data, chemical methods, ECD calculations, and 13 C-DP4+ analysis. Among them, oxalactam A ( 1 ) is a 16-membered polyenic macrolactam bearing a new skeleton of 2,9-dimethyl-azacyclohexadecane core and exhibited potent anti- Rhizoctonia solani activity with a MIC value of 10 μg/mL in vitro. The plausible biosynthetic pathway of 1 was also proposed via the alanyl protecting mechanism. Notably, three dipeptides ( 2 - 4 ) were first identified from the endophytic fungus P. oxalicum and the NMR data of cyclo( L -Trp- L -Glu) ( 2 ) was reported for the first time. In addition, the binding interactions between compound 1 and the sterol 14 α -demethylase enzyme (CYP51) were studied by molecular docking and dynamics technologies, and the results revealed that the 16-membered polyenic macrolactam could be a promising CYP51 inhibitor to develop as a new anti- Rhizoctonia solani fungicide.