Natural products as sources of new fungicides (I): synthesis and antifungal activity of acetophenone derivatives against phytopathogenic fungi.

Several series of 45 acetophenone derivatives bearing various alkyl or benzyl substituents were conveniently synthesized and their structures characterized by (1)H and (13)C NMR spectroscopy, HRMS and single-crystal X-ray analysis. Their in vitro antifungal activities against a panel of phytopathogenic fungi were evaluated by mycelial growth rate assay. Of them, 12 derivatives (e.g., 3a-c, 4c and 4e) exhibited more potent antifungal effects on some phytopathogens than a commercial fungicide hymexazol as positive control. In particular, compound 3b with IC50 values of 10-19 μg/mL was found to be the most active in this series and might be a potential lead structure for further optimization. The preliminary structure-activity relationship (SAR) studies of a series of acetophenones are also discussed.