Discovery of Natural Ethyl 3-Phenyl-2,3-dibromopropionate as an Antifungal Scaffold with Excellent Potency against Phytopathogenic Fungi

Developing agricultural fungicides from natural compounds is a popular trend. In the present study, a series of the derivatives of natural ethyl 3-phenyl-2,3-dibromopropionate were synthesized and investigated for antifungal activity, SAR, and action mode. The results found that the compounds possessed outstanding inhibition activity against nine phytopathogenic fungi at 50 μg/mL. Notably, ethyl 3-(4-trifluoromethylphenyl)-2,3-dibromopropionate (2l) had an in vitro EC50 of 1.78–4.82 μg/mL and 89.7% control efficacy against A. solani on tomato fruits at 300 μg/mL and on the ninth day, it was comparable to azoxystrobin. Meanwhile, 2l did not affect the germination rate of plant seeds at 200 μg/mL. The research on the action mode revealed that 2l disrupted mycelial morphology and cellular ultrastructure, increased the ROS level, and altered MMP and membrane permeability. Additionally, the SAR was deduced and explained via LUMO/HOMO/MEP analyses. The results make these derivatives promising leads for novel agricultural fungicides.