Synthesis and antifungal activity of 3-(difluoromethyl)-1-methyl pyrazole-4-carboxylic oxime esters

To discover lead compound with high antifungal activity, based on our previous studies, 18 novel 3-(difluoromethyl)-1-methyl pyrazole-4-carboxylic oxime esters were designed and synthesized based on the previous studies. Their structures were confirmed by ¹H NMR, ¹³C NMR and HRMS. The configuration of oxime ester was confirmed to be E by the X-ray single crystal diffraction of the compound 9g . The in vitro bioassay results showed that the target compounds displayed antifungal activities against Botrytis cinerea, Valsa mali and Gaeumannomyces graminis. Especially, the compound 9d showed excellent activity against V. mali (EC₅₀ = 0.89 μg/mL) and 9r exhibited satisfied activity against G. graminis (EC₅₀ = 3.34 μg/mL), which are better than or smilar to the lead compound L1 (E-2-chloro-6-fluorobenzaldehyde O-(1-methyl-3-phenyl-1H-pyrazole-5-carbonyl) oxime) and trifloxystrobin.