Novel fungicidal phenylethanol derivatives linking a trifluoromethyl pyrazole pharmacophore: design, synthesis, crystal structure, and biology evaluation

Abstract

In order to find compounds with novel structures and high antifungal activity, 26 phenylethanol derivatives containing a trifluoromethyl pyrazole pharmacophore were designed and synthesized by means of active group splicing. The structures of target compounds were confirmed using the ¹H NMR, ¹³C NMR and HRMS spectral analyses. The crystal structure of compound 6g was further determined using X-ray diffraction. The results of in vitro antifungal bioassay indicated that the synthesized compounds showed varying degrees of antifungal activity against four tested plant pathogens Rhizoctonia solani (R. solani), Fusarium graminearum (F. graminearum), Botrytis cinerea (B. cinerea), and Alternaria solani (A. solani). The EC₅₀ value of compound 6i against B. cinerea reached 6.05 μg mL⁻¹, which was better than that of the positive control pyrimethanil (15.91 μg mL⁻¹). Compound 6i was found to disrupt the permeability of B. cinerea cell membranes by measuring the relative conductivity. Meanwhile, a scanning electron microscopy study revealed that compound 6i could make B. cinerea mycelium become wrinkled, twisted, and clustered. The research results indicate that compound 6i could serve as the leading molecule in the design and search for novel agricultural fungicides.