Design, synthesis, and anti-fungicidal activities of sulfonyl fluoride functionalized SDHI analogs against plant pathogens.

Succinate dehydrogenase inhibitors (SDHIs) have been widely employed as agricultural fungicides due to their effectiveness and low toxicity. Recently, sulfonyl fluoride (R-OSO2F) has emerged as a promising active moiety in pesticide development. Previously, our team identified aryl sulfonyl fluoride compounds with strong antifungal activity. Expanding on this, we incorporated the sulfonyl fluoride group into the heterocyclic amide scaffold of SDHIs, designing and synthesizing 56 novel aniline-based sulfonyl fluoride derivatives. Their structures were confirmed using 1H NMR, 13C NMR, and high-resolution mass spectrometry (HRMS). Antifungal activity assays showed that compound 4a exhibited the highest inhibitory activity against Rhizoctonia solani (EC50 = 2.89 μg/mL). In bioassays on rice leaves and pot experiments, compound 4a demonstrated 50.75% protective efficacy and 32.43% curative efficacy at 200 μg/mL, comparable to that of commercial SDHI fungicide boscalid. Enzyme inhibition assays confirmed its potent suppression of succinate dehydrogenase (SDH), and molecular docking studies demonstrated binding modes similar to boscalid, with improved binding affinity attributed to the sulfonyl fluoride moiety. We developed a novel sulfonyl fluoride series, identifying 4a as a potent antifungal lead with SDHI-like action. These findings provide valuable insights and new directions for the development of sulfonyl fluorides as next-generation fungicides.