Novel Synthetic Method and Antifungal Activity Evaluation of CF ₃ –Containing Luotonin A Derivatives

Fungal diseases pose a growing threat to global food security, and natural product-derived fungicides remain a key green strategy. We synthesized 53 novel CF 3 -containing luotonin A derivatives and evaluated them against four phytopathogenic fungi. Most compounds displayed strong in vitro activity against Gaeumannomyces graminis var. tritici ( Ggt ), and several were also effective against Rhizoctonia solani, Botrytis cinerea, and Curvularia lunata . Compound 18 exhibited the highest potency, with an EC 50 of 13.6 μg/mL against Ggt, 1.6-fold more active than silthiopham (21.2 μg/mL) and 18.8-fold more active than luotonin A (256 μg/mL). Electron microscopy analysis revealed that compound 18 severely disrupted Ggt mycelial morphology and induced ROS accumulation. Molecular docking, DFT, and ESP calculations provided insights into electron distribution and charge transfer, helping to elucidate its structural characteristics and antifungal mechanisms. These results offer a solid theoretical foundation for discovering natural product-based antifungal agrochemical candidates.