Design, Synthesis, and Evaluation of Oxathiapiprolin Derivatives as Fungicidal Lead Compounds

Oxathiapiprolin (OXTP), a highly effective fungicide against oomycete pathogens, represents a novel class of fungicides. In this study, a series of novel OXTP derivatives were synthesized and evaluated for their antifungal activity. Several compounds exhibited potent inhibitory effects, with B12 and B13 demonstrating particularly strong efficacy against plant diseases caused by Phytophthora species. In addition, select derivatives showed significant in vivo activity against fungal pathogens, expanding their potential application beyond oomycetes. These compounds also displayed excellent photostability, suggesting their suitability for use under high UV exposure conditions. Mechanistic studies confirmed that oxysterol-binding protein 1 (ORP1) serves as the molecular target of OXTP derivatives in oomycetes, and that point mutations in ORP1 confer resistance. These findings highlight the potential of optimized OXTP derivatives as effective and sustainable fungicides for controlling both oomycete and fungal pathogens.