Design and Synthesis of Ferulic Acid Derivatives with Trifluoromethyl Pyrimidine and Amide Frameworks for Combating Postharvest Kiwifruit Soft Rot Fungi

Fungal diseases significantly affect the quality and safety of food and agricultural products. Pyrimidine ether compounds have shown effectiveness as commercial antifungal agents, but their prolonged or excessive use has led to resistance and pesticide residue issues, necessitating structural modifications. In this study, ferulic acid served as a framework for synthesizing a series of derivatives by introducing pyrimidine and amide groups. Compound 6w showed high efficacy against Botryosphaeria dothidea and Phomopsis sp., with EC50 values of 3.20 and 0.80 μg/mL, respectively, far outperforming Pyrimethanil (57.60 and 32.10 μg/mL). Mechanistic studies indicated that compound 6w disrupts Phomopsis sp. biofilms, causing protein and nucleic acid leakage, increased membrane permeability, and damage to the fungal mycelium. Moreover, transcriptomic and proteomic analyses revealed that 6w induces fungal detoxification responses, including the transformation of toxic compounds mediated by oxidoreductases and aromatic compound-related enzymes as well as efflux mediated by ABC transporters. This study is the first to report the antifungal efficacy of ferulic acid derivatives featuring a trifluoromethyl pyrimidine moiety against postharvest kiwifruit soft rot, providing potential for the control of fungal pathogens affecting kiwifruit storage and quality.