Synthesis and Antifungal Evaluation of a Ynone-Tethered 2-Pyrone Derivative against Phytopathogenic Fungi

Numerous fungicides are essential for controlling phytopathogens, enabling modern industrial agriculture to maximize productivity and profitability. However, the extensive use of widely employed fungicides, such as tebuconazole and carbendazim, has led to reduced efficacy due to the emergence of resistant plant-pathogenic fungi. Accordingly, in this study, we synthesized a 2-pyrone chemotype bearing a ynone substituent, designated as ynone 6 and evaluated its potential as an antifungal scaffold. This representative lead compound exhibited broad-spectrum antifungal activity against five major phytopathogens, including Fusarium graminearum and Botrytis cinerea. Ynone 6 demonstrated potent in planta control efficacy across various host tissues, including wheat spikes, fruits, and leaves, with inhibitory effects comparable to those of tebuconazole. Sensitivity screening using six knockout mutants targeting well-established antifungal pathways revealed that the sensitivity profiles of the mutants differed significantly between conidial germination and hyphal growth, suggesting that the mode of action of ynone 6 is stage-dependent and may involve multiple targets. Collectively, the potent in vitro activity of ynone 6 and its consistent in planta efficacy across multiple host-pathogen systems highlight the ynone-tethered 2-pyrone scaffold as a promising lead scaffold for the development of effective antifungal agents.