Borneol-Containing Cinnamic Acid Derivatives from Pinus yunnanensis as CYP51 Inhibitors: Design, Synthesis, and Mechanistic Study for Fungicidal Development

A cinnamic acid derivative bearing borneol SX-6, isolated and identified from Pinus yunnanensis exudates, was used as a lead compound to conduct structural optimization for the innovation of fungicidal agents. Here, thirty-five SX-6 derivatives were designed, synthesized, and evaluated for their fungicidal activities. Among them, SX-6-6 provided the EC50 values of 3.29, 8.22, and 6.68 mg/L against Botrytis cinerea, Sclerotinia sclerotiorum, and Curvularia mebaldsii, respectively, whose activities are superior or similar to those of hymexazol. Besides, photoreaction was used to transfer SX-6-6 to its Z-isomer SX-6-6i, which possessed EC50 values of 2.97 mg/L against S. sclerotiorum. In vivo experiments proved that SX-6-6 and SX-6-6i have excellent protective effects on B. cinerea and S. sclerotiorum at 200 mg/L, respectively. The action mechanism studies reveal that SX-6-6 displays fungicidal activities due to 14α-demethylase (CYP51) inhibition, which suppresses ergosterol synthesis, impairs fungal cell membrane function, and causes cell death. In addition, acute toxicity studies showed that SX-6-6 was safe for rodents at a dose of 1 g/kg. This is the first report on the application of plant protection using active derivatives from P. yunnanensis, offering a novel structural precursor for the design of fungicidal agents.