Eco-Efficient Synthesis and In Vitro Evaluation of Vanillin Derivatives for Antifungal Use against Phytopathogens

Vanillin is mainly synthesized chemically but holds significant potential for biomass valorization as it can be extracted from lignin. Recognized for its herbicidal, insecticidal, antimicrobial, and antioxidant activities, vanillin can undergo structural modifications that may reinforce these properties. An eco-efficient methodology was tested that allows the synthesis of vanillin derivatives with a yield of up to 60% of purified products. The derivatives were studied for their antifungal effect by inhibition tests on 11 phytopathogens notably infecting wheat and rapeseed. Three out of seven compounds inhibited in vitro mycelial growth by 80% for most of the studied microorganisms at a concentration of 50 μg mL–1. They displayed in vitro antifungal activity similar to that of the systemic fungicide tebuconazole. Moreover, they showed no phytotoxicity and no cytotoxicity, with significantly higher IC50 values for human skin fibroblasts and bronchial cells than tebuconazole. The broad in vitro antifungal efficiency of these vanillin derivatives, combined with their measured innocuity for plants and human cells, indicates that they could be further studied as potential active substances for alternative non-petro-sourced fungicides to control crop fungal diseases.