Bioactivity-guided mixed synthesis and evaluation of α-alkenyl-γ and δ-lactone derivatives as potential fungicidal agents

In view of the great antifungal activities of sesquiterpene lactones and natural product Tulipalin A, 52 derivatives derived from alpha-methylene-gamma-butyrolactone substructures were synthesized to study antifungal activities. In vitro and in vivo antifungal activity results revealed that compounds 2-25, which contain a gamma-butyrolactone scaffold and cinnamic aldehyde moiety, have greater potent fungicidal activity than other compounds. The preliminary structure-activity relationships (SARs) demonstrated that compounds with electron-withdrawing groups and small steric hindrance would have more desirable potency. Meanwhile, the quantitative structure-activity relationship (QSAR) model (R-2 = 0.947, F = 65.77, and S-2 = 0.0028) revealed a convincing correlation of antifungal activity against B. cinerea with molecular structures of title compounds. The present study provided a more detailed insight into the antifungal activity of the alpha-methylene-gamma-butyrolactone substructure, which provided a potential expectation for the exploration of alpha-alkenyl-gamma-butyrolactone structures in agriculture.