Green synthesis, characterization, and biochemical impacts of new bioactive isoxazoline-sulfonamides as potential insecticidal agents against the Sphodroxia maroccana Ley.

Background: Sphodroxia maroccana Ley is a pest of cork oak crops that damages the roots of seedlings and can severely impair cork oak regeneration. Since the banning of carbosulfan and chlorpyriphos, which were widely used against the larvae of Sphodroxia maroccana because of their harmful impact on the environment, until now there has been no pesticide against these pests. Therefore, it is particularly urgent to develop highly effective insecticidal molecules with novel scaffolds. Isoxazolines are a class of insecticides that act on γ-aminobutyric acid (GABA)-gated chloride channel allosteric modulators. In this work, a green synthesis of novel 3,5-disubstituted isoxazoline-sulfonamide derivatives was achieved in water via ultrasound-assisted four-component reactions, and their insecticidal activities against fourth-instar larvae of S. maroccana were evaluated.

Results: Most of the tested compounds showed insecticidal activity compared to fluralaner as positive control and commercially available insecticide. Especially, the isoxazoline-secondary sulfonamides containing halogens (Br and Cl) on the phenyl group attached to the isoxazoline, 6g (LC  = 0.31 mg/mL), 6j (LC  = 0.38 mg/mL), 6k (LC  = 0.18 mg/mL), 6L (LC  = 0.49 mg/mL), 6m (LC  = 0.24 mg/mL), 6q (LC  = 0.46 mg/mL), exhibited much higher larvicidal activity than fluralaner (LC  = 0.99 mg/mL).

Conclusion: Novel isoxazolines containing sulfonamide moieties were designed, synthesized and confirmed by two single-crystal structures of 4e and 6q. Their bioassay results showed significant larvicidal activity with significant morphological changes in vivo. These results will lay the foundation for the further discovery and development of isoxazoline-sulfonamide derivatives as novel crop protection larvicides of cork oak. © 2023 Society of Chemical Industry.