Design, Synthesis, and Insecticidal Activity of 14‐Oxime Matrine Derivatives

Harmful insects cause substantial losses in agricultural production. While chemical pesticides effectively suppress pests, they also exacerbate issues such as increased pest resistance and environmental pollution. To address these challenges, this study employed matrine as a lead compound and via a molecular hybridization approach, conjugated it with oxime‐based structure. This approach synthesized 32 previously unreported matrine‐oxime derivatives, whose insecticidal activities were systematically evaluated against key agricultural pests. The contact and stomach toxicity assays revealed that most compounds displayed promising insecticidal activity against red imported fire ant, cowpea thrips, and melon fly. Notably, compound B1 achieved a stomach toxicity mortality rate of 87.69% against fire ants at concentrations ≥ 2 mg/mL, outperforming the positive control abamectin. Structure–activity relationship (SAR) analysis demonstrated that oxime ether derivatives exhibited superior insecticidal activity compared to oxime esters, with electron‐withdrawing groups significantly enhancing potency. Moreover, the position of substituents markedly influenced efficacy. Molecular docking studies further elucidated the plausible binding modes of the derivatives with target proteins. These findings suggest that matrine‐oxime ether hybrids represent a class of highly effective and eco‐friendly insecticide candidates.