Design, Synthesis, and Biological Evaluation of Novel Osthole-Based Isoxazoline Derivatives as Insecticide Candidates

Abstract

Natural products are an abundant and environmentally friendly source for controlling plant pathogens and insect pests. Toward the development of new natural product-based pesticides, here, a series of osthole-based isoxazoline derivatives were prepared by [3 + 2] annulation and evaluated for their insecticidal activities and toxicities. The structures of all osthole-based isoxazoline derivatives were characterized by various spectral analyses, and derivative <b>B13</b> was further confirmed by X-ray crystallography. Among all the osthole derivatives, <b>B2</b> displayed the most promising growth inhibitory effect on <i>Mythimna separata</i> with a final corrected mortality rate of 96.4% ± 3.3, which was 1.80 times higher than those of both osthole and toosendanin. Derivative <b>B13</b> displayed the most promising larvicidal activity against <i>Plutella xylostella</i> with an LC₅₀ value of 0.220 mg/mL, which was superior to rotenone. Furthermore, both <b>B13</b> and <b>B21</b> also exhibited better control efficacy against <i>P. xylostella</i> than rotenone in the pot experiments. Additionally, the toxicity evaluation suggested that these osthole-based isoxazoline derivatives showed relatively low toxicity toward nontarget organisms. Given these results, osthole derivatives <b>B2</b>, <b>B13</b>, and <b>B21</b> could be deeply developed as natural insecticidal agents in agriculture.