Synthesis, insecticidal activity and molecular docking of avermectin B_2a carbamate derivatives

To improve the insecticidal activities of avermectin B_2a, the functional carbamate fragment was introduced into the C4" position of avermectin B_2a, and 21 novel avermectin B_2a C4"-carbamate derivatives were designed, synthesized, and their structures were characterized by high-resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR). The insecticidal activity against Plutella xylostella, Mythimna separata, Spodoptera frugiperda, Ostrinia furnacalis and Helicoverpa armigera was tested. The results showed that the insecticidal activities of most compounds against M. separata, S. frugiperda, O. furnacalis and H. armigera were improved to some degrees. Among them, compound Z5 showed excellent insecticidal activity against M. separata and S. frugiperda, with LC₅₀ values of 1.02 and 2.44 mg/L, respectively. Its insecticidal activity is better than that of the control avermectin B_1a, and more than 20 times higher than that of avermectin B_2a. The structure-activity relationship analysis showed that more lipophilicity of the compound can help to improve the activity of the target compound. Molecular docking studies showed that with the introduction of the functional carbamate fragment into the C4" position of avermectin B_2a, π-π interaction was formed between the benzene ring of the carbamate fragment and the aromatic ring in the receptor protein residue, which was believed to contribute the insecticidal activity of the new compounds.