含氨基甲酸酯结构的阿维菌素B_(2a)衍生物的合成、杀虫活性及分子对接

Synthesis,insecticidal activity and molecular docking of avermectin B_(2a) carbamate derivatives

对阿维菌素B_(2a)进行结构优化,在阿维菌素B_(2a)的C4"位引入氨基甲酸酯片段,设计合成21个新型C4"-氨基甲酸酯阿维菌素B_(2a)衍生物。利用高分辨质谱(HRMS)、核磁共振(NMR)等对新化合物的结构进行表征,并测试其对小菜蛾、东方黏虫、玉米螟虫、草地贪夜蛾及棉铃虫的杀虫活性。结果表明,大部分化合物对东方黏虫、玉米螟虫、草地贪夜蛾及棉铃虫的杀虫活性均有不同程度的提高,其中化合物Z5对黏虫和草地贪夜蛾表现出优异的活性,LC_(50)值分别为1.02和2.44 mg/L,均优于对照药阿维菌素B_(1a),比阿维菌素B_(2a)提升了20多倍。构效关系分析表明,增加化合物的亲脂性有助于提升目标化合物的杀虫活性。分子对接研究表明,在阿维菌素B_(2a)的C4"位引入氨基甲酸酯片段后,氨基甲酸酯片段的苯环与受体蛋白残基中的芳香环之间形成了π-π相互作用,杀虫活性得到提高。

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-πinteraction 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.