斑蝥素类化合物对小菜蛾胃毒作用的构效关系

Structure-activity relationship of cantharidin-related compounds on stomach poisoning of Plutella xylostella

【目的】研究25种斑蝥素类化合物对小菜蛾胃毒活性的构效关系,为开发高效、易得的斑蝥素类杀虫剂提供依据。【方法】以斑蝥素(Ⅰ)为原料合成了斑蝥酸(Ⅱ),以去甲斑蝥素(Ⅲ)为原料合成了去甲斑蝥酸(Ⅳ)、去甲斑蝥酰亚胺(Ⅴ)、10种N-取代去甲斑蝥酰亚胺类化合物(Ⅵ)和10种N-取代去甲斑蝥酰胺酸类化合物(Ⅶ),其结构通过1 H NMR(核磁共振氢谱)和HRMS(高分辨质谱)表征;分别测定上述化合物对小菜蛾3龄幼虫的杀虫活性。【结果】25种化合物中,Ⅰ、Ⅱ的杀虫活性最高,LC50分别为12.37和13.77mg/L;化合物Ⅲ、Ⅳ的LC50分别为140.47和129.35mg/L;Ⅴ在设定的最高质量浓度下未表现杀虫活性;除Ⅵ-8外,Ⅵ均未表现杀虫活性;Ⅶ的活性均显著高于Ⅵ,Ⅶ中活性最好的是Ⅶ-8,LC50为134.43mg/L。【结论】斑蝥素类化合物4、5位甲基的存在能极大地提高其杀虫活性;开环(二羧酸)形式的斑蝥素类化合物具有较高的杀虫活性;取代基的电负性与空间位阻效应对斑蝥素类化合物的杀虫活性有重要影响。

【Objective】 This study was to investigate the structure-activity relationship of 25 cantharidin-related compounds on stomach poisoning of Plutella xylostella L.to improve the study of pesticides using cantharidin.【Method】 Cantharidic acid（Ⅱ） was synthesized with cantharidin（Ⅰ）,while norcantharidic acid（Ⅳ）,norcantharimide（Ⅴ）,N-substituted-norcantharimide analogues（Ⅵ） and N-substituted-norcantharimide acid analogues（Ⅶ） were synthesized with norcantharidin（Ⅲ）.The structures of all compounds were confirmed by 1H NMR and HRMS.Insecticidal activities（stomach toxicities） of all compounds on P.xylostella L.were determined.【Result】 Among all the compounds studied,Ⅰ and Ⅱ showed highest toxicities while Ⅲ and Ⅳ had much lower toxicities,LC50 of Ⅰ,Ⅱ,Ⅲ,and Ⅳ were 12.37,13.77,140.47 and 129.35 mg/L,respectively.Ⅴ had no insecticidal activity.Insecticidal activities of Ⅶ were significantly higher than that of Ⅵ.The most toxic compound among Ⅶ was Ⅶ-8 with LC50 of 134.43 mg/L.【Conclusion】 Toxicities of cantharidin-related compounds can be highly increased with the existence of methyl of bit-4 and 5.Ring-opened forms of cantharidin-related compounds with showed higher insecticidal activities.Variation of electron cloud density and stereohindrance effect caused by substituent had important impact on the activities of cantharidin-related compounds.