Design, Synthesis and Evaluation of Insecticidal Activity of Novel Oxadiazine Derivatives

Background: The oxadiazine insecticides are broad-spectrum insecticides with a novel mode of action by blocking insect neuronal sodium channels. Indoxacarb is an oxadiazine insecticide to reduce cross-resistance. A series of tricyclic oxadiazine analogues were designed and synthesized in order to find novel active compounds with high bioactivities similar to that of the commercial insecticide indoxacarb. Methods: We undertook the modification of the N-aryl group of indoxacarb with various aromatic groups, including substituted benzene, naphthalene and pyridine rings. Forty-one oxadiazine analogues were synthesized, and characterized by NMR spectroscopy and elemental analysis. The insecticidal activities of the newly synthesized compounds against Nilaparvata lugens, Mythimna separata, Tetranychus cinnabarinus and Aphis medicaginis were tested. Results: The results of bioassays indicated that among all the synthesized compounds tested, eight compounds (27, 33, 35, 36, 37, 38, 39 and 40) showed 100% insecticidal activities against Mythimna separata at the concentration of 500 mg/L. Compound 17 and 25 showed 80% insecticidal activities against Mythimna separata at the concentration of 500 mg/L. Compound 6 showed 78% insecticidal activity against Aphis medicaginis at the concentration of 500mg/L. Further investigation revealed that compound 39 showed excellent insecticidal activity with an EC50 of 4.59 mg/L against Mythimna separata. Conclusion: The data suggested the following general trend of bioactivities for the substituted N-aryl groups: benzene > substituted pyridine > substituted naphthalene. The bioactivities rendered by substituted groups on the aryl rings followed the general trend of OCF3 > SCF3 > CF3> I > Br > Cl > NO2 > acyloxyl > alkoxy and hydroxyl. Among these eight active compounds, compound 39 showed to be the most potent. The insecticidal activity of compound 39 is only slightly weaker than that of indoxacarb. Compound 39 should have the potential to be developed into a novel potential insecticide with a more desirable activity profile.