Synthesis, Including Amino Acid Esters The Cis Nitenpyram Analogs Of The Insecticidal Activity And Molecular Docking Studies

To search the introduction compounds for new pesticide, and to make further researches on the structure-activity relationships (SARs) of the neonicotinoid compounds, we have focused our attentions on designing novel neonicotinoids, in which the nitenpyam structure was reserved and the amino acid alkyl ester was introduced into the leading compound through forming a tetrahydropyridine ring to fix the nitro group in the cis position. Starting from nitenpyram, several chiral or achiral amino acids were introduced and various ester groups were applied, the novel nitenpyram analogues Ia1~ Ic8 and IIa1~ IIf4 described herein were designed and synthesized as shown following:Complete assignments have been achieved for the title compounds by elemental analysis, 1H NMR, MS and IR. Meanwhile, their physic-chemical properties, spectrum properties, reaction conditions and synthetic methods were analyzed and discussed as well.The preliminary biological activities tests of the series target compounds were finished in bioassay department, Branch of National Pesticide R&D South Center of Hangzhou. The preliminary bioassay against Nilaparvata lugens showed that all nitenpyram analogues exhibited good insecticide activities at 500 mg/L, and the analogue Ib4 showed the best activity at 20 mg/L. The structure-activity relationships (SARs) indicated that the nitenpyram analogues Ia1~ Ic8 and IIa1~ IIf4 exhibited various insecticide activities in more controllable and rational manner by altering the length of amino acid and the size of ester group.Additionally, to further explore the influential factors for the bioactivities of our designed nitenpyram analogues, in the rest of this paper, the molecular docking investigation was carried out by docking the nitenpyram analogues into the active site of nAChR. The results of molecular docking suggest that the analogues with various flexibility and size show their different binding affinity to the insect nAChR. This study examined the hypothesis that neonicotinoid insecticides with ester groups might bind in a unique way at the nAChR. It is therefore fascinating to consider that the structural uniqueness of our newly designed nitenpyam analogues lead to a unique molecular recognition and binding mode, which is more important for our team to discover new introduction compounds with broad-spectrum and high insecticidal activity.