Synthesis, insecticidal activity, and ensembled docking of nitroguanidines bearing S- and R-proline.

BACKGROUND: The amino acids R- and S-proline were used to synthesize novel neonicotinoid derivatives that, after being characterized by 1 H, DEPTQ 135, and HRMS-QTOF, were evaluated for use as insecticides against Galleria mellonella (caterpillar), Sitophilus zeamais, Xylosandrus morigerus, Xyleborus affinis, and Xyleborus ferrugineus. RESULTS: Comparisons of biological activity and absolute configuration showed that the R enantiomer had excellent and outstanding insecticidal activity against the insects tested, with up to 100% mortality after 12 h compared with dinotefuran at the same concentration. CONCLUSIONS: The results suggest that compound R6 is an excellent lead enantiopure insecticide for future development in the field of crop protection. Furthermore, intermolecular interactions between nicotinic acetylcholine receptors and the R enantiomer displays a lower score which mean a higher affinity to the nAChR receptor and the π-π interactions are more stable than the S derivative. © 2023 Society of Chemical Industry.

Synthesis and Insecticidal Evaluation of Chiral Neonicotinoids Analogs: The Laurel Wilt Case.

Xyleborus sp beetles are types of ambrosia beetles invasive to the United States and recently also to Mexico. The beetle can carry a fungus responsible for the Laurel Wilt, a vascular lethal disease that can host over 300 tree species, including redbay and avocado. This problem has a great economic and environmental impact. Indeed, synthetic chemists have recently attempted to develop new neonicotinoids. This is also due to severe drug resistance to "classic" insecticides. In this research, a series of neonicotinoids analogs were synthesized, characterized, and evaluated against Xyleborus sp. Most of the target compounds showed good to excellent insecticidal activity. Generally, the cyclic compounds also showed better activity in comparison with open-chain compounds. Compounds R-13, 23, S-29, and 43 showed a mortality percent of up to 73% after 12 h of exposure. These results highlight the enantioenriched compounds with absolute R configuration. The docking results correlated with experimental data which showed both cation-π interactions in relation to the aromatic ring and hydrogen bonds between the search cavity 3C79 and the novel molecules. The results suggest that these sorts of interactions are responsible for high insecticidal activity.

l-Proline as a Valuable Scaffold for the Synthesis of Novel Enantiopure Neonicotinoids Analogs.

In this research, six neonicotinoid analogs derived from l-proline were synthesized, characterized, and evaluated as insecticides against Xyleborus affinis. Most of the target compounds showed good to excellent insecticidal activity. To the best of our knowledge, this is the first report dealing with the use of enantiopure l-proline to get neonicotinoids. These results highlighted the compound 9 as an excellent candidate used as the lead chiral insecticide for future development. Additionally, molecular docking with the receptor and compound 9 was carried out to gain insight into its high activity when compared to dinotefuran. Finally, the neurotoxic evaluation of compound 9 showed lower toxicity than the classic neonicotinoid dinotefuran.