Synthesis, Insecticidal Activities, Toxicity Assessment,\nand Environmental Implications of (<i>R</i>)- and (<i>S</i>)‑Proline-Derived Chiral Neonicotinoid Derivatives

Neonicotinoid\ninsecticides are widely employed in pest control,\nbut their potential environmental implications demand the exploration\nof safer and more sustainable alternatives. This study encompasses\na comprehensive assessment of the synthesis and toxicity of potential\ninsecticide proline-derived chiral neonicotinoid derivatives, explicitly\nfocusing on elucidating their environmental implications. Toxicity\nevaluation contained multiple models, including brine shrimp (Artemia salina), zebrafish (Danio\nrerio), and murine models compared with the commonly\nused insecticide dinotefuran. Enantioselective toxicity was observed\nin the brine shrimp assay, with the <i>R</i>-enantiomer\ndemonstrating lesser toxicity compared to the <i>S</i>-enantiomer\nand dinotefuran. In the zebrafish model, dinotefuran induced developmental\nabnormalities, such as delayed hatching and vertebral column malformation,\nwhile the <i>R</i>-enantiomer exhibited relatively lower\nsensitivity. The murine LD<sub>50</sub> study in mice revealed lower\ntoxicity levels for proline-derived insecticides than dinotefuran.\nMoreover, these chiral neonicotinoid derivatives were successfully\nsynthesized by optimizing the synthetic routes. The synthesis involved\nspecific starting materials and reaction steps, following established\nprotocols. This study contributes valuable insights into the toxicity\nprofiles of proline-derived chiral neonicotinoid derivatives and underscores\nthe significance of assessing their environmental implications. The\nsynthesized compounds provide a foundation for developing safer and\nmore sustainable insecticides to mitigate the environmental risks\nassociated with prevailing pest control practices.