Discovery of Enantiopure\n(<i>S</i>)‑Methoprene\nDerivatives as Potent Biochemical Pesticide Candidates

(<i>S</i>)-Methoprene has been widely applied\nas a powerful\nbiochemical pesticide to control disease vectors and other pestiferous\narthropods of economic importance. As a juvenile hormone analogue,\nmany products based on (<i>S</i>)-methoprene are developed\nand commercialized in the USA, Europe, and elsewhere. However, the\nagricultural use of (<i>S</i>)-methoprene and its analogues\nremains underexplored. Here, based on an intermediate derivatization\nstrategy and structural modification, a series of enantiopure (<i>S</i>)-methoprene derivatives were designed for their expected\nbioactivity against two crop-threatening pests. Six compounds showed\nmore than 2-fold stronger inhibition of emergence against Plutella xylostella than (<i>S</i>)-methoprene,\namong which one that was designated as <b>B2</b> showed even\nsuperior activity to the conventional chemical pesticide and biopesticide\nwith IE<sub>50</sub> of 0.02 mg/L. Nine compounds exhibited over 2-fold\nhigher bioactivity against Aphis craccivora growth than (<i>S</i>)-methoprene. The physicochemical\nproperty evaluation and toxicological test showed that the potent\n(<i>S</i>)-methoprene derivatives were low toxic to the\nnontarget organism and the environment. Molecular docking studies\nfurther demonstrated that the high bioactivity of <b>B2</b> may\nbe partially attributed to its great affinity for binding to juvenile\nhormone receptors of P. xylostella.\nThe current study suggests that <b>B2</b> is a biochemical pesticide\ncandidate with potency to be developed as a new agrochemical for lepidopteran\ncontrol.