Design, synthesis and herbicidal evaluation of novel ester‐functionalized N ‐phenylphthalimide derivatives containing pyridine as protoporphyrinogen IX oxidase inhibitors

BACKGROUND Protoporphyrinogen IX oxidase (PPO, EC 1.3.3.4) represents a crucial target for the development of highly effective and environmentally sustainable herbicides. Present N ‐phenylphthalimide PPO inhibitors often have limited herbicidal spectra and inadequate crop selectivity. Consequently, we concurrently incorporated pyridine and ester functional groups into the N ‐phenylphthalimide framework to create innovative, highly efficient broad‐spectrum herbicide candidate compounds. RESULTS Based on active scaffold splicing strategy, a number of structurally innovative N ‐phenylphthalimide derivatives were designed, synthesized and characterized. Glasshouse herbicidal activity assays indicated that compound II‐f13 effectively suppressed six target weed species. At 300 g ai ha −1 , compound II‐f13 demonstrated broad‐spectrum herbicidal efficacy. Meanwhile, compound II‐f13 exhibited greater crop safety compared to flumiclorac‐pentyl for Glycine max , Gossypium hirsutum and Triticum aestivum within the 75–300 g ai ha −1 dosage range. In vitro enzyme activity assays confirmed that the target compound is a typical PPO inhibitor. Moreover, molecular docking, molecular dynamics (MD),and density functional theory (DFT) calculations indicated that compound II‐f13 establishes strong hydrogen bonds with ASN‐468 of Nicotiana tabacum PPO ( Nt PPO), while also demonstrating remarkable chemical reactivity, electrostatic fields and elevated polarity. CONCLUSION Our research indicates that the novel N ‐phenylphthalimide derivative II‐f13 , which features a pyridine moiety and an ester group, is an excellent option for the discovery of new PPO inhibitor herbicide.