Design, synthesis and biological activity of novel triketone‐containing quinoxaline as HPPD inhibitor

BACKGROUND 4‐Hydroxyphenyl pyruvate dioxygenase (EC 1.13.11.27, HPPD) is one of the important target enzymes used to address the issue of weed control. HPPD‐inhibiting herbicides can reduce the carotenoid content in plants and hinder photosynthesis, eventually causing albinism and death. Exploring novel HPPD‐inhibiting herbicides is a significant direction in pesticide research. In the process of exploring new high‐efficiency HPPD inhibitors, a series of novel quinoxaline derivatives were designed and synthesized using an active fragment splicing strategy. RESULTS The title compounds were unambiguously characterized by infrared, 1H NMR, 13C NMR, and high‐resolution mass spectroscopy. The results of the in vitro tests indicated that the majority of the title compounds showed potent inhibition of Arabidopsis thaliana HPPD (AtHPPD). Preliminary bioevaluation results revealed that a number of novel compounds displayed better or excellent herbicidal activity against broadleaf and monocotyledonous weeds. Compound III‐5 showed herbicidal effects comparable to those of mesotrione at a rate of 150 g of active ingredient (ai)/ha for post‐emergence application. The results of molecular dynamics verified that compound III‐5 had a more stable protein‐binding ability. Molecular docking results showed that compound III‐5 and mesotrione shared homologous interplay with the surrounding residues. In addition, the enlarged aromatic ring system adds more force, and the hydrogen bond formed can enhance the synergy with π–π stacking. CONCLUSIONS The present work indicates that compound III‐5 may be a potential lead structure for the development of new HPPD inhibitors. Novel quinoxaline derivatives were designed and synthesized by active fragment splicing strategy. Preliminary bioevaluated results reveal that compound III‐5 had the best biological activity and had great potential for the future development of new HPPD inhibitors. © 2021 Society of Chemical Industry.