Discovery of 3‐(pyridin‐2‐yl)‐thiazolo[5′,4′:4,5]benzo[1,2‐b][1,4]oxazine‐diones as protoporphyrinogen oxidase ( PPO ) inhibitors

BACKGROUND Protoporphyrinogen oxidase (PPO) inhibitors represent an important research focus in herbicide development due to their high efficacy. Building on our previous identification of 3‐(pyridin‐2‐yl)benzothiazol‐2‐one derivatives as novel PPO inhibitors, which demonstrated potent activity against broadleaf weeds but showed limited efficacy against grasses, we employed a hybridization‐substructure splicing strategy. This approach integrated the oxazinone moiety of flumioxazin to design novel 3‐(pyridin‐2‐yl)benzothiazol‐2‐one derivatives targeting broad‐spectrum herbicidal activity. RESULTS Starting from 4‐chloro‐3‐nitroanisole or 2‐amino‐6‐methoxybenzothiazole, we prepared 26 novel 3‐(pyridin‐2‐yl)‐thiazolo[5′,4′:4,5]benzo[1,2‐b][1,4]oxazine‐diones and confirmed their structures by proton ( 1 H)‐nuclear magnetic resonance (NMR), carbon‐13 ( 13 C)‐NMR, and high‐resolution mass spectrometry (HRMS) analysis. Petri dish assays revealed that compounds 9b , 9d and 9e exhibited potent herbicidal activity against both Portulaca oleracea and Echinochloa crus‐galli at 10 μg mL −1 . Post‐emergence evaluation (75 g active ingredient (a.i.) ha −1 ) showed that compound 9b achieved 100% control efficiency against Amaranthus retroflexus , Datura stramonium, Abutilon theophrasti , Solanum nigrum and Setaria viridis, while demonstrating superior crop safety in Zea mays and Oryza sativa . Compound 9b treatment induced a dose‐dependent increase in protoporphyrin IX accumulation in plants, reaching levels of 1.37 ± 0.35 μg g −1 and 3.23 ± 0.27 μg g −1 at concentrations of 12.5 μg mL −1 and 25 μg mL −1 , respectively. CONCLUSION A new class of oxazinone‐containing 3‐(pyridin‐2‐yl)benzothiazol‐2‐one PPO inhibitors was developed, demonstrating promise as broad‐spectrum herbicide candidates. These findings provide valuable insights for future PPO herbicide research and development.