Design, Synthesis, and Biological Activity Determination of Novel Phenylpyrazole Protoporphyrinogen Oxidase Inhibitor Herbicides Containing Five-Membered Heterocycles

Abstract

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) inhibitor herbicides have attracted widespread attention in recent years as ideal herbicides due to their high efficiency, low toxicity, and low pollution. In this article, 30 phenylpyrazole derivatives containing five-membered heterocycles were designed and synthesized according to the principle of bioelectronic isoarrangement and active substructure splicing. A series of structural characterizations were performed on the synthesized compounds. The herbicide activity in greenhouse was evaluated to determine their growth inhibition effect on weeds, their IC 50 value through in vitro PPO enzyme activity measurement was calculated, and target compounds 2i and 3j that have herbicide effects comparable to pyraflufen-ethyl were selected. Crop safety experiments have shown that when the spraying concentration is 300 g of ai/ha, gramineous crops such as wheat, corn, and rice are more tolerant to compound 2i, with wheat exhibiting high tolerance, which is equivalent to the crop safety of pyraflufen-ethyl. Compound 2i can be used as a candidate herbicide for wheat, corn, and paddy fields, and the results are consistent with the cumulative concentration experiment. Molecular docking results showed that compound 2i interacted with the amino acid residue ARG-98 by forming two hydrogen bonds and interacted with the amino acid residue PHE-392 by forming two π−π stacking interactions, indicating that compound 2i has more excellent herbicidal activity than pyraflufen-ethyl and is expected to become a potential lead compound of phenylpyrazole PPO inhibitor herbicides.

Design, Synthesis, and Herbicidal Evaluation of Pyrrolidinone-Containing 2-Phenylpyridine Derivatives as Novel Protoporphyrinogen Oxidase Inhibitors

“…All chemical materials were procured from Leyan (Beijing, China) or Bide (Shanghai, China) and directly used without further purification. The 1 H, 19 F, and 13 C NMR spectra were acquired in chloroform-d solutions using a Bruker Avance III 400 MHz spectrometer (Bruker BioSpin AG, Germany). High-resolution mass spectrometry (HRMS) analysis was performed on a Thermo Fisher Q Exactive mass spectrometer (Thermo Fisher Scientific, USA).…”

“…23 The synthetic routes for compounds 2−10 are shown in Scheme 1. The detailed synthetic methods and characterization data, including 1 H, 13 C, and 19 F NMR spectra, as well as melting points, are provided in the Supporting Information.…”

Design, Synthesis, and Herbicidal Activity of Substituted 3-(Pyridin-2-yl)Phenylamino Derivatives

“…Among the developed herbicides, protoporphyrinogen oxidase inhibitors attract substantial attention due to their favorable environmental safety, low toxicity, low application dosage, and broad spectrum of weed control . For example, several structures such as diphenyl ethers, pyrimidindiones, phenylpyrazoles, pyridazinones, and N -phenyl cyclic amides have been widely and deeply explored for PPO-inhibiting herbicides development. − Protoporphyrinogen oxidase (PPO) promotes the conversion of protoporphyrin IX to protoporphyrinogen IX in the presence of external oxygen. PPO inhibitors could effectively occupy the active cavity of the PPO enzyme and, therefore, significantly reduce its catalytic activity.…”

Design, Synthesis, and Herbicidal Activity of Pyrazole Amide Derivatives as Potential Transketolase Inhibitors

“…Heterocyclic compounds, especially nitrogen-containing heterocyclic compounds, are highly effective structural groups in pesticides with a broad spectrum of bioactivity. ,− For example, pyrazole is a common five-membered heterocyclic compound, and pyrazole derivatives have good biological activities in insecticides, herbicides, medicine, etc. − Some commercial herbicides contained a pyrazole ring (Figure ), such as cypyrafluone, tripyrasulfone, bipyrazone, and cypyrafluone. Additionally, pyridine derivatives have been used as pesticide agrochemicals, including the herbicide nicosulfuron, the fungicide boscalid, etc.…”