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

Abstract

To discover protoporphyrinogen oxidase (PPO) inhibitors with robust herbicidal activity and crop safety, three types of substituted 3-(pyridin-2-yl)phenylamino derivatives bearing amide, urea, or thiourea as side chain were designed via structure splicing strategy. Postemergence herbicidal activity assessment of 33 newly prepared compounds revealed that many of our compounds such as 6a, 7b, and 8d exhibited superior herbicidal activities against broadleaf and monocotyledon weeds to commercial acifluorfen. In particular, compound 8d exhibited excellent herbicidal activities and high crop safety at a dosage range of 37.5−150 g ai/ha. PPO inhibitory studies supported our compounds as typical PPO inhibitors. Molecular docking studies revealed that compound 8d provided effective interactions with Nicotiana tabacum PPO (NtPPO) via diverse interaction models, such as π−π stacking and hydrogen bonds. Molecular dynamics (MD) simulation studies and degradation studies were also conducted to gain insight into the inhibitory mechanism. Our study indicates that compound 8d may be a candidate molecule for the development of novel herbicides.

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

“…The detailed synthetic methods and characteristic 1 H and 13 C NMR data are illustrated in the Supporting Information. Compound 1 was synthesized following the method detailed in our previous report …”

“…The synthesis of compound 1 followed the method outlined in our prior report . The synthetic routes for compounds 2 – 10 are shown in Scheme .…”

“…The postemergence herbicidal activities of compounds 4 , 7 , and 10 were evaluated against six weed species, namely, Amaranthus retroflexus ( AR ), Abutilon theophrasti ( AT ), Medicago sativa ( MS ), Echinochloa crus-galli ( EC ), Digitaria sanguinalis ( DS ), and Lolium perenne ( LP ). The herbicidal activity was evaluated at doses of 37.5–150 g ai/ha, employing methods consistent with previously reported procedures. ,, Then the postemergence herbicidal activities of compounds 4d , 4f , and 4l were tested at doses of 9.375, 18.75, 37.5, and 75 g ai/ha. FLU, SAF, and acifluorfen (ACI) served as positive controls.…”

“…In our previous work, we designed and synthesized a range of substituted 3-(pyridine-2-yl) phenylamino derivatives, incorporating amide, urea, or thiourea groups through a substructural splicing strategy. For instance, compound C - 8d developed in our group displayed excellent herbicidal activity and high crop selectivity with a dosage ranging from 37.5 to 150 g ai/ha.…”