Design, Synthesis And Herbicidal Activity Of Novel Pyrimidinedione Derivatives Containing Amide Structur

Weed management has become a worldwide agricultural production concern,resulting in severe economic losses every year.Protoporphyrinogen oxidase（PPO）is an important target for green herbicides discovery.This type of herbicide cause the accumulation of protoporphyrin IX in plants by inhibiting protoporphyrin oxidase synthesis,thus preventing them from photosynthesizing properly and killing them.Pyrimidinedione herbicides are known to be the most extensively studied plant PPO inhibitors currently on the market due to their excellent herbicidal activity.This study is based on the principle of active substructure splicing while preserving the core skeleton of pyrimidinediones,connected pyrimidinediones and N-phenylacetamide moieties which could specific control of grassy weeds through an ether bridge,designed and synthesized a series of new pyrimidinedione derivatives,aiming to discover new herbicides with excellent activity,novel structure,and environmental friendliness.The main work of this thesis is summarized as follows:1.Thirty-five new pyrimidinedione derivatives were designed and synthesized by linking pyrimidinedione and N-phenylacetamide molecules through an ether bridge,and their structures were characterized by ¹H NMR,¹³C NMR and HRMS.2.The post-emergence herbicidal activity and crop safety of the target compounds were determined using the greenhouse pot method.The results indicated that most of the target compounds exhibited excellent broad-leaved weed control.Compounds 6,34,35 showed higher than 90%weed control against broad-leaved weeds Amaranthus retrof lexus,Abutilon theophrasti and Veronica polita at a dose of 37.5 g ai/ha.Worthy of attention is Compound 34 showed higher than 90%weed control against all six test weeds,which were comparable to the control agent saflufenacil.Meanwhile,compound34 exhibited higher crop safety for cotton compared to saflufenacil.3.The in vivo inhibitory activities of compounds 20 and 34 and saflufenacil were tested against the target enzyme PPO at a dose of 150 g ai/ha.From the results,it was observed that compounds 20 and 34 significantly reduced the PPO enzyme activity in weeds in vivo,and had good inhibitory potency against PPO enzyme.Among them,the inhibitory potency of compound 34 on PPO enzyme activity was comparable to that of the control agent saflufenacil.In addition,the relative expression levels of PPO genes were verified by real-time quantitative polymerase chain reaction（RT-q PCR）,and the results were consistent with the trend of enzyme activity data.4.Molecular docking studies have elucidated that these series of compounds were driven by hydrophobicπ-πinteractions and hydrogen bonding that exert an inhibitory effect on PPO enzymatic activity.For example,compound 34 could forms hydrophobicπ-πinteractions with amino acid residues Phe392,Leu356 and Phe172 in the active site of the PPO enzyme.In addition,molecular dynamics studies also have shown that the compounds could bind tightly to PPO.