| Barnyard grass and horseweed were representative malignant weeds in paddy fields and common weeds growing in the field edge and roadside,respectively.Barnyard grass could be controlled by hormone herbicide quinclorac,while horse-weed could be controlled by serine hydroxymethyltransferase（SHMT）inhibitor caprylic acid,but the dosage was too large.The purpose of the study was to improve the efficacy of quinclorac and to develop herbicide molecules with high efficiency and low toxicity to serine hydroxymethyltransferas（SHMT）,the target of caprylic acid.The paper was divided into two parts:derivatives containing pyrazole ring were synthesized using quinclorac as lead compound and other derivatives were further optimized and synthesized.Lead compounds were obtained by virtual screening with serine hydroxymethyl transferase（SHMT）target and new derivatives were synthesized by optimizing lead compounds.Biological activity of all com-pounds was tested on barnyard grass,ryegrass,retrograde amaranth,lettuce,cu-cumber,horseweed and romaine lettuce in laboratory.The compounds with good comprehensive effect were selected for safety test of rice.The compounds with good safety were then tested in field assay.（1）Derivatives was synthesized using quinclorac as lead compoundTwenty-five 3-methyl-1h-pyrazolyl quinoline ester compounds 2-8a～2-8n,2-9a～2-9j and 2-10a～2-10b were designed and synthesized by nucleophilic addition elimination and esterification reaction through Intermediate Derivative Method and these structures were characterized.The biological activity of barnyard grass,ryegrass,lettuce and romaine lettuce in the laboratory showed that the relationship between the herbicidal effect and the benzene group on the pyrazole ring was as follows:the phenyl group on the pyrazole ring was electron-drawing group>neutral group>electron-donating group.The results were like that of substituted benzyl group on pyrazole.Compounds 2-8l,2-9h and 2-10a had good comprehensive con-troleffectonthefourweeds.Thirty-six（4-（2-nitrobenzyl）piperazin-1-yl）（phenyl）methanone derivatives 2-16aa～2-16bj were designed using lead compound 2-9h and synthesized from by nucleophilic re-action,removal tert-butylcarbonyl reaction and amide reaction.In the preliminary screening of the germination experiments of cucumber,lettuce,ryegrass and barn-yard grass,many compounds with good comprehensive effect were found.The compounds with good comprehensive effect were not related to the electronegativity of benzene ring substitution,but related to the position of benzene ring.The effect of substituents in ortho-position and meta-position was greater than that of pa-ra-position substituents.Representative compounds 2-16aa,2-16ai,2-16aq and2-16aw were selected for rescreening of soil spray and the efficacy should be im-proved.The semi-lethal concentration(EC50)of compounds 2-8l and 2-10a were 10.527and 10.367 g·ha-1,respectively.The changes of chlorophyll A,B and A+B contents in barnyard grass treated with compounds 2-8l,2-10a and quinclorac at 375 g·ha-1were observed.The chlorophyll contents of barnyard grass treated compounds 2-8l and 2-10a changed later than that of the control and 2-10a changed the most after treatment.The rice safety test of compounds 2-8l and 2-10a showed that the plant height and fresh weight of aerial parts of compound 2-10a reached 98.7%and 96.1%after 14 days,which was safe to rice compared with blank group.Compound 2-8l was 86.01%and 81.60%,which had certain toxicity to rice.（2）Derivatives were synthesized using caprylic acid as target lead com-poundUsing SHMT as the target,2163.9K compounds in HTS Compound Library were screened by Virtual Screening Workflow module of Schr（?）dinger software.The Glide module was used to dock the small molecules of each ligand with the target protein SHMT,and the top 200 compounds were obtained after three rounds of screening.The top 10%compounds were tested for biological activity against lettuce,amaranth,ryegrass and barnyard grass.It was found that these compounds had stronger inhibition on lettuce and amaranth weeds than ryegrass and barnyard grass.Compounds Z19173026,Z20016732 and Z227435258 showed the comprehensive bioactivity among them.These twenty compounds were disassembled,analyzed and classified to find the key pharmacophore.Based on the combination of pharmacophore and target protein structure Dimethyl-2-（2-（4-（2-phenoxyacetyl）piperazin-1-yl）acetamido）terephthalate derivatives 5-9aa～5-9bg were design and were synthesized by nucleophilic reaction,removal tert-butylcarbonyl reaction and amide reaction.Their structures were char-acterized.The biological activity of lettuce,amaranth,ryegrass and barnyard grass was tested in the laboratory,and it was found that the inhibition of lettuce and ama-ranth was stronger than that of ryegrass and barnyard grass.The electron donor group on benzene ring was found in the structure-activity relationship of compounds electron-donating group>neutral group>electron-drawing group.The effect of compounds 5-9aa～5-9bg at dosage of 375 g·ha-1 on horseweed showed that ten compounds could completely inhibit horseweed.The compound 5-9aj could bind to SHMT target protein and form seven hydrogen bonds and hydrophobic effect.Through the enzyme activity test of SHMT in the body of horseweed,compound5-9aj was found to have inhibitory effect on SHMT.The rice and corn safety test of compound 5-9aj showed that the plant height and fresh weight of aerial parts of reached 88.7%and 86.1%,91.4%and 83.2%after 7 days.The herbicidal effect of direct seeding of rice with compound 2-10a of 45,75,120 and 150 g·ha-1 was investigated after 14,21 and 52 days,respectively,using300 g·ha-1 quinclorac as positive control.The control effect of compound 2-10a in-creased with the increase of concentration.At the same concentration,the weeding effect at 21 days was better than that at 14 days,and the weeding effect at 52 days was worse than that at 14 days.In 2019,the herbicidal effect of 2-10a at 150 g·ha-1on barnyard grass was 94.5%,which was comparable to that of 300 g·ha-1 quinclorac.Similar results appeared in 2020.The compound 2-10a was further developed as a potential herbicide for controlling barnyard grass in paddy fields. |
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