Design,Synthesis And Herbicidal Activity Test Of Several Novel Ester-substituted Phenyluracil Inhibitors

Herbicides play an important role in agricultural production.However,with the wide use of the herbicides,more and more weeds have become resistant to herbicides on the market.As of the increasing of resistant weeds,the herbicidal effects of most of herbicides were hugely reduced,therefore it is of significance to develop new resistance slow-developing herbicides to control resistant weed.Protoporphyrinogen oxidase(PPO)herbicides are highly efficient and resistance slow-developing.Protoporphyrinogen oxidase herbicides act on a type of photosynthesis enzyme,displaying the characteristics of broad weed control spectrum,with the low toxicity to animals.Although the PPO inhibitor shows some excellent features,some defects of the commercial PPO inhibitor herbicides have been exposed gradually.For example,the conventional PPO herbicides typically show excellent weed control on broad-leaf grass,but perform poorly on grass weeds or lack selectivity on crops.Therefore,it is important to develop new PPO herbicides.In this dissertation,four PPO inhibitor herbicides were designed by computer aided drug design(CADD)using Autodock Vina program.The four compounds are listed as following:(1)2-Chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-dihydro-2H-pyrimidin-1-yl)-benzoic acid 2-hydroxy-ethyl ester;(2)2-Chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-dihydro-2H-pyrimidin-1-yl)-benzoic acid 2,3-dihydroxy-propyl ester;(3)2-Chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-dihydro-2H-pyrimidin-1-yl)-benzoic acid 2-dimethylamino-ethyl ester;(4)2-Chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-dihydro-2H-pyrimidin-1-yl)-benzoic acid 3-amino-propyl ester.All four of the compounds were synthesized through esterification.The stability of some esters compounds is particularly important for the effectiveness of drugs.Therefore,we selected one of the compounds for hydrolysis test and calculated the energy barrier of hydrolysis using Gaussian16,the compounds show high stability in solution.In the experiment of herbicidal activity test,it is concluded that all of the four compounds synthesized in this work exhibit excellent herbicidal activities,three of them showed strong inhibition on grass weeds.The 2-Chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-dihydro-2H-pyrimidin-1-yl)-benzoic acid 2-hydroxy-ethyl was selected to further test by a pesticide company.The results demonstrate that the compound shows similar herbicidal activity to saflufenacil for broad-leaf grass,and a little more efficient for grasses than those of saflufenacil.In addition,the compound has the advantage of low cost of production.