Design, Synthesis And Activity Testing Of Novel Protoporphyrinogen Oxidase Inhibitors

China has the largest population all over the world with nearly 1.4 billion population,food production of our country is a critical issue that remains to be resolved.China requires enough food to feed its nearly 1.4 billion population,so it is necessary to increase food production.Weed is a crucial factor to affect the crop yield,the crop yield loss was estimated to be 43%without weed control.The most effective way to control weed is to prevent weed from growing by using herbicides.However,the wide application of herbicides has caused serious environmental pollution because the herbicides used in the early years are usually highly toxic with a long residual period.Many environmental-friendly herbicides have been proposed and developed.But with the long-term use of herbicides,more and more weeds become resistant to herbicides.Therefore,the development of new type of environmentally friendly and resistance slow-developing herbicides are of significance for increasing crop yields.Protoporphyrinogen oxidase(PPO)is a typical target for herbicides,and the compounds containing uracil are one of important PPO classes,which inhibit the growth of weeds by combining with the PPO target.Compared with other types of herbicides,the PPO herbicides are highly efficient,quick contact action,easily degradable,and low toxic to mammals.These advantages make it occupy an important share in the herbicides industry and widely used as excellent herbicides for the weed control.At present,the study of new PPO herbicide has attracted much more attention in the world.The most successful example is the saflufenacil developed by BASF.BASF calls the saflufenacil the most successful broad-leaved herbicide in the past 20 years,but the shortcoming of saflufenacil is that the herbicide has poor effect on grass weeds.In this dissertation,Auto Dock Vina is used to dock the designed molecules with P PO.By comparing the docking results with that of saflufenacil,a new class of compo unds containing-CONHCOOR group PPO inhibitors are designed according to their bi nding mode and binding energies.Four of designed molecules are synthesized and cha racterized by a ~1H NMR and ESI-MS(the electrospray ionization mass spectrum).The herbicide activities for all the samples are also estimated.The four synthesized comp ounds are listed as following:(1)methyl-2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-(tri fluoromethyl)-2,3-dihydropyrimidin-1(6H)-yl)benzoylcarbamate(code:NCO-JC);(2)e thyl-2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-(trifluoromethyl)-2,3-dihydropyrimidin-1(6H)-yl)benzoylcarbamate(code:NCO-YC);(3)isopropyl-2-chloro-4-fluoro-5-(3-met hyl-2,6-dioxo-4-(trifluoromethyl)-2,3-dihydro-pyrimidin-1(6H)-yl)benzoylcarbamate(cod e:NCO-YB);(4)phenyl-2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-(trifluoromethyl)-2,3-dihydropyrimidin-1(6H)-yl)benzoylcarbamate(code:NCO-BF);(5)1-methyl-1H-pyrazol-5-yl 2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-(trifluoromethyl)-2,3-dihydropyrimidin-1(6H)-yl)benzoate(code:BF-BZ);(6)methyl 2-(2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-(trifluor omethyl)-2,3-dihydropyrimidin-1(6H)-yl)benzoylthio)acetate(code:BF-SH);(7)2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-(trifluoromethyl)-2,3-dihydropyrimidine-1(6H)-yl)zinc benz oate(code:BF-XY);(8)Potassium 2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-(trifluorometh yl)-2,3-dihydropyrimidin-1(6H)-yl)benzoate(code:BF-JY).Based on the herbicidal activity tests,it can be seen that NCO-JC and NCO-YC have good effects on broad-leaved weeds and grass weeds.The effects of NCO-YB and NCO-BF are relatively poor.