Design,Synthesis And Biological Activity Of Pyrimidinamine Pesticide

In order to find high-activity,low-toxic pesticide molecules,we designed and synthesized a series of pyrimidinamine derivatives using pyrimidine amine structure as a template and studied their biological activities.The content specifically includes the following modules:(1)Discovery of lead compoundsAt the beginning of this project,the pyrimidinamine fungicide,ethirimol,was selected as the template,and its structural transformation was carried out.The thiol,thioether,sulfoxide and sulfone were introduced and 10 ethirimol derivatives A1~A10 were synthesized.Then,the active fragments of the fungicides such as the fungicides diflumetorim,acaricide pyrimidifen and acetamiprid,dinotefuran,clothianidin,oxazolamide,etc.were combined and assembled to design compounds B1~B11,C1,and D1.Preliminary biological activity showed that compounds C1 and D1 were quite more potent as lead compounds.(2)Synthesis of pyrimidinamine derivativesIn view of the good insecticidal and fungicidal activity of compound C1 designed under the guidance of the combination principles,it was chosen to continue to synthesize compounds C2~C13 by substitution reaction,reduction reaction,pyrimidine cyclization,and they were structurally characterized.Besides,in view of the fact that compound D1 also has good insecticidal and fungicidal activity,the phenyloxazole pyrimidinamine derivatives were designed by plug-in method and nucleophilic addition elimination,oxazole ring formation,substitution,oximation reaction,hydrazinolysis,etc.Another series of compounds D2~D25 were synthesized and characterized.Moreover,based on the study of the relationship between structure and activity of phenyloxazolyl pyrimidinamine derivatives,the molecular design of replacing the oxazole ring with the thiazole ring was realized by the principles of bioisosterism and scaffold hopping.A series of compounds E1~E27 were synthesized by thiol,thiazole ring formation,substitution,oximation reaction and hydrazinolysis,etc.and their structures were all characterized.(3)Pesticide activity of pyrimidinamine derivativesOverall,the pyrimidinamines reported in this paper have medium to excellent levels of killing aphid and spider mites.Among them,compound C9 showed a slightly better acaricidal activity than the spirotetramat;compounds D16,D18,D20,E6,E7,E9,E15,E17,E20 and E22 all had better activities than imidacloprid.In terms of fungicidal activity,the target compounds synthesized in this subject exhibited general in vitro activity,but showed good in vivo activity against Erysiphe graminis and Puccinia sorghi.Compounds D4,D9 and E15 have better resistance to E.graminis than commercial fungicide flusilazole;compounds D20,D23,E13,E15,E21,E23 and E25 have better activity to P.sorghi than commercial tebuconazole.In terms of herbicidal activity,the target compound exhibited poor or no activity.In addition,cytotoxicity tests indicated that compound E15 is relatively less cytotoxic and has potential for further development.(4)Structure-activity relationship and properties of pyrimidinamine pesticidesA preliminary structure-activity relationship study of the target compounds revealed that the steric and electrical properties of the substituent groups on the pyrimidine ring and the benzene ring and the introduction of the chiral center have different effects on the activity.Through the 3D-QSAR study on the activity of phenyloxazole pyrimidinamine derivatives against Aphis fabae and the activity of phenylthiazole pyrimidinamine derivatives against P.sorghi,it was found that: the stereo field,electrostatic field,hydrophobic field,and hydrogen bond acceptor field have different degrees of contribution to the biological activity of the target compounds and play an important role in activity prediction and further structural optimization of the target compounds.Theoretical calculations on some pyrimidinamine derivatives in this paper showed that the phenyloxazole/thiazole structure fragment is essential for biological activity;for the target compound containing a chiral center,its R configuration may have more important biological activity.