Design, Synthesis And Biological Activity Of Novel Amide Phosphate Derivatives

Amide phosphate compounds are phosphate compounds containing amide groups,studies have found that they have broad-spectrum biological activities,such as anti-plant viruses,insecticides,weeding,sterilization,anti-tumor and other organisms.It has become a hot research topic.Amide phosphate compounds play an important role in the research and development of medicines and pesticides.In this work,a series of amide phosphate compounds were synthesized by introducing a dialkyl phosphite structure into the?-carbonyl amide,the chemical structure were characterized,biological activity was evaluated.The main results was as follows:1.A green synthesis method of amidophosphates was developed using 1,8-diazabicyclo[5.4.0]undecane-7-ene(DBU)as catalyst under solvent-free and room temperature conditions.The yield of this method can reach more than 90%under the condition of gram level and mole level,this method was used to expand the substrate,and 54 amide phosphate compounds were quickly synthesized,the structure was confirmed by ¹H NMR?¹³C NMR?³¹P NMR and HRMS and the crystal structure of C₄₈ was determined by single crystal diffractometer.2.The turbidimetric method was used to test the antibacterial activity of 46compounds,Take the commercial medicines bismerthiazol and thiazide copper as the control agents,the test results show that The EC₅₀ values of compounds C7,C8 and C41against Xanthomonas oryzae pv.Oryzae(Xoo)were lower than those of commercial control chemicals bismerthiazol(88.6?g/m L)and thiazide copper(108.4?g/m L),among them,compound C41 had better activity against Xanthomonas oryzae pv.Oryzae with EC₅₀ of 36.8±3.2?g/m L,The series of compounds have poor antibacterial activity against Xanthomonas axonopodis pv.citri(Xac).Preliminary SAR showed that when R₁was the electron-extracting group,R₂ was the cyclohexyl group,and R₃ ethyl group,the antibacterial activities against bacterial blight of rice and citrus ulcerative bacteria could be improved.3.The anti-tobacco mosaic virus(TMV)activity of this series of target compounds was tested by the half-leaf dead spot method,When the test concentration is 500?g/m L,the results showed that the therapeutic activity of compound C7(62.9%)and C8(62.7%)is equivalent to that of the control agent ningnanmycin(62.6%).The protective activity of compound C7 was 65.3%,which was better than that of ningnanmycin(58.1%).The passivation activity of compound C25 was 92.3%±1.3,which was better than that of the control drug ningnanmycin 90.5%±1.0 A simple structure-activity analysis is carried out by combining the activity data of the biological test and its chemical structure,when R₁was the bromine,R₂ was the cyclohexyl group,and R₃ ethyl group,the anti-TMV virus activity are improved.Microscale thermophoresis(MST)also showed that there is a strong interaction between compound C25 to TMV-CP.