Design,Synthesis,and Pesticidal Activities Of Heterocyclic Compounds Bearing 1,2,4-Triazolopyrimidine Skeleton

Due to the structural diversity,novel mechanism of action and biocompatibility of natural active substances,it is one of the important ways to exploit new and efficient green pesticides by using natural products as lead compounds and derivatizing their structures with active substructure splicing strategy,so as to potentially improve the biological activity of these natural active small molecules.Drawing on the experience of the design,synthesis and application of essramycin and its derivatives,this paper is dedicated to systematically carry out the creative research of high-efficiency green pesticides with marine natural product essramycin by using function-oriented theory.Through the structural modification and optimization of the core skeleton 1,2,4-triazolopyrimidine,two kinds of essramycin alkaloid derivatives were designed and synthesized,and their anti-tobacco mosaic virus(TMV)and anti plant pathogen activities were studied.The specific work content is divided into two parts:Part 1: This paper mainly focuses on the design,synthesis and bioactivity of1,2,4-triazolopyrimidinones.(1)Structural diversity derivation of natural product essramycin: A series of 1,2,4-triazolopyrimidinone derivatives containing carboxylic acid or acyl hydrazone were designed and synthesized by modifying the 2 and 6 positions of triazolopyrimidinone ring in the structure of essramycin alkaloid as the core skeleton.The effects of different substituents at 2 and 6 positions on the biological activities against TMV and plant pathogens were systematically investigated.(2)Research on anti-TMV activity:Through the systematic study on the anti TMV activity of 1,2,4-triazolopyrimidinone derivatives,it is found that most target compounds show certain anti TMV activity,compounds II-6a,II-6e～I-6i are better than commercial variety ribavirin at the concentration of 500 μg/m L.(3)Research on structure-activity relationship of anti-TMV activity: We found that the anti-TMV activity of these compounds is very sensitive to the types of functional groups.For the 6 position of pyrimidine ring,the introduction of acyl hydrazone is more conducive to the improvement of anti-TMV activity than carboxylic acid group.In addition,the induction effect of substituents also has a certain impact on their anti-TMV activity.(4)Research on fungicidal activity: By testing the fungicidal activity of the target compounds,We found that most of the target compounds showed broad-spectrum fungicidal activity against Fusarium oxysporium f.sp.Cucumeris;Cercospora arachidicola hori;Physalospora piricola;Rhizoctonia cerealis;Alternaria solani;Pyricularia grisea;Phytophthora capsica;Sclerotinia sclerotiorum.A part of compounds selectively showed medium to good biological activity against Physalospora piricola and Rhizoctonia cerealis.Among them,the inhibition rate of II-6h against Physalospora piricola was 87%.Part 2: The design,synthesis and bioactivity of 1,2,4-triazolopyrimidine amine derivatives were studied.(1)Design and synthesis of target compounds: With1,2,4-triazolopyrimidine as the core skeleton,the 7 position of pyrimidine ring was modified,different active substructures were introduced,and 1,2,4-triazolopyrimidine derivatives containing aromatic amine and amide structures were designed and synthesized.The effects of different functional groups at 7 positions on the biological activities against TMV and plant pathogens were investigated.(2)Research on anti-TMV activity: We found that the antiviral activity of most compounds is better than commercial antiviral drug ribavirin at the concentration of 500 μg/m L.For example,III-2a,III-2b,III-2e,III-2f,III-6c and III-6e show excellent anti-TMV activity(the inhibition rate was higher than50%)and the biological activity of III-2e and III-2f is close to commercial drug ningnanmycin.(3)Research on structure-activity relationship and action mechanism of anti-TMV: Compared with 1,2,4-triazolopyrimidinones,the introduction of aromatic amines and amides is conducive to the increase of anti-TMV biological activity.The types of functional groups and the number and position of substituents also have different effects on the anti-TMV activity of the compounds.In addition,using transmission electron microscopy(TEM)and molecular docking technology,it was found that there was a hydrogen bond between the highly active compound III-2f and the amino acid residues of TMV CP,which affected the self-assembly process of TMV,and then reduced the infection activity of TMV to the host plant.(4)Research on fungicidal activity: By evaluating the fungicidal activity of the target compounds,it was found that most compounds showed certain fungicidal activity against 8 plant pathogens.Among them,compound III-6g(inhibition rate was 59%)showed higher fungicidal activity against Pyricularia grisea than carbendazim(inhibition rate was 52%),and the inhibition ability of III-6h(inhibition rate was 57%)against Alternaria solani was better than commercial varieties chlorothalonil and carbendazim(inhibition rates were less than 50%).