Structural Design, Optimization And Biological Activity Study Of Novel Phenylglycine Derivative

Fungicides play an important role in modern agriculture,which can effectively control crop diseases and ensure food security.However,with the widespread use of fungicides,some problems have followed,such as drug resistance,toxicity and pesticide residues.Therefore,there is an urgent need to develop new fungicides with unique structure,safety and high efficiency to solve the increasingly serious agricultural security threat.Based on the previous work of the research group,a series of 2-phenylglycine derivatives containing 1,3,4-oxadiazole were designed and synthesized,and the inhibitory activities of the target compounds against fungi,bacteria and TMV were screened.The results of biological activity evaluation showed that compound I₁₉ had the highest antifungal activity against T.cucumeris in vitro,and the EC₅₀ value was 32.4μg/m L.At the concentration of 200μg/m L,the in vivo protective activity against rice leaves was 66.9%,which was slightly lower than that of the positive control azoxystrobin（73.2%）.In addition,the antibacterial and anti-TMV activities of these compounds were also screened.The results showed that at the concentration of 500μg/m L,compounds I₂₄（80.2%）,I₂₅（89.4%）and I₂₇（83.3%）had good passivation activity against TMV,which was equivalent to Ningnanmycin（96.3%）.At the concentration of50μg/m L,the inhibitory activity of compounds I₂₆（89.9%）,I₂₇（78.0%）and I₂₈（68.0%）against Xoo was higher than that of thiodiazole copper（18.0%）.Based on the activity study of 2-phenylglycine derivatives,the structure optimization and activity development of amino acid derivatives were carried out by structure-activity relationship analysis and active substructure splicing.Further,43target molecules were synthesized,including 1,3,4-oxadiazole,acylhydrazone,amide or sulfonamide structures.All the target compounds were confirmed by ¹H NMR,¹³C NMR,¹⁹F NMR and HRMS.The results of biological activity evaluation showed that compoundⅣ₁₁ had a good inhibitory effect on N.oryzae,and the EC₅₀ value was 17.3μg/m L.In the study of antifungal mechanism,compoundⅣ₁₁ can significantly increase the content of nucleic acid,protein and MDA,indicating thatⅣ₁₁ can destroy the integrity of the cell membrane of the mycelium after contact with the mycelium,thus affecting the normal growth of the mycelium.In addition,combined with the study of SDH enzyme activity,it is speculated that compoundⅣ₁₁ may affect the physiological functions of cell respiration and cell membrane.This study shows that2-phenylglycine derivatives have certain antifungal activity and can be further developed and designed as potential pesticide molecules.