Design,Synthesis And Antifungal Activity Of Novel Pyrazole Derivatives

The crop diseases caused by plant pathogenic fungi have seriously affected food production,therefore,the development of efficient and low-risk fungicides has become an urgent need to protect crop safety.This work designed and synthesized 25 pyrazole formamide derivatives containing bispyrazole（Chapter 2）and 22 pyrazole sulfonamide derivatives containing 1,3,4-oxadiazole groups（Chapter 3）.The structures of all compounds were characterized by ¹H NMR and ¹³C NMR,and antifungal activity tests were conducted.The compounds with good activity were selected for electron microscopy,molecular docking,and other experiments to study their preliminary mechanism of action.In work A,using succinate dehydrogenase（SDH）as the target and marketed drugs as the lead compounds,the active fragments were intercepted and linked to the drug skeleton in previous work.25 novel dipyrazole containing formamides were designed and synthesized,and their antibacterial activity against 8 plant pathogenic fungi was evaluated.The compound 1h has the best activity against S.sclerotiorum,with an EC₅₀ value of 11.58 mg/L.In vitro leaf control experiments showed that compound 1h had a good protective activity on rape leaves,and scanning electron microscope observation showed that compound 1h caused damage to S.sclerotiorum.In addition,molecular docking simulation and succinate dehydrogenase activity testing indicate that the action site of compound 1h may not be succinate dehydrogenase.On the basis of work A,work B retained the pyrazolamide skeleton and introduced 1,3,4-oxadiazole groups at position 4.Then,by connecting with benzenesulfonyl chloride,22 new pyrazolamide sulfonamide compounds were designed and synthesized,and their antibacterial activity against 10 plant pathogenic fungi was tested.The results showed that compound B17 had the optimal activity against V.mali,with the EC₅₀ value of 13.49 mg/L.Compound B11 has the highest activity against B.cinerea with the EC₅₀ value of 13.85mg/L.In vitro prevention experiments have shown that compound B17 has good protective activity against V.mali.Under electron microscope observation,compound B17 destroyed the hyphae of V.mali.Cell content experiments suggest that compound B17 may have damaged the cell membrane and cell wall of the V.mali.In summary,the experimental results show that compound 1h and compound B17 have good antifungal activity against some plant pathogenic fungi,and can be used as lead compounds in the development of agricultural fungicides.