Study On The Synthesis And Structure-Activity Relationship Of Nitrogen-Containing Compounds With Antibacterial Activity

Alkaloid compounds are one of the most representative drug structures in natural products.Drugs generally contain pyrroloindole core structures.Compound with such core structures generally have a wide range of biological activities,such as:inhibiting cancer cells,anti-Virus activity and the activity of killing plant pathogens,etc.,have high research value in plant sterilization.In this thesis,the pyrroloindole tricyclic structure is used as the key skeleton to construct a compound library and screen for its antibacterial activity.According to its structure-activity relationship,a class of highly effective antibacterial compounds is screened out for the design and development of pesticide molecules in the future.Provide basis for synthesis and structural modification.The research content is as follows:This topic uses 3-indole acetonitrile as the starting material,oxidizes its C-2 position,performs dibenzylation at the N and C positions,and then uses Li Al H4 for reduction and ring-closing reactions to obtain a tricyclic skeleton:pyrrole And indole structure.The N-8 position of the tricyclic skeleton was acylated with different acid chlorides to obtain 39 pyrroloindole compounds,including 20 4-methyl series(Y_4-1-Y_4-20),and 19 CF₃ series(Y_4-21-Y_4-39).The 39 synthesized compounds were identified by ESI-MS,¹H-NMR and ¹³C-NMR structure,and they are all new compounds.Using 96-well plate micro-dilution method,39 pyrrolo indole compounds and 6 pathogens were compared with carbendazim and amphotericin B as positive controls.They were tested for their antibacterial activity.Using the 96-well plate microdilution method by using carbendazim and amphotericin B as positive controls,39 pyrrole and indole compounds were tested against 6 pathogens（Sclerotinia sclerotiorum,Alternaria solani,Verticillium dahliae,Fusarium oxysporum,Walnut pythium and Curvularia lunata）for antibacterial activity.The results show that among the tested compounds,compound Y_4-37 has the best inhibitory effect on Sclerotinia sclerotiorum,with a minimum inhibitory concentration（MIC）value of 1.95（?）g/m L;it has the best inhibitory effect on tomato early blight It is Y_4-35,with a minimum inhibitory concentration（MIC）value of 1.95（?）g/m L;compound Y_4-31 has the best bactericidal activity against Verticillium dahliae,with a minimum inhibitory concentration（MIC）value of 15.61（?）g/m L;compound Y_4-10 The antibacterial activity against Cucumber Fusarium wilt is outstanding,with a minimum inhibitory concentration（MIC）value of 15.16（?）g/m L.Among the inhibition of Pythium aureum,the compounds Y_4-15 and Y_4-30 have the strongest antibacterial activity against the pathogen.Its minimum inhibitory concentration（MIC）value is 15.61（?）g/m L;for the inhibition of corn Curvularia spp.,compound Y_4-35,Y_4-36,Y_4-37 and compound Y_4-39 have significant antibacterial effects.The minimum inhibitory concentration The（MIC）value is 15.61（?）g/m L.Among them,compound Y_4-6,Y_4-24,Y_4-30,Y_4-32 and compound Y_4-37 showed good bacteriostatic effects on 6bacterial species.Structure-activity relationship study:The compounds that showed significant antibacterial activity against 6 plant pathogens are:Y_4-6,Y_4-10,Y_4-15,Y_4-24,Y_4-30,Y_4-31,Y_4-32,Y_4-35,Y_4-36 and compound Y_4-37are 10 compounds,among them,compound Y_4-6,Y_4-10,Y_4-24,Y_4-31,Y_4-35,Y_4-36 and compound Y_4-37structure All of them contain Cl atoms,and the Cl atoms are located at the C-2,C-5 or C-6 positions.As the number of Cl atoms increases,the antibacterial effect of the target compound is significantly enhanced,and the scope of application is wider.Among the substituents containing pyridine structure,when methyl is introduced,the antibacterial effect is improved to a certain extent,such as compound Y_4-32.When the substituent group is changed from pyridine to pyrazine structure,its antibacterial effect is the best,such as compound Y_4-37.Among the 10 target compounds,compound Y_4-6,Y_4-10 and compound Y_4-15 belong to 4-methyl series compounds,while compound Y_4-24,Y_4-30,Y_4-31,Y_4-32 The seven compounds,Y_4-35,Y_4-36 and compound Y_4-37 belong to the CF₃ series.It can be concluded that when the CF₃ group is introduced into the N and C positions of the core structure,its antibacterial activity is significantly improved.