Synthesis And Antibacterial Studies Of Dicyclic Spiropyrrolidine Indolones

With the widespread use of fungicides,the problems of environmental pollution and drug resistance of fungicides have become increasingly prominent.Therefore,the development of new fungicides with low toxicity and high efficiency has gradually become one of the hot research fields in organic synthesis.Active substructure splicing method refers to connecting two or more known effective structural fragments in a certain way,and using biological tests to observe the biological activity of the new compound designed in this way.It is one of the common methods for the development of new fungicides.Both indoloquinone and chalcone are simple compounds with good biological activity.In this thesis,two compounds were successfully spliced through1,3-dipolar cycloaddition reaction,and a series of new bicyclic spiropyrrole indolone compounds were synthesized and the antibacterial activity of bicyclic spiropyrrole indolone compounds was studied.First of all,the rapid synthesis of novel dicyclic spiropyrrolidine was reported,using[3+2]-cycloaddition of isatin N,N'-cyclic azomethine imine 1,3-dipoles,generated from the condensation of substituted isatins and pyrazolidones.Under the catalysis of potassium carbonate,1,3-dipolar cycloaddition reaction has achieved between N,N'-cyclic azomethine imine dipole and chalcone.By screening the reaction conditions,including the choice of solvent type and dosage,the choice of base type and dosage,and the ratio of reaction materials,the best reaction conditions are obtained: potassium carbonate as the catalyst,dimethyl sulfoxide as the solvent,and reaction at room temperature for 2-5 min to obtain the target product.A total of 38 cases of bicyclic spiropyrrole indolone compounds were synthesized by this method.The product yield was good(50-95%)and the diastereoselectivity was high(> 20:1).The target compounds were characterized by MS,NMR,IR,etc.,and the three-dimensional configuration of the product was explained by single crystal x-ray diffraction pattern.At the same time,a possible reaction mechanism is proposed.Then,assess the antibacterial activity of the synthetic bicyclic spiropyrrolidone indole compounds.The research models include Gram-positive bacteria(Staphylococcus aureus,Bacillus subtilis)and Gram-negative bacteria(E.coli,Pseudomonas aeruginosa).After preliminary screening,only 14 target products showed certain antibacterial activity,and the minimum antibacterial concentration and minimum bactericidal concentration of these 14 target products were determined.The results show that the compound 4e(3S,3a'S,4'S,5'R)-4'-(4-fluorophenyl)-5'-(4-nitrobenzoyl)-1-(prop-2-yn-1-yl)-3',3a',4',5'-tetrahydrospiro[indoline-3,6'-pyrrolo[1,2-b]pyrazole]-2,2'(1'H)-dione shows good bacteriostasis.