Study On The Synthesis And Structure-Activity Relationship Of Indole Compounds

The abuse of chemical pesticides has caused a serious impact on the environment and caused great harm to the survival of human beings and other organisms.Therefore,there is an urgent need to develop an efficient,low-toxic,and environmentally friendly pesticide.Indole compounds are widespread in nature and have a variety of biological activities.Based on the above reasons,this thesis modified the indole structure to obtain a stable indolopyrrole ring with multiple modification sites,modified its structure,and studied the antibacterial activity.Using indole-3-acetonitrile as the starting material,DMSO as the solvent and oxidant,37% hydrochloric acid was used to provide an acidic environment to oxidize the C-2position.The N-position and C-3 position of indole are double-benzylated with2-methylbromobenzyl bromide;then the reduction reaction is carried out with Li Al H4 as a reducing agent to obtain the indolopyrrole skeleton;through different acid chlorides and indolo The N-8 position on the pyrrole ring was acylated to obtain 39 compounds.Among them,there are 20 compounds in the 2-methyl series(H-1 to H-20).There are 19 compounds in the 3-Fluorine series(K-1 to K-19).The 39 compounds were identified as new compounds by ESI-MS,1H-NMR and 13C-NMR structure identification.The 96-well plate method was used to determine the effects of all compounds on rape sclerotinia sclerotiorum,verticillium dahliae,Alternaria solani,walnut pythium,and(Fusarium oxysporum.),Curvularia lunata(Curvularia lunata)6 kinds of bacteria inhibiting activity,biological activity test showed that most of the compounds showed certain biological activity,and some compounds showed significant antibacterial activity.For example,compounds K-18 and K-19 have the best biological activity against Sclerotinia sclerotiorum,and the minimum inhibitory concentration MIC value is 2.0 μg/m L;compounds K-15,K-16,K-17,K-18,K-19 has the best inhibitory effect on early blight of tomato,with a minimum inhibitory concentration MIC value of 2.0 μg/m L;compounds K-10 and K-17 have the best bactericidal activity against Verticillium dahliae,with the least bacteriostasis The concentration MIC value is 1.95 μg/m L;compounds K-9,K-10,and K-15 have outstanding antibacterial activity against Cucumber Fusarium wilt,and the minimum inhibitory concentration(MIC)value is 3.9 μg/m L;In the inhibition,compound K-2 has the strongest bacteriostatic activity against the pathogen,and its minimum inhibitory concentration(MIC)value is 7.8 μg/m L;for the inhibition of corn Curvularia spp.,compound K-15 has significant bacteriostatic effects,The minimum inhibitory concentration(MIC)value is 7.8 μg/m L.Among them,the compounds H-3,H-13,H-15,K-2,K-5,K-9,K-10 and K-15 all exhibited good antibacterial effects on six bacterial species.Compounds H-3,H-5,H-13,H-15 are at the N position and C-3 are compounds substituted by 2-methyl benzyl bromide,K-2,K-4,K-5,K-7,K-8,K-9,K-10,K-12,K-15,K-17,K-18 are N positions and C3 are compounds substituted with 3-fluorobenzyl bromide.These 14 compounds showed significant biological activity against the six fungi tested.The relationship between the structure of the compound and the pharmacophore group was analyzed,and it was found that the biological activity of the compound obtained by substituting the N position and C-3 position of the indole structure with 3-fluorobenzyl bromide was stronger than that of the N of the indole structure of 2-methylbromobenzyl bromide.Compounds substituted at positions and C-3 positions;compounds H-3,H-5,H-15,K-2,K-9,K-10 and K-15 have significant antibacterial activity against 6 kinds of plant pathogenic bacteria.The structure-activity relationship was studied,and it was found that the substituents of the compound were all located at the C-5 or C-6 position;in the substituents containing a pyridine structure,when methyl was introduced,the antibacterial effect was improved to a certain extent,such as compound H-3,H-5,H-15,K-8,K-9 and K-10.