Synthesis And Structure-activity Relationship Of N-2 Substituted β-carboline Compounds

Plant disease have more and more serious impact on global agriculture,resulting in a decline in the output and quality of agricultural products.Although the traditional chemical control can achieve good control effects,but also leads to serious ecological and environmental problems.Compared with traditional pesticides,antibacterial agents prepared from natural products have low toxicity,easy degradation and good selectivity,which have become a hot research topic of new pesticides in recent years.β-Carboline alkaloids are widely distributed in natural products,with antibacterial,antioxidant,antiviral,insect and other biological activities.Based on this,this thesis takes tetrahydrogen-β-Carboline as the lead compound,modifies its structure,synthesizes 20 tetrahydro-β-carboline derivatives,assays their antibacterial activity,provides candidate compounds for new pesticide antibacterial agents.1.Synthesis route:Indole-3-acetonitrile was used as starting material,Li Al H₄ as the reducing agent,and THF as the solvent to synthesize intermediate product b with yield of56%;Reaction with acetaldehyde using TFA as catalyst and DCM as solvent to synthesize tetrahydrogen through ring closure-β-Carboline skeleton,product c was obtained with a yield of 65%;Taking triethylamine as base and acylating with different acyl chlorines,20compounds were obtained by replacing different groups with N-2 of tetrahydro-β-carboline.All compounds are novel and their structures were confirmed by ¹H-NMR,¹³C-NMR,and ESI-MS.2.Activity test:With Azoxystrobin and Kresoxim-methyl as the positive control,Inhibition of hyphal growth rate was adopted,All compounds were determined for Sphaeropsis sapinea,Phytophthora nicotianae,Rhizoctonia solani,Colletotrichum gloeosporioides,Camellia oleifera colletotrichum fructicola and Coriolus versicolor;The results of activity test showed that most of the compounds showed good antibacterial activity.Compounds J2,J6,and J17 have good antibacterial activity,especially compound J2 has inhibitory rates of 98.38%and 97.04%inhibition rates against anthracis camellia and Trichoderma coloriformis,which were better than Kresoxim-methyl（66.17%and 43.26%）.3.Structure-activity relationship:In this thesis,the structure-activity relationship of tetrahydro-β-carboline derivatives was summarized.Tetrahydro-β-carboline derivatives have good bacteriostatic activity.For tetrahydro-β-carboline derivatives,the bacteriostatic activity of C-3 electron-withdrawing group was better than that of electron-donating group when benzene substituted group was introduced.When nitrogen containing heterocyclic substituents were introduced,the antibacterial activity of the compounds increased with the increase of N atom.The introduction of Cl atom also affects the antibacterial activity of the compound.Among them,when N atom was in the intermediate position,the introduction of ortho-amino group improved its antibacterial activity most obviously.