Synthesis And Antibacterial Activity Of Semi-chemicaline Skeletal Analogs

Semi-Chemicaline Skeletal Analogs is a natural product with antibacterial activity and has inhibitory activity against bacterial fungi.In this paper,the indole pyrrole skeletons were constructed simply and efficiently by the oxidative reaction,alkylation reaction and reduction reaction using the economical indole derivatives as raw materials,and then acylated to synthesize a series of compounds with the activity of anti-plant pathogenic fungi.Our project has developed an economical method for the synthesis of indolopyrrole skeleton compounds,we hope that we could do something to contribute to developing an environment-friendly antibacterial bactericide.1.Organic synthesis of natural products:(1)This project selects the economically indole-3-acetonitrile as raw material,through the catalytic action of 37% concentrated hydrochloric acid and the oxidation of dimethyl sulfoxide,the oxidation reaction occurs,to obtain yttrium oxide-3-acetonitrile(L,Yield 93%).(2)Alkylation occurs with L as a substrate,sodium hydride as a base,and the addition of 2.3 equivalents of 2-fluorobenzyl or 3-fluorobromobenzyl or 3-(trifluoromethyl)benzyl bromide in anhydrous tetrahydrofuran.The alkylation reaction occurs to obtain 1,3-benzyl substituted indole-3-acetonitrile(L1,Yield 59%;L2,Yield 51%;L3,Yield 46%;),respectively.(3)Using L1 or L2 or L3 as a substrate,add an appropriate amount of anhydrous tetrahydrofuran solvent,and add 7.5 equivalents of lithium tetrahydroaluminum to the reaction solution in batches to generate a reduction reaction to obtain an indolopyrrole tricyclic skeleton derivation respectively.(LR1,Yield 57%;LR2,Yield 58%;LR3,Yield 61%;).(4)Using LR1 or LR2 or LR3 as the substrate,anhydrous pyridine as the base,and adding 1.2 equivalents of the anhydride as the acylating reagent,acylation occurs to obtain the N-position acylated semi-waxemetane compounds(LRR1,Yield 96%;LRR2,Yield 85%;LRR3,Yield 97%;).(5)Using LR1 or LR2 or LR3 as the substrate,triethylamine as the base,and adding 1.5 equivalents of acyl chloride as acylating reagent,the acylation reaction occurs to obtain the N-position acylated semi-chalcinoids(LRR1,Yield 85%;LRR2,Yield 86%;LRR3,Yield 85%;).A total of 62 compounds with half waxy mesaconide skeletons were synthesized.The LRR-1 series(22 in total)are that 1,3 is the same substituent 2-fluorobenzyl substituted compounds,and the LRR-2 series(22 in all)are that 1,3 is the same substituent 3-fluorobenzyl substituted compounds,LRR-3 series(18 in total)are that 1,3 is the same substituent 3-(trifluoromethyl)benzyl substituted compounds,structures of compounds were confirmed by ESI-MS,1H-NMR and 13C-NMR.2.Antibacterial activity test:We use 96-well plate microdilution method to test fungi and bacterial inhibitory activities of all the Semi-Chemicaline Skeletal Analogs.The results show that the LRR-1-1 compound is more efficient to gram-negative bacteria(Escherichia coli)than(Streptomycin),MIC is 15.6 ?g/ml;LRR-1-1 compound against gram-positive bacteria(Staphylococcus aureus)is as Similar as positive control(penicillin),MIC is 16 ?g/ml;LRR-1-17 compound against Fusarium oxysporum f.sp.is more significant than three positive controls(carbendazim,amphotericin B,and chlorothalonil),MIC is 31.3 ?g/ml;LRR-2-8 compound against gram-negative bacteria(Rosa solani)compared to 2 positive controls(gentamicin and streptomycin)is more significant,MIC is 31.3 ?g/ml;LRR-2-13 compound against Verticillium dahliae has comparable activity to the positive control(chlorothalonil),MIC is 31.3 ?g/ml;LRR-3-1 compound against Aspergillus flavus has comparable activity to the positive control(Amphotericin B),MIC is 31.3 ?g / ml.