Synthesis And Antimicrobial Activity Of 2,4-Disubstituted Quinoline Alkaloids,the Key Intermediates Of Dictamnine

Dictamnine is a linear furoquinoline alkaloid,which is widely distributed not only in nature,but also has various pharmacological activities such as anti-cancer,blood pressure lowering,anti-parasitic,anti-platelet aggregation and the like.Antibacterial activity.2,4-disubstituted quinoline is an important intermediate for the synthesis of white alkali,and is also a common structural unit in popular antibacterial,anti-asthmatic,anti-tumor drugs and active natural products.Its rich biological activity makes it in medicine,pesticides and dyes.And other fields are widely used.In order to screen out quinoline alkaloids with excellent antibacterial activity,a series of 2,4-disubstituted quinoline compounds were designed and synthesized,and their inhibitory activities against common plant pathogenic fungi and Gram bacteria were determined.Explain its structure-effect relationship.The main contents and preliminary results of this study are as follows:1.Using the substituted aniline as raw material,39 2,4-dihaloquinolines（A series）were synthesized by Combes reaction;followed by Williamson reaction,13 2,4-dimethoxyquinolines were obtained.Class of compounds（B series）,three of which are new compounds.The structure was confirmed by a spectral technique such as ¹H NMR,¹³C NMR or ESI-MS.2.The inhibitory activity of the target compound against 12 common plant pathogenic fungi was determined by the linear growth rate method of mycelium and carbendazim.The results showed that most of the compounds were at 50μg/mL.The test bacteria showed different degrees of inhibitory activity,among which 36compounds had higher inhibitory activity against apple ring pathogen than carbendazim,indicating that the apple ring pathogen was its sensitive strain.Compounds A,A8,A19,A31 and A32 inhibited the six pathogens such as rice blast,wheat gibberella,corn rotundus,cabbage black spot,apple ring and watermelon wither than the oxystrobin.3.Select high-activity compounds with inhibition rate greater than 80%to further determine their antibacterial virulence.The results showed that compound A was against Curvularia lunata(EC₅₀=25.6μg/mL)and rice blast fungus(EC₅₀=45.3μg/mL).The inhibitory effect was stronger than that of ether oxystrobin(EC₅₀=89.6&52.3μg/mL);the inhibitory activity of compound A8 against tobacco brown spot pathogen(EC₅₀=25.0μg/mL)was higher than that of ether oxystrobin(EC₅₀=69.4μg/mL)Compound A19 against Curvularia lunata(EC₅₀=39.5μg/mL),Rice blast(EC₅₀=35.6μg/mL),Tobacco Red Star(EC₅₀=20.8μg/mL)and Brassica campestris(EC₅₀=19.6μg/mL)The activity was higher than that of ether oxystrobin;the inhibitory effect of compound A31 on Curvularia lunata(EC₅₀=28.9μg/mL)and Tobacco brown spot pathogen(EC₅₀=23.4μg/mL)was better than that of ether bacillus(EC₅₀=89.6&69.4μg/mL).Gg/mL).It is indicated that A19 has a broad antibacterial spectrum,and A,A8,A19 and A31 have further research value.The preliminary structure-activity relationship study showed that the antifungal activity of the benzene ring of the A series compounds changed to varying degrees after the introduction of the substituent.（1）The introduction of F into the benzene ring can significantly increase its antibacterial activity,so F is a synergistic group;the order of activity of the corresponding compounds is as follows:8 positions>6 positions>5positions>7 positions.For 8-fluoro substituted compounds,the introduction of a second substituent to the benzene ring significantly enhances its activity.（2）When a different type of substituent is introduced into the benzene ring,the corresponding activity sequence is:-F>-CH₃>-Cl>-CF₃>-Br>-OCH₃>-I>-NO₂;（3）When-CF₃ When the benzene ring is in different positions,the antibacterial activity of the corresponding compounds is quite different,and the activity of the 8-substituted products is much higher than that of the 6-substituents.When most of the B series compounds introduce a substituent into the benzene ring,their antibacterial activity is improved;among them,methyl and methoxy groups contribute more to the activity.4.The bacterial activity of 56 target compounds was determined by filter paper diffusion method.The test bacteria were Staphylococcus aureus and Escherichia coli,and the positive control was penicillin sodium.The results showed that the test compound had a certain degree of antibacterial effect against Staphylococcus aureus and Escherichia coli,but did not show ideal antibacterial activity.