Syntheis Of 3-N-Substituted 10-Methoxycanthin-6-One Derivatives And Evaluation Of Their In Vitro Antibacterial Activities

The canthin-6-ones is a subclass of ?-carboline alkaloids derived from tryptophan,which is characterized by a more D ring with significant biological activity.There are many types of alkaloids with the largest number of compounds,the most widely studied and the strong antibacterial activity.We introduced a methoxy group at the 10-position to synthesize 10-methoxycanthin-6-one and then quaternized at the 3-position to obtain twenty-two3-N-substituted derivatives.Finally using the double dilution method for antibacterial activity to study structure-activityrelationship.The results are as follows:1.Using 5-methoxytryptamine as the starting material,the selective catalytic activity of palladium-carbon catalyzed dehydrogenation was completed by low-cost,gentle Schiff base-selective region selectivity.Synthesis of 10-methoxycanthin-6-one,and the C-ring N3-position is modified to a quaternary ammonium salt derivative.A total oftwenty-two 3-N-benzylation analogs were synthesized and new compounds were synthesized.At the same time,there are four series of derivatives of different types of substituents on the benzyl group.All of the synthesized compounds were characterized by 1H-NMR,13C-NMR and ESI-MS.2.The inhibitory activity of Bacillus cereus,Ralstonia solanacearum,Bacillus subtilis,Pseudomonas syringaewere screened.Most compounds were resistant to Staphylococcus aureusand did not find significant inhibition zone(inhibition zone diameter <8 mm),and had no inhibitory effect on Staphylococcus aureus under test conditions.Therefore,the remaining four kinds of bacteria were selected to further measure the minimum inhibitory concentration(MICs)of the compound.3.The structure-activity relationship was discussed.1)The quaternization at the 3-position of 10-methoxycanthin-6-one was advantageous for antibacterial activity.2)The introduction of different substituents on the benzyl benzene ring also had an important impact.For the different halogen substituents on the benzyl group,the antibacterial activity was preliminarily I> Br> Cl> F.3)The substituted electron-donating group on the benzyl group was also different from the electron-withdrawing group.The different pairs of anions in the quaternary ammonium salt was also influential,and the exact conclusion could not be given due to the relatively small number.The position of the substituents on the benzyl group was also affected by the activity of the compound.The activity of the para-substituted compound is generally better than that of the ortho position.4)The number of substituents in the benzene ring of benzyl group also had an effect on the antibacterial activity,and the exact conclusion can not be given due to the relatively small number.