Synthesis And Antimicrobial Activity Of3-methyl-beta-carboline Derivatives

β-carboline alkaloids are an important class of natural products, and it has been a focusof research due to its various biology activities. Especially in recent years, β-carbolinealkaloids that were isolated from marine alkaloids are frequently reported, which take thestudy of β-carboline alkaloids into heat. Quantities of research showed that β-carbolinealkaloids had good inhibitory activity against cancer cells. But its toxicity is relatively strongresulting to the limit of its application. As we all known, the biological activity of suchsubstances is diverse. They not only have anticancer activity, but also have antibacterialactivity, while their antimicrobial activity is often neglected. In order to study the antibacterialactivity of these compounds and development of new fungicides further, we used indoleformaldehyde as a starting material to synthesize a class of3-methyl-β-carboline derivatives.Antibacteria and Antifungal activity were tested for all the compounds aiming at providingcandidate compounds for agricultural fungicides. The study results are as follows:L-methyl-tryptamine was synthesized from indole formaldehyde and nitroethane via theHenry reaction and reduced with LiAlH4. Then L-methyl-tryptamine reacted withformaldehyde, acetaldehyde, propionaldehyde, butyraldehyde via Picted-Spengler reaction,respectively. Products that were four1-substitution-3-methyl-β-carbolines oxidized by Pd/C,were all known compounds.Nineteen9-substitution-β-carboline derivatives were obtained by hydrocarbylation theposition of9in the3-methyl-β-carboline. Eighteen of them were new compounds. Thestructure of all compounds was identified by¹H-NMR,¹³C-NMR, DEPT and ESI-MS,respectively, and its physical data were tested accurately.Using filter paper method, all the compounds were tested on antimicrobial activity invitro againsit the five pathogenetic bacteria: Bacillus cereus, Bacillus subtills, Escherichiacoli, Staphylococcus aureus, Pseudomonas aeruginosa with streptomycin sulphate as apositive control. Antimicrobial activity test indicated that compounds Z-1, Z-4, Z-7, Z-14hadthe effective inhibitory activity against the Bacillus cereus, Bacillus subtills and Escherichiacoli, compound Z-17showed evidently inhibitory activity against Staphylococcus aureus. Allthe compounds had no inhibitory activity against Pseudomonas aeruginosa generally. Theantibacterial avtivity of all the tested compounds was weaker that the positive control. Using inhibition of spore germination method, all the compounds were tested onantifungal activity in vitro against two conventional crop pathogenic fungal: Curvularialunata （Walker）Boedijn, Botrytis cinerea with80%Mancozeb WP as a positive control.Antifungal activity test shown entire compounds had antifungal activity at concentration of100μg/mL, generally, and some of the compounds showed similar antifungal activiy to thepositive control. Toxicity test was carried out for the compounds whose spore germinationinhibition rate reached over80%, and we found the compounds Z-4, Z-10, Z-19had asignificant inhibitory activity against the spore germination of Curvularia lunata（Walker）Boedijn with EC₅₀value was13.46μg/mL,8.45μg/mL,12.88μg/mL, respectively. Thecompounds Z-4, Z-10also had an excellent inhibitory activity against the spore germinationof Botrytis cinerea with EC₅₀value was15.01μg/mL,22.31μg/mL, respectively.Conclusively,3-methyl-β-carboline derivatives had obvious antibacterial and antifungalactivity. Inhibitory activity against the bacteria had certain selectivity, and it was weakcompared with the positive control. This series of compounds had universally antifungalactivity, and some of these compounds（Z-6、Z-7、Z-8、Z-12、Z-14）had very potent inhibitoryactivity against fungal, which were expected to become a new class of agricultural fungalfungicides.