Synthesis Of Harmine Dimerization Bromide And Preliminary Study Of Their Activites

Harmine，as the most representative of the group of beta-carboline alkaloids, wasisolated from Zygophyllaceae Peganum harmala seeds, their structures and bioactivites havebeen systematic research.Derivatives synthesised mainly concentrated in1,3,6,7and9site,the overring synthesis reaction after the P-S reaction and B-N reaction. Since harmine showedsignifacant performance of cytotoxicity, recent studies mainly focused on the anti-tumormechanism and reducing toxic aganist normal cells, while the other activities rarely have beenreported.β-carbolines dimerization was first isolated from Didemnum, showing good cytotoxicity,followed by sporadic reports on synthesis and activity of β-carbolines dimerization. In orderto comprehensively evaluated β-carbolines dimerization cell activity, to explore options forefficiency and low toxicity anti-tumor drug, Our team synthesis systematicly a series ofβ-carboline alkaloid dimer, this thesis is mainly responsible for dimeric bromide synthesis in2site.In this experiment, harmine and β-carbolines as substrate synthesized a series of dimericbromide, Artemia lethal method model was used for active screening, structure-activityrelationships for preliminary discussions for further cell activity provide the basis for testing;and we also measured poisonous activity of culex larvae and Tetranychus cinabarinus Boisduto assess its potential as an insecticide. The main results are as follows:1. Harmine as a starting material, reacted with monobromide and got three intermediatecompounds；tryptamine and tryptophan as starting material to get β-carboline and1-methyl-β-carboline by P-S reaction, then five of them reacted with other five kinds ofdibromoide and synthesized22dimers bromide whose structures had been identified by¹H-NMR,¹³C-NMR and MS.19of them are new compounds.2. Toxic water feeding method was used to determine the synthesis of dimeric bromidepoisonous activity of4D Culex pipiens larvae at a concentration of80ppm conditions. Thetest results show that the different structures of the derivatives showed different activitysignificantly. And the48lethality of D-2-17is up to48%; Microslide impregnation methodwas measured the synthetic dimeric bromide insecticidal activity against Tetranychuscinabarinus Boisdu under the conditions of100ppm. The results showed that the dimeric bromide have certain insecticidal activity and D-2-10gave the better insecticidal activity with48h mortality rate up to56%; Solis modified method was used to determine the activity of killartemia under the conditions of75ppm. The results showed that the dimeric bromide havestrong cytotoxicity, the24h mortality rate of D-2-9up to98%.3. Preliminary structure-activity relationships indicate that the introduction of9-propyl itsactivity increased significantly. The activity results showed that the dimeric bromide has someinsecticidal activity can be further modified as a potential insecticide; The dimeric bromidehave high cytotoxicity and better water solubility than harmine to provide a basis for the nextcell test.