Synthesis And Antitumor Evaluation Of Alpha-aminoketones

Amino ketones are not only widely found in nature,but also play a significant role in the life system.Among them,?-aminoketones as key structural units are widely present in natural products,drugs and biologically active moleculessuch as natural productsapomorphine(-)-N-methylguanidine and carbenone,anti-tumor molecules prima-1 and APR-246,anti-depressants and smoking cessation drugs bupropion,and anti-platelet aggregation drugs clopidogrel and prasory.The ?-aminoketones have a broad reactivity,and are a key intermediate in many organic reactions.By using of ?-aminoketones as substrates,the heterocyclic compounds and the highly biologically active ?-aminoalcohols can be synthesized under simple conditions.Therefore,the development of a new method to synthesize ?-aminoketones is of great significance.In this thesis,a series of ?-aminoketones were synthesized from the simple alcohols and triazole.In this system,the simple alcohol was used as oxygen source and triazole was used as nitrogen source.The reaction features high atomic economy,high efficiency and broad substrate scope.?-amino alcohol and a tetrahydroisoquinoline which are very important in the biologically active molecule were further prepared by using the ?-aminoketone as substrates.Subsequently,we also studied the bioactivity of these amino ketones.The antitumor activity of the cells was measured by MTT colorimetry.This study provided a database to screen the anti-tumor drugs and to design the drug molecules in the later stages.This thesis mainly include the following topics:(1)A series of alcohols and triazoles were synthesized.(2)A new and efficient method for the synthesis of ?-aminoketones has been developed.(3)The ?-amino alcohol and tetrahydroisoquinoline with the ?-aminoketone structure are synthesized under the simple conditions using the ?-aminoketones as substrates,which showing that the ?-aminoketone is an important synthon in organic synthesis.(4)Six ?-aminoketones were selected to carry out the antitumor drug screening model experiment in vitro.A549,Bel7402 and HCT-8 were used to test the growth inhibition rate in vitro.The results show that these compounds have a certain inhibitory effect to the growth of tumor cells in vitro.In particular,compound 4c shows a very good growth inhibitory effect on A549 cells and has no significant inhibitory effect on the other two tumor cells.