The Studies Of Novel Oxidizing Reaction With Ruthenium Catalytic In The Air And Its Application In The Synthesis Of Mao Inhibitors

The thesis was focused on researching the oxidation reactions in the aerobic conditions with ruthenium catalytic,under this condition,the aryl?heterocyclic?-acetonitrile compounds were oxidized to amides and3-aryl acrylate,ulteriorly,the thesis studied the mechanism of the new reactions.We discovered that the?-site C-H and C-CN bonds of CN were activated by the ruthenium catalyst,finally the aryl-?heterocyclic?-acetonitrile was oxidized under the aerobic conditions,then it reacted with amines and ylides,ultimately the amides and 3-aryl acrylate were obtained.This thesis used this method for synthesizing the MAOIs amides and isoquinoline compounds,then through MAO inhibitory activity screening,we got three compounds which had the highly inhibitory activity and selectivity.Firstly,using ruthenium catalytic,the thesis studied the method and mechanism of the reaction of the preparation of amide through oxidizing aryl?heterocyclic?-acetonitrile compounds and amines.This part,we studied the rate of charge,catalyst dosage,reaction time,temperature,solvent and the choosing of substrates,by which we optimized the reaction condition.At last,we came up with the possible mechanism of the preparation of amide reaction.Secondly,using ruthenium catalytic,the thesis studied the method of thepreparationof3-arylacrylatebyoxidizingaryl-?heterocyclic?-acetonitrile compounds and ylides.This part,we studied the rate of charge,catalyst dosage,reaction time,temperature,solvent and the choosing of substrates,by which we optimized the reaction condition.Thirdly,this thesis applied the method of the preparation of amide to the synthesis of monoamine oxidase inhibitors.Through the oxidation reactions in aerobic conditions with ruthenium catalytic,the aryl?heterocyclic?-acetonitrile compounds were translated into the amides,we got 20 kinds of amides.Then,through the Bischer-Napieralski synthesis,8 kinds of the isoquinolines were got.Further,through the MAO inhibitory activity screening between the amides and isoquinolines by using fluorescence probe method,three kinds of MAOI with highly inhibitory activity and selectivity were got,thereinto,the amide compound 6l shown the highly inhibitory activity and selectivity for both of MAO-A and MAO-B,and the IC₅₀ reached the 44.371nM and26.352?M,respectively.Then it also had the highly selectivity for MAO-A,the SI was the 0.001684.Moreover,all of the isoquinolines had the better selectivity for MAO-B,the compound 10a,10b shown the inhibitory activity with the IC₅₀ 88.3?M and 101.3?M,respectively.At last,we explained the structure-function relationship between compound6l,10a and MAO by the molsoft ICM-pro AutoDockTools 1.5.6.This thesis found metal ruthenium can activate the?-site C-H and C-CN bonds of cyan,then oxidized in aerobic conditions,the aryl-?heterocyclic?acetonitrile compounds can accept nucleophilic attack of nucleophilic reagent contains amines and ylides,which offered one kind of neotype,convenient method for the synthesis of amides and 3-aryl acrylate.Their advantages were short reaction steps,highyield,substrate spectral width,moreover,the way could further extend the catalytic reaction type,enrich the ruthenium organic chemistry.This thesis screened three comnpounds that had the highly MAO inhibitory activity and selectivity,which provided important guarantee for exploiting antidepressant,parkin's syndrome and other drug lead compounds.