Analysis Of Synthesis Optimizedof Quinazolinone Derivatives

Quinazolinone alkaloids,as an important natural products and active molecules,have many pharmacological effects,such as anticancer,antibacterial,antiviral and so on.Therefore it has become a hot point in organic synthesis to explore the method of direct asymmetric synthesis of this kind of compounds.At present the methods of synthesis of quinazolinone compounds are mainly focused on intermolecular reduction and ring formation,metal complexes as catalysts for the direct condensation of ketones to quinazolinone rings and multi-step series reactions,and so on.All of these methods have their own disadvantages,such as harsh reaction conditions,expensive catalyst,complicated reaction steps and so on.Therefore,it is of great interest for researchers to explore the way to directly synthesize quinazolinone compounds with mild reaction substrates and modify the structure of their derivatives,so as to give full play to their biological activities.In view of the above research situation,this thesis has done the two aspects of work and the preliminary results obtained were listed following:?1?Under the catalysis of chiral phosphoric acid,the reaction conditions such as 15different phosphoric acid catalytic systems,5 different equivalent proportion,4 different temperature,23 different solvent systems were optimized using imines and acetylacetone as reaction templates.The optimum reaction conditions are as follows:the equivalent proportion of imines and acetylacetone is 1:10,temperature is 60?,the solvent systems is cyclopentane 1mL and H₂O 20?L,the catalysis system is 1f 5mol%.Under the optimum experimental conditions,20 quinazolinones were synthesized.The high yield and moderate enantioselectivity of quinazolinones were achieved.?2?Using tryptophan and methyl quinoline as templates,10 different catalysts,10different solvents and 3 different temperatures were optimized.The reaction of tryptophan with methyl quinoline was carried out under the condition of no catalyst at 100?and DMF as solvent.In this experiment,an innovative method was developed to obtain high purity products by centrifugation with ethanol,which made the synthesis method efficient,convenient and green.