Study On Drug Discovery-Oriented Catalytic Asymmetric Conjugate Addition Of Oxazolones And Biological Activity

Oxazolones are important,readily available five-membered nitrogen-containing heterocycles with diverse reactivity.Thery are always be utilized as a general template in the synthesis of unnatural amino acids and biologically important heterocyclic scaffolds in organic chemistry and medicine synthesis.Catalytic asymmetric transformations involving these previledged structures are sought-after in modern reaction methodologies development.This thesis covers recent achievements and advances of catalytic asymmetric reaction of oxazolones,organocatalytic conjugate of oxazolones to naphthoquinones and γ-keto-α,β-unsaturated esters and the evaluation of the biological activitity of the reaction products,which could be divided into the following four sections:Chapter 1:This chapter mainly reviewed recent literature on organocatalytic asymmetric transformations of oxazolone,including ring-opening dynamic kinetic resolution of oxazolones toward synthesis of chiral a-amino acid derivatives,1,2-and 1,4-conjugate addition and substititution of oxazolones as well as cascade reaction and annulations of oxazolones.Chapter 2:This chapter mainly centered on the quinine-derived squaramide catalyzed asymmetric Michael-type addition of oxazolones to naphthoquinones,leading to a series of aryl-substituted unnatural a-amino acid derivatives.This finding provides a simple,efficient and green method for the synthesis of highly functionalized amino acids and their analogues.Chapter 3:On the basis of the previous study,this section described the conjugate addition of oxazolone to γ-keto-α,β-unsaturated esters,providing another strategy toward important oxazolone-relevant products.Chapter 4:In this chapter,asymmetric synthesis methods as a efficient tool to detect the ultimate biological activity,the evaluation of the biological activity of the adducts from previous study was performed and prelimilary results were obtained,thus paving the way for the subsequent structural modification and other biologically relevant research.