Synthesis And Bioactivity Study Of 5-spiro(1,2,3,4-tetrahydroacridin-1-yl)-3′-aryl-4-substituted Isooxazoline Derivatives

Isoxazoline is an important class of heterocyclic compounds,which is widely used in many fields.The synthesis of spiroid heterocyclic compounds is the focus of chemical research,and its application in many fields is also concerned by chemical and biological workers.As the intermediate and raw material of organic synthesis,heterocyclic compounds have many pharmacological activities for the synthesis of natural products.Diseases that are infected during plant growth and have a considerable inhibitory effect on weeding.In addition,pesticide and pharmaceutical applications are also very extensive,such as sterilization,insecticidal and herbicide,and inhibition of the proliferation of malignant cells,which have been developed into pharmaceutical and pesticide products,and have been studied in the past.The structure fragments which have many kinds of activity are combined in the form of single bond and dense ring,which will show a variety of different activities.Most synthetic drugs develop drug resistance after a certain period of time,which shortens the life span of the drug,and the effect of treatment is getting lower and lower,even to the end of complete failure.This may be due to the weak interaction between the agent and the DNA chain,which results in poor effect.The structure of isoxazolines is modified by acridine structure fragments.The structure of the acridine ring structure and the structure of isoxazolines are mainly used to combine the two active structural fragments in the form of spiro rings to strengthen the interaction force with the DNA strands,which is expected to improve the effect of their agents.A series of spiroxazoline compounds were synthesized from acridine ketone and acetophenone oxime.Their structures were characterized by IR,~1H NMR,MS.This thesis has two parts:The first part is the literature review,mainly introduces the synthesis and application of acridine ketones and spirocyclic compounds.The second part is divided into experimental part,the main work is divided into four parts:1.A series of acridine ketones 3a-3l were synthesized from 2-nitrobenzaldehyde and its derivatives.2.A series ofβ-(1-hydroxy-1,2,3,4-tetrahydroacridin-1-yl)-1-phenylethan-1-one oxime derivatives 4a-4l were synthesized from acridine ketone derivatives andα-aryl ethyl ketone oxime derivatives.3.A series ofβ-(1-hydroxy-1,2,3,4-tetrahydroacridin-1-yl)-1-phenylethan-1-one oxime derivatives 4a-4d were synthesized via a series of ring complexes to synthesize a series of Spiroisoxazoline 5a-5d.