Construct Ion Of Several Pyridine And Pyrrole Heterocyclic Compounds With Nitroenamines As Building Blocks

Natural medicines are precious treasure-house for the prevention and treatment ofhuman diseases.The history of using natural medicines to treat diseases is very long.Heterocyclic compounds are ubiquitous in natural products.Because of their unique framework and pharmacological activity,Heterocyclic compounds have penetrated into the fields of pharmaceutical chemistry.Among them,nitrogen-containing heterocyclic compounds are most widely used in the fields of medicine and pesticide.Targeting natural medicines,it is an important way to design,synthesize and study the structure-activity of natural-like nitrogen-containing heterocyclic drugs by using modern organic synthesis methods.It is an important way to develop new medicines.In this paper,we start from the cheap and easy raw materials,and nitroeneaminesare used as the synthesis block to study the new synthesis methods of novel nitrogen-containing heterocyclic compounds which are difficult to be synthesized by conventional methods.Finally,five series of natural-like nitrogen-containing heterocyclic compounds are synthesized by simple,efficient and green methods.This paper is divided into six chapters:In chapter 1,this is the frontier part,which introduces the important role of natural drugs for human health and the significance of natural products to the research of new drugs,then introduces applications of heterocyclic compounds and the application of heterocyclic ketene amine in the synthesis of nitrogen-containing heterocyclic compounds.In chapter 2,the synthetic strategy of multicomponent and one-pot method from chromone and nitroenamine is introduced,C₂,C₄ and C₁'sites of chromone react cascade reaction,which is simple and efficient in the synthesis of chromeno[4,3-b]-pyridins with novel structures.This synthesis method conforms to the requirements of green chemistry,and the target products can be obtained by filtration and washing,with no need for the traditional purification methods(Scheme 1).Scheme 1 Synthesis of polysubstituted chromeno[4,3-b]pyridin derivativesIn chapter 3,the opening of pyrrole ring and generation of pyridine ring are realized simultaneously,the multi-substituted 4-quinolinamide derivatives with novel structure are obtained by the cascade reaction of isatin and nitroeneamines under the condition of catalyst.This synthesis method conforms to the requirements of green chemistry,and the target products can be obtained by filtration and washing,with no need for the traditional purification methods(Scheme 2).Scheme 2 Synthesis of polysubstituted 4-quinolinamide derivativesIn Chapter 4,the synthesis of novel polypyrrole derivatives containing multiple functional groups is introduced by splicing reaction from indole derivatives,which react with nitroenylamine without catalyst,with high chemical selectivity and high yield.Under optimizing the reaction conditions,the target products can be obtained by filtration and washing,with no need for the traditional purification methods(Scheme 3).Scheme 3 Synthesis of novel polypyrrole derivativesIn chapter 5,the raw isatin reacted with nitroeneimine catalyzed by acid,and resulted in new bond forming and old bond breaking through unexpected cascade reaction,forming a novel methylene derivative at C₃ position of indole-2-ketone.Due to the action of hydrogen bond,the double carbon bond in the molecule has high stereoselectivity with Z-configuration only.This synthesis method conforms to the requirements of green chemistry,and the target products can be obtained by filtration and washing,with no need for the traditional purification methods(Scheme 4).Scheme 4 Synthesis of novel methylene derivative at C3 position of indole-2-ketoneIn Chapter 6,indole derivatives react with five membered ring nitroenediamine under the condition of catalyst.The nitroenediamine attacked amido carbonyl group highly selectively instead of the ketocarbonyl group,and pyridin[2,3-b]indole derivatives,including condensed and conjugated[6+5+6+5]ring,are prepared efficiently.When the reaction time is prolonged,the large conjugated system migrates,and another isomers can be obtained.This method offers several advantages:simple operation,mild reaction and efficiency.The target products can be obtained by filtration and washing,with no need for the traditional purification methods(Scheme 5).Scheme 5 Synthesis of pyridin[2,3-b]indole and other derivativesWhen six and seven membered ring of nitroeneamines are used,the orientation of multifunctional groups of substrates plays a important role,another group of novel derivatives at indole C₃ position are synthesized.Due to the action of hydrogen bond,the double carbon bond in the molecule has high stereoselectivity with Z-configuration only.This synthesis method conforms to the requirements of green chemistry,and the target products can be obtained by filtration and washing,with no need for the traditional purification methods(Scheme 6).Scheme 6 Synthesis of derivatives at indole C3 positionIn this article,through optimizing the reaction conditions,five kinds of nitrogen-containing heterocyclic compounds are synthesized starting with simple materials,which provid some new methods and ideas for the synthesis of heterocyclic compounds.At the same time,these natural-like nitrogen-containing heterocyclic products also have some significance in medical research.