Study On The Synthesis Of Molecular Skeleton Of Nitrogen-containing Heterocyclic Drugs

Nitrogen-containing heterocyclic compounds have received extensive attention due to their high biological activities,low toxicity,good coordination ability,and varied structures.Furthermore,nitrogen-containing metal complex can exhibit excellent biological activities.Therefore,it is of great significance to study the structure and biological activity of nitrogen-containing heterocyclic compounds.This work mainly focuses on the construction of quinoline lactones and the N-nitrosohydrazides,and a series of quinoline lactones and N-nitrosohydrazides with potentially pharmaceutical activity have been synthesized in high yields.The details are listed below:(1)Construction of the quinoline lactone skeleton.Quinoline and its derivatives are indispensable raw materials and intermediates in today's chemical industry,and are widely used in pesticides,medicine,and chemical industries.The lactone skeleton is also an important structural unit in chemical synthesis intermediates,and various types of drug molecules can be obtained through transformation.Through constant screening of reaction conditions,MeCN was selected as the reaction solvent,Sc(OTf)3 was used as the reaction additive,and 60oC was used as the temperature of the reaction system.Simultaneously,10 mol%of TBPA radical cation salt was added to participate in oxygen.Next,a series of quinoline lactone derivatives with potential drug activity were synthesized.The highest reaction yield can reach 91%.Through experiments,it can be seen that the reaction conditions are mild,the raw material preparation method is simple,and the harsh reaction conditions and tedious operation steps are avoided,and the grafting of two quinoline and lactone pharmacophore structural units is realized,which is construction and pharmacy.Related quinoline lactone skeletons provide new ideas(2)Synthesis and study of N-nitroso hydrazide bioactive molecules.Compounds containing hydrazide structural units are a widely used class of pharmaceutical intermediates with high chemical reactivity and are used as synthetic precursors for many important organic molecules.Furthermore,hydrazide compounds have a wide range of biological and physiological activities such as antiviral,insecticidal,and bactericidal properties.Efficient N-nitrosation of benzoyl hydrazide derivatives was achieved using tert-butyl nitrite as a mild nitrosation reagent.By continuously screening the reaction conditions,using MeCN as the solvent for the reaction,using 25?.as the temperature of the reaction system,and using 1.2 equivalents of TBN,a series of N-nitrosobenzoylhydrazone derivatives were synthesized with the highest yields.It can reach 91%.Compared with the traditional nitrosation reaction,the reaction conditions are mild,the raw materials are easily available,and the operation method is simple.At the same time,the final product can be obtained in a relatively high yield,and N-nitrosobenzoylhydrazone is synthesized for the chemical industry.Derivatives and their pharmaceutically active molecules provide a much simpler method.Due to its unique multi-functional structure,it can be used as an intermediate for the synthesis of N-nitrosohydrazide-derived drug molecules for the industrial preparation of such drugs.(3)Exploration of functionalization of hydrazide derivatives.As mentioned before,the construction of skeletons of hydrazide compounds has attracted the attention of chemists.Through the oxidation of C-H bond and intramolecular cyclization,the functional group of hydrazide compounds was successfully achieved,and a novel heterocyclic molecule was obtained.Through continuous screening of reaction conditions,MeCN was selected as the solvent for the reaction,TBHP was used as the oxidant for the reaction,and CuBr was used as the additive of the reaction system.A new dihydrooxadiazole was synthesized at 60? as the temperature of the reaction system.Heterocyclic molecules.Compared with the traditional method for synthesizing dihydrooxadiazole-based heterocyclic molecules,the reaction conditions are milder and the operation steps are simpler.At the same time,the heterocyclic molecule has a complex structure and diverse functional groups,which provides the possibility of constructing dihydrooxadiazole-type heterocyclic molecules and further functionalization.