Synthesis Of Pyrimidine/Imidazole And Pyrroles With Chromones

As a special heterocyclic unit,chromones are widely present in natural and synthetic biomolecules,and have been developed for the treatment of cancer（for example,PIK-108,IC87361）,fungicides,phosphatidylinositol kinase inhibitors,and human sterol sulfate Esterase inhibitor,G protein coupled receptor agonist.Pyrimidine has good biological activity and is used in the treatment of cancer and AIDS.At present,many pyrimidine and pyrimidine derivatives have been approved for the treatment of various types of cancer.Imidazole compounds have good pharmacological activity,have good pharmacodynamics in the clinical treatment of cancer,and are the main pharmacophore in a variety of cancer drugs at present.Pyrrole is a special heterocyclic ring,which also exists in many natural products,and the structure of pyrrole also exists in many existing drugs.In the first chapter,the synthesis and pharmacological effects of pyrimidines,imidazoles and pyrrole rings,the reaction profiles and biological activities of chromones are summarized.In the chapter two,a three-component one-pot method was used to obtain pyrimidine biaryl compounds.One-pot reaction with 3-formyl chromone,enaminone,amidine hydrochloride,acetonitrile was heated to reflux,and 25 pyrimidine compounds were obtained under the catalysis of potassium tert-butoxide,and the yield was 50-83%.A new synthetic route is provided for the synthesis of pyrimidine biaryl rings,which increases the diversity of pyrimidine compounds.In the third chapter,the cyclization of isocyanide with C-C and carbon-heteroatom multiple bonds has been proven to be a reliable platform for the construction of biologically active heterocycles.The unique properties of isocyanide make it a nucleophile and electrophile.Novel imidazoles were synthesized by the three-component reaction of A+2B.α-isocyanoacetate was reacted with 3-cyanochromone,THF was used as solvent,Ag₂CO₃ was added as catalyst,heating under reflux to obtain 21 imidazoles,yield was71-80%.In the fourth chapter,novel functionalized pyrrole derivatives were synthesized by A+2B three-component tandem reaction.Usingα-isocyanoacetate and3-formylchromone as reaction substrates,Ag₂CO₃ as catalyst,and 1,4-dioxane as solvent,25 pyrrole derivatives were obtained by heating under reflux with a yield of80-87%.Synthesis of pyrrole derivatives with complex structures in a one-pot cascade reaction rather than multiple steps provides the impetus to design new substrates.