The Application Of Radical Addition/Cyclization Reactions In The Synthesize Of Pharmaceutical Precursors

Heterocyclic compounds have research prospects and comprehensive applications not only in industrial and agricultural production,but also in pharmaceutical field.As common pharmaceutical intermediates,O,N and P-containing cyclic compounds,given the special structures and properties,have been the hot topic of organic synthesis and pharmaceutical chemistry.On the basis of previous reports,combined with our group’s research direction,this paper introduces the development of simple and efficient methods for synthesizing O,N and P heterocyclic compounds by radical addition cascade cyclization pathways.This paper mainly includes the following three parts:1、Coumarin compounds are widely exist in plants and exhibit a broad range of pharmacological properties.Herein,we successfully developed an silver-mediated domino radical addition/cyclization reaction of diarylphosphine oxides with propynoic acid derivatives.Aryl propionate as a template substrate,promoted by silver nitrate,MeCN as a solvent,60℃,and under nitrogen protection,to obtain 3-phosphorylated coumarins.The advantages of this method are high efficiency and good substrate compatibility and so on.2、Phosphoric indoles are the main structural units of common organic light materials,and also exhibit unique biological activities.Based on this,under the same reaction conditions as(1),propargyl amide/propionic acid alkyl ester and diaryl phosphorus as the starting material,a simple and efficient method was developed for the synthesis of benzophosphole oxides,showing high regioselectivity and excellent functional group compatibility.3、The presence of pyrrolidine in bioactive natural products and pharmaceutical molecules has been well documented.Such as Leonurus,Campanumaea pilosula,Palaeosporine and atropine alkaloids.Replacing the carbon atom in the original drug with silicon atom can increase the selectivity of the drug,improve the efficacy,and provide more possibilities for new drug development.Herein,we take 1,6-alkyne/1,6-diene as the reaction substrate,promoted by visible light,Eosin Y as the photosensitization agent,MeCN as the solvent,under room temperature by nitrogen,with(TMS)3SiH reaction to synthesize a series of hydrosilyl pyrrolidines.In addition,replacing(TMS)3SiH with diaryl phosphorus oxide,also successfully obtain hydrophosphoryl pyrrolidine compounds.The current method features green efficiency,less use of catalyst,high atomic economy.