Study On The Preparation And Anticancer Activity Of 2H-azirines

Nitrogen-containing heterocyclic not only widely found in nature but also has become an important building block in pharmaceutical,pesticide and organic functional materials.Therefore,the development of new reactions,new methods and new strategies for the synthesis of nitrogen-containing heterocyclic compounds is very important.2H-Azirines are very important class of compounds not only due to their biological activity but also because they are versatile building blocks for organic synthesis.Due to the high degree of ring strain of smallest of the nitrogen-unsaturated heterocycles and imine bond,these heterocycles undergo reactions in which they can function either as a nucleophile or as an electrophile.Reactions with nucleophiles always involve the initial addition to the imine bond.Thus,the nucleophilic substitution reaction of 2H-azirines at C-2 position is considered as difficulty and challenge in organic synthesis.Very recently,our group have developed potassium iodine-promoted nucleophilic substitution reaction between 2-acyloxy-2H-azirines and carboxylic acids.Inspired by the results of this work,we set out to see if a parallel reaction would take place between 2-acyloxy-2H-azirines and an amine compound which could result in the C-N bond formation via the expected intermolecular nucleophilic substitution reaction.Moreover,we also investigated the anticancer activity of 2H-azirines compound.The researches in the paper are as follows:1.A new strategy for sodium carbonate-mediated substitution reaction between2H-azirines and 1H-benzotriazole is reported.This protocol provides an effective way for construction 2-?benzotriazol-1-yl?-2H-azirines.The optimal reaction condition:2-acyloxy-2H-azirines?1 mmol?,1H-benzotriazole?1.1 mmol?and Na₂CO₃ in DMF at room temperature for 2h.The advantages of this reaction are mild conditions,metal-free and easy operation.2.A novel strategy to synthesize highly functionalized oxazoles has been successfully developed via a base-mediated intermolecular substitution between 2-acyloxy-2H-azirines and N-nucleophile with a subsequent ring expansion of a 2H-azirine intermediate.The optimal reaction condition:2-acyloxy-2H-azirines?1 mmol?,N-nucleophile?1.1 mmol?and NaH in DMF at 100?for 2h.This method provides straightforward access to highly substituted oxazoles with high efficiency and excellent functional group compatibility under metal-free reaction conditions.3.In addition,we also studied the anticancer activity of 2-benzotriazole-2H-azirines.We tested a series of 2-benzotriazole-2H-azirines derivatives for anticancer activity against hepatocellular carcinoma cells?HepG-2?and breast cancer cell lines?T-47D?,and methyl-substituted compounds have high antitumor activity.