Regio- and Diastereoselective Synthesis of Spiropyrroloquinoxaline Grafted Indole Heterocyclic Hybrids and Evaluation of Their Anti-Mycobacterium Tuberculosis Activity

Abstract

An efficient and eco compatible approach for the regio- and stereoselective synthesis of structurally diverse novel hybrid heterocycles comprising spiropyrrolidine, indenoquinoxaline and indole structural units in excellent yields, has been achieved through a one-pot multicomponent process involving 1,3-dipolar cycloaddition as a key step. The 1,3-dipolar component is the azomethine ylide generatedin situfrom indenoquinoxaline andl-tryptophan and reacts with various substituted beta-nitrostyrenes affording the spiroheterocyclic hybrids. The ring system thus created possesses two C-C and three C-N bonds and four adjacent stereogenic carbons, one of which is quaternary and the reaction proceeded with full diastereomeric control. All the synthesized compounds were assayed for theirin vitroactivity againstMycobacterium tuberculosisH37Rv using MABA assay. Interestingly, the compound bearing a 2-fluoro substituent on the aryl ring displayed an equipotent activity (MIC 1.56 mu g mL(-1)) to ethambutol againstMycobacterium tuberculosisH37Rv.