Regio- and diastereoselective synthesis of spiropyrroloquinoxaline grafted indole heterocyclic hybrids and evaluation of their anti-<i>Mycobacterium tuberculosis</i> 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 generated <i>in situ</i> from indenoquinoxaline and l-tryptophan and reacts with various substituted β-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 their <i>in vitro</i> activity against <i>Mycobacterium tuberculosis</i> H37Rv using MABA assay. Interestingly, the compound bearing a 2-fluoro substituent on the aryl ring displayed an equipotent activity (MIC 1.56 μg mL^-1) to ethambutol against <i>Mycobacterium tuberculosis</i> H37Rv.