Facile three-component domino reactions in the regioselective synthesis and antimycobacterial evaluation of novel indolizines and pyrrolo[2,1-a]isoquinolines

The domino reactions of pyridine/isoquinoline, bromoacetonitrile/ethyl bromoacetate and a series of β-nitrostyrenes in the presence of triethylamine afforded novel tri-/disubstituted indolizines and pyrrolo[2,1-a]isoquinolines regioselectively, presumably via substitution-dipole generation-1,3-dipolar cycloaddition-elimination and/or aromatisation sequence. In vitro screening of all the seventeen compounds synthesized against Mycobacterium tuberculosis H37Rv discloses that ethyl 2-(4-fluorophenyl)pyrrolo[2,1-a]isoquinoline-3-carboxylate displays maximum potency with minimum inhibitory concentration (MIC) of 1.0 μM, being 7.6 and 4.7 times more potent than the standard first line TB drugs, ethambutol and ciprofloxacin, respectively.