A stereo, regioselective synthesis and discovery of antimycobaterium tuberculosis activity of novel β-lactam grafted spirooxindolopyrrolidine hybrid heterocycles

Abstract

A stereo- and regioselective synthesis of hitherto unexplored novel class of β-lactam embedded spirooxindolopyrrolidine hybrid heterocycles have been accomplished via ionic liquid accelerated [3 + 2]-cycloaddition reaction process. The expected unusual lactonization/lactamization product could not be observed even in traces. The in vitro antimycobacterium tubercular activity of the synthesized spiroheterocyclic hybrids were assessed against Mycobacterium tuberculosis H37Rv. Among them, the compounds with no substitution and chlorosubstitution on the oxindole ring showed the most potent activity with a MIC 0.78 μg/mL and 1.56 μg/mL, respectively which were two-fold and equal activity than the standard drug, ethambutol (MIC = 1.56 μg/mL).

Keywords

• Spirooxindolopyrrolidines
• β-lactam
• 1,3-Dipolar cycloaddition reaction
• Ionic liquids
• DFT study
• Mycobacterium tuberculosis activity