Novel three-component domino reactions of ketones, isatin and amino acids: Synthesis and discovery of antimycobacterial activity of highly functionalised novel dispiropyrrolidines

One-pot three-component domino reactions of cyclic mono ketones, isatin and sarcosine/phenylglycine furnishing highly functionalised dispiropyrrolidines in moderate yields are described. The reaction when performed with cyclic amino acid, proline resulted in the dimerization of azomethine ylides. These compounds have been screened for their in vitro activity against Mycobacterium tuberculosis H37Rv (MTB) using agar dilution method. Among thirty eight compounds screened, 1-methylpyrrolo(spiro[2.3′]-5-bromooxindole)spiro[3.2″]-1″-nitrosotetrahydro-4″(1H)-pyridinone (4t) was found to be the most active with MIC of 1.98 μM against MTB and was 3.86 and 25.64 times more potent than the standard first line TB drugs, ethambutol and pyrazinamide respectively.

Graphical abstractThe domino reactions of cyclic mono ketones and isatin with sarcosine/phenylglycine furnished highly functionalised dispiropyrrolidines, while proline afforded the dimer of azomethine ylides. These compounds showed good in vitro activity against Mycobacterium tuberculosis. Figure optionsDownload full-size imageDownload as PowerPoint slide