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 microM against MTB and was 3.86 and 25.64 times more potent than the standard first line TB drugs, ethambutol and pyrazinamide respectively.
Kumar
Raju Suresh
RS
Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai 625021, India.
Rajesh
Stephen Michael
SM
Perumal
Subbu
S
Banerjee
Debjani
D
Yogeeswari
Perumal
P
Sriram
Dharmarajan
D
D000596:Amino Acids / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D007510:Isatin / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D000596:Amino Acids; D000900:Anti-Bacterial Agents; D007659:Ketones; D011759:Pyrrolidines; D007510:Isatin