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

作者：Kumar Raju Suresh; Rajesh Stephen Michael; Perumal Subbu^*; Banerjee Debjani; Yogeeswari Perumal; Sriram Dharmarajan

来源：European Journal of Medicinal Chemistry, 2010, 45(1): 411-422.

DOI：10.1016/j.ejmech.2009.09.044

• Cascade reactions
• Isatin
• Sarcosine
• Phenylglycine
• Spiropyrrolidines
• Anti-tubercular activity

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-methyl-pyrrolo(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 mu M against MTB and was 3.86 and 25.64 times more potent than the standard first line TB drugs, ethambutol and pyrazinamide respectively.

• 出版日期2010-1