Catalyst free sequential one-pot reaction for the synthesis of 3-indole propanoates/propanoic acid/propanamides as antituberculosis agents

A highly efficient catalyst free one pot four component synthesis of highly functionalized three-substituted indole derivatives has been reported. Thus, sequential catalyst free condensation of readily available aldehydes with Meldrum's acid followed by Michael addition of indole resulting three carbon component condensed product and concurrent decarboxylation by the nucleophilic attack of ethanol/water/amines affords three-indole propanoates/propanoic acid/propanamides in affordable yields. Further, synthesized compounds and standard drugs were evaluated against Mycobacterium tuberculosis H37Rv strain by Alamar blue assay method. Majority of the compounds exhibited the superior activity and specifically compound 4d has MIC 1.6 mu g/ml, which is better than the reference drugs used.

Automated summary

An efficient catalyst-free method for synthesizing highly functionalized three-substituted indole derivatives has been reported, involving sequential condensation and Michael addition reactions. The synthesized compounds showed promising activity against Mycobacterium tuberculosis H37Rv strain, with compound 4d exhibiting particularly superior effectiveness.