A facile synthesis and antimycobacterial evaluation of novel spiro-pyrido-pyrrolizines and pyrrolidines

An efficient synthesis of 1-methyl-3-[( E)-arylmethylidene]tetrahydro-4(1 H)-pyridinones was achieved by the reaction of 1-methyl-4-piperidone and aromatic aldehydes in the presence of pyrrolidine under solvent-free microwave irradiation. These dipolarophiles upon cycloaddition with nitrile oxide an...

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Published in:European journal of medicinal chemistry 2009-09, Vol.44 (9), p.3821-3829
Main Authors: Ranjith Kumar, Raju, Perumal, Subbu, Senthilkumar, Palaniappan, Yogeeswari, Perumal, Sriram, Dharmarajan
Format: Article
Language:English
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Summary:An efficient synthesis of 1-methyl-3-[( E)-arylmethylidene]tetrahydro-4(1 H)-pyridinones was achieved by the reaction of 1-methyl-4-piperidone and aromatic aldehydes in the presence of pyrrolidine under solvent-free microwave irradiation. These dipolarophiles upon cycloaddition with nitrile oxide and azomethine ylides afford stereoselectively novel spiro-isoxazolines, pyrrolizines and pyrrolidines respectively in excellent yields. The spiro compounds were screened for their in vitro activity against Mycobacterium tuberculosis H37Rv (MTB), multi-drug resistant M. tuberculosis (MDR-TB) and Mycobacterium smegmatis (MC 2) using agar dilution method. Among the synthesized compounds, 1-methyl-4-(2,4-dichlorophenyl)pyrrolo(spiro[2.3″]oxindole)spiro[3.3′]-1′-methylpiperidin-4′-one was found to be the most active with a minimum inhibitory concentration (MIC) of 1.76 and 0.88 μM against MTB and MDR-TB respectively. 1-Methyl-3-[( E)-arylmethylidene]tetrahydro-4(1 H)-pyridinones upon cycloaddition with azomethine ylides afford novel spiro-pyrido-pyrrolizines and pyrrolidines in excellent yields stereoselectively. These spiro-heterocycles exhibit promising in vitro antimycobacterial activity against Mycobacterium tuberculosis. [Display omitted]
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2009.05.010