A solvent free, four-component synthesis and 1,3-dipolar cycloaddition of 4(H)-pyrans with nitrile oxides: Synthesis and discovery of antimycobacterial activity of enantiomerically pure 1,2,4-oxadiazoles

作者：Almansour Abdulrahman I; Kumar Raju Suresh^*; Arumugam Natarajan; Sriram Dharmarajan

来源：European Journal of Medicinal Chemistry, 2012, 53: 416-423.

DOI：10.1016/j.ejmech.2012.04.021

• Antitubercular activity
• Mycobacterium tuberculosis
• Multi-drug resistant tuberculosis
• 1,3-Dipolar cycloaddition
• Pyrans
• 1,2,4-Oxadiazoles

Four-component reactions of (R)-1-(1-phenylethyl)tetrahydro-4(1H)-pyridinone, aromatic aldehydes and malononitrile in a 1:2:1 molar ratio in the presence of solid sodium ethoxide under solvent free conditions afforded an inseparable mixture of two diastereomeric 4(H)-pyrans in near quantitative yields. These compounds upon 1,3-dipolar cycloaddition with nitrile oxides furnished two enantiomerically pure 1,2,4-oxadiazoles in moderate yields, which were screened for in vitro activity against Mycobacterium tuberculosis H37Rv (MTB) and multi-drug resistant M. tuberculosis (MDR-TB). Among the compounds screened, compound 10h was found to be the most active in vitro with a MIC value of 0.07 and 0.14 mu M against MTB and MDR-TB respectively.

• 出版日期2012-7