title: 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.
abstract: 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 μM against MTB and MDR-TB respectively.
authors.affiliation: Department of Chemistry, College of Science, King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: Abdulrahman I
authors.initials: AI
authors.lastname: Almansour
authors.forename: Raju
authors.initials: R
authors.lastname: Suresh Kumar
authors.forename: Natarajan
authors.initials: N
authors.lastname: Arumugam
authors.forename: Dharmarajan
authors.initials: D
authors.lastname: Sriram
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D060326:Chemistry Techniques, Synthetic; D055808:Drug Discovery; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D009570:Nitriles / Q000737:chemistry*; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010087:Oxides / Q000737:chemistry*; D010880:Piperidines / Q000737:chemistry; D011714:Pyrans / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000900:Anti-Bacterial Agents; D009570:Nitriles; D010069:Oxadiazoles; D010087:Oxides; D010880:Piperidines; D011714:Pyrans; C032727:piperidine