title: [Synthesis and transformations of ethyl 1,4-dihydro-4-oxo(1)benzofuro(3,2-b)pyridine-3-carboxylic acid esters: new antibacterial agents].
abstract: The title compound 7 was synthesized from potassium 3-amino-[1]benzofuran-2-carboxylate (1) by Gould-Jacobs-reaction. The pyridone 7 reacted with ethyl iodide by N- and O-alkylation to give 9 and 10, while methyl iodide only yielded the N-methylpyridone 11. The 4-chloropyridine 15 was obtained by heating 7 in phosphoryl chloride. Alkaline saponification of the esters 7, 9-11 and 15 afforded the carboxylic acids 8, 12-14 and 16. The carbaldehydes 19 and 22 were prepared from the ethylesters 10 and 15 by boranate reduction to the carbinoles 17 and 20 followed by dehydrogenation with activated manganese dioxide. The aldehyde 22 reacted with beta-aminocrotonic acid esters to yield the 1,4 dihydropyridines (DHP) 23. The pyridines 24 were formed by chemical or electrochemical dehydrogenation of the DHP 23. The tetrazole 27 was accessible from the aldehyde 22 via the aldoxime 25 and the nitrile 26. The pyridone 7 reacted with tosylisocyanate to yield the 4-tosylaminopyridine 28, which after alkylation to form 29 followed by detosylation to give 30 and subsequent alkaline hydrolysis produced the 4-aminonicotinic acid 31. The investigation The N-ethylpyridone-3-carboxylic acid 12 showed antibacterial activity comparable to the reference substance nalidixic acid against Pseudomonas aeruginosa, Escherichia coli and Bacillus megaterium.
authors.affiliation: Institut für Pharmazeutische Chemie, Technischen Universität Braunschweig, Germany. k.goerlitzer@tu-bs.de
authors.forename: K
authors.initials: K
authors.lastname: Görlitzer
authors.forename: C
authors.initials: C
authors.lastname: Kramer
authors.forename: C
authors.initials: C
authors.lastname: Boyle
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D001572:Benzofurans / Q000138:chemical synthesis* / Q000494:pharmacology; D002708:Chlorella / Q000187:drug effects; D004095:Dihydropyridines / Q000138:chemical synthesis / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D011728:Pyridones / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001572:Benzofurans; D004095:Dihydropyridines; D011728:Pyridones; C415478:ethyl 1,4-dihydro-4-oxo(1)benzofuro(3,2-b)pyridine-3-carboxylate