{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T15:10:42Z","timestamp":1767971442368,"version":"3.49.0"},"reference-count":30,"publisher":"Walter de Gruyter GmbH","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,6,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Recent studies directed to the design of compounds targeting the <jats:italic>bc<\/jats:italic>\n                  <jats:sub>1<\/jats:sub> protein complex of <jats:italic>Plasmodium falciparum,<\/jats:italic> the parasite responsible for most lethal cases of malaria, identified quinolones (4-oxo-quinolines) with low nanomolar inhibitory activity against both the enzyme and infected erythrocytes. The 4-oxo-quinoline 3-ester chemotype emerged as a possible source of potent <jats:italic>bc<\/jats:italic>\n                  <jats:sub>1<\/jats:sub> inhibitors, prompting us to expand the library of available analogs for SAR studies and subsequent lead optimization. We now report the synthesis and structural characterization of unexpected ethyl 6-methyl-7-iodo-4-(3-iodo-4-methylphenoxy)-quinoline-3-carboxylate, a 4-aryloxy-quinoline 3-ester formed during attempted preparation of 6-methyl-7-iodo-4-oxo-quinoline-3-carboxylate (4-oxo-quinoline 3-ester). We propose that the 4-aryloxy-quinoline 3-ester derives from 6-methyl-7-iodo-4-hydroxy-quinoline-3-carboxylate (4-hydroxy-quinoline 3-ester), the enol form of 6-methyl-7-iodo-4-oxo-quinoline-3-carboxylate. Formation of the 4-aryloxy-quinoline 3-ester confirms the impact of quinolone\/hydroxyquinoline tautomerism, both on the efficiency of synthetic routes to quinolones and on pharmacologic profiles. Tautomers exhibit different cLogP values and interact differently with the enzyme active site. A structural investigation of 6-methyl-7-iodo-4-oxo-quinoline-3-carboxylate and 6-methyl-7-iodo-4-hydroxy-quinoline-3-carboxylate, using matrix isolation coupled to FTIR spectroscopy and theoretical calculations, revealed that the lowest energy conformers of 6-methyl-7-iodo-4-hydroxy-quinoline-3-carboxylate, lower in energy than their most stable 4-oxo-quinoline tautomer by about 27 kJ mol<jats:sup>\u22121<\/jats:sup>, are solely present in the matrix, while the most stable 4-oxo-quinoline tautomer is solely present in the crystalline phase.<\/jats:p>","DOI":"10.1515\/pac-2016-1119","type":"journal-article","created":{"date-parts":[[2017,2,1]],"date-time":"2017-02-01T10:02:45Z","timestamp":1485943365000},"page":"765-780","source":"Crossref","is-referenced-by-count":5,"title":["On the ordeal of quinolone preparation via cyclisation of aryl-enamines; synthesis and structure of ethyl 6-methyl-7-iodo-4-(3-iodo-4-methylphenoxy)-quinoline-3-carboxylate"],"prefix":"10.1515","volume":"89","author":[{"given":"Pedro","family":"Horta","sequence":"first","affiliation":[{"name":"CCMAR and Department of Chemistry and Pharmacy , F.C.T., University of Algarve , P-8005-039 Faro , Portugal"},{"name":"Department of Chemistry , University of Liverpool , Liverpool L69 7ZD , UK"}]},{"given":"Marta S. 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