التفاصيل البيبلوغرافية
| العنوان: |
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 |
| المؤلفون: |
Horta, Pedro, Henriques, Marta SC, Bras, Elisa M, Murtinheira, Fernanda, Nogueira, Fatima, O'Neill, Paul M, Paixao, Jose A, Fausto, Rui, Cristiano, Maria LS |
| بيانات النشر: |
Walter de Gruyter GmbH |
| سنة النشر: |
2017 |
| المجموعة: |
The University of Liverpool Repository |
| الوصف: |
Abstract Recent studies directed to the design of compounds targeting the bc 1 protein complex of Plasmodium falciparum, 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 bc 1 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−1, are solely present in the matrix, while the most stable 4-oxo-quinoline tautomer is ... |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| العلاقة: |
Horta, Pedro, Henriques, Marta SC, Bras, Elisa M, Murtinheira, Fernanda, Nogueira, Fatima, O'Neill, Paul M, Paixao, Jose A, Fausto, Rui and Cristiano, Maria LS (2017) 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. PURE AND APPLIED CHEMISTRY, 89 (6). pp. 765-780. |
| DOI: |
10.1515/pac-2016-1119 |
| الإتاحة: |
https://doi.org/10.1515/pac-2016-1119Test
http://livrepository.liverpool.ac.uk/3072807Test/ |
| رقم الانضمام: |
edsbas.D5E660FB |
| قاعدة البيانات: |
BASE |
