RESUMEN
A series of cyclopenta[c]pyridine aldosterone synthase (AS) inhibitors were conveniently accessed using batch or continuous flow Kondrat'eva reactions. Preparation of the analogous cyclohexa[c]pyridines led to the identification of a potent and more selective AS inhibitor. The structure-activity-relationship (SAR) in this new series was rationalized using binding mode models in the crystal structure of AS.
Asunto(s)
Citocromo P-450 CYP11B2/antagonistas & inhibidores , Inhibidores Enzimáticos del Citocromo P-450/síntesis química , Inhibidores Enzimáticos del Citocromo P-450/farmacología , Piridinas/síntesis química , Piridinas/farmacología , Técnicas de Química Sintética , Citocromo P-450 CYP11B2/química , Inhibidores Enzimáticos del Citocromo P-450/química , Humanos , Modelos Moleculares , Conformación Proteica , Piridinas/química , Relación Estructura-ActividadRESUMEN
Acrylamide (AA) formation during coffee roasting happens rapidly, reaching a peak value within the first minutes of roasting followed by a fast decrease to reach an asymptote at approximately 200 µg/kg. Today, the mechanisms by which AA is reduced during roasting remain unclear. In this research, the fate of AA during roasting followed by drip brewed-like extraction was studied using 14C-radiolabeled (14C-AA) and 13C-labeled (13C3-AA) materials. Results showed that 28% of the spiked 14C-AA was lost during the roasting process, presumably by degradation to volatile compounds and 25% was non-extractable; therefore, appeared bound to the matrix. About 50% of initial AA went into the water extract, either unchanged or transformed by conjugation/binding. The release of bound acrylamide was further evidenced by increasing levels of 13C3-AA over prolonged roasting times. In addition, the absence of 14C activity in the hexane extracts suggested acrylamide not to bind to any lipophilic material.
Asunto(s)
Acrilamida/química , Café/química , Manipulación de Alimentos , Acrilamida/análisis , Radioisótopos de Carbono , CalorRESUMEN
We report the optimization of a neglected reaction for the rapid and direct conversion of oxazoles into N-substituted imidazoles. The utility of this microwave-promoted reaction for diversity-oriented synthesis is demonstrated in the preparation of >40 N-substituted imidazoles, including α-imidazolyl esters.
Asunto(s)
Imidazoles/química , Imidazoles/síntesis química , Oxazoles/química , Técnicas de Química Sintética , Ésteres , MicroondasRESUMEN
A continuous flow inverse-electron-demand Kondrat'eva reaction has been developed that provides direct access to cycloalka[c]pyridines from unactivated oxazoles and cycloalkenes. Annulated pyridines obtained by this one-step process are valuable scaffolds for medicinal chemistry.