RESUMEN
Spiropiperidine naphthyridinone inhibitors of Staphylococcus aureus and Escherichia coli FabI have been prepared. Compounds 14a and 14c were identified as having sub-nanomolar E. coli FabI activity and are among the most potent FabI inhibitors yet described. The structural model of 14a bound to E. coli FabI is shown.
Asunto(s)
Antibacterianos/farmacología , Enoil-ACP Reductasa (NADH)/antagonistas & inhibidores , Enoil-ACP Reductasa (NADH)/metabolismo , Escherichia coli/enzimología , Naftiridinas/farmacología , Piperidinas/farmacología , Compuestos de Espiro/farmacología , Staphylococcus aureus/enzimología , Antibacterianos/química , Dominio Catalítico , Enoil-ACP Reductasa (NADH)/química , Modelos Moleculares , Naftiridinas/química , Piperidinas/química , Unión Proteica , Compuestos de Espiro/química , Relación Estructura-ActividadRESUMEN
A method for the catalytic vinylation of protected monosaccharides bearing a single free hydroxyl function has been developed. Reaction of representative primary, secondary, and anomeric sugar hydroxyl functions with butyl vinyl ether as the reactant and solvent and (phen)Pd(OAc)(2) (phen = 1,10-phenanthroline ligand) as the catalyst gives the corresponding vinylated sugar products in 36-79% yield. The catalyst requires the presence of traces of oxygen in the reaction mixture to prevent decomposition to Pd(0).