RESUMEN
This study focuses on the synthesis of 1,7- and 3,4-indole-fused lactones via a simple and efficient reaction sequence. The functionalization of these "oxazepino-indole" and "oxepino-indole" tricycles is carried out by palladium catalysed CC coupling, nucleophilic substitution or 1,3-dipolar cycloaddition. The evaluation of their activity against Mycobacterium tuberculosis shows that the "oxazepino-indole" structure is a new inhibitor of M. tuberculosis growth in vitro.
Asunto(s)
Antibacterianos/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Antibacterianos/síntesis química , Antibacterianos/química , Relación Dosis-Respuesta a Droga , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Relación Estructura-ActividadRESUMEN
In this study, we screen three heterocyclic structures as potential inhibitors of UDP-galactopyranose mutase (UGM), an enzyme involved in the biosynthesis of the cell wall of Mycobacterium tuberculosis. In order to understand the binding mode, docking simulations are performed on the best inhibitors. Their activity on Mycobacterium tuberculosis is also evaluated. This study made it possible to highlight an "oxazepino-indole" structure as a new inhibitor of UGM and of M. tuberculosis growth in vitro.
Asunto(s)
4-Butirolactona/análogos & derivados , Antituberculosos/síntesis química , Inhibidores Enzimáticos/síntesis química , Indoles/síntesis química , Transferasas Intramoleculares/antagonistas & inhibidores , Tuberculosis/tratamiento farmacológico , 4-Butirolactona/síntesis química , 4-Butirolactona/farmacología , Antituberculosos/farmacología , Evaluación Preclínica de Medicamentos , Inhibidores Enzimáticos/farmacología , Humanos , Indoles/farmacología , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Estructura Molecular , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/enzimología , Unión ProteicaRESUMEN
The efficiency and the selectivity of the Pd-catalyzed oxidation, in carboxylic acids, of terminal alkenes are strongly improved in the presence of a base. The methodology is particularly well adapted for the oxidation of homoallylic alcohols, for which the resulting acyloxylated products are obtained selectively as E-isomers in fair to good yields.
RESUMEN
Under palladium(II)-catalyzed and oxidative conditions, the coupling of furans with styrenes leads to the formation of Heck-type products in medium to good yields. The reaction is highly regio- and stereoselective, giving trans-olefins predominantly.
Asunto(s)
Alquenos/síntesis química , Furanos/química , Paladio/química , Estirenos/química , Catálisis , Oxidación-Reducción , Oxígeno/química , EstereoisomerismoRESUMEN
The Pd(OCOCF3)2/[(HOCH2CH2NHCOCH2)2NCH2]2-catalyzed oxidation of o-allylphenol with H2O2 in water/methanol affords a syn and anti mixture of 2-(1,2-dihydroxypropyl)phenol and 2-(2-hydroxy-1-methoxypropyl)phenol. Mechanistic experiments and ESI-MS studies support a pathway wherein isomerization of the C=C bond followed by its epoxidation and oxirane opening led to the products. Recycling of the catalytic system led to gradual lost of activity.
