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Quiralidad axial inducida en la reducción de cetonas asimétricas biocatalíticas
Rubén Agudo1, Gheorghe-Doru Roiban, Manfred T Reetz
1Department of Chemistry, Philipps-Universität Marburg, Hans-Meerwein Str., 35032 Marburg, Germany.
Journal of the American Chemical Society
|October 19, 2012
Resumen
Las deshidrogenasas de alcohol catalizan la reducción asimétrica de cetonas en alcoholes quirales, superando el rendimiento de los catalizadores de metales de transición. La evolución dirigida permitió la reversión de la enantioselectividad para sintetizar bloques de construcción quirales valiosos.
Área de la Ciencia:
- Química orgánica es la química orgánica.
- La biocatálisis por biocatálisis.
- Síntesis asimétrica de síntesis.
Sus antecedentes:
- Los alcoholes quirales son bloques de construcción cruciales en productos farmacéuticos y productos químicos finos.
- La reducción asimétrica de las cetonas procirales es una transformación clave en la síntesis de los alcoholes quirales.
- Desarrollar catalizadores eficientes y selectivos para esta reducción sigue siendo un desafío significativo.
Objetivo del estudio:
- Para lograr la reducción asimétrica catalítica de las ciclohexanonas de 4-alquilideno a alcoholes de configuración R.
- Explorar el potencial de la evolución dirigida para revertir la enantioselectividad.
- Para utilizar los alcoholes quirales sintetizados en reacciones catalíticas posteriores.
Principales métodos:
- Reducción enzimática utilizando alcohol deshidrogenasas.
- Evolución dirigida a través de la mutagenesis por saturación.
- Reacciones en cascada catalizadas por el paladio.
Principales resultados:
- Alta enantioselectividad (hasta el 99% ee) para los alcoholes R utilizando alcohol deshidrogenasas.
- Inversión exitosa de la enantioselectividad a los alcoholes S (hasta el 98% ee) a través de la evolución dirigida.
- Utilidad demostrada de los alcoholes R y S en reacciones en cascada catalizadas por Pd.
Conclusiones:
- Las deshidrogenasas de alcohol son altamente efectivas para la reducción asimétrica de cetonas procirales, produciendo alcoholes de configuración R con excelente enantioselectividad.
- La evolución dirigida ofrece una poderosa estrategia para afinar la actividad enzimática y lograr la enantioselectividad opuesta.
- Los alcoholes quirales sintetizados sirven como intermediarios versátiles para la síntesis de moléculas complejas a través de reacciones en cascada.
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