Resolución cinética dinámica de los beta-haloalcoholes racémicos: acceso directo a los epóxidos enriquecidos con
Robert M Haak1, Florian Berthiol, Thomas Jerphagnon
1Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands.
Journal of the American Chemical Society
|September 20, 2008
Resumen
Este estudio presenta una resolución cinética doble quimio-enzimática directa (DKR) de los beta-haloalcoholes racémicos. Produce eficientemente epoxidos ópticamente activos en un solo paso utilizando una enzima mutante y un catalizador de iridaciclo.
Área de la Ciencia:
- Química orgánica es la química orgánica.
- La biocatálisis por biocatálisis.
- Enzimología Enzimología.
Sus antecedentes:
- Los beta-haloalcoholes racemicos son productos intermedios sintéticos comunes.
- Los métodos eficientes para producir epoxidos enantiopuros son cruciales en la síntesis orgánica.
- Los métodos existentes para la resolución cinética pueden ser de varios pasos y menos eficientes.
Objetivo del estudio:
- Desarrollar un método quimio-enzimático directo para la resolución cinética de los beta-haloalcoholes racémicos.
- Para lograr la síntesis de epoxidos ópticamente activos en un solo paso.
- Identificar catalizadores efectivos tanto para el cierre del anillo asimétrico como para la racemización.
Principales métodos:
- Utilizó una deshalogenasa de haloalcohol mutante (HheC Cys153Ser Trp249Phe) para el cierre asimétrico del anillo.
- Se empleó un nuevo catalizador de iridaciclo (iridaciclo 3) para la racemización del enantiómero beta-haloalcohol no reaccionado.
- Se realizó una resolución cinética doble quimio-enzimática directa (DKR) en una sola olla.
Principales resultados:
- Se logró con éxito la DKR quimioenzimática directa de los beta-haloalcoholes racémicos.
- Produjo los correspondientes epóxidos ópticamente activos con alta enantiopuridad.
- Demostró la alta eficiencia de la enzima mutante HheC y el catalizador del iridaciclo 3.
Conclusiones:
- El DKR quimioenzimático desarrollado es un método de un solo paso altamente eficiente para acceder a los epoxidos ópticamente activos.
- La combinación de un mutante enzimático a medida y un catalizador de racemización de iridaciclo eficaz ofrece una estrategia poderosa.
- Este enfoque proporciona una ruta simplificada a valiosos bloques de construcción quirales a partir de materiales de partida racémicos.
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