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Síntesis enantiocomplementaria de γ-nitrocetonas utilizando carboligasas diseñadas y evolucionadas

Xavier Garrabou¹, Rebecca Verez¹, Donald Hilvert¹

¹Laboratory of Organic Chemistry, ETH Zurich , 8093 Zurich, Switzerland.

Journal of the American Chemical Society

|December 20, 2016

Resumen

Las aldolasas artificiales, enzimas diseñadas, pueden crear moléculas quirales como las gamma-nitrocetonas. Estos versátiles biocatalizadores ofrecen nuevas vías para la evolución en el laboratorio y la síntesis práctica de valiosos componentes químicos.

Área de la Ciencia:

Biocatálisis
Ingeniería de enzimas
Síntesis orgánica

Sus antecedentes:

Las enzimas artificiales ofrecen actividades catalíticas versátiles.
Las funciones enzimáticas promiscuas pueden ser puntos de partida para la evolución en el laboratorio.
La aldoasa artificial RA95.5-8 utiliza la catálisis de aminas para las reacciones de carboligación.

Objetivo del estudio:

Explorar las capacidades catalíticas de las variantes de aldolasa artificial RA95.5-8.
Para demostrar la síntesis asimétrica de las gamma-nitrocetonas.
Para mostrar la utilidad de las enzimas de ingeniería en la síntesis orgánica compleja.

Principales métodos:

Evolución dirigida y diseño computacional de aldolas artificiales.
Las reacciones de tipo Michael catalizadas por enzimas.
Síntesis asimétrica de las gamma-nitrocetonas.
Reacciones en cascada de una sola y varias etapas.

Principales resultados:

Las variantes RA95.5-8 catalizan la síntesis enantioselectiva de las gamma-nitrocetonas.
Se identificaron dos reacciones tipo Michael enantiocomplementarias distintas.
Adición de acetona a los nitrostirenos mediante catálisis de enamina.
Adición de nitroalcanos a las cetonas conjugadas activadas por iones de iminio.
Se desarrolló una reacción en cascada de tres enzimas para la síntesis de una sola vasija de gamma-nitrocetonas.

Conclusiones:

Las aldolasas artificiales exhiben una notable versatilidad química.
Las enzimas diseñadas proporcionan rutas prácticas a los sintones quirales.
Estos biocatalizadores son herramientas valiosas para la síntesis asimétrica y la evolución en el laboratorio.

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