Journal article
Enantiocomplementary Synthesis of γ-Nitroketones Using Designed and Evolved Carboligases.
- Garrabou X Laboratory of Organic Chemistry, ETH Zurich , 8093 Zurich, Switzerland.
- Verez R Laboratory of Organic Chemistry, ETH Zurich , 8093 Zurich, Switzerland.
- Hilvert D Laboratory of Organic Chemistry, ETH Zurich , 8093 Zurich, Switzerland.
- 2016-12-20
Published in:
- Journal of the American Chemical Society. - 2017
English
Artificial enzymes created by computational design and directed evolution are versatile biocatalysts whose promiscuous activities represent potentially attractive starting points for divergent evolution in the laboratory. The artificial aldolase RA95.5-8, for example, exploits amine catalysis to promote mechanistically diverse carboligations. Here we report that RA95.5-8 variants catalyze the asymmetric synthesis of γ-nitroketones via two alternative enantiocomplementary Michael-type reactions: enamine-mediated addition of acetone to nitrostyrenes, and nitroalkane addition to conjugated ketones activated as iminium ions. In addition, a cascade of three aldolase-catalyzed reactions enables one-pot assembly of γ-nitroketones from three simpler building blocks. Together, our results highlight the chemical versatility of artificial aldolases for the practical synthesis of important chiral synthons.
- Language
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- English
- Open access status
- closed
- Identifiers
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- DOI 10.1021/jacs.6b11928
- PMID 27992715
- Persistent URL
- https://sonar.rero.ch/global/documents/134516
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