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Stereoselective C-C bond formation catalysed by engineered carboxymethylproline synthases.

Journal
Nature Chemistry
Publisher
Nature Publishing Group
Publication Date
May 01, 2011
Volume
3
Issue
5
Identifiers
DOI: 10.1038/nchem.1011
Keywords
Disciplines
  • Biology
  • Chemistry
  • Engineering
License
Unknown

Abstract

The reaction of enol(ate)s with electrophiles is used extensively in organic synthesis for stereoselective C-C bond formation. Protein-based catalysts have had comparatively limited application for the stereoselective formation of C-C bonds of choice via enolate chemistry. We describe protein engineering studies on 5-carboxymethylproline synthases, members of the crotonase superfamily, aimed at enabling stereoselective C-C bond formation leading to N-heterocycles via control of trisubstituted enolate intermediates. Active site substitutions, including at the oxyanion binding site, enable the production of substituted N-heterocycles in high diastereomeric excesses via stereocontrolled enolate formation and reaction. The results reveal the potential of the ubiquitous crotonase superfamily as adaptable catalysts for the control of enolate chemistry.

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