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- Title
Stereoselective C-C bond formation catalysed by engineered carboxymethylproline synthases.
- Authors
Hamed, Refaat B.; Gomez-Castellanos, J. Ruben; Thalhammer, Armin; Harding, Daniel; Ducho, Christian; Claridge, Timothy D. W.; Schofield, Christopher J.
- 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.
- Subjects
MOLECULAR recognition; CARBONYL compounds; ELECTROPHILES; ORGANIC synthesis; PROTEIN engineering; STEREOCHEMISTRY; ENZYMES; CATALYSTS; NITROGEN cycle; HETEROCYCLIC compounds
- Publication
Nature Chemistry, 2011, Vol 3, Issue 5, p365
- ISSN
1755-4330
- Publication type
Article
- DOI
10.1038/nchem.1011