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

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 engine...

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التفاصيل البيبلوغرافية
المؤلفون الرئيسيون: Hamed, R, Gomez-Castellanos, JR, Thalhammer, A, Harding, D, Ducho, C, Claridge, T, Schofield, C
التنسيق: Journal article
اللغة:English
منشور في: 2011
الوصف
الملخص: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.