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Highly diastereoselective and enantioselective olefin cyclopropanation using engineered myoglobin-based catalysts.

ABSTRACT: Using rational design, an engineered myoglobin-based catalyst capable of catalyzing the cyclopropanation of aryl-substituted olefins with catalytic proficiency (up to 46,800 turnovers) and excellent diastereo- and enantioselectivity (98-99.9%) was developed. This transformation could be carried out in the presence of up to 20?g?L(-1) olefin substrate with no loss in diastereo- and/or enantioselectivity. Mutagenesis and mechanistic studies support a cyclopropanation mechanism mediated by an electrophilic, heme-bound carbene species and a model is provided to rationalize the stereopreference of the protein catalyst. This work shows that myoglobin constitutes a promising and robust scaffold for the development of biocatalysts with carbene-transfer reactivity.

SUBMITTER: Bordeaux M

PROVIDER: S-EPMC4470557 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Highly diastereoselective and enantioselective olefin cyclopropanation using engineered myoglobin-based catalysts.

Bordeaux Melanie M Tyagi Vikas V Fasan Rudi R

Angewandte Chemie (International ed. in English) 20141223 6

Using rational design, an engineered myoglobin-based catalyst capable of catalyzing the cyclopropanation of aryl-substituted olefins with catalytic proficiency (up to 46,800 turnovers) and excellent diastereo- and enantioselectivity (98-99.9%) was developed. This transformation could be carried out in the presence of up to 20 g L(-1) olefin substrate with no loss in diastereo- and/or enantioselectivity. Mutagenesis and mechanistic studies support a cyclopropanation mechanism mediated by an elect ...[more]

PMID: 25538035

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