Journal article
Investigating Substrate Scope and Enantioselectivity of a Defluorinase by a Stereochemical Probe.
- Wang JB Department of Chemistry, Philipps-University , Hans-Meerwein-Strasse 4, 35032 Marburg, Germany.
- Ilie A Department of Chemistry, Philipps-University , Hans-Meerwein-Strasse 4, 35032 Marburg, Germany.
- Yuan S Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Fédérale de Lausanne (EPFL) , CH B3 495 (Bâtiment CH) Station 6, CH-1015 Lausanne, Switzerland.
- Reetz MT Department of Chemistry, Philipps-University , Hans-Meerwein-Strasse 4, 35032 Marburg, Germany.
- 2017-07-26
Published in:
- Journal of the American Chemical Society. - 2017
English
The possibility of a double Walden inversion mechanism of the fluoracetate dehalogenase FAcD (RPA1163) has been studied by subjecting rac-2-fluoro-2-phenyl acetic acid to the defluorination process. This stereochemical probe led to inversion of configuration in a kinetic resolution with an extremely high selectivity factor (E > 500), showing that the classical mechanism involving SN2 reaction by Asp110 pertains. The high preference for the (S)-substrate is of synthetic value. Wide substrate scope of RPA1163 in such hydrolytic kinetic resolutions can be expected because the reaction of the even more sterically demanding rac-2-fluoro-2-benzyl acetic acid proceeded similarly. Substrate acceptance and stereoselectivity were explained by extensive molecular modeling (MM) and molecular dynamics (MD) computations. These computations were also applied to fluoroacetic acid itself, leading to further insights.
- Language
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- English
- Open access status
- closed
- Identifiers
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- DOI 10.1021/jacs.7b06019
- PMID 28741946
- Persistent URL
- https://sonar.ch/global/documents/231487
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