title: Nitrile as Activating Group in the Asymmetric Bioreduction of β-Cyanoacrylic Acids Catalyzed by Ene-Reductases.
abstract: Asymmetric bioreduction of an (E)-β-cyano-2,4-dienoic acid derivative by ene-reductases allowed a shortened access to a precursor of pregabalin [(S)-3-(aminomethyl)-5-methylhexanoic acid] possessing the desired configuration in up to 94% conversion and >99%ee. Deuterium labelling studies showed that the nitrile moiety was the preferred activating/anchor group in the active site of the enzyme over the carboxylic acid or the corresponding methyl ester.
authors.affiliation: Department of Chemistry, Organic & Bioorganic Chemistry, University of Graz Heinrichstrasse 28, A-8010 Graz, Austria, ; phone: (+43)-316-380-5332 ; e-mail: kurt.faber@uni-graz.at.
authors.forename: Christoph K
authors.initials: CK
authors.lastname: Winkler
authors.affiliation: Department of Chemistry, Organic & Bioorganic Chemistry, University of Graz Heinrichstrasse 28, A-8010 Graz, Austria, ; phone: (+43)-316-380-5332 ; e-mail: kurt.faber@uni-graz.at.
authors.forename: Dorina
authors.initials: D
authors.lastname: Clay
authors.affiliation: Department of Chemistry, Organic & Bioorganic Chemistry, University of Graz Heinrichstrasse 28, A-8010 Graz, Austria, ; phone: (+43)-316-380-5332 ; e-mail: kurt.faber@uni-graz.at.
authors.forename: Nikolaus G
authors.initials: NG
authors.lastname: Turrini
authors.affiliation: Department of Chemistry, Organic & Bioorganic Chemistry, University of Graz Heinrichstrasse 28, A-8010 Graz, Austria, ; phone: (+43)-316-380-5332 ; e-mail: kurt.faber@uni-graz.at.
authors.forename: Horst
authors.initials: H
authors.lastname: Lechner
authors.affiliation: Department of Chemistry, Organic & Bioorganic Chemistry, University of Graz Heinrichstrasse 28, A-8010 Graz, Austria, ; phone: (+43)-316-380-5332 ; e-mail: kurt.faber@uni-graz.at.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kroutil
authors.affiliation: Pfizer Global Supply, Process Development Centre Loughbeg, County Cork, Ireland.
authors.forename: Simon
authors.initials: S
authors.lastname: Davies
authors.affiliation: Pfizer Global Supply, Process Development Centre Loughbeg, County Cork, Ireland.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Debarge
authors.affiliation: Pfizer Global Supply, Process Development Centre Loughbeg, County Cork, Ireland.
authors.forename: Pat
authors.initials: P
authors.lastname: O'Neill
authors.affiliation: Pfizer Worldwide R&D, Chemical R&D Eastern Point Rd, Groton, CT 06340, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Steflik
authors.affiliation: Pfizer Worldwide R&D, Chemical R&D Eastern Point Rd, Groton, CT 06340, USA.
authors.forename: Mike
authors.initials: M
authors.lastname: Karmilowicz
authors.affiliation: Pfizer Worldwide R&D, Chemical R&D Eastern Point Rd, Groton, CT 06340, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Wong
authors.affiliation: Department of Chemistry, Organic & Bioorganic Chemistry, University of Graz Heinrichstrasse 28, A-8010 Graz, Austria, ; phone: (+43)-316-380-5332 ; e-mail: kurt.faber@uni-graz.at.
authors.forename: Kurt
authors.initials: K
authors.lastname: Faber
keywords: C=C reduction; biocatalysis; cyanoacrylates; ene-reductases; pregabalin