title: Chemoenzymatic asymmetric synthesis of pregabalin precursors via asymmetric bioreduction of β-cyanoacrylate esters using ene-reductases.
abstract: The asymmetric bioreduction of a library of β-cyanoacrylate esters using ene-reductases was studied with the aim to provide a biocatalytic route to precursors for GABA analogues, such as pregabalin. The stereochemical outcome could be controlled by substrate-engineering through size-variation of the ester moiety and by employing stereochemically pure (E)- or (Z)-isomers, which allowed to access both enantiomers of each product in up to quantitative conversion in enantiomerically pure form. In addition, stereoselectivities and conversions could be improved by mutant variants of OPR1, and the utility of the system was demonstrated by preparative-scale applications.
authors: Department of Chemistry, Organic & Bioorganic Chemistry, University of Graz, Heinrichstrasse 28, A-8010 Graz, Austria.
authors: Christoph K
authors: CK
authors: Winkler
authors: Dorina
authors: D
authors: Clay
authors: Simon
authors: S
authors: Davies
authors: Pat
authors: P
authors: O'Neill
authors: Paul
authors: P
authors: McDaid
authors: Sebastien
authors: S
authors: Debarge
authors: Jeremy
authors: J
authors: Steflik
authors: Mike
authors: M
authors: Karmilowicz
authors: John W
authors: JW
authors: Wong
authors: Kurt
authors: K
authors: Faber
mesh_terms: D055162:Biocatalysis; D003487:Cyanoacrylates / Q000737:chemistry*; D004952:Esters; D010088:Oxidoreductases / Q000737:chemistry*; D000069583:Pregabalin; D013237:Stereoisomerism; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D003487:Cyanoacrylates; D004952:Esters; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D010088:Oxidoreductases