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Chemoenzymatic asymmetric synthesis of pregabalin precursors via asymmetric bioreduction of ?-cyanoacrylate esters using ene-reductases.

ABSTRACT: The asymmetric bioreduction of a library of ?-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.

SUBMITTER: Winkler CK

PROVIDER: S-EPMC3579311 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Chemoenzymatic asymmetric synthesis of pregabalin precursors via asymmetric bioreduction of β-cyanoacrylate esters using ene-reductases.

Winkler Christoph K CK Clay Dorina D Davies Simon S O'Neill Pat P McDaid Paul P Debarge Sebastien S Steflik Jeremy J Karmilowicz Mike M Wong John W JW Faber Kurt K

The Journal of organic chemistry 20130128 4

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 ad ...[more]

PMID: 23316696

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