Nitrile as Activating Group in the Asymmetric Bioreduction of β-Cyanoacrylic Acids Catalyzed by Ene-Reductases.

Autor: Winkler CK; 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., Clay D; 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., Turrini NG; 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., Lechner H; 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., Kroutil W; 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., Davies S; Pfizer Global Supply, Process Development Centre Loughbeg, County Cork, Ireland., Debarge S; Pfizer Global Supply, Process Development Centre Loughbeg, County Cork, Ireland., O'Neill P; Pfizer Global Supply, Process Development Centre Loughbeg, County Cork, Ireland., Steflik J; Pfizer Worldwide R&D, Chemical R&D Eastern Point Rd, Groton, CT 06340, USA., Karmilowicz M; Pfizer Worldwide R&D, Chemical R&D Eastern Point Rd, Groton, CT 06340, USA., Wong JW; Pfizer Worldwide R&D, Chemical R&D Eastern Point Rd, Groton, CT 06340, USA., Faber K; 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.
Jazyk: angličtina
Zdroj: Advanced synthesis & catalysis [Adv Synth Catal] 2014 May 26; Vol. 356 (8), pp. 1878-1882. Date of Electronic Publication: 2014 Apr 09.
DOI: 10.1002/adsc.201301055
Abstrakt: 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.
Databáze: MEDLINE
Nepřihlášeným uživatelům se plný text nezobrazuje