title: An Enantio- and Diastereoselective Chemoenzymatic Synthesis of α-Fluoro β-Hydroxy Carboxylic Esters.
abstract: The trans-o-hydroxybenzylidene pyruvate aldolase-catalysed reactions between fluoropyruvate and many (hetero)aromatic aldehydes yield aldol adducts without subsequent dehydration. Treatment of the reaction products with hydrogen peroxide yields the corresponding syn-configured α-fluoro β-hydroxy carboxylic acids which have >98 % ee. The overall chemoenzymatic approach, in which fluoropyruvate serves as a fluoroacetate equivalent, may be exploited in the synthesis of polar building blocks and fragments with potential value in drug discovery.
authors.affiliation: School of Chemistry and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK.
authors.forename: James K
authors.identifier: 0000-0002-1764-5919
authors.initials: JK
authors.lastname: Howard
authors.affiliation: School of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK.
authors.forename: Marion
authors.initials: M
authors.lastname: Müller
authors.affiliation: School of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK. a.berry@leeds.ac.uk.
authors.forename: Alan
authors.identifier: 0000-0003-3502-0426
authors.initials: A
authors.lastname: Berry
authors.affiliation: School of Chemistry and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK. a.s.nelson@leeds.ac.uk.
authors.forename: Adam
authors.identifier: 0000-0003-3886-363X
authors.initials: A
authors.lastname: Nelson
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D055162:Biocatalysis; D002264:Carboxylic Acids / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D004952:Esters / Q000737:chemistry; D006899:Mixed Function Oxygenases / Q000737:chemistry / Q000378:metabolism*; D008968:Molecular Conformation; D016958:Pseudomonas putida / Q000201:enzymology; D011773:Pyruvates / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000447:Aldehydes; D002264:Carboxylic Acids; D004952:Esters; D011773:Pyruvates; C000610682:fluoropyruvate; C116609:3-hydroxybutanal; D006899:Mixed Function Oxygenases
keywords: aldolase; asymmetric catalysis; chemoenzymatic synthesis; organofluorine compounds