title: One-pot synthesis of enantiopure 3,4-dihydroisocoumarins through dynamic reductive kinetic resolution processes.
abstract: A straightforward chemoenzymatic synthesis of enantiopure 4-alkyl-3-methyl-3,4-dihydroisocoumarins through a ketoreductase-catalyzed one-pot dynamic reductive kinetic resolution is reported. E. coli/ADH-A cells have shown outstanding diastereo- and enantioselectivity toward the bioreduction of a series of racemic ketones, with the use of anion exchange resins or triethylamine being compatible in the same aqueous reaction medium. The so-obtained enantiopure alcohols were subsequently cyclized in acid media affording the corresponding lactones in good to excellent conversions (72-96%) and excellent selectivities (dr ≥99:1 and ee >99%).
authors.affiliation: Organic and Inorganic Chemistry Department, University of Oviedo, Avenida Julián Clavería s/n. Oviedo 33006, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Mangas-Sánchez
authors.forename: Eduardo
authors.initials: E
authors.lastname: Busto
authors.forename: Vicente
authors.initials: V
authors.lastname: Gotor
authors.forename: Vicente
authors.initials: V
authors.lastname: Gotor-Fernández
mesh_terms: D000837:Anion Exchange Resins / Q000737:chemistry; D055162:Biocatalysis; D002384:Catalysis; D004926:Escherichia coli / Q000737:chemistry* / Q000378:metabolism*; D049934:Isocoumarins / Q000138:chemical synthesis* / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry; D007700:Kinetics; D007783:Lactones / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010084:Oxidation-Reduction; D013237:Stereoisomerism
chemical_list: D000837:Anion Exchange Resins; D049934:Isocoumarins; D007659:Ketones; D007783:Lactones