title: Enantioselective, ketoreductase-based entry into pharmaceutical building blocks: ethanol as tunable nicotinamide reductant.
abstract: The use of NADH- and NADPH-dependent ketoreductases to access enantioenriched pharmaceutical building blocks is reported. Seven structurally diverse synthons are obtained, including those for atomoxetine (KRED 132), talampanel (RS1-ADH and CPADH), Dolastatin (KRED 132), and fluoxetine (KRED 108/132). Ethanol may be used as stoichiometric reductant, regenerating both nicotinamide cofactors, particularly under four-electron redox conditions. Its favorable thermodynamic and economic profile, coupled with its advantageous dual cosolvent role, suggests a new application for biomass-derived ethanol.
authors.affiliation: Department of Chemistry, University of Nebraska, Lincoln, Nebraska 68588-0304, USA.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Broussy
authors.forename: Ross W
authors.initials: RW
authors.lastname: Cheloha
authors.forename: David B
authors.initials: DB
authors.lastname: Berkowitz
mesh_terms: D000426:Alcohol Dehydrogenase / Q000378:metabolism*; D000818:Animals; D000431:Ethanol / Q000378:metabolism*; D006801:Humans; D007659:Ketones / Q000378:metabolism; D009536:Niacinamide / Q000378:metabolism*; D019163:Reducing Agents / Q000378:metabolism*; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D007659:Ketones; D019163:Reducing Agents; D009536:Niacinamide; D000431:Ethanol; D000426:Alcohol Dehydrogenase