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Updated: Jun 26, 2026

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Enantioselective, ketoreductase-based entry into pharmaceutical building blocks: ethanol as tunable nicotinamide
Sylvain Broussy1, Ross W Cheloha, David B Berkowitz
1Department of Chemistry, University of Nebraska, Lincoln, Nebraska 68588-0304, USA.
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.
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