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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.

SUBMITTER: Broussy S

PROVIDER: S-EPMC6027600 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

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Enantioselective, ketoreductase-based entry into pharmaceutical building blocks: ethanol as tunable nicotinamide reductant.

Broussy Sylvain S Cheloha Ross W RW Berkowitz David B DB

Organic letters 20090101 2

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, couple ...[more]

PMID: 19128188

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