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

Sylvain Broussy, Ross W. Cheloha, David B Berkowitz

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

(Chemical Equation Presented) 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 (RSt-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.

Original languageEnglish (US)
Pages (from-to)305-308
Number of pages4
JournalOrganic Letters
Volume11
Issue number2
DOIs
Publication statusPublished - Jan 15 2009

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ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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