Asymmetric bioreductions: application to the synthesis of pharmaceuticals

Michel Chartrain, Randolph Greasham, Jeffrey Moore, Paul Reider, David Robinson, Barry Buckland

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Selected examples of asymmetric bioreductions of pharmaceutically relevant prochiral ketones are reviewed. These data show that microbial screens lead to the identification of appropriate biocatalysts, and that the use of miniaturized and semi-automated technology can greatly reduce both labor and lead times. The same data also highlight the need to evaluate a relatively large and/or diverse microbial population (highlighting biodiversity). We also found that in many instances the luxury of producing either enantiomers with high optical purity, enantiocomplementarity, can be achieved when employing different microbial strains. Process development studies reviewed here demonstrate that it is possible in some cases to understand and control the production of an unwanted enantiomer or by-product. Finally, a specific example, the asymmetric bioreduction of a ketone by Candida sorbophila, shows that process development studies which optimized, the bioreduction environmental conditions (pH, temperature...), the addition of ketone, and the implementation of a nutrient feeding strategy in conjunction with the use of a defined cultivation medium were key in achieving increased bioreduction rates and product titers. When scaled-up in pilot plant bioreactors, the bioreduction process supported the production of several kilograms of (R)-alcohol (enantiomeric excess (e.e.)>98%), with an isolated product yield of about 80%.

Original languageEnglish (US)
Pages (from-to)503-512
Number of pages10
JournalJournal of Molecular Catalysis - B Enzymatic
Volume11
Issue number4-6
DOIs
StatePublished - Jan 22 2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Bioengineering
  • Biochemistry
  • Process Chemistry and Technology

Keywords

  • Assymetric bioreductions
  • Fermentation
  • Ketones
  • Process development

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