Biocatalytic racemization of sec-alcohols and α-hydroxyketones using lyophilized microbial cells
Biocatalytic racemization of aliphatic and aryl-aliphatic sec-alcohols and α-hydroxyketones (acyloins) was accomplished using whole resting cells of bacteria, fungi, and one yeast. The mild (physiological) reaction conditions ensured the suppression of undesired side reactions, such as elimination or condensation. Cofactor and inhibitor studies suggest that the racemization proceeds through an equilibrium-controlled enzymatic oxidation–reduction sequence via the corresponding ketones or α-diketones, respectively, which were detected in various amounts. Ketone formation could be completely suppressed by exclusion of molecular oxygen.
Keywordssec-alcohols Acyloins Isomerization Biotransformation Racemization
This study was performed in cooperation between project P18537-B03 of the Austrian Science Fund (FWF) and BASF AG (Ludwigshafen) within the Research Centre Applied Biocatalysis. Financial support by the FWF, the FFG, the City of Graz, and the Province of Styria is gratefully acknowledged. Sonja Heumann and Georg Gübitz from the Graz University of Technology are cordially thanked for their valuable advice in applied microbiology and for the donation of Nocardia G and Nocardia H.
- Cheng Y, Zhang F, Rano TA, Lu Z, Scheleif WA, Gabryelski L, Olsen DB, Stahlhunt M, Rutkowski CA, Lin JH, Jin L, Emini EA, Chapman KT, Tata JR (2002) Indinavir analogues with blocked metabolism sites as HIV protease inhibitors with improved pharmacological profiles and high potency against PI-Resistant viral strains. Bioorg Med Chem Lett 12:2419–2422CrossRefGoogle Scholar
- Mueller M, Wolberg M, Schubert T, Hummel W (2005) Enzyme-catalyzed regio- and enantioselective ketone reductions. In: Advances in Biochemical Engineering/Biotechnology (eds) Technology transfer in biotechnology: from lab to industry to production. Springer, Berlin Heidelberg New York, pp 261–287Google Scholar
- Smallridge AJ, Trewhalla MA, Maurice A, Wilkinson AK (2003) Methods for the synthesis of amines such as ephedrine and intermediates via reductive animation of ketones. Patent WO 2003018531 A1 20030306Google Scholar