Preparative access to medicinal chemistry related chiral alcohols using carbonyl reductase technology |
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Authors: | Andrew S Rowan Thomas S Moody Roger M Howard Toby J Underwood Iain R Miskelly Yanan He Bo Wang |
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Institution: | 1. Biocatalysis & Isotope Chemistry Group, Almac, 20 Seagoe Industrial Estate, Craigavon BT63 5QD, Northern Ireland, UK;2. Chemical Research & Development, Pfizer Ltd, Sandwich Laboratories, Ramsgate Road, Kent, UK;3. Royal Society of Chemistry, Thomas Graham House, Science Park, Milton Road, Cambridge, UK;4. Biotools, Inc., 17546 Bee Line Highway, Jupiter, FL 33458, USA |
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Abstract: | Libraries of highly enantioenriched secondary alcohols in both enantiomeric forms were synthesised by enzymatic reduction of their parent ketones using selectAZyme? carbonyl reductase (CRED) technology. Commercially available CREDs were able to reduce a range of substrate classes efficiently and with very high enantioselectivity. Matching substrate classes to small subsets of CREDs enabled the fast development of preparative bioreductions and the rapid generation of 100–1500 mg samples of chiral alcohols in typically >95% ee and the majority in ?99.0% ee. The conditions for small scale synthesis were then scaled up to 0.5 kg to deliver one of the chiral alcohols, (S)-1-(4-bromophenyl)-2-chloroethanol, in 99.8% ee and 91% isolated yield. |
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