Ketone Reductase Biocatalysis in the Synthesis of Chiral Intermediates Toward Generic Active Pharmaceutical Ingredients

• DOI: 10.1021/acs.oprd.0c00120
• Publication Date: 2020-06-02T19:35:03Z
• Authors: Marina Y. Raynbird; Joanne B. Sampson; Dan A. Smith; Siân M. Forsyth; Jonathan D. Moseley; Andrew S. Wells
• Keywords: Biocatalysis; Enantiomeric excess

A range of generic active pharmaceutical ingredients were examined for potential chiral alcohol motifs and derivatives within their structures that could be employed as key synthetic intermediates. For seven (APIs), eight precursor ketones acquired then subjected to reduction by >400 commercially available ketone reductases from different suppliers. Positive screening results achieved five screened, with multiple each successful ketone. Selectivity was typically >99.5% ee in most cases, including the opposite enantiomer. The three best examples optimized quickly scaled up 1 L scale high conversion isolated yield while retaining selectivity desired This work illustrates where a wide enzymes are available, productive give either enantiomer can readily identified many rapidly produce alcohols. approach is particularly applicable generating API