Preparation of pharmaceutical important fluorinated 1-arylethanols using isolated enzymes

Fluorinated 1-arylethanols are important building blocks in medicinal chemistry especially for preparing kinase inhibitors for cancer therapy, NK1 receptor antagonists and drugs used in treatment of osteoporosis. Asymmetric reduction of carbonyl groups using enzymes is one of the key technologies to obtain such molecules in enantiomerically pure form. By using isolated enzymes coupled with cofactor recycling, highly concentrated, robust and economical processes can be developed. The aim of this review is to give an overview of biocatalytic carbonyl reduction with special focus on processing of fluoro containing 1-arylethanones with enzymes in cell free systems. The methodologies applied to improve the reactions are highlighted, alongside potential application of the building blocks in bioactive compounds. Enzymatic ketone reduction is concluded to be most beneficial as compared to chemo catalytic methods in transformations of highly fluorinated and therefore electron deficient ketones. A high enantiomeric excess can be achieved, and by changing the catalyst, both enantiomers are accessible. High rates are often seen for such electron deficient ketones, and the reactions have a favourable equilibrium position.