Asymmetric Synthesis of CF3-Substituted β-Hydroxyketones and 1,3-Diols by Engineered Ketoreductases

Chiral CF₃-substituted β-hydroxy ketones and 1,3-diols were prepared via the ketoreductase-catalyzed asymmetric reduction of the corresponding benzoyl trifluoroacetones. The variants of two ketoreductases, LfSDR1 and CgKR1, were screened or engineered for stereocomplementary synthesis of CF₃-substituted β-hydroxy ketones with up to >99% conversions and up to >99% enantiomeric excess (ee) values. In addition, the cascade reduction or one pot reduction of diketones could afford the CF₃-substituted 1,3-diols with up to >99% ratios and >99% ee values.