Huang_2025_Bioorg.Chem_164_108858

Optically pure (S)-1-phenylethanol, a crucial synthetic intermediate widely applied in the pharmaceutical and food industries, is currently produced via well-established biological methods primarily relying on ketoreductase-mediated asymmetric synthesis and lipase-catalyzed kinetic resolution. This study presents a biocatalytic approach utilizing haloalkane dehalogenase DbjA for the kinetic resolution of racemic 1-chloro-1-phenylethane in organic solvents to synthesize (S)-1-phenylethanol. Following systematic optimization of reaction conditions, the system achieved an enantiomeric excess (ee) of 97 % for (S)-1-chloro-1-phenylethane and an (S)-1-phenylethanol yield of 46 % (ee > 99 %), demonstrating exceptional enantioselectivity (E = 536). Moreover, the catalytic system was effective in the conversion of diversely substituted aromatic substrates. Notably, a 50-fold scale-up of the reaction with the model substrate maintained a 42 % yield of (S)-1-phenylethanol with 98 % ee. This successful strategy offers a novel synthetic pathway for producing chiral 1-phenylethanol derivatives, which serve as valuable synthetic intermediates and flavoring agents.