Highly efficient resolution of mandelic acid using lipase from Pseudomonas stutzeri LC2-8 and a molecular modeling approach to rationalize its enantioselectivity

•High efficient resolution of (R,S)-mandelic acid was achieved using lipase LC2-8.•Lipase LC2-8 exhibited high substrate concentration tolerance and enantioselectivity.•Enantioselectivity of lipase was rationalized by analysis of molecular modeling.

Mandelic acid, a key precursor of chiral synthons, was successfully acylated in diisopropyl ether. The reaction was catalyzed by the lipase from Pseudomonas stutzeri LC2-8, and vinyl acetate was employed as acyl donor. Under the optimized reaction conditions, a resolution of 180 mM (55 g/L) mandelic acid was achieved. (S)-O-Acetyl mandelic acid was enantioselectivity formed in >99% ee at a yield close to the maximum theoretical value for kinetic resolution (50%). The highly substrate tolerable and enantioselective nature of lipase LC2-8 suggests that it is of great potential for the practical resolution of racemic mandelic acid. Additionally, the high enantiopreference of lipase LC2-8 toward (S)-mandelic acid in acetylation was also rationalized through molecular docking and molecular dynamics simulations.

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