Aim and Objective: The enzymatic method are used for the direct resolution of racemic atenolol.
The catalytic activities of nine commercially available lipases were firstly compared, then all enzymes were
tested for the kinetic resolution of (R,S)-atenolol by enantioselective acetylation in different reaction mediums.
Additionally, the effects of the acetylating agent and its concentration were also investigated. The most effective
conversion and the best enantioselectivity were achieved using lipase from Candida rugosa (OF).
Material and Method: Kinetic resolution of racemic atenolol was performed in various organic solvents with
the use of nine commercially available lipases. Additionally, the influence of different acetylating agents on
efficiency of studied kinetic resolution was tested. The enantioselective acetylation was begun by the addition
of native lipase to reaction mixture. Finally the samples were withdrawn at established time points and then
evaporated and redissolved in pure acetonitrile, filtered, and injected into the UPLC-MS/MS system.
Results: Among all tested catalytic systems the best results were obtained with the use of Candida rugosa OF
lipase, toluene as the reaction medium and isopropenyl acetate as the acetylating agent. The aforementioned
catalytic system made it possible to obtain enantiomerically pure (S)-atenolol acetate with eep = 92.9 %, with
conversion c = 46.3 % and enantioselectivity E = 66.9.
Conclusion: The reported results confirmed that nine commercially available lipases have different effects on
the kinetic resolution of (R,S)-atenolol. The type of lipase, the concentration and type of the acetylating
agent and the reaction medium have significant impacts on the efficiency of the catalyst system. However, it is
necessary to optimize the methods for the kinetic resolution of chiral drugs to obtain enantiomerically pure
products, and thus it is not possible to find a universal catalytic system for all syntheses, as each enzymatic
process requires an individual approach.