The Use of Ion Liquids as a Trojan Horse Strategy in Enzyme-Catalyzed Biotransformation of (R,S)-Atenolol

Abstract

The enzymatic method was used for the direct biotransformation of racemic atenolol. The catalytic activities of commercially available lipases from Candida rugosa were tested for the kinetic resolution of (R,S)-atenolol by enantioselective acetylation in various two-phase reaction media containing ionic liquids. The composed catalytic system gave the possibility to easy separate substrates and products of the conducted enantioselective reaction and after specific procedure to reuse utilized enzymes in another catalytic cycle.

Synthesis of Enantiopure (S)-Atenolol by Utilization of Lipase-Catalyzed Kinetic Resolution of a Key Intermediate

“…The racemic compound with t R = 14.15 min and t R = 16.94 min is anticipated to be the enantiomers of the amide product 4d ( Scheme 4 ). Chałupka (Sikora) et al claim that they have succeeded in resolving racemic atenolol with Candida rugosa lipase with vinyl acetate as the acyl donor and ionic liquids/toluene as the solvent yielding 94% ee of the ( S )-atenolol acetate [ 11 ]. However, the absolute configuration of this product has not been confirmed.…”

“…Sikora et al reported in 2020 the kinetic resolution of racemic atenolol catalyzed by lipase from Candida rugosa with isopropenyl acetate as the acyl donor, resulting in the acetate of ( S )-atenolol in 94% ee . The authors present no evidence of the absolute configuration of this acetate, nor of the unreacted ( R )-atenolol [ 11 , 12 ]. The authors have previously published several articles on lipase catalyzed kinetic resolution of racemic atenolol with the amide of ( S )-atenolol presented as the acetate [ 13 , 14 , 15 ].…”

Sustainable Synthesis of the Active Pharmaceutical Ingredient Atenolol in Deep Eutectic Solvents

“…Most of these methods rely on the use of toxic or expensive unusual catalysts [ 9 , 10 , 11 , 12 , 13 ], Volatile Organic Compound (VOC)-based harmful solvents [ 9 , 10 , 11 , 12 ], as well as high reaction temperatures [ 14 ], harsh reaction conditions, long reaction times [ 15 ], and solubility issues [ 16 ], which can hamper the efficiency and scalability of the synthesis. Various strategies have been proposed for the enzymatic kinetic resolution of racemic atenolol, as well as for the enantioselective synthesis of the ( S )-enantiomer to which the maximum 1-blocking activity is attributed [ 17 , 18 , 19 , 20 , 21 ]. Although the efficient methods that lead to the formation of enantiomerically pure ( S )-atenolol can be of interest to the pharmaceutical industry and academia, the proposed routes use multistep procedures with a low overall yield, thus not aligning with the current environmental challenges [ 17 , 18 , 19 ].…”