The Utilization of Two-Phase Catalytic System in Enantioselective Biotransformation of Racemic Atenolol

Chałupka, Joanna; Sikora, Adam; Marszałł, Michał Piotr

doi:10.3390/catal12091068

Cited by 3 publications

(3 citation statements)

References 42 publications

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“…Since the biocatalysts can be easily separated from the substrate and the product, the lipase can be reused in another reaction. This approach has been comprehensively described elsewhere in kinetic resolutions of various racemic compounds using ionic liquids [ 29 , 48 , 49 ]. Furthermore, it should be emphasized that the solubility of racemic clopidogrel carboxylic acid in organic solvents is relatively low and requires more significant volumes of the reaction medium, which could have a negative impact on the environment.…”

Section: Discussionmentioning

confidence: 99%

Bio-Approach for Obtaining Enantiomerically Pure Clopidogrel with the Use of Ionic Liquids

Chałupka

Sikora

Ziegler-Borowska

et al. 2023

IJMS

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Clopidogrel is a chiral compound widely used as an antiplatelet medication that lowers the risk of blood clots, strokes, and heart attacks. The main aim of the study presented herein was to obtain (S)-clopidogrel, which is commercially available in treatments, via the kinetic resolution of racemic clopidogrel carboxylic acid with the use of lipase from Candida rugosa and a two-phase reaction medium containing an ionic liquid. For this purpose, the enantioselective biotransformation of clopidogrel carboxylic acid and chiral chromatographic separation with the use of a UPLC-MS/MS system were optimized. The best kinetic resolution parameters were obtained by using a catalytic system containing lipase from Candida rugosa OF as a biocatalyst, cyclohexane and [EMIM][BF4] as a two-phase reaction medium, and methanol as an acyl acceptor. The enantiomeric excess of the product was eep = 94.21% ± 1.07 and the conversion was c = 49.60% ± 0.57%, whereas the enantioselectivity was E = 113.40 ± 1.29. The performed study proved the possibility of obtaining (S)-clopidogrel with the use of lipase as a biocatalyst and a two-phase reaction medium containing an ionic liquid, which is in parallel with green chemistry methodology and does not require environmentally harmful conditions.

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Section: Discussionmentioning

confidence: 99%

Bio-Approach for Obtaining Enantiomerically Pure Clopidogrel with the Use of Ionic Liquids

Chałupka

Sikora

Ziegler-Borowska

et al. 2023

IJMS

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“…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 ].…”

Section: Introductionmentioning

confidence: 99%

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

Hansen,

Tennfjord,

Blindheim

et al. 2024

IJMS

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(S)-Atenolol ((S)-2-(4-(2-Hydroxy-3-(isopropylamino)propoxy)phenyl)acetamide) has been synthesized in >99% enantiomeric excess (ee) with the use of Candida antarctica lipase B from Syncozymes (Shanghai, China), in a kinetic resolution of the corresponding racemic chlorohydrin. A catalytic amount of base was used in deprotonation of the phenol building block. The enantiopurity of the chlorohydrin building block remained unchanged upon subsequent amination to yield the final drug. All four steps in the synthesis protocol have been optimized compared to previously reported methods, which makes this new protocol more sustainable and in accordance with green chemistry principles. The overall yield of (S)-atenolol was 9.9%, which will be further optimized.

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“…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 ].…”

Section: Introductionmentioning

confidence: 99%

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

Procopio,

Siciliano,

Perri

et al. 2024

IJMS

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Atenolol, one of the top five best-selling drugs in the world today used to treat angina and hypertension, and to reduce the risk of death after a heart attack, faces challenges in current synthetic methods to address inefficiencies and environmental concerns. The traditional synthesis of this drug involves a process that generates a large amount of waste and other by-products that need disposal. This study presents a one-pot DES-based sustainable protocol for synthesizing atenolol. The use of the DES allowed the entire process to be conducted with no need for additional bases or catalysts, in short reaction times, under mild conditions, and avoiding chromatographic purification. The overall yield of atenolol was 95%. The scalability of the process to gram-scale production was successfully demonstrated, emphasizing its potential in industrial applications. Finally, the ‘greenness’ evaluation, performed using the First Pass CHEM21 Metrics Toolkit, highlighted the superiority in terms of the atom economy, the reaction mass efficiency, and the overall process mass intensity of the DES-based synthesis compared with the already existing methods.

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The Utilization of Two-Phase Catalytic System in Enantioselective Biotransformation of Racemic Atenolol

Cited by 3 publications

References 42 publications

Bio-Approach for Obtaining Enantiomerically Pure Clopidogrel with the Use of Ionic Liquids

Bio-Approach for Obtaining Enantiomerically Pure Clopidogrel with the Use of Ionic Liquids

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

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

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