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Open AccessArticle

Lipase-Catalyzed Kinetic Resolution of Alcohols as Intermediates for the Synthesis of Heart Rate Reducing Agent Ivabradine

Department of Chemistry, Materials and Chemical Engineering Giulio Natta, Politecnico di Milano, Via Mancinelli 7, 20131 Milano, Italy
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Catalysts 2021, 11(1), 53; https://doi.org/10.3390/catal11010053
Received: 13 December 2020 / Revised: 27 December 2020 / Accepted: 30 December 2020 / Published: 1 January 2021
(This article belongs to the Special Issue Biocatalytic Resolution of Chiral Molecules)
Ivabradine (Corlanor®), is a chiral benzocycloalkane currently employed and commercialized for the treatment of chronic stable angina pectoris and for the reduction in sinus tachycardia. The eutomer (S)-ivabradine is usually produced via chiral resolution of intermediates, by employing enantiopure auxiliary molecules or through preparative chiral HPLC separations. Recently, more sustainable biocatalytic approaches have been reported in literature for the preparation of the chiral amine precursor. In this work, we report on a novel biocatalyzed pathway, via a resolution study of a key alcohol intermediate used as a precursor of the chiral amine. After screening several enzymatic reaction conditions, employing different lipases and esterases both for the esterification and hydrolysis reactions, the best result was achieved with Pseudomonas cepacia Lipase and the final product was obtained in up to 96:4 enantiomeric ratio (e.r.) of an ivabradine alcohol precursor. This enantiomer was then efficiently converted into the desired amine in a facile three step synthetic sequence. View Full-Text
Keywords: lipase; esterase; kinetic resolution; biocatalysis; chiral alcohol; ivabradine lipase; esterase; kinetic resolution; biocatalysis; chiral alcohol; ivabradine
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MDPI and ACS Style

Morandini, A.; Rossetti, A.; Sacchetti, A. Lipase-Catalyzed Kinetic Resolution of Alcohols as Intermediates for the Synthesis of Heart Rate Reducing Agent Ivabradine. Catalysts 2021, 11, 53. https://doi.org/10.3390/catal11010053

AMA Style

Morandini A, Rossetti A, Sacchetti A. Lipase-Catalyzed Kinetic Resolution of Alcohols as Intermediates for the Synthesis of Heart Rate Reducing Agent Ivabradine. Catalysts. 2021; 11(1):53. https://doi.org/10.3390/catal11010053

Chicago/Turabian Style

Morandini, Anna; Rossetti, Arianna; Sacchetti, Alessandro. 2021. "Lipase-Catalyzed Kinetic Resolution of Alcohols as Intermediates for the Synthesis of Heart Rate Reducing Agent Ivabradine" Catalysts 11, no. 1: 53. https://doi.org/10.3390/catal11010053

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