Effect of Reaction Parameters on the Lipase-Catalyzed Kinetic Resolution of (RS )-Metoprolol

Racemic metoprolol is a selective ß1-blocker, which is used in cardiovascular disease treatment. It has been found that (S)-metoprolol has a higher affinity to bind the ß-adrenergic receptor compared to (R)-metoprolol. Moreover, the regulatory authorities’ high market demand and guidelines have incr...

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Bibliographic Details
Published in:ASEAN Journal of Chemical Engineering
Main Authors: Rajin, Mariani, Zulkifli, Asiah binti, Abang, Sariah, Anissuzzaman, S.M, Kamaruddin, Azlina Harun
Other Authors: Ministry of Higher Education (MOHE) of Malaysia (Grant no: FRGS/1/2017/TK02/UMS/02/1)
Format: Article in Journal/Newspaper
Language:English
Published: Department of Chemical Engineering, Universitas Gadjah Mada 2020
Subjects:
Beta-blocker
Chiral drug
Metoprolol
Kinetic resolution
Lipase
Antarc*
Antarctica
Online Access:https://jurnal.ugm.ac.id/AJChE/article/view/51857
https://doi.org/10.22146/ajche.51857
Description
Summary:Racemic metoprolol is a selective ß1-blocker, which is used in cardiovascular disease treatment. It has been found that (S)-metoprolol has a higher affinity to bind the ß-adrenergic receptor compared to (R)-metoprolol. Moreover, the regulatory authorities’ high market demand and guidelines have increased the preference for single enantiomer drugs. In this work, the lipase-catalyzed kinetic resolution of racemic metoprolol was performed to obtain the desired enantiomer. The type of lipase, acyl donor, and solvent were screened out. This was achieved by Candida antarctica B lipase-catalyzed transesterification of racemic metoprolol in hexane and vinyl acetate as the solvent and an acyl donor, which gave maximum conversion of (S)-metoprolol (XS) of 52%, enantiomeric excess of substrate, (ees) of 92% and product (eeP) of 90% with enantiomeric ratio (E) of 62. This method can be considered as green chemistry, which can be applied to produce other enantiopure beta-blockers.

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