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

https://doi.org/10.22146/ajche.51857

Mariani Rajin(1*), Asiah binti Zulkifli(2), Sariah Abang(3), S.M Anissuzzaman(4), Azlina Harun Kamaruddin(5)

(1) Chemical Engineering Program, Faculty of Engineering, Universiti Malaysia Sabah, Kota Kinabalu, Sabah
(2) Chemical Engineering Program, Faculty of Engineering, Universiti Malaysia Sabah, Kota Kinabalu, Sabah
(3) Chemical Engineering Program, Faculty of Engineering, Universiti Malaysia Sabah, Kota Kinabalu, Sabah
(4) Chemical Engineering Program, Faculty of Engineering, Universiti Malaysia Sabah, Kota Kinabalu, Sabah
(5) School of Chemical Engineering, Engineering Campus, Universiti Sains Malaysia, Nibong Tebal, Penang
(*) Corresponding Author

Abstract


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.


Keywords


Beta-blocker; Chiral drug; Metoprolol; Kinetic resolution; Lipase

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DOI: https://doi.org/10.22146/ajche.51857

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ASEAN Journal of Chemical Engineering  (print ISSN 1655-4418; online ISSN 2655-5409) is published by Chemical Engineering Department, Faculty of Engineering, Universitas Gadjah Mada.