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

Mariani Rajin; Asiah Zulkifli; Sariah Abang; S. M. Annissuzzaman; Azlina Harun Kamaruddin

Mariani Rajin Chemical Engineering Program, Faculty of Engineering, Universiti Malaysia Sabah, Kota Kinabalu, Sabah
Asiah Zulkifli Chemical Engineering Program, Faculty of Engineering, Universiti Malaysia Sabah, Kota Kinabalu, Sabah
Sariah Abang Chemical Engineering Program, Faculty of Engineering, Universiti Malaysia Sabah, Kota Kinabalu, Sabah
S. M. Annissuzzaman Chemical Engineering Program, Faculty of Engineering, Universiti Malaysia Sabah, Kota Kinabalu, Sabah
Azlina Harun Kamaruddin School of Chemical Engineering, Engineering Campus, Universiti Sains Malaysia, Nibong Tebal, Penang

Keywords: Beta-blocker, Chiral drug, Metoprolol, Kinetic resolution, Lipase

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 (X_S) of 52%, enantiomeric excess of substrate, (ee_s) of 92% and product (ee_P) 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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