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

  • 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 (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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Published
2020-06-30
How to Cite
Rajin, M., Zulkifli, A., Abang, S., Annissuzzaman, S. M., & Kamaruddin, A. H. (2020). Effect of Reaction Parameters on the Lipase-Catalyzed Kinetic Resolution of (RS )-Metoprolol. ASEAN Journal of Chemical Engineering, 20(1), 20-30. Retrieved from https://jurnal.ugm.ac.id/v3/AJChE/article/view/9096
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Articles