Reactions catalyzed by various types of hydrolases are predominant among biotransformations. Lack of sensitive cofactors, which have to be recycled, makes them particularly attractive for organic synthesis. Among hydrolytic enzymes lipases and esterases are frequently used because they accept a broad range of substrates and often exhibit high enantioselectivity. Lipase-catalyzed reactions in organic solvents are becoming increasingly important in enantioselective synthetic chemistry, as the reactions which are sensitive to water can be effectively carried out in organic media.

Biocatalytic methods of obtaining homochiral β-blockers that are focused on production of versatile precursors are widely described in literature. Halohydrins are the established intermediates in the preparation of optically active β-blockers. Their resolution by esterhydrolases has been described as a standard alternative in preparation of the homochiral propranolol, atenolol, practolol [1].

In this study we report lipase-catalyzed kinetic resolution of a chiral intermediate H1 of bupranolol (BUP):1-chloro-3-(2-chloro-
5-methylphenoxy)propan-2-ol.
Bupranolol demonstrates antagonistic activity against all known subtypes of β-adrenoceptors (β-AR), including the low affinity state of β₁-AR (also known as atypical β-adrenoceptors) [2]. It contains a chiral center and studies in vitro proved that among 12 β-blocking agents - levorotatory enantiomer of BUP is the most potent [3]. The structure of BUP is similar to that of most other β-blockers; a tertiary butyl group replaces the more common isopropyl group and it contains substituents in ortho- and meta- positions of phenyl ring.

References
[1] Żelaszczyk, D. et al. Curr Med Chem, 2007, 14: 53-65;
[2] Malinowska, B. et al. Kardiol Pol, 2005, 63 (Supl. 2): 399-408;
[3] Joseph, S S. et al. Naunyn-Schmiedeberg’s Arch Pharmacol, 2004, 369: 525–532.

Acknowledgements

This work was supported by the Polish Ministry of Science and Higher Education grant No N405 018 32/1604.

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