Chemoenzymatic Route for the Synthesis of (S)‐Moprolol,a Potential β‐Blocker |
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| Authors: | Saptarshi Ghosh Jayeeta Bhaumik Linga Banoth Sooram Banesh Uttam Chand Banerjee |
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| Affiliation: | Department of Pharmaceutical Technology, National Institute of Pharmaceutical Education and Research, Punjab, India |
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| Abstract: | A biocatalytic route for the synthesis of a potential β‐blocker, (S)‐moprolol is reported here. Enantiopure synthesis of moprolol is mainly dependent on the chiral intermediate, 3‐(2‐methoxyphenoxy)‐propane‐1,2‐diol. Various commercial lipases were screened for the enantioselective resolution of (RS)‐3‐(2‐methoxyphenoxy)propane‐1,2‐diol to produce the desired enantiomer. Among them, Aspergillus niger lipase (ANL) was selected on the basis of both stereo‐ and regioselectivity. The optimized values of various reaction parameters were determined such as enzyme (15 mg/mL), substrate concentration (10 mM), organic solvent (toluene), reaction temperature (30 °C), and time (18 h).The optimized conditions led to achieving >49% yield with high enantiomeric excess of (S)‐3‐(2‐methoxyphenoxy)propane‐1,2‐diol. The lipase‐mediated catalysis showed regioselective acylation with dual stereoselectivity. Further, the enantiopure intermediate was used for the synthesis of (S)‐moprolol, which afforded the desired β‐blocker. Chirality 28:313–318, 2016. © 2016 Wiley Periodicals, Inc. |
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| Keywords: | β ‐blocker lipase stereoselectivity enantiopure moprolol |
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