title: Chemoenzymatic Route for the Synthesis of (S)-Moprolol, a Potential β-Blocker.
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.
authors.affiliation: Department of Pharmaceutical Technology, National Institute of Pharmaceutical Education and Research, Nagar, Punjab, India.
authors.forename: Saptarshi
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Department of Pharmaceutical Technology, National Institute of Pharmaceutical Education and Research, Nagar, Punjab, India.
authors.forename: Jayeeta
authors.initials: J
authors.lastname: Bhaumik
authors.affiliation: Department of Pharmaceutical Technology, National Institute of Pharmaceutical Education and Research, Nagar, Punjab, India.
authors.forename: Linga
authors.initials: L
authors.lastname: Banoth
authors.affiliation: Department of Pharmaceutical Technology, National Institute of Pharmaceutical Education and Research, Nagar, Punjab, India.
authors.forename: Sooram
authors.identifier: http://orcid.org/0000-0001-8229-8557
authors.initials: S
authors.lastname: Banesh
authors.affiliation: Department of Pharmaceutical Technology, National Institute of Pharmaceutical Education and Research, Nagar, Punjab, India.
authors.forename: Uttam Chand
authors.initials: UC
authors.lastname: Banerjee
mesh_terms: D000215:Acylation; D000319:Adrenergic beta-Antagonists / Q000737:chemistry* / Q000378:metabolism; D055162:Biocatalysis; D002384:Catalysis; D008049:Lipase / Q000737:chemistry* / Q000378:metabolism; D050198:Phenoxypropanolamines / Q000138:chemical synthesis*; D020005:Propanols / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: C000609710:3-(2-methoxyphenoxy)propane-1,2-diol; D000319:Adrenergic beta-Antagonists; D050198:Phenoxypropanolamines; D020005:Propanols; C009976:moprolol; D008049:Lipase
keywords: enantiopure; lipase; moprolol; stereoselectivity; β-blocker