BIOCATALYTIC SYNTHESIS OF (S)-MOPROLOL
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Scheme 6. Synthesis of (S)-moprolol 6 from the enantiopure diol.
(
at ~4.1 ppm) at the final stage, indicating that the secondary
1
alcohol remained intact or unreacted. H NMR signal of meth-
ylene protons adjacent to primary hydroxyl group appeared at
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3.7 ppm as a multiplate. In final compound (S)-6, the proton
10:4261–4264.
signal shifted upfield (~2.7 ppm) due to the change in the
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1
0
the reaction steps (four steps reported by Kamal et al. ) from
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CONCLUSION
Efficient chemoenzymatic synthesis of the enantiomerically
pure (S)-moprolol is reported in this study with improved over-
all yield and high ee. Among the various commercial lipases
screened, ANL showed both regio- and stereoselectivity for
the transesterification of (RS)-3 with vinyl acetate as the acyl
donor to afford the key intermediate (S)-3 for the synthesis
of (S)-moprolol. Various reaction parameters were optimized
such as reaction time, solvent, temperature, enzyme, and
substrate concentration for the kinetic resolution of (RS)-
1
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3
-(2-methoxy-phenoxy)propane-1,2-diol (3). Under the opti-
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(
S)-5 (50%) with high ee. By the deacylation of enantiopure
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acylated derivative, the chiral diol intermediate was obtained,
which was further used for the synthesis of (S)-moprolol.
Synthesizing the enantiopure diol by enzymatic resolution is
comparatively cheaper over the chemical route, which makes
the process cost-effective. The enzymatic switch towards the
synthesis of (S)-moprolol sets an excellent example of green
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1
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ACKNOWLEDGMENTS
SG acknowledges the financial support by Indian Council of
Medical Research, Govt. of India to carry out this research
project. LB acknowledges Council of Scientific and Industrial
Research, Govt. of India for providing financial support for
this work. JB and LB contributed equally to this work.
SUPPORTING INFORMATION
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2
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Additional supporting information may be found in the
online version of this article at the publisher’s web-site.
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Chirality DOI 10.1002/chir