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Synfacts 2010(5): 0503-0503  
DOI: 10.1055/s-0029-1219648
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of Montelukast

Contributor(s): Philip Kocienski
J. Liang*, J. Lalonde, B. Borup, V. Mitchell, E. Mundorff, N. Trinh, D. A. Kochrekar, R. N. Cherat, G. G. Pai
Codexis, Inc., Redwood City, USA and Arch PharmaLabs Limited, Mumbai, India
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Publication History

Publication Date:
22 April 2010 (online)

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Significance

Montelukast sodium (Singulair®) is a leukotriene receptor antagonist prescribed for the treatment of asthma and allergies. Workers at Codexis used directed evolution and high-throughput screening to engineer a robust and efficient ketoreductase enzyme (CDX-026) that accomplished the asymmetric reduction of ketone A, which is essentially water insoluble, at a loading of 100 g/L in the presence of ca. 70% organic solvents at 45 ˚C. The (S)-alcohol B was obtained in >95% yield in >99.9% ee and in >98.5% purity on a >500 mol scale.