Efficient, chemoenzymatic process for manufacture of the Boceprevir bicyclic [3.1.0]proline intermediate based on amine oxidase-catalyzed desymmetrization
| Autor: | Aleksey Zaks, Guy Gloor, James Lalonde, Ben Mijts, George T. F. Wong, Matt Tobin, Gjalt W. Huisman, Sheela Muley, Xiyun Zhang, Alexandre Ambrogelly, Azzeddine Lekhal, Tao Li, Tim Brennan, Jack Liang, Lisa M. Newman |
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| Rok vydání: | 2012 |
| Předmět: |
Amine oxidase
Proline Stereochemistry Chemistry Pharmaceutical Strecker amino acid synthesis Biochemistry Desymmetrization Antiviral Agents Catalysis chemistry.chemical_compound Colloid and Surface Chemistry Boceprevir Catalytic Domain Moiety Humans Monoamine Oxidase Bicyclic molecule Enantioselective synthesis Temperature Reproducibility of Results General Chemistry Hepatitis C Oxygen Kinetics chemistry Drug Design Amine gas treating |
| Zdroj: | Journal of the American Chemical Society. 134(14) |
| ISSN: | 1520-5126 |
| Popis: | The key structural feature in Boceprevir, Merck’s new drug treatment for hepatitis C, is the bicyclic [3.1.0]proline moiety “P2”. During the discovery and development stages, the P2 fragment was produced by a classical resolution approach. As the drug candidate advanced through clinical trials and approached regulatory approval and commercialization, Codexis and Schering–Plough (now Merck) jointly developed a chemoenzymatic asymmetric synthesis of P2 where the net reaction was an oxidative Strecker reaction. The key part of this reaction sequence is an enzymatic oxidative desymmetrization of the prochiral amine substrate. |
| Databáze: | OpenAIRE |
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