<i>Gordonia hydrophobica</i> Nitrile Hydratase for Amide Preparation from Nitriles
The active pharmaceutical ingredient levetiracetam has anticonvulsant properties and is used to treat epilepsies. Herein, we describe the enantioselective preparation of the levetiracetam precursor 2-(pyrrolidine-1-yl)butanamide by enzymatic dynamic kinetic resolution with a nitrile hydratase enzyme...
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MDPI AG
2021-10-01
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| Online Access: | https://www.mdpi.com/2073-4344/11/11/1287 |
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| author | Birgit Grill Melissa Horvat Helmut Schwab Ralf Gross Kai Donsbach Margit Winkler |
| author_facet | Birgit Grill Melissa Horvat Helmut Schwab Ralf Gross Kai Donsbach Margit Winkler |
| author_sort | Birgit Grill |
| collection | DOAJ |
| description | The active pharmaceutical ingredient levetiracetam has anticonvulsant properties and is used to treat epilepsies. Herein, we describe the enantioselective preparation of the levetiracetam precursor 2-(pyrrolidine-1-yl)butanamide by enzymatic dynamic kinetic resolution with a nitrile hydratase enzyme. A rare representative of the family of iron-dependent nitrile hydratases from <i>Gordonia hydrophobica</i> (<i>Gh</i>NHase) was evaluated for its potential to form 2-(pyrrolidine-1-yl)butanamide in enantioenriched form from the three small, simple molecules, namely, propanal, pyrrolidine and cyanide. The yield and the enantiomeric excess (<i>ee</i>) of the product are determined most significantly by the substrate concentrations, the reaction pH and the biocatalyst amount. <i>Gh</i>NHase is also active for the hydration of other nitriles, in particular for the formation of <i>N</i>-heterocyclic amides such as nicotinamide, and may therefore be a tool for the preparation of various APIs. |
| first_indexed | 2024-03-10T05:38:25Z |
| format | Article |
| id | doaj.art-806021d901a34b0cb1bbf25b458befe4 |
| institution | Directory Open Access Journal |
| issn | 2073-4344 |
| language | English |
| last_indexed | 2024-03-10T05:38:25Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Catalysts |
| spelling | doaj.art-806021d901a34b0cb1bbf25b458befe42023-11-22T22:44:58ZengMDPI AGCatalysts2073-43442021-10-011111128710.3390/catal11111287<i>Gordonia hydrophobica</i> Nitrile Hydratase for Amide Preparation from NitrilesBirgit Grill0Melissa Horvat1Helmut Schwab2Ralf Gross3Kai Donsbach4Margit Winkler5Austrian Center of Industrial Biotechnology GmbH, Krenngasse 37, 8010 Graz, AustriaInstitute for Molecular Biotechnology, Graz University of Technology, NAWI Graz, Petersgasse 14, 8010 Graz, AustriaAustrian Center of Industrial Biotechnology GmbH, Krenngasse 37, 8010 Graz, AustriaPharmaZell GmbH, Rosenheimer Str. 43, 83064 Raubling, GermanyPharmaZell GmbH, Rosenheimer Str. 43, 83064 Raubling, GermanyAustrian Center of Industrial Biotechnology GmbH, Krenngasse 37, 8010 Graz, AustriaThe active pharmaceutical ingredient levetiracetam has anticonvulsant properties and is used to treat epilepsies. Herein, we describe the enantioselective preparation of the levetiracetam precursor 2-(pyrrolidine-1-yl)butanamide by enzymatic dynamic kinetic resolution with a nitrile hydratase enzyme. A rare representative of the family of iron-dependent nitrile hydratases from <i>Gordonia hydrophobica</i> (<i>Gh</i>NHase) was evaluated for its potential to form 2-(pyrrolidine-1-yl)butanamide in enantioenriched form from the three small, simple molecules, namely, propanal, pyrrolidine and cyanide. The yield and the enantiomeric excess (<i>ee</i>) of the product are determined most significantly by the substrate concentrations, the reaction pH and the biocatalyst amount. <i>Gh</i>NHase is also active for the hydration of other nitriles, in particular for the formation of <i>N</i>-heterocyclic amides such as nicotinamide, and may therefore be a tool for the preparation of various APIs.https://www.mdpi.com/2073-4344/11/11/1287small moleculedynamic kinetic resolutionlevetiracetamnitrile hydrataseamino amideamino nitrile |
| spellingShingle | Birgit Grill Melissa Horvat Helmut Schwab Ralf Gross Kai Donsbach Margit Winkler <i>Gordonia hydrophobica</i> Nitrile Hydratase for Amide Preparation from Nitriles Catalysts small molecule dynamic kinetic resolution levetiracetam nitrile hydratase amino amide amino nitrile |
| title | <i>Gordonia hydrophobica</i> Nitrile Hydratase for Amide Preparation from Nitriles |
| title_full | <i>Gordonia hydrophobica</i> Nitrile Hydratase for Amide Preparation from Nitriles |
| title_fullStr | <i>Gordonia hydrophobica</i> Nitrile Hydratase for Amide Preparation from Nitriles |
| title_full_unstemmed | <i>Gordonia hydrophobica</i> Nitrile Hydratase for Amide Preparation from Nitriles |
| title_short | <i>Gordonia hydrophobica</i> Nitrile Hydratase for Amide Preparation from Nitriles |
| title_sort | i gordonia hydrophobica i nitrile hydratase for amide preparation from nitriles |
| topic | small molecule dynamic kinetic resolution levetiracetam nitrile hydratase amino amide amino nitrile |
| url | https://www.mdpi.com/2073-4344/11/11/1287 |
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