The sustainable synthesis of levetiracetam by an enzymatic dynamic kinetic resolution and an ex-cell anodic oxidation

Sebastian Arndt; Birgit Grill; Helmut Schwab; Georg Steinkellner; Dominik Weis; Urska Pogorevcnik; Alexander Nauth; Karl Gruber; Till Opatz; Kai Donsbach; Siegfried R. Waldvogel; Margit Winkler

doi:10.1039/D0GC03358H

The sustainable synthesis of levetiracetam by an enzymatic dynamic kinetic resolution and an ex-cell anodic oxidation

Sebastian Arndt, Birgit Grill, Helmut Schwab, Georg Steinkellner, Dominik Weis, Urska Pogorevcnik, Alexander Nauth, Karl Gruber, Till Opatz, Kai Donsbach, Siegfried R. Waldvogel, Margit Winkler

Publikation: Beitrag in einer Fachzeitschrift › Artikel › Begutachtung

Abstract

Levetiracetam is an active pharmaceutical ingredient widely used to treat epilepsy. We describe a new synthesis of levetiracetam by a dynamic kinetic resolution and a ruthenium-catalysed ex-cell anodic oxidation. For the enzymatic resolution, we tailored a high throughput screening method to identify Comamonas testosteroni nitrile hydratase variants with high (S)-selectivity and activity. Racemic nitrile was applied in a fed-batch reaction and was hydrated to (S)-(pyrrolidine-1-yl)butaneamide. For the subsequent oxidation to levetiracetam, we developed a ligand-free ruthenium-catalysed method at a low catalyst loading. The oxidant was electrochemically generated in 86% yield. This route provides a significantly more sustainable access to levetiracetam than existing routes. This journal is

Originalsprache	englisch
Seiten (von - bis)	388-395
Seitenumfang	8
Fachzeitschrift	Green Chemistry
Jahrgang	23
Ausgabenummer	1
DOIs	https://doi.org/10.1039/D0GC03358H
Publikationsstatus	Veröffentlicht - 7 Jan. 2021

ASJC Scopus subject areas

Umweltverschmutzung
Umweltchemie

Fields of Expertise

Human- & Biotechnology

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10.1039/D0GC03358HLizenz: CC BY-NC 4.0

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http://www.scopus.com/inward/record.url?scp=85099731233&partnerID=8YFLogxK

1 Posterpräsentation

Sustainable synthesis of levetiracetam: enzymatic dynamic kinetic resolution and an ex-cell anodic oxidation
Margit Winkler (Redner/in), Birgit Grill (Beitragende/r), Karin Reicher (Beitragende/r), Helmut Schwab (Beitragende/r), Urska Pogorevcnik (Beitragende/r), Sebastian Arndt (Beitragende/r), Alexander Nauth (Beitragende/r), Georg Steinkellner (Beitragende/r), Gernot Strohmeier (Beitragende/r), Karl Gruber (Beitragende/r), Kai Donsbach (Beitragende/r), Siegfried R. Waldvogel (Beitragende/r) & Till Opatz (Beitragende/r)
19 Juli 2021 → 22 Juli 2021
Aktivität: Vortrag oder Präsentation › Posterpräsentation › Science to science

4 Poster
2 Artikel
2 Patent

Enantioselective chemo-enzymatic synthesis of optically active amino amide compounds
Grill, B. (Erfinder), Winkler, M. (Erfinder), Schwab, H. (Erfinder), Strohmeier, G. (Erfinder), Donsbach, K. (Erfinder), Waldvogel, S. R. (Erfinder), Arndt, S. (Erfinder) & Weis, D. (Erfinder), 15 Juni 2023, Patent Nr. US20230183177A1, 23 Apr. 2021, Prioritätsnr. EP20171351.8
Publikation: Schutzrecht › Patent
Enzymatic dynamic kinetic resolution and ex-cell anodic oxidation for Levetiracetam synthesis
Winkler, M., Grill, B., Reicher, K., Schwab, H., Arndt, S., Nauth, A., Steinkellner, G., Donsbach, K., Waldvogel, S. R. & Opatz, T., 15 Nov. 2022.
Publikation: Konferenzbeitrag › Poster
Enantioselective chemo-enzymatic synthesis of optically active amino amide compounds
Grill, B. (Erfinder), Winkler, M. (Erfinder), Schwab, H. (Erfinder), Strohmeier, G. (Erfinder), Donsbach, K. (Erfinder), Waldvogel, S. R. (Erfinder), Arndt, S. (Erfinder) & Weis, D. (Erfinder), 28 Okt. 2021, Patent Nr. WO2021/214283 A1, Prioritätsdatum 24 Apr. 2020, Prioritätsnr. EP20171351.8
Publikation: Schutzrecht › Patent

Dieses zitieren

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abstract = "Levetiracetam is an active pharmaceutical ingredient widely used to treat epilepsy. We describe a new synthesis of levetiracetam by a dynamic kinetic resolution and a ruthenium-catalysed ex-cell anodic oxidation. For the enzymatic resolution, we tailored a high throughput screening method to identify Comamonas testosteroni nitrile hydratase variants with high (S)-selectivity and activity. Racemic nitrile was applied in a fed-batch reaction and was hydrated to (S)-(pyrrolidine-1-yl)butaneamide. For the subsequent oxidation to levetiracetam, we developed a ligand-free ruthenium-catalysed method at a low catalyst loading. The oxidant was electrochemically generated in 86% yield. This route provides a significantly more sustainable access to levetiracetam than existing routes. This journal is",

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AU - Weis, Dominik

AU - Pogorevcnik, Urska

AU - Nauth, Alexander

AU - Gruber, Karl

AU - Opatz, Till

AU - Donsbach, Kai

AU - Waldvogel, Siegfried R.

AU - Winkler, Margit

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The sustainable synthesis of levetiracetam by an enzymatic dynamic kinetic resolution and an ex-cell anodic oxidation

Abstract

ASJC Scopus subject areas

Fields of Expertise

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Sustainable synthesis of levetiracetam: enzymatic dynamic kinetic resolution and an ex-cell anodic oxidation

Publikationen

Enantioselective chemo-enzymatic synthesis of optically active amino amide compounds

Enzymatic dynamic kinetic resolution and ex-cell anodic oxidation for Levetiracetam synthesis

Enantioselective chemo-enzymatic synthesis of optically active amino amide compounds

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