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

Research output: Contribution to journal › Article › peer-review

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

Original language	English
Pages (from-to)	388-395
Number of pages	8
Journal	Green Chemistry
Volume	23
Issue number	1
DOIs	https://doi.org/10.1039/D0GC03358H
Publication status	Published - 7 Jan 2021

ASJC Scopus subject areas

Pollution
Environmental Chemistry

Fields of Expertise

Human- & Biotechnology

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10.1039/D0GC03358HLicence: CC BY-NC 4.0

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

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",

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

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doi = "10.1039/D0GC03358H",

language = "English",

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AU - Arndt, Sebastian

AU - Grill, Birgit

AU - Schwab, Helmut

AU - Steinkellner, Georg

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

PY - 2021/1/7

Y1 - 2021/1/7

N2 - 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

AB - 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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JF - Green Chemistry

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

Abstract

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

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

Cite this

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

Access to Document

Other files and links

Fingerprint

Activities

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

Research output

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

Cite this