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

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

Access to Document

10.1039/D0GC03358HLicence: CC BY-NC

Link to publication in Scopus

Fingerprint Dive into the research topics of 'The sustainable synthesis of levetiracetam by an enzymatic dynamic kinetic resolution and an ex-cell anodic oxidation'. Together they form a unique fingerprint.

Cite this

The sustainable synthesis of levetiracetam by an enzymatic dynamic kinetic resolution and an ex-cell anodic oxidation. / Arndt, Sebastian; Grill, Birgit ; Schwab, Helmut; Steinkellner, Georg; Weis, Dominik; Pogorevcnik, Urska; Nauth, Alexander; Gruber, Karl; Opatz, Till; Donsbach, Kai; Waldvogel, Siegfried R.; Winkler, Margit.

In: Green Chemistry, Vol. 23, No. 1, 07.01.2021, p. 388-395.

Research output: Contribution to journal › Article

Arndt, Sebastian ; Grill, Birgit ; Schwab, Helmut ; Steinkellner, Georg ; Weis, Dominik ; Pogorevcnik, Urska ; Nauth, Alexander ; Gruber, Karl ; Opatz, Till ; Donsbach, Kai ; Waldvogel, Siegfried R. ; Winkler, Margit. / The sustainable synthesis of levetiracetam by an enzymatic dynamic kinetic resolution and an ex-cell anodic oxidation. In: Green Chemistry. 2021 ; Vol. 23, No. 1. pp. 388-395.

@article{4bde75364e144b978b11542fa0d9a876,

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",

year = "2021",

month = jan,

day = "7",

doi = "10.1039/D0GC03358H",

language = "English",

volume = "23",

pages = "388--395",

journal = "Green Chemistry",

issn = "1463-9262",

publisher = "Royal Society of Chemistry",

number = "1",

}

TY - JOUR

T1 - The sustainable synthesis of levetiracetam by an enzymatic dynamic kinetic resolution and an ex-cell anodic oxidation

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

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

U2 - 10.1039/D0GC03358H

DO - 10.1039/D0GC03358H

M3 - Article

VL - 23

SP - 388

EP - 395

JO - Green Chemistry

JF - Green Chemistry

SN - 1463-9262

IS - 1

ER -