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 journalArticle

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 languageEnglish
Pages (from-to)388-395
Number of pages8
JournalGreen Chemistry
Volume23
Issue number1
DOIs
Publication statusPublished - 7 Jan 2021

ASJC Scopus subject areas

  • Pollution
  • Environmental Chemistry

Fields of Expertise

  • Human- & Biotechnology

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