6533b85dfe1ef96bd12be6d0
RESEARCH PRODUCT
The sustainable synthesis of levetiracetam by an enzymatic dynamic kinetic resolution and an ex-cell anodic oxidation
Siegfried R. WaldvogelTill OpatzGeorg SteinkellnerMargit WinklerHelmut SchwabKarl GruberAlexander M. NauthUrska PogorevcnikBirgit GrillKai DonsbachSebastian ArndtDominik Weissubject
Active ingredientbiologyNitrile010405 organic chemistry010402 general chemistrybiology.organism_classification01 natural sciencesPollutionCombinatorial chemistry0104 chemical sciencesKinetic resolutionCatalysischemistry.chemical_compoundchemistryNitrile hydrataseYield (chemistry)medicineEnvironmental ChemistryComamonas testosteroniLevetiracetammedicine.drugdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2021-01-01 | Green Chemistry |