Asymmetric Synthesis of Trisubstituted Piperidines via Biocatalytic Transamination and Diastereoselective Enamine or Imine Reduction
Abstract: Substituted piperidine rings are a common motif in natural products and pharmaceutical drugs. The asymmetric synthesis of piperidines bearing multiple stereocentres remains a challenge, and current approaches often rely on lengthy reaction sequences and ‘chiral pool’ strategies. Herein, we report multi‐enzymatic and chemo‐enzymatic methods that allow the preparation of piperidines with three chirality centres in only two steps from achiral diketoester precursors. Stereocontrol is achieved by a highly enantioselective transamination leading to optically pure (ee >99%) enamine or imine intermediates, followed by diastereoselective reduction of these unsaturated N‐heterocycles using either platinum (0)‐catalysed flow hydrogenation or enzymatic imine reduction. In the latter case, coupling of the two biocatalytic reactions in a concurrent one‐pot process is possible, thus reducing the synthetic sequence to a single biotransformation. In total, nine trisubstituted piperidines were prepared in high stereoisomeric purities (dr ≥98:2) and isolated yields of up to 73%. Lead‐likeness analysis of five representative products using an open‐source webtool suggests that these compounds possess considerable application potential as building blocks in drug discovery.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Asymmetric Synthesis of Trisubstituted Piperidines via Biocatalytic Transamination and Diastereoselective Enamine or Imine Reduction ; day:23 ; month:02 ; year:2023 ; extent:16
Advanced synthesis & catalysis ; (23.02.2023) (gesamt 16)
- Creator
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Petermeier, Philipp
Kohlfuerst, Christoph
Torvisco, Ana
Fischer, Roland C.
Mata, Alejandro
Dallinger, Doris
Kappe, Christian Oliver
Schrittwieser, Joerg H.
Kroutil, Wolfgang
- DOI
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10.1002/adsc.202300050
- URN
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urn:nbn:de:101:1-2023022314134158881608
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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14.08.2025, 10:58 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Petermeier, Philipp
- Kohlfuerst, Christoph
- Torvisco, Ana
- Fischer, Roland C.
- Mata, Alejandro
- Dallinger, Doris
- Kappe, Christian Oliver
- Schrittwieser, Joerg H.
- Kroutil, Wolfgang
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