Bifunctional Imine Reductase Cascades for the Synthesis of Saturated <i>N</i>-Heterocycles
Saturated <i>N</i>-heterocycles constitute a vital scaffold for pharmaceutical chemistry but are challenging to access synthetically, particularly asymmetrically. Here, we demonstrate how imine reductases can achieve annulation through tandem inter- and intramolecular reductive amination processes. Imine reductases were used in combination with further enzymes to access unsubstituted, α-substituted, and α,α'-disubstituted <i>N</i>-heterocycles from simple starting materials in one pot and under benign conditions. This work shows the remarkable flexibility of these enzymes to have broad activity against numerous substrates derived from singlular starting materials.
Authors
- Rachel S. Heath (ORCID: https://orcid.org/0000-0003-1910-8268)
- Sarah L. Montgomery (ORCID: https://orcid.org/0000-0003-3703-4338)
- Juan Mangas‐Sánchez (ORCID: https://orcid.org/0000-0002-3364-1512)
- Sebastian C. Cosgrove (ORCID: https://orcid.org/0000-0001-9541-7201)
- James R. Marshall (ORCID: https://orcid.org/0000-0002-4581-9832)
- Keith R. Mulholland
- Jeremy I. Ramsden (ORCID: https://orcid.org/0000-0002-0714-1880)
- Nicholas J. Turner (ORCID: https://orcid.org/0000-0002-8708-0781)
- Bruna Zucoloto da Costa (ORCID: https://orcid.org/0000-0003-3208-5056)
- Sasha R. Derrington
Institutions
- University of Manchester (GB)
- AstraZeneca (Poland) (PL)
- Keele University (GB)
Publication Details
- Journal
- ACS Catalysis
- Published
- 2024-09-19
- DOI
- https://doi.org/10.1021/acscatal.4c03832
- Citations
- 11
- Primary Topic
- Asymmetric Hydrogenation and Catalysis
- Type
- article
- Field-Weighted Citation Impact
- 1.74
Funders
- Engineering and Physical Sciences Research Council
- European Research Council