Bifunctional Imine Reductase Cascades for the Synthesis of Saturated N-Heterocycles

Ramsden, Jeremy I.; Zucoloto da Costa, Bruna; Heath, Rachel S.; Marshall, James R.; Derrington, Sasha R.; Mangas-Sanchez, Juan; Montgomery, Sarah L.; Mulholland, Keith R.; Cosgrove, Sebastian C.; Turner, Nicholas J.

Abstract

Saturated N-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 N-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.

Citation

Ramsden, J. I., Zucoloto da Costa, B., Heath, R. S., Marshall, J. R., Derrington, S. R., Mangas-Sanchez, J., …Turner, N. J. (2024). Bifunctional Imine Reductase Cascades for the Synthesis of Saturated N-Heterocycles. ACS catalysis, 14(19), 14703-14710. https://doi.org/10.1021/acscatal.4c03832

• Journal Article Type: Article
• Acceptance Date: Sep 13, 2024
• Online Publication Date: Sep 19, 2024
• Publication Date: Oct 4, 2024
• Deposit Date: Oct 4, 2024
• Journal: ACS Catalysis
• Electronic ISSN: 2155-5435
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 14
• Issue: 19
• Pages: 14703-14710
• DOI: https://doi.org/10.1021/acscatal.4c03832
• Keywords: imine reductase; reductive aminase; cyclization; N-heterocycles
• Public URL: https://keele-repository.worktribe.com/output/948161
• Publisher URL: https://pubs.acs.org/doi/10.1021/acscatal.4c03832