Skip to main content

Research Repository

Advanced Search

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.

Authors

Jeremy I. Ramsden

Bruna Zucoloto da Costa

Rachel S. Heath

James R. Marshall

Sasha R. Derrington

Juan Mangas-Sanchez

Sarah L. Montgomery

Keith R. Mulholland

Nicholas J. Turner



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