Transaminase triggered aza-Michael approach for the enantioselective synthesis of piperidine scaffolds

Ryan, James; �iau?iulis, Mindaugas; Gomm, Andrew; Macia, Beatriz; O'Reilly, Elaine; Caprio, Vittorio

Abstract

The expanding “toolbox” of biocatalysts opens new opportunities to redesign synthetic strategies to target molecules by incorporating a key enzymatic step into the synthesis. Herein, we describe a general biocatalytic approach for the enantioselective preparation of 2,6-disubstituted piperidines starting from easily accessible pro-chiral ketoenones. The strategy represents a new biocatalytic disconnection, which relies on an ω-TA-mediated aza-Michael reaction. Significantly, we show that the reversible enzymatic process can power the shuttling of amine functionality across a molecular framework, providing access to the desired aza-Michael products.

Citation

Ryan, J., Šiaučiulis, M., Gomm, A., Macia, B., O'Reilly, E., & Caprio, V. (in press). Transaminase triggered aza-Michael approach for the enantioselective synthesis of piperidine scaffolds. Journal of the American Chemical Society, 138(49), https://doi.org/10.1021/jacs.6b07024

• Journal Article Type: Article
• Acceptance Date: Nov 10, 2016
• Online Publication Date: Nov 10, 2016
• Deposit Date: Jan 9, 2017
• Publicly Available Date: Jan 9, 2017
• Journal: Journal of the American Chemical Society
• Print ISSN: 0002-7863
• Electronic ISSN: 1520-5126
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 138
• Issue: 49
• DOI: https://doi.org/10.1021/jacs.6b07024
• Public URL: https://nottingham-repository.worktribe.com/output/829291
• Publisher URL: http://pubs.acs.org/doi/abs/10.1021/jacs.6b07024
• Contract Date: Jan 9, 2017