Organocatalytic access to a cis-Cyclopentyl-gamma-amino acid: an intriguing model of selectivity and formation of a stable 10/12-helix from the corresponding gamma/alpha-peptide

Fanelli, R., Berta, D., Foldes, T., Rosta, E., Atkinson, R. A., Hofmann, H.-J., Shankland, K. ORCID: https://orcid.org/0000-0001-6566-0155 and Cobb, A. (2020) Organocatalytic access to a cis-Cyclopentyl-gamma-amino acid: an intriguing model of selectivity and formation of a stable 10/12-helix from the corresponding gamma/alpha-peptide. Journal of the American Chemical Society, 142 (3). pp. 1382-1393. ISSN 1520-5126 doi: 10.1021/jacs.9b10861

Abstract/Summary

In this study, we have developed a highly enantioselective organocatalytic route to the (1S,2R)-2-(aminomethyl)cyclopentane-1-carboxylic acid monomer precursor, which has a cis-configuration between the C- and N-termini around the cyclopentane core. Kinetic measurements show that the product distribution changes over time due to epimerization of the C1 center. Computations suggest the cis-selectivity is a result of selective C-C bond formation, whilst subsequent steps appear to infuence the selectivity at higher temperature. The resulting gamma-amino acid residue was incorporated into a novel gamma/alpha-peptide which forms a well-ordered 10/12-helix with alternate H-bond directionality in spite of the smallest value of the zeta-angle yet observed for a helix of this type. This highly dened structure is a result of the narrow range of potential zeta-angles in our monomer. In contrast, the larger range of potential zeta-values observed for the corresponding trans-system can be fulfilled by several competing helical structures.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/88074
Identification Number/DOI	10.1021/jacs.9b10861
Refereed	Yes
Divisions	Interdisciplinary centres and themes > Chemical Analysis Facility (CAF) Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Pharmaceutics Research Group
Publisher	American Chemical Society
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