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Organocatalytic Access to a cis-Cyclopentyl-γ-amino Acid: An Intriguing Model of Selectivity and Formation of a Stable 10/12-Helix from the Corresponding γ/α-Peptide

Research output: Contribution to journalArticle

Rossana Fanelli, Dénes Berta, Tamás Földes, Edina Rosta, Robert Andrew Atkinson, Hans-Jörg Hofmann, Kenneth Shankland, Alexander J A Cobb

Original languageEnglish
Pages (from-to)1382-1393
Number of pages12
JournalJournal of the American Chemical Society
Volume142
Issue number3
Early online date10 Dec 2019
DOIs
Accepted/In press10 Dec 2019
E-pub ahead of print10 Dec 2019
Published22 Jan 2020

King's Authors

Abstract

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, while subsequent steps appear to influence the selectivity at higher temperature. The resulting γ-amino acid residue was incorporated into a novel γ/α-peptide, which forms a well-ordered 10/12-helix with alternate H-bond directionality in spite of the smallest value of the ζ-angle yet observed for a helix of this type. This highly defined structure is also a result of the narrow range of potential ζ-angles in our monomer. In contrast, the larger range of potential ζ-values observed for the corresponding trans-system can be fulfilled by several competing helical structures.

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