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
posted on 2019-12-23, 21:29authored byRossana Fanelli, Dénes Berta, Tamás Földes, Edina Rosta, Robert Andrew Atkinson, Hans-Jörg Hofmann, Kenneth Shankland, Alexander J. A. Cobb
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.