“The Role of the Chiral cis-1,3-Disubstituted 2,2-Dimethylcyclobutane Motif in the Conformational Bias of Several Types of γ-Peptides” by Jordi Aguilera, Juan A. Cobos, Raquel Gutiérrez-Abad, Carles Acosta, Pau Nolis, Ona Illa, Rosa M. Ortuño. Eur. J. Org. Chem. 2013 (early view). DOI: 10.1002/ejoc.201300066
Three series of new γ-peptides have been synthesized by starting from conveniently protected cis-3-amino-2,2-dimethylcyclobutane-1-carboxylic acid derivatives. The first series is constructed with only one enantiomer of this γ-amino acid, whereas in the second one both enantiomeric cyclobutane residues are joined in alternating fashion. The high degrees of rigidity in these γ-peptides induce the adoption of extended but sterically constrained conformations in both cases. The third series is the product of alternation of a cyclobutane residue with linear γ-aminobutyric acid (GABA). Conformational bias in these three systems accounts for the cyclobutane being a major disrupting factor to the formation of strong intramolecular hydrogen bonds, leading to extended conformations. In contrast, investigation of cyclobutane/GABA hybrid γ-peptides of a fourth series, in which the carbocyclic moiety is not a part of the polyamide skeleton but acts as a chiral polyfunctional platform, reveals that these peptides are able to produce intramolecular hydrogen bonds leading to well defined folded conformations.
© 2013 – 2020, Pau. All rights reserved by the author(s) and Universitat Autonoma de Barcelona except for texts and images already copyrighted by third parties (e.g. journal publishers) and used here under the fair use provision.