The role of the chiral cis-1,3-disubstituted 2,2-dimethylcyclobutane motif in the conformational bias of several types of γ-peptides

Jordi Aguilera, Juan A. Cobos, Raquel Gutiérrez-Abad, Carles Acosta, Pau Nolis, Ona Illa, Rosa M. Ortuño

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12 Citations (Scopus)

Abstract

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 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Original languageEnglish
Pages (from-to)3494-3503
JournalEuropean Journal of Organic Chemistry
Issue number17
DOIs
Publication statusPublished - 1 Jun 2013

Keywords

  • Conformation analysis
  • Heterochirality
  • Homochirality
  • Hydrogen bonds
  • Peptidomimetics
  • Polyfunctional platforms

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