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The Role of the Chiral cis ‐1,3‐Disubstituted 2,2‐Dimethylcyclobutane Motif in the Conformational Bias of Several Types of γ‐Peptides
Author(s) -
Aguilera Jordi,
Cobos Juan A.,
GutiérrezAbad Raquel,
Acosta Carles,
Nolis Pau,
Illa Ona,
Ortuño Rosa M.
Publication year - 2013
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201300066
Subject(s) - chemistry , cyclobutane , intramolecular force , stereochemistry , moiety , steric effects , hydrogen bond , enantiomer , homochirality , peptidomimetic , peptide , molecule , organic chemistry , ring (chemistry) , biochemistry
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.