Synthesis and conformational studies of γ-aminoxy peptides

Abstract

We have synthesized a series of γ-aminoxy acids, including unsubstituted and γ4-Ph-, γ4-alkyl-, and γ3,4-cyclohexyl-substituted systems. Coupling of these monomers to oligomers can be realized using EDCl/HOBt (or HOAt) as the coupling agent. γ-Aminoxy peptides can form 10-membered-ring intramolecular hydrogen bonds - so-called "γ N-O turns" - between adjacent residues, the extent of which is controlled by the nature of the side chain of each γ-aminoxy acid residue, increasing from the unsubstituted γ-aminoxy peptide to the γ4-alkyl aminoxy peptides to the γ4-phenyl- and γ3,4-cyclohexyl-substituted aminoxy peptides. The presence of two consecutive homochiral 10-membered-ring intramolecular hydrogen bonds leads to the formation of a novel helical structure. Theoretical studies on a series of model peptides rationalize very well the experimentally observed conformational features of these γ-aminoxy peptides. © 2008 American Chemical Society.