Synthesis and conformational studies of γ-aminoxy peptides

We have synthesized a series of gamma-aminoxy acids, including unsubstituted and gamma(4)- Ph-, gamma(4)-alkyl-, and gamma(3,4)-cyclohexyl-substituted systems. Coupling of these monomers to oligomers can be realized using EDCl/HOBt (or HOAt) as the coupling agent. gamma-Aminoxy peptides can form 10-membered-ring intramolecular hydrogen bonds-so-called "gamma N-O turns"-between adjacent residues, the extent of which is controlled by the nature of the side chain of each gamma-aminoxy acid residue, increasing from the unsubstituted gamma-aminoxy peptide to the gamma(4)-alkyl aminoxy peptides to the gamma(4)-phenyl- and gamma(3,4)-cyclohexyl-substituted aminoxy pepticles. 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 gamma-aminoxy peptides.