Chiral α-Aminoxy Acid/Achiral Cyclopropane α-Aminoxy Acid Unit as a Building Block for Constructing the α N-O Helix

The monomer 1 derived from achiral 1-(aminoxy)cyclopropanecarboxylic acid (OAcc) and oligopeptides 2-9 consisting of a chiral alpha-aminoxy acid and an achiral alpha-aminoxy acid such as OAcc were synthesized and their structures characterized. The eight-membered-ring intramolecular hydrogen bond, namely the alpha N-O turn, was formed between adjacent residues independent of their chirality. However, the helix formation was sequence-dependent. Dipeptide 2 bearing chiral alpha-aminoxy acid (D-OAA) at the N-terminus and achiral OAcc at the C-terminus preferentially adopted a right-handed 1.8(8) helical structure, but dipeptide 3 (OAcc-D-OAA) did not. Theoretical calculation results, in good agreement with experimental ones, revealed that the biased handedness of alpha N-O turn found in OAcc residue depends on its preceding chiral residue. It was then found that the helical conformation was destroyed in the case of oligopeptides 6 and 7 [OAA-(OAcc)(n), n = 2, 3]. The crystal structure of tripeptide 8 ((PrCO)-Pr-i-D-OVal-OAcc-D-OVal-(NHBu)-Bu-i) further disclosed the helical structure formed by three consecutive homochiral alpha N-O turns. This study has uncovered achiral aminoxy acid residues such as the OAcc unit as a useful building block to be incorporated into chiral aminoxy peptides to mimic chiral helix structure.