Topographically constrained aromatic α-aza-amino acids. Part 2. New azaTic-containing peptides: Synthesis, conformation, and intramolecular NH…N interaction

Abstract

The new pseudodipeptide Boc-azaTic-Leu-OMe ( 1), incorporating the conformationally and topographically constrained 3,4-dihydro-2(1 H)-phthalazinecarboxylic acid (azaTic) residue, has been synthesized together with the three related models Boc-azaTic-NHMe ( 3), MeCO-azaTic-Gly-OMe ( 4), and azaTic-Leu-OMe ( 6). Both the epimers of 1, generated by opposite absolute configuration at an azaTic nitrogen stereogenic centre, have been found in the asymmetric unit of the crystal. The conformational perturbations, deriving by the introduction of the azaTic residue into a peptide backbone, are described and the nature of the NH…N interaction, which gives rise to a typical backbone folding closing a 5-membered ring, has been studied.