1,2,3‐Triazole‐Containing Azamacrocycles from Chiral Triazolopeptoids: Synthesis and Solid‐State Studies

Two new chiral 1,2,3‐triazole‐containing macrocyclic oligoamides (i. e.: triazolopeptoid 4 and 5) were obtained through solid‐phase synthesis of linear precursors followed by high dilution macrocyclization reaction. Theoretical (DFT) and spectroscopic (NMR) studies revealed the intricate interplay between the Nα‐chiral side chains and their conformational attitudes. BH3‐mediated reduction of the tertiary amide groups of known 1–3 and newly synthesized 4 gave novel azamacrocycles 6–9. Detection of borane complexes of azamacrocycles 6 and 9 (i. e.: 10 and 11), corroborated by X‐ray diffraction studies, demonstrated the peculiar properties of 1,2,3‐triazole‐containing macrorings. Conformational studies and synthetic applications of chiral macrocyclic triazolopeptoids, a class of peptidomimetics, are described. Reduction of amide bonds in the backbone afforded new azamacrocycles, containing 1,2,3 triazole moieties. X‐ray crystallographic studies highlighted their complexation abilities.