Cleavable Amide Bond: Mechanistic Insight into Cleavable 4‑Aminopyrazolyloxy Acetamide at Low pH

The cleavage of amide bonds under
mild acidic conditions is a rare
chemical event. N-Acetamide bond of peptides is extremely
stable even under the strongest organic acid trifluoromethanesulfonic
acid. This report mechanistically describes a new cleavable amide
bond in 4-aminopyrazolyloxy acetamide peptide analogues under mild
acidic conditions such as trifluoroacetic acid (10–20%) or
HCl (0.1–4.0 N) at room temperature, and the formation of unusual
lactam from 4-aminopyrazolyloxy acetic acid after evaporation of solvent.
This is a rare chemical event in peptide bond, which could be explored
as acid-sensitive protecting group of free amines.