Synthesis of O ‐Acyl Isopeptides

O ‐Acyl isopeptides, in which the N ‐acyl linkage on the hydroxyamino acid residue (e.g., Ser and Thr) is replaced with an O ‐acyl linkage, generally possess superior water‐solubility to their corresponding native peptides, as well as other distinct physicochemical properties. In addition, O ‐acyl isopeptides can be rapidly converted into their corresponding native peptide under neutral aqueous conditions through an O ‐to‐ N acyl migration. By exploiting these characteristics, researchers have applied the O ‐acyl isopeptide method to various peptide‐synthesis fields, such as the synthesis of aggregative peptides and convergent peptide synthesis. This O ‐acyl‐isopeptide approach also serves as a means to control the biological function of the peptide in question. Herein, we report the synthesis of O ‐acyl isopeptides and some of their applications.