Self-Activating Click Reaction of Peptides

Significance

A use of amine bases (e.g., Et₃N, DIPEA) is essential for the Cu(I)-mediated Huisgen 1,3-dipolar cycloaddition in general. The authors found a rate acceleration of this reaction (Sharpless click reaction) by adding less basic histidine derivatives. Thus, the reaction of 1 and 2 with CuI in the presence of a histidine derivative (4, 5, or 6) in DMF gave the coupling product 3 in 100% yield (eq. 1). The authors also reported a self-activating click reaction system of polymer-supported azides and acetylene-containing peptides having an N ^im-benzylhistidine unit in the presence of external bases.