An expedient synthesis of peptidyl N-alkylamides by “HOPE” strategy

We have developed an expedient approach, “HOPE” (hybrid orthogonal protocol with ease) strategy for the synthesis of peptidyl N-alkylamides. This new strategy was characterized by following points: incorporating Boc and Fmoc protocols together on Merrifield resin, removal of SPG (side-chain protecting groups) without the damage of linker structure on the resin, and the ammonolysis of linker as the last step could achieve the introducing N-alkylamide structure into C-terminal and releasing product from resin-support simultaneously. In present work, eight peptidylamides with different alkylsubstitution at C-terminal were conveniently synthesized by HOPE strategy.