Application of Dimedone Enamines as Protecting Groups for Amines and Peptides

A simple protocol for the protection of amines was realized through a base-catalyzed one-pot reaction of dimedone, beta-nitroalkene, and amine. Employing this strategy, a variety of amines/amino acids were protected in excellent yields. These acid/base stable protected amines can be deprotected by either ethylene diamine or hydrazine hydrate under mild conditions. The practical application of this orthogonal protecting group was demonstrated by the synthesis of cyclic peptide melanotan II via SPPS.