Development of a solid‐phase traceless‐Ugi multicomponent reaction for backbone anchoring and cyclic peptide synthesis

Abstract

AbstractA new one‐pot methodology to anchor peptides by their backbone to a solid support using an isocyanide‐based multicomponent reaction is described. The approach uses a microwave‐assisted Ugi four‐component reaction to simultaneously condense and bind an N‐protected amino acid and an amino ester to a supported aldehyde. Afterward, the generated backbone anchored dipeptide can be used in solid‐phase peptide synthesis to prepare head‐to‐tail cyclic peptides. Moreover, we also show that peptide fragment ligation can be performed with the described one‐pot anchoring. The backbone anchored peptides can be efficiently released from the resin by microwave‐assisted acidolysis with trifluoroacetic acid. This straightforward one‐pot anchoring approach was also applied to condense fragments and prepare a variety of linear and macrocyclic peptides.