Multicomponent synthesis of tripeptides containing pipecolic acid derivatives: selective induction of cis- and trans-imide bonds into peptide backbones

A simple approach to several tripeptides consisting of two terminal glycine fragments and a central pipecolic acid derivative was found via a multicom ponent reaction starting from tetrahydropyridines. The protected peptides 2 a-g were formed in high yields and with different substitution patterns of the central heterocyclic amino acid. In cases where chiral imines were used the target compounds were obtained with remarkable diastereoselectivity. T he influence of different substituents attached to the pipecolic acid fragm ent on N-terminal amide isomerism was investigated using X-ray crystallogra phy and NMR spectroscopic methods.