Inverse γ‐Turn‐Inspired Peptide: Synthesis and Analysis of Segetalin A Indole Hemiaminal (Eur. J. Org. Chem. 34/2015)

The cover picture shows the reversible cyclization of a peptide aldehyde, which is based on the cyclic hexapeptide Segetalin A. The traffic light symbolizes the formation of the species involved in this reaction. The substitution of a peptide bond for an imine transforms the irreversible macrocyclization of peptides into a reversible process. The inherent cyclization tendency of a linear peptide is then analyzable through the equilibrium between aldehyde and imine by virtue of the higher reactivity of the corresponding linear peptide aldehyde. The tryptophan side chain of Segetalin A aldehyde forms a 12‐membered cyclic indole hemiaminal instead of the 18‐membered macrocyclic imine expected. In this article on 7443 ff , A. Geyer et al. analyze this uncommon hemiaminal, which shows that the biosynthesis of cyclic peptides is not necessarily based on linear precursor peptides with a high inherent macrolactamization tendency.