4-Substituted prolines, useful reagents in enantioselective synthesis and conformational restraints in bioactive peptidomimetics design

Among the substituted prolines, 4-substituted ones deserve particular attention. The ring conformation and the puckering preference of the prolyl ring is strongly affected by insertion of the substituent and a great number of peptides containing this non-canonical amino acids have been investigated in the last five years. Moreover, the distance of the substituent from the functions involved in peptide chain formation, create a minimum steric hindrance thus offering the opportunity for conjugation with other chemical objects with low perturbation of the peptide chain.