Proline Derived Spirobarbiturates as Highly Effective β-Turn Mimetics Incorporating Polar and Functionalizable Constraint Elements

A practical and efficient synthesis of spirobarbiturates of type III is reported when NH acidity of the imide function of the hydrophilic linker element allowed the introduction of different substituents. Structural characterization, which was based on both X-ray crystallography and spectroscopic investigations, indicated type II β-turn formation. Introduction of the molecular scaffold into solid phase peptide synthesis gave rise to spirocyclic neuropeptide analogs.