δ-Valerolactamic Quaternary Amino Acid Derivatives: Enantiodivergent Synthesis and Evidence for Stereodifferentiated β-Turn-Inducing Properties.

Enantiopure () and () cyclic α,α-disubstituted amino acid derivatives displaying a δ-valerolactam side chain were prepared from a common isoxazolidine precursor. The ()-configured δ-valerolactam was converted into diastereoisomeric pseudopeptides to investigate its ability to induce secondary structures in peptidomimetics. Conformational studies of these pseudopeptides were carried out in the solid state (X-ray diffraction), in solution (NMR analyses), and (computer-aided conformational analysis), which demonstrated that such quaternary amino acids induce β-turn conformations stable enough to be retained in polar media (DMSO). Incorporation of this new type of α,α-disubstituted amino acid into a representative pseudopeptidic sequence by - then -elongation and -debenzylation is also described herein and could serve for the synthesis of various structured peptidomimetics.