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

Enantiopure (R) and (S) cyclic alpha,alpha-disubstituted amino acid derivatives displaying a δ-valerolactam side chain were prepared from a common isoxazolidine precursor. The (R)-configured δ-valerolactam 11 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 in silico (computer-aided conformational analysis), which demonstrated that such quaternary amino acids induce beta-turn conformations stable enough to be retained in polar media (DMSO). Incorporation of this new type of alpha,alpha-disubstituted amino acid into a representative pseudopeptidic sequence by N- then C-elongation and N-debenzylation is also described herein and could serve for the synthesis of various structured peptidomimetics.

Références

Titre
δ-Valerolactamic Quaternary Amino Acid Derivatives: Enantiodivergent Synthesis and Evidence for Stereodifferentiated beta-Turn-Inducing Properties
Type de publication
Article de revue
Année de publication
2021
Revue
The Journal of Organic Chemistry
Volume
86
Ticket
12
Pagination
8041-8055
Soumis le 26 mai 2021