Synthesis and conformational analysis of pentapeptides containing enantiomerically pure 2,2-disubstituted glycines

Abstract

The synthesis and conformational analysis of model pentapeptides with the sequence Z-Leu-Aib-Xaa-Gln-Valol is described. These peptides contain two 2,2-disubstituted glycines (α,α-disubstituted α-amino acids), i.e., Aib (aminoisobutyric acid) and a series of unsymmetrically substituted, enantiomerically pure amino acids Xaa. These disubstituted amino acids were incorporated into the model peptides via the ‘azirine/oxazolone method’.
Conformational analysis was performed in solution by means of NMR techniques and in the solid state by X-ray crystallography. Both methods show that the backbones of thesemodel peptides form helical conformations, as is expected for 2,2-disubstitued glycinecontaining peptides.