Aza-peptides. II. X-ray structures of aza-alanine and aza-asparagine-containing peptides

In order to determine the structural consequences of the N alpha/C alpha H exchange in aza-peptides, we have solved the crystal molecular structures of some derivatives containing the aza-analogue of asparagine [Z-AzAsn(Me)-NMe2 (1), Z-AzAsn(Me)-Pro-NHiPr (2) and Piv-Pro-AzAsn(Me)-NHiPr (5)], aspartic acid [Z-AzAsp(OEt)-Pro-NHiPr (3) and alanine (Boc-AzAla-Pro-NHiPr (4)], by using X-ray diffraction. They reveal that the alpha-nitrogen accommodates a pyramidal (1-4) or planar (5) structure depending on the sequence. When pyramidal, the alpha-nitrogen assumes the R (D-like) chirality. All of the derivatives but 1 adopt either a beta 1-folded (2-4) or beta n-folded (5) structure in which the (AzAsn)N3H bond is intramolecularly hydrogen-bonded to the alpha-nitrogen.