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 these model peptides adopt helical conformations, as expected for 2,2‐disubstitued glycine‐containing peptides.

Synthesis of Z‐Protected Aib‐ and Phe(2Me)‐Containing Pentapeptides and Their Crystal Structures

“…4(4) φ ( -57.4 (7) -111.0 (5) 179.4 (4) -57(1); -52 (1) -50(1); -54 (1) 49.4 (6) 45.2 (6) (2) 163 (2) 3.052 (2) 171 (2) 3.013 (2) 166 (1) (S,S)-8e 3.007 (4) 165 (4) 2.872 (4) 166 (4) …”

“…Introduction. -Since the elaboration of the 'azirine/oxazolone method' as a convenient protocol for the synthesis of Aib-containing peptides [1][2][3], this procedure has been used successfully for the preparation of model peptides [2c] [3][4][5][6], sterically congested oligopeptides [7] [8], and peptaibols [2d] [9][10][11]. It has also been shown that the method can be adopted to solid-phase methodology [12].…”