Synthesis of Poly-Aib Oligopeptides and Aib-Containing Peptides via the 'Azirine/Oxazolone Method', and their crystal structures

Abstract

The protected poly-Aib oligopeptides Z-(Aib)n-N(Me)Ph with n = 2 – 6 were prepared according to the 'azirine/oxazolone method', i.e., by coupling amino or peptide acids with 2,2,N-trimethyl-N-phenyl-2H-azirin-3-amine (1a) as an Aib synthon (Scheme 2). Following the same concept, the segments Z-(Aib)3-OH (9) and H-L-Pro-(Aib)3-N(Me)Ph (20) were synthesized, and their subsequent coupling with N,N’-dicyclohexylcarbodiimide (DCC)/ZnCl2 led to the protected heptapeptide Z-(Aib)3-L-Pro-(Aib)3-N(Me)Ph (21; Scheme 3). The crystal structures of the poly-Aib oligopeptide amides were established by X-ray crystallography confirming the 310-helical conformation of Aib peptides.