Synthesis of Poly‐Aib Oligopeptides and Aib‐Containing Peptides via the ‘Azirine/Oxazolone Method’, and Their Crystal Structures

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‐2 H ‐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)/ZnCl 2 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 3 10 ‐helical conformation of Aib peptides.