Collect. Czech. Chem. Commun. 2009, 74, 901-925
Published online 2009-05-19 11:33:09

Synthesis of Aib-containing cyclopeptides via the ‘azirine/oxazolone method’

Ingeborg Dannecker-Dörig, Anthony Linden and Heinz Heimgartner*

Institute of Organic Chemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland


The cyclic pentapeptide cyclo[Gly-Phe(2Me)-Aib-Aib-Gly], containing three α,α-disubstituted α-amino acids, was prepared by cyclization of H-Gly-Phe(2Me)-Aib-Aib-Gly-OH with diphenyl phosporazidate (DPPA) in 60% yield. The synthesis of the linear precursor was performed by using the ‘azirine/oxazolone method’, in which the α,α-disubstituted α-amino acids were introduced by coupling of the corresponding amino or peptide acid with a 2,2-disubstituted 3-amino-2H-azirine. Whereas the cyclization of an analogous hexapeptide afforded the cyclopeptide in 42% yield, the corresponding tetrapeptide yielded a 1:2 mixture of the monomeric and dimeric cyclopeptide. In the case of the tripeptide H-Gly-Phe(2Me)-Aib-OH, the cyclization with DPPA led to the dimeric cyclohexapeptide exclusively.

Keywords: α-Amino acids; 3-Amino-2H-azirines; Peptides; α,α-Disubstituted amino acids; Cyclizations; X-Ray diffraction.

References: 97 live references.