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Updated: May 11, 2026

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
Published on: August 22, 2018
Attempts toward the synthesis of the peptaibol antiamoebin by using the 'azirine/oxazolone method'
Pia Blaser1, Werner Altherr, Anthony Linden
1Organisch-chemisches Institut der Universität Zürich, Winterthurerstrasse 190, CH-8057 Zürich.
Abstract:
The two segments, 1-9 and 10-16, of the peptaibol antibiotic antiamoebin I, i.e., the nonapeptide Ac-Phe-Aib-Aib-Aib-D,L-Iva-Gly-Leu-Aib-Aib-OH (15) and the heptapeptide Z-Hyp-Gln-D,L-Iva-Hyp-Aib-Pro-Pheol (34), have been prepared as mixtures of the epimers containing D,L-Iva. All α,α-disubstituted α-amino acids were introduced by the 'azirine/oxazolone method', in which amino or peptide acids are coupled with the corresponding 2H-azirin-3-amines, followed by selective hydrolysis of the terminal amide bond. The amino acids Hyp and Gln were introduced as Z-protected(4) ) (2S,4R)-4-(tert-butoxy)proline (19) and methyl N-[bis(4-methoxyphenyl)methyl]glutamine (26). Coupling of peptide segments was achieved via the 'mixed anhydride' method, the DCC/HOBt or TBTU/HOBt strategy. The crystal structure of the segment 6-9 was determined by X-ray crystallography and displayed the presence of a β-turn conformation.
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