Synthesis of Bis-Aminoazirines and their Application in Peptide Synthesis

Peter Köttgen, Anthony Linden and Heinz Heimgartner*

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

* Corresponding author: E-mail: heimgart@oci.uzh.ch

Abstract
The ’cyclohexane-bridged’ bis-(3-amino-2H-azirines) cis- and trans-N,N’-dimethyl-N,N’-diphenyl-1,7-diazadispiro[2.2.2.2]deca-1,7-diene-2,8-diamine (cis-21 and trans-21) were synthesized from the corresponding bis-thioamide 20 by consecutive treatment with COCl2, 1,4-diazabicyclo[2.2.2]octane (DABCO) and NaN3. The reaction of these bis-azirines with different natural α-amino acids gave peptide amides 23. In addition, hydrolysis of the C-terminal amide groups of 23c and subsequent coupling with the Aib synthon 2, i.e., 2,2,N-trimethyl-N-phenyl-2H-azirin-3-amine, showed the applicability of building blocks 21 for peptide synthesis and peptide chain ligation.

Keywords: 2H-azirin-3-amines, α,α-disubstituted α-amino acids, aminoisobutyric acid (Aib), peptide synthesis