Synthesis of Bis-Aminoazirines and their Application in Peptide Synthesis

The scyclohexane-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 alfa-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.