Synthesis of Bis-Aminoazirines and their Application in Peptide Synthesis

摘要

The 'cyclohexane-bridged' bis-(3-amino-2H-azirines) cis- and trans-N,N'-dimethyl-N,N'-diphenyl-1,7-diazadispi-ro[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-azi-rines with different natural a-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.