Synthesis of gem-diamino acid derivatives by a Hofmann rearrangement

Starting from commercially available N-protected l-alpha-amino acids, N,N'-protected gem-diaminic units were obtained by a two-step methodology. A Hofmann reaction performed using a primary alcohol as the solvent to trap the isocyanate intermediate represents the key step of the new synthetic procedure. Then, the methodology was applied to alpha-carbamoyl alpha'-carboxyl aziridines, also functionalized with l-alpha-amino esters and stable gem-diaminic units characterized by an aziridine ring and by a retro-peptide modification were obtained. The use of the latter units in the retro-peptide chemistry allows to obtain modified peptides containing an aziridine ring able to behave as an electrophilic site and as a biomimetic structural analog of proline.