Solid-phase synthesis of N,N′-unsymmetrically substituted ureas: application to the synthesis of carbaza peptides

The synthesis of Boc- or Fmoc-monoprotected propylenediamine derivatives is reported starting from N-protected α-amino acids. The introduction of these building blocks on solid support via the formation of a urea moiety leads to a new pseudopeptide family (CαCH2CH2Nα(R)CONHCα). Two carbonylating reagents, i.e N,N′-carbonyldiimidazole and triphosgene, as well as different coupling procedures, have been tested to optimize the Boc and Fmoc solid-phase synthesis of a model peptide incorporating this isosteric replacement.