An atom-economic N-to-C-directed
solid-phase peptide synthesis
is reported that uses benzyl (Bn) or (benzhydryl-carbamoyl)-methyl
(BcM) esters of amino acids as the building blocks, which facilitate
efficient hydrazinolysis, convenient conversion to acyl azide, and
robust amidation with the next amino acid ester. This method is free
of coupling reagents and free of protection on the side-chain OH,
CO2H, CONH2, etc., therefore exhibiting a significantly
improved atom economy compared to those of BOC- or Fmoc-based C-to-N-directed
approaches.