N-Acyl Sulfonamide Linker for Peptide Synthesis

Significance

The authors describe a novel approach to solid-phase synthesis using the N-acyl sulfonamide linker. Thus, resin-bound sulfonyl azide 1 was treated with Boc- or Fmoc-protected amino thioacids in the presence of 2,6-lutidine as a base in DMF for 3-6 hours at room temperature to give the N-acyl sulfonamide 2. The resulting N-acyl sulfonamide 2 is a convenient linker for use in Boc- or Fmoc-based solid-phase peptide synthesis to give the resin-bound N-peptidyl sulfonamide 3. Activation of the N-peptidyl sulfonamide 3 via a microwave-assisted alkylation procedure and subsequent treatment with functionalized nucleo­philes yields C-terminally modified peptides.