Protection of ψ(CH₂NH) Peptide Bond with 2, 4-Dimethoxybenzyl Group in Solid-Phase Peptide Synthesis

Abstract

The reductive alkylation of a resin-bound amine by the Boc-amino aldehyde/NaBH₃CN method is accompanied with undesirable double alkylation at Xaaψ(CH₂NH)Gly sequences. To prevent the double alkylation, the utility of the 2, 4-dimethoxybenzyl (Dmb) group for secondary amine protection was investigated. By using this group, Leu-enkephalin and dynorphin (1-8) analogs containing the ψ(CH₂NH) peptide bond between residues Tyr¹/Gly² or Gly²/Gly³ were synthesized in high yields.