Preparation of sterically hindered peptides using trifluoroacetyl protection: incorporation of N-alkyl-α,α-dialkyl amino acids into N-alkyl amino acids

Abstract

We have established a synthetic method for sterically hindered sequences, specifically the motif of N-alkyl-α,α-dialkyl amino acids to N-alkyl amino acids. The method consists of two steps, exploiting the unique properties of the trifluoroacetyl group for N-protection: enhancing the electrophilicity of Tfa-protected N-H amino acids, and increasing the acidity of the N-H moiety to enable site-selective N-alkylation.