Abstract
N-Substituted glycines (NSG) constitute mimics of natural amino acids, and bring stability to peptide analogues. We developeda method to synthesize NSG bearing reactive secondary heterofunctionality. It was shown that persilylation could be used for temporary protection of reactive groups present on the substrate, with the aim of selectively alkylating the amine groups. NSG ready for peptide coupling were obtained by C-terminal deprotection and N-terminal protection of the resulting amino acid derivatives. This method was applied to prepare N-alkylated glycines as analogues of serine, cysteine, tyrosine and tryptophan. The last two derivatives were obtained in good yields and N-homotyrosine (NhTyr) has been introduced into a peptide sequence of interest using automated solid-phase peptide synthesis (SPPS).