Synthesis of Peptide Nucleic Acid Monomers via N-Alkylation of Nosyl-protected Amino Acids with N-Boc Bromoethyl Amine

摘要

We have developed an alternate and effective pathway for completely protected peptide nucleic acid (PNA) monomer synthesis. The process involves alkylation of nosyl protected amino acids with N-Boc protected bromoethyl amine followed by deprotection of the nosyl group and condensation of thymine-1-acetic acid which was chosen as a nucleobase. The key intermediates, chiral/achiral PNA backbone, were obtained with an average overall yield of 50–60%. The glycine, valine, alanine and serine derived PNA monomers were prepared in four steps, starting from readily available materials and this result suggests that our approach is executable in all amino acids.