Synthesis of Amino-Acid-Derived Nucleo(side/tide) Analogs for Peptide-Derived Enantiospecific Nucleic Acid Analogs

A convergent and cost-effective strategy to synthesize enantiospecific nucleoside/ nucleotide analogs from readily available α-amino acids has been described. Both (L)- and (D)-methionine were transformed in four steps to the corresponding key intermediates (L)- and (D)- 2-(tert-butyloxycarbonylamino)-4-bromomethyl butyrate. Nucleophilic displacement of the bromide by nucleic acid bases (e.g., adenine, thymine, guanine, cytosine) provided the enantiomerically pure monomers required for the solid-phase synthesis of novel peptide-derived enantiospecific nucleic acid analogs.