A Convenient Asymmetric Synthesis of a β-amino Ester with Additional Functionalization as a Precursor for Peptide Nucleic Acid (PNA) Monomers

Abstract

We report the asymmetric synthesis of di-3-pentyl (3S,αS,7E)-3-N-benzyl-N- α-methylbenzylamino-dec-7-enedioate (9), which contains the correct functionalization to produce δ-amino acid derivatives to be used as monomers for Peptide Nucleic Acid (PNA) formation With this aim, thymine-pentanoic acid 15 and some of its ester derivatives were obtained, their reactivity was studied and the noteworthy ethyl ester 12 was quantitatively produced by transesterification of methyl ester 11, thus paving the way for the synthesis of the thymine-containing amino ester IV, which has been designed as a building block for a Nucleic-Acid analog with a chiral, flexible peptide backbone

Keywords

• Peptide nucleic acids (PNA)
• thymine derivatives
• transesterification
• asymmetric synthesis
• β-amino acids.