Stereoselective Synthesis of a Thymine Derivative of (S)-2-Hydroxy-4-(2-aminophenyl)butanoic Acid. A Novel Building Block for the Synthesis of Aromatic Peptidic Nucleic Acid Oligomers¹

Abstract

The synthesis of a thymine derivative of (S)-2-hydroxy-4-(2-aminophenyl)butanoic acid, compound 1, was achieved in high enantiomeric purity. The acyclic pyrimidine analog (S)-1 is a useful building block for the synthesis of a novel class of oligomers, the aromatic peptide nucleic acids (APNA, Scheme ). The APNA tetramer 18 was prepared from the amino acid monomer (S)-1 using classical peptide synthesis. UV absorption spectra and 1H NMR data of this tetramer suggested that base stacking interactions in the APNA oligomers may be favorable.

Versatility of peptide nucleic acids (PNAs): role in chemical biology, drug discovery, and origins of life

“…Many modifications in the backbone and nucleobases are also done, and new conjugates are denoted differently as shown in Tables ,…”

Peptide Nucleic Acids (PNAs), A Chemical Overview

“…In recent years, a In 1997, Tsantrizos et al reported the design and synthesis of the first peptide nucleic acid analogueue having an aromatic moiety as an integral part of its backbone, which they termed aromatic peptide nucleic acids (APNA) [135] (Fig 29). Preliminary hybridisation experiments with DNA and RNA identified monomer (102) as the most promising lead structure from this class of analogues [136,137].…”

Structural Preorganization of Peptide Nucleic Acids: Chiral Cationic Analogues with Five- or Six-Membered Ring Structures

“…These analogues were designed in order to investigate possible π stacking interactions and their stabilizing effects on duplex-triplex structures. [74] The aromatic PNA was subjected to further modification by replacing it with another aromatic N-(2-aminobenzyl)glycine backbone ( Figure 27). [75] An efficient synthetic procedure amenable for parallel or combinatorial preparation of APNA building blocks with high degree of structural diversity was developed.…”