Orthogonal Synthesis of Xeno Nucleic Acids

• Published in: Chemistry : a European journal 2016-12, Vol.22 (50), p.17945-17948
• Main Authors: Fiers, Guillaume, Chouikhi, Dalila, Oswald, Laurence, Al Ouahabi, Abdelaziz, Chan-Seng, Delphine, Charles, Laurence, Lutz, Jean-François
• Format: Article
• Language: English
• Subjects: Acids; Alkynes; Alkynes - chemistry; Amines; Amino Acid Sequence; Azides - chemistry; Carboxylic acids; Carboxylic Acids - chemistry; Catalysis; Chemical Sciences; Chemistry; Copper - chemistry; Coupling; Cycloaddition Reaction; iterative chemistry; Nucleic acids; Nucleic Acids - chemical synthesis; Nucleic Acids - chemistry; orthogonal synthesis; Other; sequence-controlled polymers; solid-phase synthesis; Strategy; Synthesis; Triazoles
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201604386

Sequence‐defined peptide triazole nucleic acids (PTzNA) were synthesized by means of a solid‐phase orthogonal “AB+CD” iterative strategy. In this approach, AB and CD building blocks containing carboxylic acid (A), azide (B), alkyne (C), and primary amine (D) functions are assembled together by successive copper‐catalyzed azide–alkyne cycloaddition (CuAAC) and acid–amine coupling steps. Different PTzNA genetic sequences were prepared using a library of eight building blocks (i.e., four AB and four CD building blocks). An orthogonal protecting‐group‐free approach for the synthesis of sequence‐controlled peptide triazole nucleic acids on a solid support is described. This “AB+CD” iterative strategy uses two building blocks (AB and CD) carrying four functions, a carboxylic acid (A) and an azide (B) or an alkyne (C) and a primary amine (D), involved in successive acid–amine couplings and copper‐catalyzed azide–alkyne cycloadditions.