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Volume 21, Issue 3
  • ISSN: 1573-4064
  • E-ISSN: 1875-6638

Abstract

Introduction

Nowadays, use of phosphate modifications in oligonucleotide backbone has become a common approach for imbuing its structure with the desired beneficial properties. The recent advances in successful application of different classes of phosphate modifications in the design of therapeutic oligonucleotides have led to a renewed interest in the development of approaches for introducing diverse classes of phosphate modifications.

Methods

This study aims to investigate the efficiency and optimize protocols for the application of the iodine-amine oxidation reaction to produce various N-alkyl phosphoramidate oligonucleotide derivatives during the conventional solid-phase phosphoramidite synthesis method.

Results

Various solvents and drying reagents were tested, and it was evaluated that even minor traces of water in a reaction mixture had a significant impact on yield. Using set of commercially available amines, it was shown that steric accessibility is a more critical parameter than nucleophilicity of the amino group in oxidative amination reaction. It was demonstrated that through use of amino alcohols and diamines during iodine-amine oxidation step various branched oligonucleotide structures can be synthesized.

Conclusion

The obtained data indicates that the oxidative amination approach can be a promising tool for preparing various oligonucleotide derivatives during solid-phase synthesis without the use of specialized phosphoramidite monomers.

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2025-05-03

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Application of Iodine-Amine Oxidation Approach in the Synthesis of Various N-Alkyl Phosphoramidate Oligonucleotide Derivatives
Med. Chem. 21, 229 (2025); https://doi.org/10.2174/0115734064325532241002105426
/content/journals/mc/10.2174/0115734064325532241002105426
/content/journals/mc/10.2174/0115734064325532241002105426
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  • Article Type:     Research Article
Keyword(s): branched structures; iodine-amine oxidation; Modified oligonucleotides; N-alkyl phosphoramidates; oxidative amination; phosphoramidite synthesis

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