Details

Autor(en) / Beteiligte

• Ota, Kenji
• Nagao, Kazunori
• Hata, Dai
• Sugiyama, Haruki
• Segawa, Yasutomo
• Tokunoh, Ryosuke
• Seki, Tomohiro
• Miyamoto, Naoya
• Sasaki, Yusuke
• Ohmiya, Hirohisa

Titel

Synthesis of tertiary alkylphosphonate oligonucleotides through light-driven radical-polar crossover reactions

Ist Teil von

• Nature communications, 2023-10, Vol.14 (1), p.6856-6856, Article 6856

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Abstract Chemical modification of nucleotides can improve the metabolic stability and target specificity of oligonucleotide therapeutics, and alkylphosphonates have been employed as charge-neutral replacements for naturally-occurring phosphodiester backbones in these compounds. However, at present, the alkyl moieties that can be attached to phosphorus atoms in these compounds are limited to methyl groups or primary/secondary alkyls, and such alkylphosphonate moieties can degrade during oligonucleotide synthesis. The present work demonstrates the tertiary alkylation of the phosphorus atoms of phosphites bearing two 2’-deoxynuclosides. This process utilizes a carbocation generated via a light-driven radical-polar crossover mechanism. This protocol provides tertiary alkylphosphonate structures that are difficult to synthesize using existing methods. The conversion of these species to oligonucleotides having charge-neutral alkylphosphonate linkages through a phosphoramidite-based approach was also confirmed in this study.