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

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 ar

SUBMITTER: Ota K 

PROVIDER: S-EPMC10618202 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature