Independent Generation and Reactivity of Uridin-2′-yl Radical

The uridin-2′-yl radical (<b>1</b>) has been proposed as an intermediate during RNA oxidation. However, its reactivity has not been thoroughly studied due to the complex conditions under which it is typically generated. The uridin-2′-yl radical was independently generated from a benzyl ketone (<b>2a</b>) via Norrish type I photocleavage upon irradiation at λ_max = 350 nm. Dioxygen and β-mercaptoethanol are unable to compete with loss of uracil from <b>1</b> in phosphate buffer. Thiol trapping competes with uracil fragmentation in less polar solvent conditions. This is ascribed mostly to a reduction in the rate constant for uracil elimination in the less polar solvent. Hydrogen atom transfer to <b>1</b> from β-mercaptoethanol occurs exclusively from the α-face to produce arabinouridine. Mass balances range from 72 to 95%. Furthermore, the synthesis of <b>2a</b> is amenable to formation of the requisite phosphoramidite for solid-phase oligonucleotide synthesis. This and the fidelity with which the urdin-2′-yl radical is generated from <b>2a</b> suggest that this precursor should be useful for studying the radical’s reactivity in synthetic oligonucleotides