Generation of 4′-Carbon Radicals via 1,5-Hydrogen Atom Transfer for the Synthesis of Bridged Nucleosides
Yuta Ito, Koichi Mizuno, Sanae Sumise, Airi Kimura, Nozomi Noguchi, Yasufumi Fuchi, Yoshiyuki Hari
Abstract
The rapid and facile generation of 4′-carbon radicals from oxime imidates of nucleosides via 1,5-hydrogen atom transfer induced by iminyl radicals was developed. The cyclization of 4′-carbon radicals with olefins, followed by the hydrolysis of imidate residues, provided various 2′-O,4′-C- and 3′-O,4′-C-bridged nucleosides. This operationally simple approach can be applied to the few-step syntheses of 6′S-methyl-2′-O,4′-C-ethylene-bridged 5-methyluridine (6′S-Me-ENA-T) and S-constrained ethyl-bridged 5-methyluridine (S-cEt-T).
Topics & Concepts
ChemistryRadicalHydrogen atomCarbon atomOximeCarbon fibersHydrogenHydrolysisMedicinal chemistryPhotochemistryCombinatorial chemistryOrganic chemistryRing (chemistry)Composite numberAlkylMaterials scienceComposite materialRadical Photochemical ReactionsSulfur-Based Synthesis TechniquesCatalytic C–H Functionalization Methods