Abstract
2'-Deoxy-6, 2'-methano-cyclouridine, a carbon-bridged cyclonucleoside fixed in a high-anti conformation, was synthesized. Treatment of a 3', 5'-O-protected 6-cyano-2'-O-imidazolythiocarbonyluridine with tri-n-butyltin hydride afforded a 6, 2'-oxomethano-cyclouridine derivative in low yield. Base treatment of 5-bromo-2'-deoxy-2' (S)-ethoxycarbonylmethyl-3', 5'-O-(tetraisopropyldisiloxane-1, 3-diyl) uridine resulted in an intramolecular Michael reaction followed by dehydrobromination to give the 6, 2'-cyclonucleoside. The latter was de-ethoxycarbonylated by treatment with sodium chloride and water in dimethylsulfoxide followed by desilylation to furnish the title compound.
