Serendipitous Synthesis of 5-Hydroxyuridine from 2′,3′- O -Isopropylidene N 4-Acetylcytidine by Hypervalent Iodine(III)-Mediated Reaction

Whereas BAIB-TEMPO oxidation of 2 ',3 '-O-TBDMS-N4-ace-tylcytidine results in the expected 5 '-carboxylic acid nucleoside, its2 ',3 '-O-isopropylidene analogue reacts in a radically different way. We have demonstrated here that hypervalent iodine(III) in water triggers an unprecedented oxidative cyclization leading to a mixture of C5-substi-tuted O6,5 '-cyclo-5,6-dihydrouridines. This mixture of cyclouridinescan be opened under basic conditions and, after deprotection, yields 5-hydroxyuridine, an important post-transcriptional modification of uri-dine at the wobble position (U34) of bacterial tRNA. NMR experimental values and calculations were performed to provide further insight on the specific reactivity of 2 ',3 '-O-isopropylidene N4-acetylcytidine.