STUDIES ON THE SYNTHESIS OF S-5',6-METHANO-5'-THIOURIDINES

Two approaches to the synthesis of the title compounds are described. In the first route, a reactive 5-oxo-6-methylene pyrimidine intermedia te that is generated by treating the bis-acetylated or bis-benzoylated nucleosides 10 and 11 with sodium hydroxide undergoes intramolecular attack by the 5'-thiol group to afford the 5-hydroxy cyclonucleoside 1 2. In the second and higher yielding approach, the S-5',6-methano link age is established by an internal allylic displacement reaction that o ccurs when the 5-bromo-6-mmethyl nucleoside 24 is treated with base. T he conformational properties of S-5',6-methano-5'-thiouridine (3) and certain long-range spin-spin couplings observed in the NMR spectra of the intermediate nucleosides are discussed.