Studies on the Synthesis of S^5′,6-Methano-5′-Thiourldines

Abstract

Two approaches to the synthesis of the title compounds are described. In the first route, a reactive 5-oxo-6-methylene pyrimidine intermediate 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 12. In the second and higher yielding approach, the S_5′,6-methano linkage is established by an internal allylic displacement reaction that occurs when the 5-bromo-6-methyl nucleoside 24 is treated with base. The 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.