4'-THIONUCLEOSIDES VIA IN-SITU PYRANOSE-FURANOSE REARRANGEMENTS - A SHORT SYNTHESIS OF THE ANTIHERPES AGENT 2'-DEOXY-5-ETHYL-4'-THIOURIDINE VIA DIRECT COUPLING OF A SILYLATED PYRIMIDINE BASE WITH A 4-THIOPYRANOSE SUGAR

Methyl 2-deoxy-3,4-0-thiocarbonyl-beta-D-ribopyranoside was converted into the thione carbonate by reaction with thiophosgene. Bromide ion-catalyzed 0-S rearrangement produced methyl 2-deoxy-3-0,4-S-carbonyl-4-thio-beta-D-ribopyranoside (3a) and the 3-0,4-S isomer 3b. The carbonates were cleaved with ammonia and the 3-0,4-S pyranoside sugar coupled with bis(trimethylsilyl)-5-ethyluracil using trimethylsilyl triflate to provide the antiherpes agent 2'-deoxy-5-ethyl-4'-thiouridine 9. The reaction proceeded via in, situ pyranoside rearrangement-of the sugar and subsequent coupling. The pyranoside sugar could also be converted to the furanoside form with Dowex H+ acid resin and coupled in conventional fashion to give the nucleoside. Coupling of methyl 4-0-carbamoyl-2-deoxy-3-thio-beta-D-ribopyranoside (4b) with the bis(trimethylsilyl)-5-ethyluracil gave 1-[2-[2-(hydroxymethyl)thiiran-1-yl]-1-methoxyethyl]-5-ethyluracil.