Sulfur Isosteres of Orotidine

Abstract

Abstract The preparation of 6 substituted pyrimidine nucleosides has received limited attention and undoubtedly reflects the difficulty in synthesizing nucleosides of this type. Condensation of & substituted pyrimidines with suitable sugar derivatives leads to the formation of mixtures of N3 and N1 nucleosides where the N3 isomer usually predominates1. This is exemplified by the direct ribosylation of the silyl derivative of 6-methyl-thiouracil, which furnished only the N3 ribonucleoside2. Ueda and coworkers' adcfessed this problem with moderate success. When 5′- O-acetyl-2′,3′-O-isopropylidine5bromouridine c1) was reacted with cyan- ide ion, a Michael-type addition occurred at C6 with concomitant dehycfo- brominatim to give the corresponding Gcyanowidine in quantitative yield. Treatment of 1(Scheme 1) with benzyl mercaptan, however furnished a 1:1 mixture of the C6 and C5 isomers 2 and 3 grespectively4. Attempts to alter the course of this reaction so that 2 predominated met with little success. It is wo...