Synthesis of 2',3'-dideoxy-3'-hydroxymethylcytidine; A unique antiviral nucleoside

The synthesis of 2',3'-dideoxy-3'-hydroxymethylcytidine 1 was accomplished using two different approaches. First, uridine and cytidine were used to prepare the key intermediate epoxides 15 and 31 which were opened with cyanide, deoxygenated by elimination to vinyl nitriles 17 and 36, and reduced by 1,4 hydride addition to the saturated nitriles 18 and 37. Secondly, a novel Rh-catalyzed hydroformylation reaction of 2',3'-didehydro-2',3'-dideoxycytidine 46 was used to prepare 1 in four steps. The attempted use of 2'-deoxyuridine and 2'-deoxycytidine to prepare 1 is also discussed. (C) 1997 Elsevier Science Ltd.