John Arnold Werner

Synthesis of 2′,3′-dideoxy-3′-hydroxymethylcytidine; a unique antiviral nucleoside

Abstract 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.

STUDIES ON THE PHOSPHORYLATION OF LY303366

Abstract Phosphorylation of LY303366 ( 1 ) was studied in THF and DMF. Benzyl phosphate 2 could be prepared in excellent yield using LiOH as the base. Both 2 and the derived phosphonic acid monosodium salt 3 were prone to undergo hydrolytic dephosphorylation.