Nucleosides. 132. Synthesis of 5–(2' '-deoxy-β-D-arabinofuranosyl)-1-methyluracils from 1-Methyl-ψ-uridine. The First Direct Introduction of the 2'-Substituent to C-2' in the “Up” Configuration by Nucleophilic Reactions. Studies Directed toward the Synthesis of 2'-Deoxy 2'-Substituted arabino Nucleosides 3¹

A general method is developed for the synthesis of pyrimidine C-nucleosides containing the 2'-substituted-2'-deoxyarabinofuranosyl moiety from a preformed ribo C-nucleoside by direct nucleophilic displacement reactions. 1-Methyl-ψ-uridine (1) was converted to the 2',3'-O-acetonate 2 which was mesylated to 3. Treatment of 3 in aqueous acetic acid gave 5'ψ-uridine (4) which was converted in three steps to 4,5'ψ-uridine (7) via the 2',3'-O-carbonate 5 and the anhydro C-nucleoside 6. 3'-O-Acetyl-2'-O-triflyl-4,5'-anhydro-ψ-uridine (8) was prepared in two steps from 7. The 2'-triflate function was directly displaced by various nucleophiles by treatment with LiCl, LiBr, NaN₃, and NaOAc to afford the corresponding 4,5'-anhydro C-nucleosides (9) with the 2'-substituent in the “up” arabino configuration. The anhydro linkage of 9 was readily hydrolyzed by treatment with Dowex 50 (H⁺) in aqueous solution to give the respective '-deoxy-2'β-D-arabinofuranosyl)-1-methyluracils (10).