Acyclopyrimidine C-nucleosides. Synthesis of acyclopseudoisocytidine and its derivatives

Acyclopseudouridine (IV), acyclopseudoisocytidine (VII), and their 1-methyl derivatives (V and VIII) were synthesized from 5-hydroxymethyluracil (I). Acyclopseudouridine (IV) was conveniently prepared from the condensation of 5-hydroxymethyluracil (I) with ethylene glycol under acidic condition. Compound IV also could be prepared from 5-chloromethyluracil, however, this procedure was found to be inferior to the direct condensation method. Methylation of IV with dimethylformamide dimethyl acetal gave 1,3-dimethylacyclopseudouridine (VI) which was subsequently converted to acyclopseudoisocytidine (VII). 1-Methyl derivatives V and VIII were obtained from the selective methylation of IV and VII, respectively. 5-Hydroxymethyluracil also reacted with 2-mercaptoethanol to give the sulfide derivative (IX).