The preparation of 2'-deoxy-2'-fluoro-1',2'-seconucleosides as potential antiviral agents

The preparation of (R,R)-1,3-dibenzyl-4-fluorobutane-1,2,3-triol (6) from D-isoascorbic acid and subsequent chloromethylation of this chiron made possible the synthesis of a series of 2'-deoxy-2'-fluoro-1',2'-seconucleosides. Among them were the uridine (10), thymidine, (11), 5-iodouridine (14), ribavirin (17), and guanosine (19) analogues. They were evaluated for antiviral activity primarily against RNA viruses and found to be inactive. In addition to the aforementioned acyclonucleosides, the 3',5'-cyclic phosphates of the uridine (22) and thymidine (23) analogues were prepared from their respective 4-nitrophenyl 3',5'-cyclic phosphate triesters. The triesters were also examined for antiviral activity, but like their nucleoside counterparts exhibited only marginal activity.