Synthesis, antiviral, antibacterial and antitumor cell activities of 2'-deoxy-2'-fluoropuromycin

A procedure for the synthesis of 2'-deoxy-2'-fluoropuromycin (1b) was developed. Ring opening of the lyxo-epoxide (4) or nucleophilic displacement of the 3'-O-mesylate (5) by an azide ion afforded two azido nucleosides, 6a and 7a. The major product (7a) was reacted with diethylaminosulfur trifluoride (DAST) to give the 2'-fluoronucleoside (8), which was converted to the 3'-aminonucleoside (9) by hydrogenation. Compound 9 was condensed with an amino acid by the conventional method and subsequently deprotected by acid to give 1b. Compounds 1b, 6b and 7b exhibited no selective antiviral activity against several DNA and RNA viruses. Compound 1b had weak antibacterial activity (minimum inhibitory concentration approximately 25-50 micrograms/ml) and was cytotoxic to several tumor cell lines (L1210, Molt 4, CEM) at a concentration of about 5 microM. This antitumor cell activity may be attributed to inhibition of protein biosynthesis.