Synthesis and Biologic Activity of 2'-Fluoro-2-halo Derivatives of 9-β-D-Arabinofuranosyladenine

Article abstract of DOI:10.1021/jm00080a029

The synthesis of 2-halo-9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)adenines (4b and 4d) by coupling the 2,6-dihalopurine with 3-acetyl-5-benzoyl-2-deoxy-2-fluoro-D-arabinofuranosyl bromide (2) followed by replacement of the 6-halogen with concomitant removal of the acyl blocking groups is described. 2-Fluoroadenine derivative 4g had to be prepared by the diazotization-fluorination of 2-aminoadenine nucleoside 4e.All three nucleosides provided good increases in life span of mice inoculated with P388 leukemia.The best results were obtained when the compounds were administered q3h*8 on days 1, 5, and 9 after implantation of the leukemia cells.The 2',3'-dideoxynucleoside 5b, prepared by deacetylation of 4f and deoxygenation of the resultant 4h followed by removal of the benzoyl group of 5a, was slightly active against HIV in cell culture.