Synthesis and biological activity of 4 '-C-hydroxymethyl-2 '-fluoro-D-arabinofuranosylpurine nucleosides

A series of 4 ' -C-hydroxymethyl-2-fluoro-D-arabinofuranosylpurine nucleosi des was prepared and evaluated for cytotoxicity. The details of a convenien t synthesis of the carbohydrate precursor 4-C-hydroxymethyl-3,5-di-O-benzoy l-2-fluoro-alpha -D-arabinofuranosyl bromide (13) are presented. Proof of t he structure and configuration at all chiral centers of the sugars and the nucleosides were obtained by proton NMR. All five target nucleosides were e valuated for cytotoxicity in human tumor cell lines. The 4 ' -C-hydroxymeth yl clofarabine analogue (16 beta) showed slight cytotoxicity in CCRF-CEM le ukemia cells.