AWrcrct: Synthesis of T-deoxy-2'-C-ethynyl-l-BD-arabinofuranosyluracil @c), -thymine. (80, and -cytosine (11) has been done by stereospecific radical deoxygenation of the comspondhtg 2'-tert-TMSpropargyl mthoxalyl eaters with BugSnH in the presence of AIBN. 2'-Deoxy-2'Ghexynyl derivative 8d was also prepared m&r similar conditioos. On the other hand, the deoxygenation of the phenyipropargyl or propargyl esters gave complex mixtures due to hydrostannylation of the triple bonds. The radical deoxygenation of nucleoside derivatives having tertiary hydroxyl groups, which ate readily obtained by nucleophilic additions of carbanions to the corresponding ketones, has provided biologically interesting branched nucleosides. 2-5 We have designed (2'5+)-2'-&oxy-2'-C-methy1-1-~-Darabinofuranosy1cytosine (SMDC)*a.e.S as well as (2'S)-2'-deoxy-2'-C-fluoromethyl-l-B-D-arranosylcytosine (SFDC)*a as antimetabolites, and they had cytotoxicity spectra similar to that of l-~-D-arabinofuranosylcytosine (at&), which is currently used as an antileukemic agent. We also reported that (2's)-2'-deoxy-2-Cmethyl-1-p-D-arabinofuranosyl-5-iodouracil (SMIU) showed potent anti-HSV-1 activity in vitro while showing no toxicity.2f On the other hand, 2'-C-cyano-2'-deoxy-l-~-D-arabinofuranosylcytosine (CNDAC) has also been designed based upon the hypothesis that introduction of an electron-withdrawing group at the 2'8 position of 2'-deoxycytidine would exert a potentially DNA-strand-breaking effect.415 Eventually, CNDAC showed excellent antitumor activity against various human tumor cells including human solid tumors in vitro as well as in vivo.~~cJ Although it is still unknown whether the activity of CNDAC is related to our hypothesis, these results prompted us to synthesize nucleosides bearing an alkynyl group as an electronwithdrawing functionality at the 2'8 position to study the structure-activity relationship of the 2'8 substituent.