Synthesis and biological evaluation of 2′-substituted-4′-selenoribofuranosyl pyrimidines as antitumor agents

The 2′-substituted-4′-selenoribofuranosyl pyrimidines 3a-3j were synthesized from D-ribose and assayed for anticancer activity. The 2′-azido and 2′-fluoro groups with a ribo configuration were introduced by the regioselective opening of the O₂,2′-anhydronucleosides with sodium azide and (HF)_x-pyridine, respectively. Among the compounds tested, only 2′-fluoro derivative 3j was found to exhibit significant anticancer activity, but was much less potent than the corresponding 2′-arabino analogue 2c. This study will provide medicinal chemists with the insight into the identification of structural requirements for the anticancer activity for the developments of biologically active nucleosides.