An Alternative Pathway to Ribonucleoside β‑Hydroxyphosphonate Analogues and Related Prodrugs

Nucleoside β-(<i>S</i>)-hydroxyphosphonate analogues have recently proven to be interesting bioactive compounds as 5′-nucleotidase inhibitors. These derivatives were obtained in a pyrimidine series through an ex-chiral pool pathway or the stereoselective reduction of a β-ketophosphonate intermediate. Herein, an original synthesis of these compounds using nucleoside epoxide intermediates, containing either a pyrimidine or a purine as nucleobase, was explored and allowed the direct synthesis of the corresponding bis <i>S</i>-acyl-2-thioethyl (SATE) prodrugs.