PHOSPHONYLATION OF 5’-DEOXY-5-FLUOROURIDINE AND 1-?-D-ARABINOFURANOSYLCYTOSINE WITH DISODIUM DIPHOSPHONATE

Abstract

Phosphonylations of 5’-deoxy-5-fluorouridine (5’-DFUR) and 1--D-arabinofuranosylcytosine (Ara C) in aqueous solution were successfully performed using disodium diphosphonate (DP, Na2P2O5H2). The former reaction resulted in the synthesis of both 3’-phosphonyl-5’-DFUR and 2’-phosphonyl-5’-DFUR, with an overall yield of 100%. The reaction of 1--D-arabinofuranosylcytosine (Ara C) with DP gave 5’-phosphonyl-Ara C, 3’-phosphonyl-Ara C and 2’-phosphonyl-Ara C in a total yield of more than 35%. The optimal condition for the phosphonylation of either 5’-DFUR or Ara C with DP was determined to be a 1:10 ratio of 5’-DFUR or Ara C to DP and a solution pH of 11. The phosphonylated products of 5’-DFUR and Ara C were stable at 10 oC and 25 oC, respectively, over the pH range of 7 to 9. A proposed mechanism for the reactions of 5’-DFUR and Ara C with DP was developed. (Received Nov 10, 2020; Accepted Nov 30, 2020)