The preparation of 3H-labeled acyclic nucleoside phosphonates and study of their stability

Abstract

9-(2-Phosphonomethoxyethyl)-2,6-diamino-[8- 3 H]purine ( 4 ), 9-(2-phosphonomethoxyethyl)-[8- 3 H]guanine ( 6 ) and ( R )-9-(2-phosphonomethoxypropyl)-[8- 3 H]adenine ( 11 ) with specific activities of 10.9, 7.9 and 16 Ci/mmol, respectively, were prepared by a catalytic dehalogenation of the corresponding 8-bromo derivatives 1 , 2 and 9 . The rate of the exchange of the tritium label on C-8 of the purine ring in title compounds with the hydrogen of water under physiological pH at 20 °C was studied using 3 H NMR. The loss of 3 H-label attained 7% in [8- 3 H]tenofovir ( 11 ), 10% in [8- 3 H]PMEDAP ( 4 ) and 12% in [8- 3 H]PMEG ( 6 ) after the period of 3 weeks. Storage at a temperature of –196 °C in liquid nitrogen ensured a better than 97% radiochemical purity of the prepared labeled compounds even after a six-month period.