Collect. Czech. Chem. Commun. 2010, 75, 757-766
Published online 2010-07-30 09:11:20

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

Tomáš Elbert*, Petra Břehová and Antonín Holý

Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i., Flemingovo nám. 2, 166 10 Prague 6, Czech Republic


9-(2-Phosphonomethoxyethyl)-2,6-diamino-[8-3H]purine (4), 9-(2-phosphonomethoxyethyl)-[8-3H]guanine (6) and (R)-9-(2-phosphonomethoxypropyl)-[8-3H]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 3H NMR. The loss of 3H-label attained 7% in [8-3H]tenofovir (11), 10% in [8-3H]PMEDAP (4) and 12% in [8-3H]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.

Keywords: Tritium; 3H NMR; Acyclic nucleotide analogues; 3H-label stability; Tenofovir; Adefovir; Radioactive labelling.

References: 11 live references.