Synthesis of 8-oxo-dGTP and its β,γ-CH2-, β,γ-CHF-, and β,γ-CF2- analogues

Abstract Three novel 8-oxo-dGTP bisphosphonate analogues of 3 in which the bridging β,γ-oxygen is replaced by a methylene, fluoromethylene or difluoromethylene group (4-6, respectively) have been synthesized from 8-oxo-dGMP 2 by reaction of its morpholine 5’-phosphoramidate 14 or preferably, its N-methylimidazole 5’-phosphoramidate 15 with n-tributylammonium salts of the appropriate bisphosphonic acids, 11-13. The latter method also provides a convenient new route to 3. Analogues 4-6 may be useful as mechanistic probes for the role of 3 in abnormal DNA replication and repair.