Synthesis Of 8-Oxo-Dgtp And Its Beta,Gamma-Ch2-, Beta,Gamma-Chf-, And Beta,Gamma-Cf2- Analogues

Three novel bisphosphonate analogues of 8-oxo-dGTP 3 in which the bridging beta,gamma-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 tri-n-butylammonium 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. (C) 2021 Elsevier Ltd. All rights reserved.