Isosteric triphosphonate derivatives of 2′,3′-dideoxy-2′, 3′-didehydroadenosine and 3′-deoxy-2′,3′- didehydrothymidine and their β,γ-substituted analogues were synthesized. Their substrate properties toward a number of reverse transcriptases of the human immunodeficiency and avian myeloblastosis viruses, human DNA polymerases α and β, and the Klenow fragment of Escherichia coli DNA polymerase I were studied. © 2007 Pleiades Publishing, Inc.