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5′-O-Benzoyl-3′-(tetrazole-2”-yl)-3′-deoxythymidine and its 5”-substituted derivatives were obtained by the reaction of 5′-O-benzoyl-2,3′-anhydrothymidine with triethylammonium salts of either tetrazole or 5-substituted tetrazoles. Debenzoylation of these compounds yielded 3′-(tetrazole-2”-yl)-3′-deoxythymidine and its 5”-derivatives. Structures of two of them were confirmed by X-ray analysis. Both 3′-(tetrazole-2”-yl)-3′-deoxythymidine and 3′-(5”-methyltetrazole-2”-yl)-3′-deoxythymidine have anti-conformation with respect to the glycosidic bond, and 2′-endo-3′-exo-conformation of the sugar residue with gauche + orientation relative to the C4′-C5′ bond. 3′-(Tetrazole-2”-yl)-3′-deoxythymidine 5′-triphosphate exhibited poor termination substrate properties towards avian myeloblastosis virus reverse transcriptase and did not serve as a substrate for other employed DNA polymerases.

Two approaches for the synthesis of 3′-N-alkylated 3′-amino-3′-deoxythymidines were developed, including both the reaction of 3′-amino-3′-deoxythymidine with aldehydes followed by the sodium borohydride reduction and preparation of the triphenylphosphinimine derivative and subsequent reaction with alkyl iodide. 5′-Triphosphates of the synthesized compounds were shown to be terminating substrates for human immunodeficiency virus and avian myeloblastosis virus reverse transcriptases as well as for DNA polymerase β from rat liver. At the same time these compounds did not demonstrate the properties of a terminating substrate in DNA synthesis catalyzed by human DNA polymerases α, ∊, and I from E. coli.

5′-Phosphonates of natural 2′-deoxynucleosides and ribonucleosides were synthesized by condensation of 3′-O-acylated 2′-deoxynucleosides or 2′,3′-substituted (2′,3′-O-isopropylidene, 2′,3′-O-methoxymethylene or 2′,3′-O-ethoxymethylene) ribonucleosides. As condensing agents, either N,N′-dicyclohexylcarbodiimide or 2,4,6-triisopropylbenzenesulphonyl chloride were used. Nucleoside 5′-ethoxycarbonylphosphonates were converted into corresponding nucleoside 5′-aminocarbonylphosphonates by action of ammonia in methanol or aqueous ammonia. 5′-Hydrogenphosphonothioates of thymidine and 3′-deoxythymidine were obtained by reaction of phosphinic acid in the presence of pivaloyl chloride with 3′-O-acetylthymidine or 3′-deoxythymidine, respectively, followed by addition of powedered sulfur. 5′-O-methylenephosphonates of thymidine and 2′-deoxyadenosine were prepared by intramolecular reaction of corresponding 3′-O-iodomethylphosphonates under basic conditions. All compounds were tested for inhibition of several...

The presence of reporter or ligand groups in 2′-deoxynucleoside 5′-triphosphates (dNTP) makes it possible to monitor the diffusion of these compounds into cell and to observe their incorporation into DNA. Here we present the synthesis of new dNTPs modified at α-, β,γ- or γ-phosphates of types I-IV, and containing reporter or ligand groups at the C5 position of dUTP.