Synthesis, Conformation of 3′-(Tetrazole-2″-yl)-3′-deoxythymidine and its 5″-Derivatives. Substrate Properties of 3′-(Tetrazole-2″-yl)-3′-deoxythymidine 5′-Triphosphate

Abstract

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.