Synthesis, Molecular and Crystal Structure of 3’-N-Alkylamino-3’-Deoxythymidines and Some Biochemical Properties of their Phosphorous Esters

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, ε, and I from E. coli.