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, ∊, and I from E. coli.