One-Pot Synthesis of Aryl Phosphoramidate Derivatives of AZT/d4T as Anti-HIV Prodrugs

Arbuzov reaction of aryl phosphorodichloridite with mixture of one equivalent of AZT or d4T and one equivalent of tert-butyl alcohol led to the corresponding AZT/d4T aryl H-phosphonate diesters, and the following reaction of the H-phosphonate diesters with amino acid methyl esters in the presence of N-chlorosuccinimide (NCS) produced membrane-soluble anti-HIV prodrugs AZT/d4T aryl phosphoramidate derivatives in good yields.