C. McKenna, T. Ye, J. N. Levy
May 1, 1990
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Influential Citations
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Journal
Phosphorus Sulfur and Silicon and The Related Elements
Abstract
Abstract Investigations of phosphonates and related biophosphate analogues as inhibitors of viral nucleic acid polymerases are summarized. General syntheses of α-halo phosphonoacetic acid (PAA) and methanediphosphonic acid (MDP) derivatives have been extended to preparation of seven α-halo phenyl (phosphonomethyl) phosphinates (PhMpP). Two phosphonates containing potentially reactive α-keto groups, oxophosphonoacetate (phosphonoglyoxalate, COPAA) and oxomethanediphosphonate (carbonyldiphosphonate, COMDP) are discussed. A convenient, two-step synthesis of trisodium thiophosphonoformate (TPFA) from trimethyl phosphonoformate (Me3PFA) [via Me3TPFA) is presented. TPFA selectively inhibits HIV-1 reverse transcriptase (RT) relative to both human DNA polymerase α (pol α) and four herpesvirus DNA polymerases. The significance of membrane Na+/Pi cotransport inhibition by phosphonates is briefly addressed.