Trisodium phosphonoformate

Preparation of trisodium phosphonoformate — Reaction of a chloroformate with a trialkyl phosphite and cleavage of the ester linkages... 

To the resultant triethyl phosphonoformate (105 g, 0.5 mol) was added sodium hydroxide solution (250 ml, 10 M) over a period of 15 min at ambient temperature. The solution became hot, and ethanol by-product boiled off from the reaction mixture. Upon cooling, a precipitate formed, which was recrystallized from water to give colorless crystals of the pure trisodium phosphonoformate hexahydrate (27.5 g, 19%), which exhibited IR and NMR spectra and x-ray crystal analysis in accord with the proposed structure. 

R. P. Iyer, J. H. Boal, L. R. Phillips, D. R. Thakker, W. Egan, Synthesis, Hydrolytic Behavior, and Anti-HIV Activity of Selected Acyloxyalkyl Esters of Trisodium Phosphonoformate (Foscarnet Sodium) , J. Pharm. Sci. 1994, 83, 1269- 1273. 

Common Name Foscarnet sodium Foscarnetum natricum Trisodium phosphonoformate... 

The wet substance is recrystallized in 570 ml of water by heating to 423 g (4.77 mol) of sodium hydroxide liquid cone, is added to 400 ml of water. The solution is heated to about 50°C and 167 g (0.795 mol) of triethyl phosphonoformate is added at this temperature. The reaction mixture is then heated to about 90°C and ethanol formed is distilled off. After about 1 hour at 90-95°C the reaction mixture is cooled to about 20°C and the product is filtered off. The yield of trisodium phosphonoformate hexahydrate wet is 248... 

The wet substance is recrystallized in 570 ml of water by heating to 90°C in order to obtain a clear solution and then cooling to about 20°C. After filtration and washing with 50 ml of water at 18-22°C 187 g (74% of theoretical yield) of trisodium phosphonoformate hexahydrate is obtained. This substance contains about 2% free water, which can be eliminated by drying. 

Foscarnet (trisodium phosphonoformate) is an inorganic pyrophosphate analog, which inhibits many DNA polymerases, retroviral reverse transcriptase, and some RNA polymerases, and has antiviral activity against all of the herpes viruses and HIV. Foscarnet... 

Iyer, R.P., Phillips, L.R., Biddle, J.A., Thakker, D.R., Egan, W., Aoki, S., and Mitsuya, H., Synthesis of acyloxyalkyl acylphosphonates as potential prodrugs of the antiviral, trisodium phosphonoformate (foscarnet sodium). Tetrahedron Lett., 30, 7141, 1989. 

CHEMISTRY AND ANTIVIRAL ACTIVITY Foscarnet (trisodium phosphonoformate) is an inorganic pyrophosphate analog that inhibits herpesviruses and HIV. 

The antiviral agent foscamet (trisodium phosphonoformate) has been measured in plasma by HPLC using an ODS-modified silica column with ED. Pettersson et al used PGEs (Ei +0.75, E2 +0.90 V vs Pd). The eluent was methanol-aq. phosphate buffer (43 mmol L , pH 6.8) (25 + 75) containing tetrahexylammonium hydrogen sulfate (ImmolL ). Sample preparation involved ultrafiltration and... 

Synonyms Dihydroxyphosphinecarboxylic acid oxide trisodium salt foscamet trisodium phosphonoformate Trade Names Foscavir Use Antiviral... 

---