Phosphonoacetic acids

Phosphonoacetic acid antiviral activity, 6, 771 Phosphoprotein phosphatases activation... 

Herrin, T.R. and Fairgrieve, J.S., Triglyceride Ester of Phosphonoacetic Acid Having Antiviral Activity, U.S. Patent 4,150,125, 1979. 

In 1969, Szantay and co-workers published a linear synthesis of (+)-yohimbine and (—)-P-yohimbine (75) in full detail (220). Tetracyclic key intermediate 400, obtained from 3,4-dihydro-p-carboline and a properly substituted a,p-unsatu-rated ketone (173), was treated with a proper phosphonoacetic acid derivative to give unsaturated nitrile 401 or unsaturated ester 402. Catalytic reduction of the latter resulted almost exclusively in 404 with normal stereo arrangement, while reduction of 401 supplied a mixture of normal and epialloindolo[2,3-a] quinolizines 403 and 405, respectively. Dieckmann ring closure of diester 404 gave 18a-methoxycarbonylyohimbone (407) as the thermodynamically favored... 

In many cases nucleic acid polymerases are zinc-dependent enzymes. Hutchinson et al.45 have drawn upon the use of phosphonoacetic acid and phosphonoformic acid and introduced mono- and bis-thiopyrophosphate. They propose that the inhibition of influenza virus occurs by inhibition of RNA transcriptase45. By using 31P-NMR they... 

Phosphonoacetic acid] (carboxylic acid) [Phosphonoformate] (carboxylic acid)... 

Sodium hydride (10 mmol) dispersed in 10 ml toluene was added to phosphonoacetic acid triethyl ester (10 mmol) followed by 2-bromo-3-methoxycarbonyl-5-phthaloylimidobutyric acid methyl ester (10 mmol) dissolved in 70 ml toluene and the mixture stirred for 24 hours at ambient temperature. Thereafter, the solution was neutralized with 1 ml ethereal HCl, concentrated, purified by chromatography on silica gel with acetone/toluene, 1 1, and the product isolated as a colorless oil in 60% yield. 

Method B Diethyl phosphonoacetic acid was incorporated onto a pMeBHA resin with BOP as the activating reagent. The carbanion was generated with DBU/MgBr2 (3 equiv) in DMF at 25 °C, then the Boc amino aldehyde was added. The resin was shaken for 20 h at 25 °C. On using these conditions, 96% rield and 9% epimerization were obtained. 

Sano, S., Takemoto, Y., Nagao, Y. (E)-Selective Horner-Wadsworth-Emmons reaction of aryl alkyl ketones with bis(2,2,2-trifluoroethyl)phosphonoacetic acid. Tetrahedron Lett. 2003,44, 8853-8855. 

The literature on antiviral screening for HHV-6 and HHV-7 is sparse and has been reviewed elsewhere (1,3-5). Cell systems for viral propagation have included primary human peripheral blood and cord blood lymphocytes (CBL), and T-cell lines. Methods for monitoring viral replication have included examining infected cultures for cytopathic effect, immunofluorescence analysis, quantitation of viral DNA, and focus-forming assays. Phosphonoformic acid (foscarnet), phosphonoacetic acid, and ganciclovir inhibit HHV-6 and HHV-7... 

Oxoalkyl Acids. - P-Ketophosphonates have been synthesised in good yields by treatment of the carbanion of diethyl phosphonoacetic acid with acyl... 

Kim, D.Y., and Choi, Y.J., Synthesis of a-fluoro-P-keto phosphonates from a-fluoro phosphonoacetic acid, Synth. Commun., 28, 1491, 1998. 

Corbel, B., L Hoslis-Kcrvclla, I., and Haelters, J.-P, Acylation of diethyl phosphonoacetic acid via the MgClj/EtjN system. A practical synthesis of P-keto phosphonates. Synth. Commun., 30, 609. 2000. Kim, D.Y., and Suh, K.H., Solid phase acylation of phosphonoacetates. Synthesis of P-keto phosphonates from polymer bound phosphonoacetate, Synth. Commun.. 29. 1271, 1999. 

Imaev, M.G., Shakirova, A.M., and Galeeva, R.A.. Organophosphorus compounds with an active methylene group. Part 3. The synthesis of some esters and carboxyanilides of phosphonoacetic acid, Zh. Obshch. Khim., 36, 1230, 1966 J. Gen. Chem. USSR (Engl. Transl.), 36. 1245. 1966. 

Mel nikov, N.N., Mandel baum, Y.A., and Lomakina, V.I., Organic insectofungicides. Part 46. Synthesis of some derivatives of phosphonoacetic acid, Zh. Obshch. Khim., 29, 3289, 1959 Chem. Abstr., 54, 142151, 1960. 

Herrin, T.R., Fairgrieve, J.S., Bower, R.R., Shipkowitz, N.L.. and Mao. J.C.-H., Synthesis and antiherpes simplex activity of analogs of phosphonoacetic acid, J. Med. Chem., 20, 660, 1977. Tomoskozi, L, Mechanism of the reaction of styrene oxide with phosphonate-carhanions. Tetrahedron, 19, 1969, 1963. 

---