- New (α-hydroxyalkyl)phosphorus amphiphiles: Synthesis and dissociation constants
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Direct synthesis of free (α-hydroxyalkyl)phosphinic acid amphiphiles 1 can be readily realized by sonication of the heterogeneous mixture of 50% aqueous hypophosphorous acid and long-chain aldehydes in the presence of catalytic amounts of hydrochloric aci
- Albouy, Dominique,Brun, Alice,Munoz, Aurelio,Etemad-Moghadam, Guita
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- Protection of Phosphonate Function by Means of Ethoxycarbonyl Group. A New Method for Generation of Reactive Silyl Phosphite Intermediates
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Nucleoside ethoxycarbonylphosphonates were prepared by condensation of appropriately protected nucleosides with ethoxycarbonylphosphonic acid.They were easily converted by treatment with 1 M NaOH followed by trimethylsilylation to highly reactive bis(trimethylsilyl) nucleoside phosphite intermediates which were allowed in situ to react with water, diphenyl disulfide, 2,2'-dipyridyl disulfide, and aldehydes to afford the corresponding nucleoside phosphonates, nucleoside S-phenyl phosphorothioates, nucleoside phosphates, and nucleoside α-hydroxy phosphonates in good yields, respectively.The nucleoside phosphonates were further converted to nucleosides under mild acidic conditions.Thus, the ethoxycarbonyl group proved to serve as a versatile protecting group for not only H-P(O) but also HO-P(O) and hydroxy groups of sugars.
- Sekine, Mitsuo,Mori, Hiroyuki,Hata, Tsujiaki
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- Direct Approach to α-Hydroxyphosphonic and α,ω-Dihydroxyalkane-α,ω-bisphosphonic Acids by the Reduction of (Bis)acylphosphonic Acids
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Acylphosphonic and bisacylphosphonic acid sodium salts were directly reduced by sodium borohydride to the corresponding hydroxyphosphonates and dihydroxyalkanebisphosphonates. The solution conformation of the (bis)hydroxyphosphonic acid sodium salts, eluc
- Chen, Ravit,Breuer, Eli
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- Synthesis, spectral analysis, theoretical studies, molecular dynamic simulation and comparison of anticorrosive activity of an ester and an acid α-Hydroxyphosphonates
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Diethyl [hydroxy (phenyl) methyl] phosphonate ester (DHPMP) and [hydroxy (phenyl) methyl] phosphonate acid (HPMPA) have been synthetized and their structures were confirmed by IR, UV–Vis, 1H, 13C and 31P NMR spectroscopies
- Bourzami, Riadh,Ouksel, Louiza,Chafai, Nadjib
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- Silyl Phosphite Equivalents: 2,2,2-Trichloroethoxycarbonylphosphonates
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2,2,2-Trichloroethoxycarbonylphosphonates were converted directly by treatment with Zn-Me3SiCl into silyl phosphites which in situ reacted with aldehydes to give α-hydroxyphosphonates in good yields.
- Sekine, Mitsuo,Yamagata, Hiraku,Hata, Tsujiaki
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- Hydrolysis and alcoholysis of phosphinates and phosphonates
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Phosphinic and phosphonic acids useful intermediates and biologically active compounds may be prepared from their esters: phosphinates and phosphonates, respectively, by acid-catalyzed hydrolysis either on conventional heating or on MW irradiation. The transesterification of alkyl phosphinates took place only in the presence of suitable ionic liquids as the catalysts. In the cases of phenylphosphonates, depending on the nature of the ionic liquid, the formation of the ester was accompanied by the fission of the C–O bond.
- Harsági, Nikoletta,Keglevich, Gy?rgy,Sz?ll?si, Betti,Varga, Petra Regina
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- Optimization and a Kinetic Study on the Acidic Hydrolysis of Dialkyl α-Hydroxybenzylphosphonates
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The two-step acidic hydrolysis of α-hydroxybenzylphosphonates and a few related derivatives was monitored in order to determine the kinetics and to map the reactivity of the differently substituted phosphonates in hydrolysis. Electron-withdrawing substituents increased the rate, while electron-releasing ones slowed down the reaction. Both hydrolysis steps were characterized by pseudo-first-order rate constants. The fission of the second P-O-C bond was found to be the rate-determining step.
- Harsági, Nikoletta,Rádai, Zita,Szigetvári, áron,Kóti, János,Keglevich, Gy?rgy
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- Synthesis and anticancer cytotoxicity with structural context of an α-hydroxyphosphonate based compound library derived from substituted benzaldehydes
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We synthesized substituted benzaldehyde derived α-hydroxyphosphonates (αOHP), α-hydroxyphosphonic acids (αOHPA) and α-phosphinoyloxyphosphonates (αOPP) and characterized their cytotoxicity against a panel of cancer cell lines. A library containing 56 analogues was screened against Mes-Sa parental and Mes-Sa/Dx5 multidrug resistant uterine sarcoma cell lines, using a fluorescence-based cytotoxicity assay. The cytotoxicity screening revealed that dibenzyl-αOHPs and dimethyl-α-diphenyl-OPPs were the most active clusters, which encouraged us to synthesize further dibenzyl-α-diphenyl-OPP derivatives that elicited pronounced cell killing. Further structure-activity relationships showed the relevance of hydrophobicity and the position of substituents on the main benzene ring as determinants of toxicity. The most active analogs proved to be equally, or even more toxic to the multidrug resistant (MDR) cell line Mes-Sa/Dx5, suggesting these compounds may overcome P-glycoprotein mediated multidrug resistance by evading the drug transporter.
- Rádai, Zita,Windt, Tímea,Nagy, Veronika,Füredi, András,Kiss, Nóra Zsuzsa,Ranelovi?, Ivan,Tóvári, József,Keglevich, Gy?rgy,Szakács, Gergely,Tóth, Szilárd
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p. 14028 - 14035
(2019/09/18)
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- Green synthesis and cytotoxic activity of dibenzyl α-hydroxyphosphonates and α-hydroxyphosphonic acids
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A series of dibenzyl α-hydroxyphosphonates and the corresponding α-hydroxyphosphonic acids, mostly new compounds, have been synthesized. The dibenzyl α-hydroxyphosphonates have been obtained in the Pudovik reaction of substituted benzaldehydes and dibenzyl phosphite in the presence of triethylamine as the catalyst. The amount of the solvent was minimized during the reaction, and the workup involved crystallization from the reaction mixture. A new protocol was developed to transform the dibenzyl 1-hydroxyphosphonates to the corresponding phosphonic acids by catalytic hydrogenation. The derivatives prepared were screened as potential cytotoxic agents against Mes-Sa human uterine sarcoma cell line.
- Rádai, Zita,Szeles, Petra,Kiss, Nóra Zsuzsa,Heged?s, László,Windt, Tímea,Nagy, Veronika,Keglevich, Gy?rgy
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- Isoprenoid Biosynthesis Inhibitors Targeting Bacterial Cell Growth
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We synthesized potential inhibitors of farnesyl diphosphate synthase (FPPS), undecaprenyl diphosphate synthase (UPPS), or undecaprenyl diphosphate phosphatase (UPPP), and tested them in bacterial cell growth and enzyme inhibition assays. The most active compounds were found to be bisphosphonates with electron-withdrawing aryl-alkyl side chains which inhibited the growth of Gram-negative bacteria (Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa) at ~1–4 μg mL?1levels. They were found to be potent inhibitors of FPPS; cell growth was partially “rescued” by the addition of farnesol or overexpression of FPPS, and there was synergistic activity with known isoprenoid biosynthesis pathway inhibitors. Lipophilic hydroxyalkyl phosphonic acids inhibited UPPS and UPPP at micromolar levels; they were active (~2–6 μg mL?1) against Gram-positive but not Gram-negative organisms, and again exhibited synergistic activity with cell wall biosynthesis inhibitors, but only indifferent effects with other inhibitors. The results are of interest because they describe novel inhibitors of FPPS, UPPS, and UPPP with cell growth inhibitory activities as low as ~1–2 μg mL?1.
- Desai, Janish,Wang, Yang,Wang, Ke,Malwal, Satish R.,Oldfield, Eric
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p. 2205 - 2215
(2016/10/22)
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- Synthesis and herbicidal activity of novel dialkoxyphosphoryl aryl methyl 2-(4,6-dimethoxypyrimidin-2-yloxy) benzoate derivatives
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A series of dialkoxyphosphoryl aryl methyl 2-(4,6-dimethoxy-pyrimidin-2- yloxy) benzoate derivatives was designed and synthesized. All new compounds were identified by elemental analysis, infrared (IR), 1H-NMR, and mass spectrometry (MS). Their herbicidal
- Jin, Chuanfei,He, Hongwu
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p. 1397 - 1403
(2011/10/04)
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- METHODS AND SYSTEMS FOR PREPARING IRREVERSIBLE INHIBITORS OF PROTEIN TYROSINE PHOSPHATASES
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Described herein are the preparation and use of novel bromo- phosphonomethylphenylalanine amino acid derivatives (BrPmp) and BrPmp-containing peptides as specific, irreversible protein tyrosine phosphatase inhibitors, which are suitable for application in peptide synthesis. These derivatives are particularly advantageous since their synthesis is both easy and scalable, and they are suitable for peptide synthesis. The BrPmp derivatives described herein can be appropriately protected to allow for solid phase peptide synthesis (SPPS) and incorporation into peptides for preparation of protein tyrosine phosphatase inhibitors and inhibitor libraries. The peptides and peptide libraries can be used to identify new protein tyrosine phosphatase specific sequences and profile protein tyrosine phosphatase activity in cell lysates, diagnostic samples and biopsy samples.
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- A protected l-bromophosphonomethylphenylalanine amino acid derivative (BrPmp) for synthesis of irreversible protein tyrosine phosphatase inhibitors
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Protein tyrosine phosphatases (PTPs) are important therapeutic targets for medicinal chemists and biochemists. General strategies for the development of inhibitors of these enzymes are needed. Several modular strategies which rely on phosphotyrosine mimics are known for PTP inhibitors. Previous strategies include phosphonomethylphenylalanine (Pmp) derivatives which act as competitive inhibitors. Pmp amino acid derivatives have been used to develop specific inhibitors by incorporation into sequences recognized by the PTP of interest. We report the synthesis of a new phosphonotyrosine analog, l- phosphonobromomethylphenylalanine (BrPmp), which acts as an inhibitor of PTPs. The BrPmp derivative was prepared as an Fmoc-protected amino acid which can be used in standard solid phase peptide synthesis (SPPS) methods. The synthesis of the protected amino acid derivative requires 11 steps from tyrosine with a 30% overall yield. Enzyme inhibition studies with the PTP CD45 demonstrate that BrPmp derivatives are irreversible inhibitors of the enzyme. A tripeptide which incorporated BrPmp had increased inhibitory potency against PTP relative to BrPmp alone, confirming that the incorporation of BrPmp into peptide sequences provides additional context to improve enzyme binding.
- Tulsi, Naresh S.,Downey, A. Michael,Cairo, Christopher W.
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experimental part
p. 8679 - 8686
(2011/02/25)
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- Synthesis of functionalized 1-trimethylsiloxy-substituted O-trimethylsilyl alkylphosphonites and their derivatives
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Nucleophilic addition of trimethylsilyl esters of tricoordinate organophosphorus acids to various functionalized aldehydes with vinyl, aryl, and heterocyclic fragments is proposed as a convenient method for the synthesis of new 1-trimethylsiloxysubstituted alkylphosphonites and their derivatives at mild conditions. Also the new functionalized derivatives of these phosphonites, including amino groups as well as certain properties of these compounds as important precursors of new functionalized 1-hydroxyalkylorganophosphorus acids, are presented.
- Prishchenko, Andrey A.,Livantsov, Mikhail V.,Novikova, Olga P.,Livantsova, Ludmila I.,Petrosyan, Valery S.
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p. 352 - 359
(2008/09/20)
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- Small ligands interacting with the phosphotyrosine binding pocket of the Src SH2 protein
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Various small fragments bearing phosphate, phosphonate or phosphonic acid moieties have been prepared through parallel synthesis and their binding potencies evaluated on the Src SH2 protein using a BIAcore assay. This provided us insight into the requirement of the Src SH2 pTyr binding pocket and some promising small ligands have been characterised.
- Deprez, Pierre,Mandine, Eliane,Gofflo, Dominique,Meunier, Stephane,Lesuisse, Dominique
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p. 1295 - 1298
(2007/10/03)
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- Application of silicon-phosphorus based reagents in synthesis of aminophosphonates. Part 2: Reactions of N-(Triphenylmethyl)-aldimines with the silylated phosphorus acid esters
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Reactions of silylated phosphorus acid esters with N-triphenylmethylaldimines (N-tritylaldimines) were investigated. N-Tritylmethaneimine reacts at room temperature with a mixture of P(OMe)3 and Me3SiBr forming the corresponding aminophosphonate derivatives in high yield. Other N-tritylimines are resistant toward the silylated reagents at room temperature, but undergo a similar phosphorylation reaction at elevated temperatures to form the expected aminophosphonic acids.
- Boduszek,Soroka
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p. 1105 - 1111
(2007/10/03)
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- Novel hydroxyphosphonate inhibitors of CD-45 tyrosine phosphatase
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CD-45 tyrosine phosphatase [E.C. 3.1.3.48] is an important player in the regulation of cell activation and proliferation in hematopoetic cells. As part of a program in immune response modulation, we prepared the first series of small organic molecule inhibitors of CD-45. The preparation and in vitro screening of these hydroxyphosphonates is described herein.
- Frechette, Roger F.,Ackerman, Caridad,Beers, Scott,Look, Rich,Moore, John
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p. 2169 - 2172
(2007/10/03)
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- PHOSPHONYLATION BY TETRAPHOSPHORUS HEXOXIDE
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The general usefulness of P4O6 as starting material for the preparation of inorganic and organic phosphorus compounds is demonstrated by reactions of P4O6 with nucleophilic and electrophilic compounds.
- Schuelke, Ulrich
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p. 623 - 626
(2007/10/02)
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