- Syntheses and GABA receptor binding properties of 4-amino-1-, 2-, and 3- hydroxybutylphosphinic acids
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Novel racemic 4-amino-1-, 2-, and 3-hydroxybutylphosphinic acids and the corresponding 4-amino-1-, 2-, and 3-hydroxybutyl methylphosphinic acids have been synthesized. The phosphinic acid groups are bioisosteres of the carboxylic acid group, and some of these hydroxy amino acids are GABA(B) antagonists. The novel phosphinic acids were evaluated for their GABA(A) and GABA(B) receptor binding properties using rat brain synaptosomes and were also tested for GABAergic activity in a guinea pig ileum model. None of the phosphinic acids tested were found to be active.
- Kehler, Jan,Ebert, Bjarke,Dahl, Otto,Krogsgaard-Larsen, Povl
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- Isostructural series of nine-coordinate chiral lanthanide complexes based on triazacyclononane
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Nonadentate ligands based on triazacyclononane incorporating pyridyl-2-phosphinate groups form an isostructural series of complexes with Ln ions in the solid state and in solution. The Ln ion is effectively shielded from the solvent environment. Crystal structures reveal a rigid C 3-symmetric tricapped trigonal-prismatic coordination geometry that is maintained in solution for the methyl and phenylphosphinate series, as shown by multinuclear NMR analysis. Variable-temperature measurements of the field dependence of the water proton relaxivity in gadolinium complexes indicate that these systems exclude solvent from the primary coordination environment and minimize the second sphere of solvation. The electronic relaxation time for the gadolinium methylphosphinate complex has been estimated to be 550 (±150) ps by EPR and NMR methods, compared to values of around 0.30-0.05 ps for the terbium-ytterbium series, deduced by analyzing the field dependence (4.7-16.5 T) of the 31P NMR longitudinal relaxation times. Values are compared with analogous azacarboxylate ligand complexes, supporting a key role for donor atom polarizability in determining the electronic relaxation. Spectral emission behavior in solution of samarium, europium, terbium, and dysprosium complexes is compared, and the resolved RRR-λ and SSS-Δ complexes show strong circularly polarized luminescence. The molecular quadratic hyperpolarizability βHLS has been measured in solution using hyper-Raleigh light-scattering methods, for the whole series of lanthanide complexes of one ligand. The values of βHLS reach a maximum around the center of the series and are not simply dependent on the number of f electrons, suggesting a dominant contribution from the octupolar rather than the dipolar term.
- Walton, James W.,Carr, Rachel,Evans, Nicholas H.,Funk, Alexander M.,Kenwright, Alan M.,Parker, David,Yufit, Dmitry S.,Botta, Mauro,De Pinto, Sara,Wong, Ka-Leung
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- Enhanced selectivity for Mg2+ with a phosphinate-based chelate: APDAP: versus APTRA
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o-Aminophenol-N,N,O-triacetate, known as APTRA, is one of the most well-established ligands for targeting magnesium ions but, like other aminocarboxylate ligands, it binds Ca2+ much more strongly than Mg2+. The synthesis of an O-phosphinate analogue of APTRA is reported here, namely o-aminophenol-N,N-diacetate-O-methylene-methylphosphinate, referred to as APDAP. Metal binding studies monitored using UV-visible spectroscopy show that the affinity of APDAP for Ca2+ is reduced by over two orders of magnitude compared to APTRA, and for Zn2+ by over three orders of magnitude, whereas the affinity for Mg2+ is attenuated to a much lesser extent, by a factor of only about 7. The selectivity towards Mg2+ is thus substantially improved. DFT calculations support the notion that longer P-O and P-C bonds in APDAP (compared to corresponding C-O and C-C bonds in APTRA) favour a larger angle at the metal, an effect that is less unfavourable for smaller ions like Mg2+ than for larger ions such as Ca2+. Derivatives of APDAP can be anticipated that will offer improved sensing of Mg2+ in the presence of Ca2+, in the physiologically important millimolar concentration range.
- Walter, Edward R. H.,Fox, Mark A.,Parker, David,Williams, J. A. Gareth
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- Synthetic method of methyl hypophosphite
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The invention relates to a method for synthesizing methyl hypophosphite, which is prepared by reacting methyl phosphine dichloride and alcohol serving as raw materials in a continuous flow reactor. The method is simple in technological process, few in side reaction, capable of reducing generation of toxic substances, low in after treatment cost, high in production efficiency, high in yield and purity, good in safety and suitable for industrial production.
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Paragraph 0043-0045; 0046-0048
(2020/10/30)
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- Preparation method of glufosinate ammonium intermediate methylphosphinic acid monoester
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The invention discloses a preparation method of glufosinate ammonium intermediate methylphosphinic acid monoester. The preparation method includes the steps that o-methylphosphinic chloride and sulfohydrate are made to react under the alkaline condition to obtain methyl thiophosphonate, and methyl thiophosphonate is subjected to desulfurization reaction to obtain the glufosinate ammonium intermediate methylphosphinic acid monoester. The preparation method has the advantages that raw materials can be easily obtained, construction of P-C bonds is not needed, the process operation is simple and convenient, the production cost and the requirement on equipment are reduced, and the preparation method is suitable for industrial production.
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Paragraph 0055; 0057
(2018/07/15)
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- Synthesis method of synthetic intermediate methyl phosphite monoester of glufosinate ammonium
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The invention belongs to the technical field of synthesis of glufosinate ammonium and in particular relates to a synthesis method of a synthetic intermediate methyl phosphite monoester of glufosinateammonium. Aiming at the common problem of an existing methyl phosphite monoester synthesis method that the cost is too high so that the existing methyl phosphite monoester synthesis method is not applicable to large-scale industrial production, the synthesis method provided by the technical scheme comprises the following steps: [1], enabling methylphosphonothioic dichloride to react with a hydroxyl compound under the action of an alkali A, so as to obtain diethyl methylphosphonothionate; [2], dissolving the diethyl methylphosphonothionate into a solvent B to prepare a diethyl methylphosphonothionate solution; carrying out hydrolysis reaction under the action of an alkali B to generate methylphosphonothioic monoester; [3], dissolving the methylphosphonothioic monoester into a solvent C to prepare a methylphosphonothioic monoester solution; carrying out desulfurization reaction on the methylphosphonothioic monoester solution under the action of a catalyst to prepare the methyl phosphitemonoester. The synthesis method provided by the invention is applicable to a glufosinate ammonium synthesis industry.
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Paragraph 0075; 0076
(2018/09/08)
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- Methyl asia phosphine acid ester compound synthesis and purification method
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The invention relates to a synthesis and purification method of methyl phosphinate compounds. The method concretely comprises the following steps: adding brine to a solution containing a methyldialkyl phosphinate and magnesium chloride mixture in an inert solvent at a low temperature, and separating to obtain methylalkyl phosphinate or methyldialkyl phosphinate. The method solves the post-treatment and purification difficulties of a Grignard reagent method, and has the advantages of industrial production, effective reduction of the generation of methyl phosphonous acid, mild process conditions, and excellent reaction yield and product quality.
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Paragraph 0064; 0065; 0066
(2018/02/04)
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- A kind of preparation method for treating keratoconjunctival
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The invention belongs to the field of chemical synthesis, and in particular relates to a novel method for preparing herbicide, namely glufosinate-ammonium. The method comprises the following steps: conducting addition reaction on methyl phosphonic acid ester compounds and DL-2-hydroxy-3-crotonic acid ester compounds to obtain hydroxybutyric acid ester derivatives, and conducting acidification and ammonification reaction on the hydroxybutyric acid ester derivatives to obtain a glufosinate-ammonium compound. The method can avoid using high-toxic cyanide and obviously shortens a reaction route, so that the reaction steps of a process for preparing glufosinate-ammonium are reduced, the operation is simpler and more convenient, and many times of recrystallization is not needed for removing ammonium salt. The cost is reduced, and the method is completely suitable for large-scale production.
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Paragraph 0035; 0036
(2017/01/12)
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- Pyridylphosphinate metal complexes: Synthesis, structural characterisation and biological activity
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For the first time, a series of 25 pseudo-octahedral pyridylphosphinate metal complexes (Ru, Os, Rh, Ir) has been synthesised and assessed in biological systems. Each metal complex incorporates a pyridylphosphinate ligand, a monodentate halide and a capping η6-bound aromatic ligand. Solid- and solution-state analyses of two complexes reveal a structural preference for one of a possible two diastereomers. The metal chlorides hydrolyse rapidly in D2O to form a 1:1 equilibrium ratio between the aqua and chloride adducts. The pKa of the aqua adduct depends upon the pyridyl substituent and the metal but has little dependence upon the phosphinate R′ group. Toxicity was measured in vitro against non-small cell lung carcinoma H460 cells, with the most potent complexes reporting IC50 values around 50 μM. Binding studies with selected amino acids and nucleobases provide a rationale for the variation in toxicity observed within the series. Finally, an investigation into the ability of the chelating amino acid l-His to displace the phosphinate O-metal bond shows the potential for phosphinate complexes to act as prodrugs that can be activated in the intracellular environment.
- Cross, Jasmine M.,Gallagher, Natalie,Gill, Jason H.,Jain, Mohit,McNeillis, Archibald W.,Rockley, Kimberly L.,Tscherny, Fiona H.,Wirszycz, Natasha J.,Yufit, Dmitry S.,Walton, James W.
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supporting information
p. 12807 - 12813
(2016/08/24)
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- Grass ammonium phosphine method for the preparation of
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The invention belongs to the field of chemical synthesis, and particularly relates to a new preparation method of a glufosinate-ammonium weed killer. The preparation method is characterized in that methyl phosphorus dichloride reacts with alcohol so as to prepare a methyl phosphonate compound IV, and then the methyl phosphonate compound IV reacts with acrolein so as to prepare a methyl propionaldehyde phosphonate compound II; the methyl propionaldehyde phosphonate compound II is subjected to Bucherer-Bergs ring-closure reaction so as to prepare a hydantoin derivative shown in a formula III, and the hydantoin derivative is subjected to hydrolysis reaction so as to prepare the glufosinate-ammonium compound shown in a formula I. The preparation method of the glufosinate-ammonium has the advantages that required conditions are mild, the detection is easy, the required raw materials are easily available and low in cost, the yield of the obtained product is high, the obtained product has high purity, and ammonium salt is removed without needing recrystallization over and over again.
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Paragraph 0071; 0072; 0073
(2017/01/17)
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- NEUROLOGICALLY-ACTIVE COMPOUNDS
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The invention provides a compound of the formula (I): wherein R is methyl, ethyl, propyl, isopropyl, butyl, pentyl, neo-pentyl or cyclohexyl, or a salt or solvate thereof. These compounds are selective GABAC receptor antagonists. The invention also provides pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof. The invention also provides methods of enhancing the cognitive activity of an animal and methods of stimulating memory capacity in an animal, comprising the step of administering to the animal an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof.
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Page/Page column 23
(2008/06/13)
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- Design and synthesis of haptens for antibody catalyzed hydrolysis of organophosphoms nerve agents
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Haptens bearing phosphorane and α-hydroxyphosphinate structures have been designed and synthesized for the selection of monoclonal antibodies with phosphatase like activity in order to detoxify highly toxic organophosphorus chemical weapons such as VX.
- Renard, Pierre-Yves,Vayron, Philippe,Taran, Frederic,Mioskowski, Charles
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p. 281 - 284
(2007/10/03)
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- A stereoselective process for the preparation of novel phosphonoalkylphosphinates
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We have devised both a contiguous and a stepwise strategy for the synthesis of the pyridylaminomethane-based class of phosphonoalkylphosphinates (PAPs) that form via the intermediacy of the phosphonoethoxyaminomethane XIa. The PAPs result from condensation of picolines and phosphonoacetals in high chemoselective yield. Following reduction of aminopyridine IIIb, the unprecedented Pt(0)-catalyzed epimerization of the chelated amidine [(hydroxy)methylphosphinyl]-[(3-methyl-2-piperidinyl-idene)amino]methylphosphonic acid (IIIa) yielded a single racemic pair of PAPs (IIIc). The epimerization was found to occur more slowly than amidine formation itself.
- Ebetino, Frank H.,Berk, Jeffrey D.
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p. 135 - 142
(2007/10/03)
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- PHOSPHORUS CONTAINING COMPOUNDS AND USE AS HYPOTENSIVES
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Phosphorus containing compounds of the formula STR1 wherein X is a substituted or unsubstituted imino or amino acid and A is STR2 These compounds possess angiotensin converting enzyme activity and are thus useful as hypertensive agents.
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- Phosphonamidate compounds
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Phosphonamidates of the formula STR1 wherein X is an amino acid or ester. These compounds possess angiotensin converting enzyme inhibition activity and enkephalinase inhibition activity. Thus they are useful as hypotensive and analgesic agents.
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