- Tuning amino acid dehydrogenases with featured sequences for L-phosphinothricin synthesis by reductive amination
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Biosynthesizing unnatural chiral amino acids is challenging due to the limited reductive amination activity of amino acid dehydrogenase (AADH). Here, for the asymmetric synthesis of L-phosphinothricin from 2-oxo-4-[(hydroxy)(methyl)phosphinoyl]butyric acid (PPO), a glutamate dehydrogenase gene (named GluDH3) from Pseudomonas monteilii was selected, cloned and expressed in Escherichia coli (E. coli). To boost its activity, a “two-step”-based computational approach was developed and applied to select the potential beneficial amino acid positions on GluDH3. L-phosphinothricin was synthesized by GluDH-catalyzed asymmetric amination using the D-glucose dehydrogenase from Exiguobacterium sibiricum (EsGDH) for NADPH regeneration. Using lyophilized E. coli cells that co-expressed GluDH3_V375S and EsGDH, up to 89.04 g L?1 PPO loading was completely converted to L-phosphinothricin within 30 min at 35 °C with a space-time yield of up to 4.752 kg·L?1·d?1. The beneficial substitution V375S with increased polar interactions between K90, T193, and substrate PPO exhibited 168.2-fold improved catalytic efficiency (kcat/KM) and 344.8-fold enhanced specific activity. After the introduction of serine residues into other GluDHs at specific positions, forty engineered GluDHs exhibited the catalytic functions of “glufosinate dehydrogenase” towards PPO.
- Cheng, Feng,Li, Heng,Li, Qing-Hua,Xie, Dong,Xue, Ya-Ping,Zhang, Kai,Zheng, Yu-Guo
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Read Online
- L-GLUFOSINATE INTERMEDIATE AND L-GLUFOSINATE PREPARATION METHOD
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Provided are L-glufosinate intermediate preparation method or L-glufosinate preparation method, the method, for preparing L-glufosinate intermediate or L-glufosinate from an L-homoserine derivative, comprising a step of preparing a compound of Chemical Formula 2 from a compound of Chemical Formula 1.
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Paragraph 0160-0162
(2022/02/05)
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- A Single-Transaminase-Catalyzed Biocatalytic Cascade for Efficient Asymmetric Synthesis of l-Phosphinothricin
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A single-transaminase-catalyzed biocatalytic cascade was developed by employing the desired biocatalyst, ATA-117-Rd11, that showed high activity toward 2-oxo-4-[(hydroxy)(methyl)phosphinoyl] butyric acid (PPO) and α-ketoglutarate, and low activity against pyruvate. The cascade successfully promotes a highly asymmetric amination reaction for the synthesis of l-phosphinothricin (l-PPT) with high conversion (>95 %) and>99 % ee. In a scale-up experiment, using 10 kg pre-frozen E. coli cells harboring ATA-117-Rd11 as catalyst, 80 kg PPO was converted to ≈70 kg l-PPT after 24 hours with a high ee value (>99 %).
- Cheng, Feng,Li, Ju-Mou,Zhou, Shi-Peng,Liu, Qi,Jin, Li-Qun,Xue, Ya-Ping,Zheng, Yu-Guo
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p. 345 - 348
(2020/10/02)
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- Preparation method of glufosinate-ammonium
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The invention relates to a preparation method of glufosinate-ammonium (I). The method comprises the step of reacting an enantiomerically pure compound of formula (II) with a compound of formula (III) in the presence of a Lewis acid, wherein Hal is a halogen; PG is hydrogen or an amino protecting group; Z is OX or OY; R1 is a C1-C16 alkyl group, cyclohexyl group, cyclopentyl group or phenyl group, and each group can be substituted by hydrogen, a C1-C6 alkyl group, a C1-C6 alkoxy group or a dialkylamino group; R2 is a C1-C8 alkyl group, a C1-C8 ether group or a phenyl group; X and Y are respectively and independently alkyl, alkenyl or aryl; and chiral carbon atoms are marked with *. According to the method disclosed by the invention, high-purity glufosinate-ammonium can be obtained with high yield.
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Paragraph 0052-0053; 0055-0057; 0059-0061; 0063-0065
(2021/08/14)
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- Development of a biocatalytic cascade for synthesis of 2-oxo-4-(hydroxymethylphosphinyl) butyric acid in one pot
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2-Oxo-4-(hydroxymethylphosphinyl) butyric acid (PPO) is an important precursor compound for the broad-spectrum herbicide l-glufosinate (L-PPT). In this study, the gene of d-amino acid oxidase (DAAO) was cloned and expressed in Escherichia coli. By coupling exogenous catalase (CAT), a biocatalytic cascade was constructed for synthesis of PPO in one pot. The bioprocess was optimized on a 300 mL scale reaction by one factor at a time optimization. The conversion of this biocatalytic cascade achieved 46.8% towards 400 mM DL-PPT within 4 h. These results indicated that DAAO could be applied to the large-scale bioproduction of PPO and provide a promising route for the asymmetric synthesis of L-PPT by bio-enzymatic methods using PPO as the substrate.
- Xu, Jianmiao,Zhang, Kai,Cao, Huiting,Li, Heng,Cheng, Feng,Cao, Chenghao,Xue, Ya-Ping,Zheng, Yu-Guo
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p. 190 - 197
(2020/07/30)
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- Biocatalytic asymmetric synthesis of L-phosphinothricin using a one-pot three enzyme system and a continuous substrate fed-batch strategy
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Transamination catalyzed by an aminotransferase is becoming a key tool for the production of chiral amine pharmaceuticals and agrochemicals owing to its excellent enantioselectivity and green credentials. To overcome the unfavorable thermodynamic equilibrium and the inhibition by the byproduct α-ketoglutaric acid in the transamination of 2-oxo-4-[(hydroxy)(methyl)phosphinoyl]butyric acid (PPO) to form the promising herbicide L-phosphinothricin (L-PPT), a tri-enzymatic cascade reaction system was developed by combining a robust glutamate dehydrogenase to recycle the byproduct to the amino donor L-glutamate in situ, together with a cofactor recycling process catalyzed by an alcohol dehydrogenase. Moreover, a continuous substrate fed-batch strategy was employed to alleviate the decomposition of PPO and applied to scale-up the cascade reaction to 90 L, yielding 111.4 g/L (615.4 mM) L-PPT in 99.7% yield and >99.9% ee with an productivity of 15.9 g/L?h. This combination of improved biocatalyst system and process engineering should prove to be economically competitive for industrial applications.
- Zhou, Haisheng,Meng, Lijun,Yin, Xinjian,Liu, Yayun,Wu, Jianping,Xu, Gang,Wu, Mianbin,Yang, Lirong
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- Semi-rational hinge engineering: modulating the conformational transformation of glutamate dehydrogenase for enhanced reductive amination activity towards non-natural substrates
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The active site is the common hotspot for rational and semi-rational enzyme activity engineering. However, the active site represents only a small portion of the whole enzyme. Identifying more hotspots other than the active site for enzyme activity engineering should aid in the development of biocatalysts with better catalytic performance. Glutamate dehydrogenases (GluDHs) are promising and environmentally benign biocatalysts for the synthesis of valuable chirall-amino acids by asymmetric reductive amination of α-keto acids. GluDHs contain an inter-domain hinge structure that facilitates dynamic reorientations of the domains relative to each other. Such hinge-bending conformational motions of GluDHs play an important role in regulating the catalytic activity. Thus, the hinge region represents a potential hotspot for catalytic activity engineering for GluDHs. Herein, we report semi-rational activity engineering of GluDHs with the hinge region as the hotspot. Mutants exhibiting significantly improved catalytic activity toward several non-natural substrates were identified and the highest activity increase reached 104-fold. Molecular dynamics simulations revealed that enhanced catalytic activity may arise from improving the open/closed conformational transformation efficiency of the protein with hinge engineering. In the batch production of three valuablel-amino acids, the mutants exhibited significantly improved catalytic efficiency, highlighting their industrial potential. Moreover, the catalytic activity of several active site tailored GluDHs was also increased by hinge engineering, indicating that hinge and active site engineering are compatible. The results show that the hinge region is a promising hotspot for activity engineering of GluDHs and provides a potent alternative for developing high-performance biocatalysts toward chirall-amino acid production.
- Liu, Yayun,Meng, Lijun,Wu, Jianping,Yang, Lirong,Yin, Xinjian,Zhou, Haisheng
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p. 3376 - 3386
(2020/06/09)
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- Method for preparing L-glufosinate-ammonium
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The invention belongs to the field of organic synthesis, and particularly relates to a method for preparing L-glufosinate-ammonium (I) or salt thereof. A compound represented by formula (II) or a saltthereof reacts with a compound represented by formula (III), and no matter whether an intermediate is separated or not, a product obtained by the reaction is subjected to a hydrolysis reaction to obtain L-glufosinate-ammonium (I) or a salt thereof. Compared with an existing L-glufosinate-ammonium synthesis route, the method is a new chemical synthesis route, the steps are simple, the atom economyis high, an L-glufosinate-ammonium product with a high ee value can be obtained without chiral catalysis, and the method has a potential industrialization application value.
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Paragraph 0033-0039
(2020/10/30)
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- Method for preparing L-glufosinate-ammonium
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The invention relates to a method for preparing L-glufosinate-ammonium. Compared with an existing method, the method of the invention is a new chemical synthesis route, is simple in steps, easily available in raw materials and controllable in cost, can obtain the L-glufosinate-ammonium product with the high ee value without chiral catalysis, and has potential industrial application value.
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Paragraph 0039; 0046-0047; 0050
(2020/09/23)
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- Method for preparing L-glufosinate-ammonium
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The invention relates to a method for preparing L-glufosinate-ammonium. Compared with an existing method, the method of the invention is a new chemical synthesis route, is simple in steps, easily available in raw materials and controllable in cost, can obtain the L-glufosinate-ammonium product with the high ee value without chiral catalysis, and has potential industrial application value.
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Paragraph 0030; 0043-0045
(2020/09/23)
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- Method for preparing L-glufosinate-ammonium
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The invention relates to a method for preparing L-glufosinate-ammonium. According to the method, cheap and easily available L-homoserine is used as an initial raw material, L-glufosinate-ammonium witha high ee value is prepared through a three-step reaction, chiral catalysis is not needed, the cost is low, and the method has a potential industrial application value.
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Paragraph 0047; 0057-0059; 0065; 0075-0077
(2020/09/23)
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- METHODS FOR IMPROVING YIELDS OF L-GLUFOSINATE
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Compositions and methods for the production of L-glufosinate are provided. The method involves converting racemic glufosinate to the L-glufosinate enantiomer or converting PRO to L-glufosinate in an efficient manner. In particular, the method involves the specific amination of PRO to L-glufosinate, using L-glutamate, racemic glutamate, or another amine source as an amine donor. PRO can be obtained by the oxidative deamination of D-glufosinate to PRO (2- oxo-4-(hydroxy(methyl)phosphinoyl)butyric acid) or generated via chemical synthesis. PRO is then converted to L-glufosinate using a transaminase in the presence of an amine donor. When the amine donor donates an amine to PRO, L-glufosinate and a reaction by product are formed. Because the PRO remaining represents a yield loss of L-glufosinate, it is desirable to minimize the amount of PRO remaining in the reaction mixture. Degradation, other chemical modification, extraction, sequestration, binding, or other methods to reduce the effective concentration of the by-product, i.e., the corresponding alpha ketoacid or ketone to the chosen amine donor will shift the reaction equilibrium toward L-glufosinate, thereby reducing the amount of PRO and increasing the yield of L-glufosinate. Therefore, the methods described herein involve the conversion or elimination of the alpha ketoacid or ketone by-product to another product to shift the equilibrium towards L-glufosinate.
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Page/Page column 32
(2020/03/29)
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- Preparation method of glufosinate-ammonium
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The invention discloses a preparation method of glufosinate-ammonium. The preparation method comprises the following steps that 1, in alkaline environment, 4-(hydroxymethyl phosphono)-2-carbonyl butyric acid (I) and a benzylamine solution react to produce 2-[( phenyl amino)-4-(methyl sodium phosphate)-sodium butyrate (II); 2, 2-[(phenyl amino)-4-(methyl sodium phosphate)-sodium butyrate (II) is subjected to acid hydrolysis to obtain glufosinate-ammonium (III). Compared with the prior art, the preparation method has the advantages that the conditions are mild; the yield of the glufosinate-ammonium is high; the purity is high.
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Paragraph 0034;0037-0038; 0042-0044; 0047-0048
(2020/06/30)
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- Artificial Biocatalytic Cascade with Three Enzymes in One Pot for Asymmetric Synthesis of Chiral Unnatural Amino Acids
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Two biocatalytic reactions, transamination catalyzed by transaminases and reductive amination catalyzed by amino acid dehydrogenases, can be used for asymmetric synthesis of optically pure unnatural amino acids. However, although transaminases show a great diversity and broad substrate spectrum, most transaminase reactions are reversible, while amino acid dehydrogenases catalyze reductive amination irreversibly but with strict substrate specificity. Accordingly, herein we developed a tri-enzyme one-pot reaction system to exploit the respective advantages of transaminases and amino acid dehydrogenases, while overcoming the disadvantages of each. In this work, representatives of all four subgroups of transaminases coupled with different amino acid dehydrogenases to produce five l- and four d- unnatural amino acid products, using ammonia and the co-enzyme NAD(P)H, which is regenerated by a robust alcohol dehydrogenase with 2-propanol as cheap cosubstrate. The complete conversion and high enantiopurity (ee > 99 %) of the products, demonstrated it as an ideal alternative for asymmetric synthesis of chiral amino acid compounds.
- Zhou, Haisheng,Meng, Lijun,Yin, Xinjian,Liu, Yayun,Xu, Gang,Wu, Jianping,Wu, Mianbin,Yang, Lirong
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supporting information
p. 6470 - 6477
(2019/11/02)
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- Efficient racemization of N-phenylacetyl-D-glufosinate for L-glufosinate production
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Most amino acids contain chiral centres and exist as both D-enantiomer and L-enantiomer. The optically pure enantiomer is often more valuable than the racemate. Enzymatic resolution provides an effective strategy to obtain optically pure amino acids but often results in large amounts of unwanted isomer. In this study, optically pure L-glufosinate (L-PPT) was obtained by coupling amidase-mediated hydrolysis of N-phenylacetyl-D,L-glufosinate with racemization of N-phenylacetyl-D-glufosinate (NPDG), which exclusively exhibits effective herbicidal properties compared with its D-enantiomer. To improve the yield of L-PPT, the racemization reaction conditions were optimized, and through single-factor experiments, the optimal reaction temperature, reaction time, and mole ratio of phenylacetic acid to NPDG were determined to be 150°C, 30?minutes, and 1.5, respectively. The response surface methodology was applied to further optimize the racemization conditions, and the final yield of L-PPT reached 96.13% with optimum reaction temperature of 154°C, reaction time of 23?minutes, and phenylacetic acid/NPDG mole ratio of 1.7, respectively. Moreover, adding a small amount of acetic anhydride further raised the yield of L-PPT to 97.02%.
- Xu, Jian-Miao,Li, Fang-Long,Xue, Ya-Ping,Zheng, Yu-Guo
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p. 513 - 521
(2019/07/02)
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- Refined glufosinate acid aquo-complex crystals and preparation method thereof
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The invention belongs to the field of pesticides and discloses refined glufosinate acid aquo-complex crystals and a preparation method thereof. The refined glufosinate acid aquo-complex crystals are refined glufosinate acid-aquo-complex crystals. An X-ray powder diffraction spectrogram represented by diffraction angles: 2theta+/-0.2 degrees of the quo-complex crystals shows characteristic diffraction peaks (shown as a figure 1) at 2theta: 14.67 degrees, 17.17 degrees, 20.83 degrees, 22.23 degrees, 22.43 degrees, 23.12 degrees, 25.99 degrees, 27.66 degrees, 30.68 degrees, 34.69 degrees and 41.34 degrees. The characteristic diffraction peaks are obviously different from those in the prior art. The refined glufosinate acid-aquo-complex crystals have good performance and are quite suitable foractual applications. The invention also discloses a preparation method for the refined glufosinate acid-aquo-complex crystals. The preparation method is simple and mild and suitable for industrial production.
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Paragraph 0037-0048
(2019/03/06)
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- Driving Transamination Irreversible by Decomposing Byproduct Α-Ketoglutarate into Ethylene Using Ethylene-Forming Enzyme
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The transformations of transaminases have been extensively studied as an approach to the production of chiral amino moieties. However, the low equilibrium conversion of the reaction is a critical disadvantage to transaminase application, and a strategy for shifting the reaction equilibrium is essential. Herein, we have developed a novel method to effectively prevent the reversibility of transamination by fully decomposing byproduct α-ketoglutarate into ethylene and carbon dioxide in situ using ethylene-forming enzyme (EFE). Two transaminases and one EFE were expressed in E. coli and purified to be used in the cascade reaction. After optimal reaction conditions were determined based on the enzymatic properties, a cascade reaction coupling transaminase with EFE was conducted and showed high efficiency in the synthesis of l-phosphinothricin. Finally, using this approach with only an equivalent amount of amino donor l-glutamate increased the conversions of various keto acids from 99%. This strategy shows great potential for transamination using glutamate as the amino donor.
- Meng, Li-Jun,Liu, Ya-Yun,Zhou, Hai-Sheng,Yin, Xin-Jian,Wu, Jian-Ping,Wu, Mian-Bin,Xu, Gang,Yang, Li-Rong
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p. 3309 - 3314
(2018/10/02)
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- Fine glufosinate ammonium synthesizing method
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The invention belongs to the technical field of organic compound synthesis and specifically relates to a fine glufosinate ammonium synthesizing method. According to the fine glufosinate ammonium synthesizing method disclosed by the invention, L-3,6-bis(2-halogen ethyl)-2,5-diketone piperazine and methyl phosphorous monoester are utilized as raw materials to be synthesized, compound shown in an intermediate formula (III) is synthesized through alkylation reaction, and fine glufosinate ammonium can be prepared by hydrolysis reaction. As the L-3,6-bis(2-halogen ethyl)-2,5-diketone piperazine rawmaterial contains a chiral carbon center, the fine glufosinate ammonium with required conformation can be prepared by simple reaction; thus, the whole synthesizing process is simple, easy and practical; furthermore, the raw materials are easy to obtain, so that production cost is reduced; in addition, an alkylation catalyst is utilized in the reaction to promote reaction process, so that a productyield is improved, and industrial production is beneficiated.
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Paragraph 0061; 0064
(2018/09/21)
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- Preparation method of fine glufosinate
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The invention belongs to the technical field of organic compound synthesis and relates to a preparation method of fine glufosinate, in particular to a preparation method of fine glufosinate with L-homoserine as a raw material. According to the preparation method of fine glufosinate, L-homoserine prepared through a biological fermentation method serves as an initial raw material, L-3,6-di(2-halogenethyl)-2,5-diketopiperazine is prepared through the steps such as azeotropic dehydration and halogenation, a Serhiy Arbuzov reaction is conducted between L-3,6-di(2-halogen ethyl)-2,5-diketopiperazine and methyl phosphonic acid dibutyl, and fine glufosinate is prepared through a hydrolysis reaction. Compared with an existing preparation technology, the preparation method of fine glufosinate has the advantages that the total yield of fine glufosinate is greatly increased, the technological process is simple, and fine glufosinate is suitable for industrial production.
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Paragraph 0062; 0066
(2018/09/28)
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- Glufosinate ammonium preparation method
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The invention relates to a glufosinate ammonium preparation method. According to the present invention, nitro is introduced by using a simple and economical method, and is reduced under a mild condition so as to introduce amino group as the key step, such that the method for introducing amino by using other expensive amino acid derivatives or other toxic nitrogen-containing compounds is avoided, and the amino protection and deprotection during the reaction is eliminated; and the preparation method has advantages of simple reaction process, mild condition, simple and easily-available raw materials, simple operation and good atom economy, and is extremely suitable for industrial production.
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Paragraph 0028; 0032
(2018/07/07)
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- Process for preparing glufosinate acid with hydrogenation method
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The invention discloses a process for preparing precursor glufosinate acid of glufosinate acid with a catalytic hydrogenation method. The process comprises the following steps: firstly, reacting N-ethyl acetamidomalonate with 2-[ethyoxyl(methyl)phosphonyl] acetaldehyde under the actions of an acid binding agent and a dehydrating agent to generate an intermediate, namely, 2-acetamido-4-[ethyoxyl(methyl)phosphonyl]butyl-2-olefine acid ester; secondly, separating and purifying the intermediate, performing hydrogenation by taking ethanol as a solvent under the catalytic action of a hydrogenation catalyst to obtain a product, namely, 2-acetamido-4-[ethyoxyl(methyl)phosphonyl]ethyl butyrate, wherein the two-step yield can be 85 percent or more; lastly, performing deprotection with concentrated hydrochloric acid, and removing the hydrochloric acid to obtain the glufosinate acid. The process has the advantages of easiness in reaction and post-treatment operation, high yield, recyclability of the hydrogenation catalyst and the like, and has a very wide industrial prospect.
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Paragraph 0012; 0029
(2018/07/30)
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- NOXIOUS ARTHROPOD CONTROL AGENT CONTAINING AMIDE COMPOUND
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An object of the present invention is to provide a compound having the controlling activity on a noxious arthropod, and a noxious arthropod controlling agent containing an amide compound of formula (I): wherein X represents a nitrogen atom or a CH group, p represents 0 or 1, A represents a tetrahydrofuranyl group or the like, R1, R2, R3, R4, R5, R6 and R7 represent a hydrogen atom or the like, n represents 1 or 2, Y represents an oxygen atom or the like, m represents any integer of 0 to 7, and Q represents a C1-8 chain hydrocarbon group optionally having a phenyl group or the like, has the excellent noxious arthropod controlling effect.
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- Highly Efficient and Divergent Construction of Chiral γ-Phosphono-α-Amino Acids via Palladium-Catalyzed Alkylation of Unactivated C(sp3)-H Bonds
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Chiral γ-phosphono-α-amino acids play a crucial role in inhibitors of natural enzymes, as well as agonists and antagonists of metabotropic glutamate receptors. In this paper, an efficient and general protocol for the construction of chiral γ-phosphono-α-amino acids via Pd-catalyzed AQ-directed C(sp3)-H alkylation of α-amino acid derivatives is developed. The reaction shows reactivity between methylene C(sp3)-H bonds with phosphonated alkyl iodides with high yields, enantioselectivity, and diastereomeric ratios, which enables access to a wide range of challenging and important γ-phosphono-α-amino acids in large scale. Meanwhile, δ-phosphono-α-amino acid and δ-phosphono-propionic acid derivatives can also be successfully obtained. The derivatization reaction in the synthesis of l-AP4 and l-phosphinothricin highlight the applicability of this method.
- Yang, Qiang,Yang, Shang-Dong
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p. 5220 - 5224
(2017/08/17)
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- A aminonitrile preparation method and process for the preparation of the intermediates of glufosinate
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The invention discloses a preparation method of amino-nitrile and an intermediate for preparing glufosinate-ammonium. The preparation method disclosed by the invention aims at solving the problem of low glufosinate-ammonium yield by using acetal in the existing methods. Different from the existing methods for preparing glufosinate-ammonium, the method disclosed by the invention comprises the following steps: firstly reacting acetal with acetylchloride to obtain an enol ether intermediate, reacting the enol ether intermediate with sodium cyanide to obtain amino-nitrile, and finally hydrolyzing the amino-nitrile to obtain the glufosinate-ammonium. The method has the advantages of higher reaction yield and capacity of remarkably reducing the production cost of the glufosinate-ammonium.
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Paragraph 0037; 0042-004
(2017/08/25)
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- LJ reaction in the preparation wittich reagent and application of glufosinate in
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The present invention relates to an application of a new LJ intramolecular isomerization reaction in preparation of a wittig reagent and a herbicide of glufosinate-ammonium. With the application, a new approach of a synthesis route for preparing the wittig reagent and the glufosinate-ammonium is developed, the disadvantages of the existing wittig reaction are improved, and the industrial design of the glufosinate-ammonium production is improved.
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Paragraph 0099; 0101
(2017/12/04)
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- Refined glufosinate preparation method
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The invention discloses a refined glufosinate preparation method. The refined glufosinate preparation method comprises the steps that 1, L-methionine and alpha-halogenated carboxylic acid or its derivative react under the effect of a phase transfer catalyst to obtain L-homoserine lactone hydrogen halide salt; 2, the L-homoserine lactone hydrogen halide salt and an amino protective reagent react to obtain a compound IV; 3, the compound IV performs ring-opening reaction with dihalogen sulfoxide, phosgene, triphosgene (BTC) or trimethyl halogenosilane to obtain a compound V, and the compound V is subjected to subsequent reaction treatment to obtain refined glufosinate, wherein the phase transfer catalyst is a quaternary ammonium salt phase transfer catalyst. The preparation method greatly improves the yield of the refined glufosinate, intermediate products revolved in reaction are easy to detect, the conditions are mild, and the refined glufosinate preparation method is suitable for industrial production.
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Paragraph 0059-0067; 0111; 0112; 0113
(2017/06/02)
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- A L-glufosinates-N-carboxylic acid anhydride, and its preparation and use
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The invention discloses an L-phosphinothricin-N-carboxylic anhydride, and preparation and application thereof. The method comprises the following steps: by using wet thallus obtained by carrying out fermentation culture on Arthrobacter nicotinovorans WYG001 or dry thallus obtained by carrying out freeze-drying on the wet thallus as an enzyme source, DL-phosphinothricin-N-carboxylic anhydride as a substrate and a 0.1 mol/L phosphate buffer solution with the pH value of 7.0 as a reaction medium, reacting at 20-50 DEG C at the rate of 200 rpm; and after the reaction is complete, separating and purifying the reaction solution to obtain the L-phosphinothricin-N-carboxylic anhydride, and carrying out hydrolysis ring-opening decarboxylation reaction to obtain the L-phosphinothricin. The thallus disclosed by the invention has the advantages of high regioselectivity, high reaction conversion rate, simple downstream separation, low energy consumption and small environmental pollution, and is suitable for industrial production. The L-phosphinothricin-N-carboxylic anhydride can be subjected to simple heating hydrolysis decarboxylation to obtain the optically pure L-phosphinothricin.
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Paragraph 0088-0089
(2017/03/18)
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- Grass amine phosphine method for the preparation of
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The invention discloses a Glufosinate-ammonium and its derivative improved preparation method, the method comprises the following steps: diethyl methyl-phoshphonite, acraldehyde and acetic anhydride are subjected to an addition reaction, a reactant, sodium cyanide (editpotassium cyanide for replacing) and an ammonia water solution of ammonium chloride are subjected to an improved STRECKER reaction without separation, the product is subjected to hydrolysis and ammonification for forming salt to obtain Glufosinate-ammonium. The preparation method has the characteristics of high selectivity and high yield.
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Sheet 0018; 0022; 0035; 0040; 0041; 0042; 0043
(2017/04/28)
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- A kind of preparation method for treating keratoconjunctival and wherein the intermediate preparation method
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The invention relates to the technical field of pesticides and particularly relates to a method for preparing glufosinate-ammonium and a preparation method for an intermediate thereof. The method is characterized by comprising the following steps of: taking phosphorus trichloride and phosphite ester as raw materials, preparing chlorophosphite ester under the catalysis of the mixture of triethylamine, N,N-dimethylformamide or pyridine and hexamethylphosphoramide, preparing methylmagnesium chloride from chloromethane and magnesium metal, preparing methyl phosphite ester by reacting the chlorophosphite ester with methylmagnesium chloride, carrying out an addition reaction on the methyl phosphite ester and acrolein, carrying out a Strecker reaction on the product of the addition reaction, sodium cyanide, ammonium chloride and ammonia water under the catalysis of montmorillonite-supported lewis acid, and carrying out hydrolyzing and purifying after finishing the Strecker reaction, so as to obtain the high-purity glufosinate-ammonium. The method provided by the invention has the advantages that side reactions are few, products are high in purity and easy to separate, and catalysts and solvents are easy to obtain, regenerate and recycle; and the production cost is lowered, and the method is accordant with the trend of green chemical industry and is suitable for industrial production.
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Paragraph 0119; 0120
(2017/03/08)
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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 0067; 0069; 0070
(2017/01/17)
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- Purification method of glufosinate
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The invention relates to a purification method of glufosinate. The method comprises the following steps: adding a glufosinate hydrochloride crude product into a solvent, adding amino acid and an aqueous solution of alkali, reacting for 0.5-1.5 h, adjusting pH of the reaction system to 1-7, filtering and drying to obtain glufosinate-ammonium acid; and dissolving glufosinate-ammonium acid in a solvent, introducing ammonia gas and carrying out a salt-forming reaction, precipitating a glufosinate solid, filtering and drying to obtain high-purity glufosinate. According to the purification technology, use of fatty amine which is hard to remove and high-risk oxirane and epoxypropane is avoided. The steps are simple. The obtained glufosinate has low content of inorganic salt, high purity, high yield and high safety. In addition, water or alcohol is used as a solvent in the technological process, and a neutralization reaction is carried out by the use of ammonia water and inorganic base. The purification method accords with the ecology and economy principle, and has a good industrial prospect. In addition, purification is carried out by addition of amino acid, and purification efficiency and product purity are higher.
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Paragraph 0027
(2016/11/02)
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- The purification process of a grass ammonium phosphine
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The invention provides a glufosinate purifying technology including the following steps: (1) adding glufosinate hydrochloride to alcohol R1OH, adding R2NH2 for ammoniation, adjusting the pH to 7.0-14.0, cooling and filtering, removing a solvent from a filtrate to obtain glufosinate ammonium salt and a small amount of organic impurities; (2) dissolving the glufosinate ammonium salt obtained by the steps (1) in an appropriate amount of water, leading in CO2 for neutralizing to the pH of 2.0-5.0, adding a proper amount of alcohol R3OH for precipitation of glufosinate acid, centrifugally filtrating to obtain the glufosinate acid which contains a small amount of ammonium hydrogen carbonate or organic amine carbonates; (3) heating for drying a glufosinate acid filtering cake obtained by the step (2) for decomposition and volatilization of the ammonium hydrogen carbonate or organic amine carbonates to obtain high purity glufosinate acid. The glufosinate purifying technology is simple in steps, the obtained glufosinate is low in inorganic salt content and high in purity, and compared with a traditional technology using epoxy ethane and epoxy propane, the purifying technology using carbon dioxide for separation of glufosinate hydrochloride and HCl is more economical, and high in safety, and has a higher industrialization prospect.
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Paragraph 0022-0028
(2016/10/10)
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- Method for preparing high-purity glufosinate-ammonium by organic alkali process
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The invention discloses a method for preparing high-purity glufosinate-ammonium by an organic alkali process. The method comprises the following steps: by using a glufosinate-ammonium hydrochloride solution as a raw material, filtering the raw material, concentrating, directly adding tertiary amine R1R2R3N1 into the concentrated solution under the heating condition of 60-80 DEG C, and keeping the temperature to carry out hydrochloric acid removal reaction; after the reaction finishes, cooling to -3 to -8 DEG C to precipitate a glufosinate-ammonium free acid crude product; adding alcohol into the crude product, pulping, and filtering, wherein the obtained filter cake is glufosinate-ammonium free acid; adding alcohol into the glufosinate-ammonium free acid, heating to 30-50 DEG C, introducing ammonia gas to react; and after the reaction finishes, cooling to crystallize, filtering, and drying to obtain the glufosinate-ammonium with the purity of at least 88%.
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Paragraph 0045
(2016/10/20)
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- Purification method for glufosinate-ammonium
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The invention relates to a purification method for glufosinate-ammonium. The method comprises the following steps that a glufosinate-ammonium hydrochloride crude product is dissolved into a solvent, then, alkaline is added to be subjected to a reaction, the pH value is adjusted to be 7-10, reduced pressure distillation is performed to remove some solvent, then filtering is performed to remove ammonium chloride and other undissolved substances; acid is added into the reaction solution to be subjected to a reaction, the pH value is adjusted to be 1-4.5, and then filtering and drying are performed to obtain glufosinate-ammonium acid; the glufosinate-ammonium acid is dissolved into the solvent, then, ammonia gas is introduced to be subjected to a salt forming reaction, glufosinate-ammonium solid is separated out, and filtering and drying are performed to obtain high-purity glufosinate-ammonium. According to the purification technology, fatty amine hard to remove and high-risk ethylene oxide and epoxypropane are prevented from being used, the steps are simple, the obtained glufosinate-ammonium is low in inorganic salt content and high in purity, yield and safety, water or alcohol is used as the solvent in the technological process, ammonium hydroxide and inorganic base are used for being subjected to a neutral reaction, the glufosinate-ammonium conforms to the environment-friendly and economical principle, and the good industrial prospect is achieved.
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Paragraph 0026
(2017/02/09)
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- A glufosinate hydrochloride by the method of preparation grass ammonium phosphine acid (by machine translation)
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The present invention discloses a one-glufosinate hydrochloride by the method of preparation grass ammonium phosphine acid, firstly the glufosinate hydrochloric acid salt is dissolved in the alcohol, then adding ammonia in and after the, precipitated grass ammonium phosphine acid. The method of the invention not only can be obtained in high yield high-purity grass ammonium phosphine acid, but also can save a large amount of water and alcohol, is suitable for industrial application. (by machine translation)
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Paragraph 0023-0032; 0033; 0034
(2017/05/16)
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- Spectroscopic characterization and mechanistic investigation of P-methyl transfer by a radical SAM enzyme from the marine bacterium Shewanella denitrificans OS217
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Natural products containing carbon-phosphorus bonds elicit important bioactivity in many organisms. l-Phosphinothricin contains the only known naturally-occurring carbon-phosphorus-carbon bond linkage. In actinomycetes, the cobalamin-dependent radical S-adenosyl-l-methionine (SAM) methyltransferase PhpK catalyzes the formation of the second C-P bond to generate the complete C-P-C linkage in phosphinothricin. Here we use electron paramagnetic resonance and nuclear magnetic resonance spectroscopies to characterize and demonstrate the activity of a cobalamin-dependent radical SAM methyltransferase denoted SD-1168 from Shewanella denitrificans OS217, a marine bacterium that has not been reported to synthesize phosphinothricin. Recombinant, refolded, and reconstituted SD-1168 binds a four-iron, four-sulfur cluster that interacts with SAM and cobalamin. In the presence of SAM, a reductant, and methylcobalamin, SD-1168 surprisingly catalyzes the P-methylation of N-acetyl-demethylphosphinothricin and demethylphosphinothricin to produce N-acetyl-phosphinothricin and phosphinothricin, respectively. In addition, this enzyme is active in the absence of methylcobalamin if the strong reductant titanium (III) citrate and hydroxocobalamin are provided. When incubated with [methyl-13C] cobalamin and titanium citrate, both [methyl-13C] and unlabeled N-acetylphosphinothricin are produced. Our results suggest that SD-1168 catalyzes P-methylation using radical SAM-dependent chemistry with cobalamin as a coenzyme. In light of recent genomic information, the discovery of this P-methyltransferase suggests that S. denitrificans produces a phosphinate natural product.
- Allen, Kylie D.,Wang, Susan C.
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p. 2135 - 2144
(2015/02/02)
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- METHOD FOR PRODUCING GLUFOSINATE P FREE ACID
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The present invention provides a method for producing crystalline glufosinate P free acid with high purity from glufosinate P hydrochloride salt. In addition, the present invention also provides a method comprises a process of: dissolving glufosinate P hydrochloride salt in a solvent which is a mixed solvent of water and an alcohol(s) selected from the group of methanol, ethanol, propyl alcohol and isopropyl alcohol, and a ratio of water to the alcohol(s) is from 1:3 to 1:100 by volume; crystallizing glufosinate P free acid after neutralizing by addition of a base.
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Paragraph 0043; 0044
(2014/08/19)
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- METHOD FOR PRODUCING PHOSPHORUS-CONTAINING -AMINO ACID AND PRODUCTION INTERMEDIATE THEREOF
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A method for efficiently producing L-2-amino-4-(hydroxymethylphosphinyl)-butanoic acid, useful as a herbicide, by a catalytic asymmetric synthesis reaction with a high asymmetric yield. The method comprises a step wherein a compound represented by the bel
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Page/Page column 13
(2009/06/27)
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- METHOD FOR PRODUCING L-2-AMINO-4-(HYDROXYMETHYLPHOSPHINYL)- BUTANOIC ACID
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Disclosed is a method for efficiently and highly selectively producing L-2-amino-4-(hydroxymethylphosphinyl)-butanoic acid, which is useful as a herbicide, through a catalytic asymmetric synthesis reaction. Specifically disclosed is a method for producing L-2-amino-4-(hydroxymethylphosphinyl)-butanoic acid which is characterized in that a dehydroamino acid is subjected to an asymmetric hydrogenation by using a rhodium catalyst represented by the formula (2) below and having an optically active cyclic phosphine ligand, and then the resulting product is subjected to hydrolysis: [Rh(R4)(L)]X (2) [where R4 represents 1,5-cyclooctadien or norbornadien; L represents a substance represented by the following formula (6): (wherein R5 and R8 respectively represent a C1-4 alkyl group; R6 and R7 respectively represent hydrogen atom or hydroxyl group; and Y represents a group selected from groups represented by the following formula (7): (where Me represents methyl group)).].
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Page/Page column 9
(2008/06/13)
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- Method of manufacturing a dry water-soluble herbicidal salt composition
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A method of manufacturing a solid, water-soluble herbicidal composition comprising a water-soluble salt of a herbicidal compound is disclosed. The herbicidal compound is a water-insoluble compound that includes a carboxylic acid functionality, such as a phenoxy-substituted carboxylic acid compound or a substituted benzoic acid compound, and is sufficiently pure to form a dry, solid herbicidal salt composition after interaction with a suitable neutralizing base, such as ammonia, an alkylamine, a dialkylamine, a trialkylamine, a hydroxyalkylamine, a dihydroxyalkylamine, an alkaline salt of an alkali metal or a combination thereof. The dry herbicidal salt composition includes at least about 90% by weight of the water-soluble herbicidal salt, and dissolves rapidly and essentially completely in water to form an aqueous herbicidal solution including up to about 75% by weight of the water-soluble herbicidal salt.
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- Asymmetric Synthesis of Phosphorus Analogues of Dicarboxylic α-Amino Acids
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An efficient approach to the asymmetric synthesis of phosphorus analogues of dicarboxylic α-amino acids is described.The method of choice consists in the reaction of the nickel(II) complex (4) of the Schiff's base derived from (S)-o-benzophenone 3 and glycine with the appropriate alkyl halide, substituted with an alkylphosphonate group.The reactions were carried out in MeCN at 25 deg C, with solid KOH as catalyst.Michael-type base-catalysed addition of vinylphosphonate and vinylphosphinate to complex 4 in dimethylformamide (DMF)at 50 - 70 deg C could also be employed.Significant diastereoselectivity (90percent d.e.) was observed for the alkylation of complex 4.Optically pure (S)-phosphinothricine, (S)-2-amino-3-phosphonopropanoic acid, (S)-2-amino-4-phosphonobutanoic acid and (S)-2-amino-5-phosphonopentanoic acid were obtained after the alkylated diastereoisomeric complexes had been separated on SiO2 and hydrolysed with aq.HCl.The initial chiral reagent 3 was recovered (60 - 85 percent).Novel amino acids 9, having free carboxy groups and esterified phosphonic and phosphinic groups, could also been obtained as intermediates due to the mild conditions of the decomposition of the alkylated diastereoisomeric complexes.
- Soloshonok, Vadim A.,Belokon, Yuri N.,Kuzmina, Nadezhda A.,Maleev, Victor I.,Svistunova, Nataly Yu.,et al.
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p. 1525 - 1530
(2007/10/02)
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- Phenoxycarboxylic acid compounds and herbicide comprising it as active ingredient
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A novel phenoxycarboxylic acid of formula (I) is disclosed. The compound is effective as herbicide for eradicating broad-leaved weeds. A combination of the phenoxylcarboxylic acid and a N-phosphonomethylglycine or a glufosinate which is known as a herbicide is very effective for eradicating both broad-leaved weeds and narrow-leaved weeds.
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- 4-phosphorus-2-phthalimidobutyrate intermediates
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Phosphinylbutanoic acids, such as phosphinothricin, can be prepared by reacting racemic 4-halo-2-phthalimidobutyrates with a tricoordinate phosphorus compound represented by the formula: wherein R1 is methyl or ethyl, and R2 is selected from the group consisting of alkoxy having from one to six carbon atoms, aryloxy, and trialkylsilyloxy groups having from one to twelve carbon atoms, to form an intermediate compound; and hydrolyzing the intermediate compound to form the phosphinylbutanoic acids.
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- Asymmetric Synthesis of (+)-Phosphinothricin and Related Compounds by the Michael Addition of Glycine Schiff Bases to Vinyl Compounds
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(S)-(+)-Phosphinothricin was prepared in good optical yield by th Michael addition of chiral glycine Schiff base derived from (S)-2-hydroxy-3-pinanone to vinyl phosphorus compound. (R)-(-)-Phosphinothricin, an enantiomeric isomer, can also be prepared from the same chiral glycine Schiff base by choosing suitable reaction temperature.
- Minowa, Nobuto,Hirayama, Masao,Fukatsu, Shunzo
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p. 1761 - 1766
(2007/10/02)
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- AN EFFICIENT ASYMMETRIC SYNTHESIS OF BOTH ENANTIOMERS OF PHOSPHINOTHRICIN
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An efficient synthesis of both enantiomers of phosphinothricin 1 by alkylation of metalated chiral bis-lactim ethers is described.
- Zeiss, Hans-Joachim
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p. 1255 - 1258
(2007/10/02)
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- FACILE SYNTHESIS OF D,L-PHOSPHINOTHRICIN FROM METHYL 4-BROMO-2-PHTHALIMIDOBUTYRATE
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Synthetic versatility of the title bromide is illustrated by simple preparations of D,L-phosphinothricin, D,L-2-amino-4-phosphonobutyric acid, and aminocyclopropanecarboxylic acid.
- Logusch, E. W.
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p. 5935 - 5938
(2007/10/02)
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- Process for preparing optically active [(3-amino-3-carboxy)propyl-1]_phosphinic acid derivatives
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Disclosed is a novel process for optically active [(3-amino-3-carboxy)propyl-1]phosphinic acid derivatives, which comprises reacting a Shiff's base with a derivative of vinylphosphinate in the presence of a base, and subjecting the resulting compound to hydrolysis to form the optically active [(3-amino-3-carboxy)propyl-1]phosphinic acid derivatives as either [L-(3-amino-3-carboxy)propyl-1]phosphinic acid derivatives or [D-(3-amino-3-carboxy)propyl-1]phosphinic acid derivatives.
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