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WO2025219237A1 - Procédé de préparation d'acide 2-oxo-4-(hydroxy(méthyl)phosphinoyl)butyrique - Google Patents

Procédé de préparation d'acide 2-oxo-4-(hydroxy(méthyl)phosphinoyl)butyrique

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Publication number
WO2025219237A1
WO2025219237A1 PCT/EP2025/060006 EP2025060006W WO2025219237A1 WO 2025219237 A1 WO2025219237 A1 WO 2025219237A1 EP 2025060006 W EP2025060006 W EP 2025060006W WO 2025219237 A1 WO2025219237 A1 WO 2025219237A1
Authority
WO
WIPO (PCT)
Prior art keywords
formula
glufosinate
process according
carried out
ppo
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/EP2025/060006
Other languages
English (en)
Inventor
Gunther Zimmermann
Srividhya SUNDARAM
Michael Breuer
Alexandre GUTHERTZ
Peter OECHSLE
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
BASF SE
Original Assignee
BASF SE
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by BASF SE filed Critical BASF SE
Publication of WO2025219237A1 publication Critical patent/WO2025219237A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
    • C07F9/301—Acyclic saturated acids which can have further substituents on alkyl
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P9/00—Preparation of organic compounds containing a metal or atom other than H, N, C, O, S or halogen
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/0004—Oxidoreductases (1.)
    • C12N9/0006—Oxidoreductases (1.) acting on CH-OH groups as donors (1.1)

Definitions

  • the present invention relates to a process for the preparation of 2-oxo-4- (hydroxy(methyl)phosphinoyl)butyric acid (PPO).
  • the present invention relates to the catalytic oxidation of a diol precursor to 2-oxo-4-(hydroxy(methyl)phosphinoyl)butyric acid (PPO).
  • the herbicide glufosinate is a non-selective, foliarly applied herbicide considered to be one of the safest herbicides from a toxicological or environmental standpoint.
  • Current commercial chemical synthesis methods for glufosinate yield a racemic mixture of L- and D-glufosinate (Duke et al. 2010 Toxins 2:1943-1962).
  • L-glufosinate also known as phosphinothricin or (S)-2-amino-4-(hydroxy(methyl)phosphonoyl)butanoic acid
  • D-glufosinate is much more potent than D-glufosinate (Ruhland et al. (2002) Environ. Biosafety Res. 1:29-37).
  • WO 2024/051121 Al discloses a method for preparing a pesticide intermediate 4- (hydroxymethylphosphonyl)-2-carbonylbutyric acid (PPO).
  • the method disclosed therein comprises the step of mixing acryloyl chloride, a first solvent, a polymerization inhibitor, a catalyst and potassium ferrocyanide. This reaction results in the formation of acryloyl cyanide, which is a highly toxic compound, which can be absorbed through skin, mouth, and inhalation.
  • industrial application of such a method requires a secure safety protocol and measures to ensure that it is followed. This makes the overall process complicated, prone to error, expensive and still bears the risk of a hazard.
  • glufosinate and/or glufosinate salts more particularly glufosinate, glufosinate- sodium or glufosinate-ammonium.
  • glufosinate and/or glufosinate salts more particularly glufosinate, glufosinate- sodium or glufosinate-ammonium.
  • a group is defined to comprise at least a certain number of embodiments, this is meant to also encompass a group which preferably consists of these embodiments only.
  • the terms “first”, “second”, “third” or “(a)”, “(b)”, “(c)”, “(d)” etc. and the like in the description and in the claims, are used for distinguishing between similar elements and not necessarily for describing a sequential or chronological order. It is to be understood that the terms so used are interchangeable under appropriate circumstances and that the embodiments of the invention described herein are capable of operation in other sequences than described or illustrated herein.
  • first”, “second”, “third” or “(a)”, “(b)”, “(c)”, “(d)”, “i”, “ii” etc. relate to steps of a method or use or assay there is no time or time interval coherence between the steps, i.e. the steps may be carried out simultaneously or there may be time intervals of seconds, minutes, hours, days, weeks, months or even years between such steps, unless otherwise indicated in the application as set forth herein above or below. It is to be understood that this invention is not limited to the particular methodology, protocols, reagents etc. described herein as these may vary.
  • the term “does not comprise” or “free of” means in the context that the composition of the present invention is free of a specific compound or group of compounds, which may be combined under a collective term, that the composition does not comprise said compound or group of compounds in an amount of more than 0.8 % by weight, based on the total weight of the composition. Furthermore, it is preferred that the composition according to the present invention does not comprise said compounds or group of compounds in an amount of more than 0.5 % by weight, preferably the composition does not comprise said compounds or group of compounds at all.
  • p/atinum-group meta/s denotes the chemically closely related metals platinum, palladium, iridium, rhodium, ruthenium, and osmium, which in nature generally occur together.
  • platinum or palladium, especially platinum is preferred.
  • aqueous alkaline medium denotes a reaction mixture that reacts alkaline, i.e. which has a pH value of larger than 7.
  • the present invention is concerned with a process for preparing 2-oxo-4- (hydroxy(methyl)phosphinoyl)butyric acid (PPO) of formula (I) comprising oxidizing in an oxidating step (0) a diol of formula (Ila) and/or a hydroxymethyl ketone according to formula (lib):
  • This process enables an easy access to PPO, as the diol can be produced e.g. by radical addition of methylphosphinic acid butyl ester to 3,4-dihydroxy butene or its acetylated derivative and follow up acidic deprotection.
  • the oxidizing step according to the process of the present invention can be carried out in the presence of a chemical catalyst (OC) or an enzyme (OE).
  • OC chemical catalyst
  • OE enzyme
  • oxidating step (0) is carried out in the presence of an enzyme (OE).
  • the enzyme present in the oxidating step (OE) is an Oxidoreductase ECI enzyme.
  • the Oxidoreductase ECI enzyme is selected from the group consisting of EC1.1, EC1.2 or EC1.10, more preferably EC1.1.1, EC1.1.3, EC1.2.1, EC1.2.3.
  • the Oxidoreductases ECI enzyme is an enzyme according to SEQ ID NO:10.
  • not only one enzyme can be used, but combinations of Oxidoreductases ECI, preferably a combination of the classes EC1.1 and EC1.2.
  • the oxidating step (OE) the of process is preferably carried out at a temperature in the range of from 25 to 45 ° C, more preferably 30 to 42 ° C, and most preferably 35 to 40 ° C.
  • the oxidating step (OE) of the process is carried out in an aqueous solution, preferably a buffered aqueous solution.
  • the pH value of the buffered aqueous solution is in the range of from 8.8 to 7.2, most preferably the pH value of the buffered aqueous solution is 7.
  • the buffer aqueous solution is a solution of ammonia in water or isopropyl amine in water.
  • the oxidating step (OE) of the process is carried out for a period in the range of from 5 to 48 h.
  • the oxidating step (OE) is carried out in an ex vivo environment.
  • the oxidating step of the process of the present invention is an oxidating step (OE) in the presence of an enzyme, preferably of an Oxidoreductase ECI enzyme, the whole process according to the present invention is carried out in an ex vivo environment.
  • the oxidating step (OE) of the process of the present invention is preferably carried out in the presence of a Catalase enzyme in addition to the Oxidoreductase ECI enzyme, preferably a Catalase enzyme according to CAS-Nr. 9001-05-2. It has been surprisingly found that the presence of the Catalase enzyme significantly improves the yields of the compound according to formula (I). Without wishing to be bound by theory it is believed that the improvement in yield is caused by the removal of intermediately formed hydrogen peroxide from the reaction mixture in the oxidating step.
  • the chemical catalyst of the oxidating step (OC) is preferably a platinumgroup metal catalyst.
  • the oxidizing step (OC) is carried out in an aqueous solution in the presence of a gas comprising molecular oxygen and an activator. More preferably, the oxidizing step (OC) is carried out in an aqueous solution of an alkali in the presence of a gas comprising molecular oxygen and an activator.
  • the platinum-group metal used as the catalyst in the oxidating step (OC) can be added to the reactants in a variety of forms, for example in elementary, i.e. metallic, form, for instance as so-called “black", in combination with other platinum-group metals or in the form of a compound, for example as an oxide or also in the form of some other compound.
  • the platinum-group metal used as the catalyst in the oxidating step (OC) is present in metallic form.
  • the platinum-group metal catalyst used as the catalyst in the oxidating step (OC) is selected from platinum and palladium.
  • the platinum-group metals used as the catalyst in the oxidating step (OC) can be applied to supports.
  • the support of the platinum-group metal catalyst as used in the oxidating step (OC) is selected from the group consisting of active charcoal, graphite, kieselguhr, silica gel, spinels, aluminum oxide, asbestos, calcium carbonate, magnesium carbonate, barium sulphate, or organic support material.
  • Active charcoals have proved particularly suitable, for example, inexpensive pulverulent active charcoals, produced from wood, which are extensively used for decolorizing purposes.
  • the platinum-group metal catalyst used in the oxidating step (OC) of the process according to the present invention is a supported platinum-group metal catalyst, more preferably a charcoal supported platinum-group metal catalyst.
  • the amount of the platinum-group metal comprised in the supported platinum-group metal catalyst as used in the oxidating step (OC) of the process according to the present invention can be less than 10 wt.-% with respect to the total weight of the platinum-metal group catalyst, preferably is in the range of from 0.1 to 5 wt.-%.
  • the platinum-group metal catalyst as used in the oxidating step (OC) of the process according to the present invention preferably comprises an activator. More preferably, the activator is selected from lead and/or a compound thereof and/or bismuth and/or a compound thereof.
  • the amounts in which the platinum-group metal catalysts are used in the oxidating step (OC) of the process according to the present invention depend on the desired rate of oxidation, the form of the catalyst, the nature and amount of the activator, and so on, and can in a specific case easily be determined by preliminary experiments.
  • the amount of platinum-group metal used per mole compounds according to formulae (Ila) of (lib) in the oxidating step (OC) of the process according to the present invention is less than 1,000 mg. In most cases sufficiently high reaction rates are achieved with an amount of platinum-group metal of 20 to 400 mg per mole of compounds according to formulae (Ila) or (lib).
  • the activator is present in an amount of less than 0.1 mole or more with respect to the amount of compounds according to formulae (Ila) or (lib), more preferably of 5 x 10’ 5 to 1 x 10’ 1 mole, even more preferably 1 x 10’ 4 to 1 x 10’ 2 mole.
  • the activator as used in the oxidating step (OC) of the process according to the present invention preferably comprise the metals lead and/or bismuth as such, that is to say in the elementary form, and/or in the form of their compounds, for example as oxides, or as salts of hydracids, such as chlorides, bromides, iodides, sulfides, selenides and tellurides; or as salts of inorganic oxy-acids, such as nitrates, nitrites, phosphites, phosphates, sulfates, carbonates, perchlorates, antimonates, arsenates, selenites, selenates, and borates; or as salts of oxy-acids derived from transition metals, for example vanadates, niobates, tantalates, chromates, molybdates, tungstates, and permanganates; or as salts of organic aliphatic or aromatic acids,
  • the activator used in the oxidating step (OC) of the process according to the present invention preferably comprises one or more compounds selected from the group consisting of lead in elemental form, bismuth in elemental form, lead in oxide form, bismuth in oxide form, lead in hydracid salt form, bismuth in hydracid salt form, lead in form of a salt of an inorganic oxyacid, bismuth in form of a salt of an inorganic oxyacid, lead in form of a salt of a transition-metal-comprising oxyacid, bismuth in form of a salt of a transition-metal- comprising oxyacid, lead in form of a salt of an organic aliphatic or aromatic acid, and bismuth in form of a salt of an organic aliphatic or aromatic acid, more preferably is selected from lead in elemental form and bismuth in elemental form, and most preferably is bismuth in elemental form.
  • the oxidating step (OC) in the oxidating step (OC), combinations of these activators with one another and/or with other elements or compounds, not specified as an activator, can also be used.
  • the activators as used in the oxidating step (OC) of the process according to the present invention may be present in various valency levels or in a mixture of valency levels. Furthermore, changes in valency may also occur during the reaction. If the activators have not already been added as oxides and/or hydroxides, it is possible that they become entirely or partially converted to these in the alkaline medium. After the reaction, the platinum-group metal catalyst can be filtered off together with the sparingly soluble activator and be reused in further oxidation reactions. Losses of platinum-group metal catalyst and/or activator, if these occur, must be made up.
  • the activator used in the oxidating step (OC) of the process according to the present invention can be added to the reactants as a solid, preferably in a finely divided form, or in the form of a solution. It is also possible to add the activator when preparing the platinum- group metal catalyst, or to impregnate the platinum-group metal catalyst with the activator.
  • the activator can also serve as a support for the platinum metal. Preferably, the activator is incorporated into the platinum-group metal catalyst.
  • the oxidating step (OC) of the process according to the present invention is carried out in the presence of a chemical catalyst, the oxidating step (OC) is preferably carried out in the presence of an aqueous alkaline medium.
  • the alkali of the aqueous alkaline medium of the oxidating step (OC) of the process according to the present invention can be added to a solution or suspension of the compounds according to formulae (Ila) or (lib) in water, or the compounds according to formulae (Ila) or (lib) can be dissolved or suspended in the aqueous alkaline solution.
  • the amount of alkali is chosen to provide 0.3 to 5, preferably 0.5 to 3, equivalents of alkali per mole of compounds according to formulae (Ila) or (lib) to be oxidized.
  • the use of from 0.9 to 2 equivalents of alkali per mole of compounds according to formulae (Ila) or (lib) to be oxidized is particularly preferred.
  • the alkali is selected from the list consisting of sodium hydroxide, potassium hydroxide, or carbonate, more preferably the alkali is selected from the list consisting of sodium hydroxide or potassium hydroxide, and most preferably the alkali is sodium hydroxide.
  • the concentration of the organic compounds in the aqueous alkaline reaction solution is in general selected so that both the diol according to formula (Ila), the ketone according to formula (lib), and the PPO according to formula (I) formed are present in solution under the reaction conditions.
  • the diol according to formula (Ila) and/or the ketone according to formula (lib) should be added in portions to the oxidation mixture, preferably together with part of the alkali.
  • the final concentration of organic compounds in the reaction mixture is in the range of from 5 to 30 wt.% with respect to the total weight of the oxidation mixture.
  • the possible reaction temperature of the oxidating step (OC) of the process according to the present invention ranges from the solidification point to the boiling point of the reaction mixture.
  • the oxidating step (OC) is carried out at a temperature of from 10 to 100 ° C, preferably 25 to 85 ° C, and most preferably 45 to 65 ° C.
  • the aerating step in the oxidizing step (OC) of the process according to the present invention can be carried out by bubbling gas comprising molecular oxygen through the reaction mixture.
  • the gas comprising molecular oxygen can be applied under a pressure of 0.5 to 10 atm.
  • the gas comprising molecular oxygen as used in the oxidating step (OC) of the process according to the present invention can be pure oxygen or air.
  • the oxidating step of the process of the present invention when being carried out in the presence of a chemical catalyst, preferably a platinum-group metal catalyst, is preferably carried out in the presence of a Catalase enzyme, preferably a Catalase enzyme according to CAS-Nr. 9001-05-2. It has been surprisingly found that the presence of the Catalase enzyme significantly improves the yields of the compound according to formula (I). Without wishing to be bound by theory it is believed that the improvement in yield is caused by the removal of intermediately formed hydrogen peroxide from the reaction mixture in the oxidating step.
  • the reaction temperature is preferably in the range of from 25 to 45 ° C, more preferably 30 to 42 ° C, and most preferably 35 to 40 ° C
  • the present invention is concerned with the use of a mixture comprising 2- oxo-4-(hydroxy(methyl)phosphinoyl)butyric acid (PPO) according to formula (I) and aditionally a diol according to formula (Ila) and/or a hydroxymethyl ketone according to formula (lib):
  • PPO 2- oxo-4-(hydroxy(methyl)phosphinoyl)butyric acid
  • glufosinate and/or glufosinate salts more particularly glufosinate, glufosinate- sodium or glufosinate-ammonium.
  • the PPO is preferably used to produce glufosinate, preferably L-glufosinate, by aminating the PPO to L-glufosinate by a transaminase (TA) enzyme, by aminating the PPO to L-glufosinate by an L-amino acid dehydrogenase (LAAD) enzyme, or by chemical conversion.
  • the PPO is used to produce glufosinate, preferably L-glufosinate, by aminating the PPO to L-glufosinate by a transaminase (TA) enzyme or by aminating the PPO to L-glufosinate by an L-amino acid dehydrogenase (LAAD) enzyme.
  • the PPO is used to produce glufosinate, preferably L-glufosinate, by aminating the PPO to L-glufosinate by a transaminase (TA) enzyme, the aminating is preferably carried out in the presence of an amine group from one or more amine donors. If the PPO is used to produce glufosinate, preferably L-glufosinate, by aminating the PPO to L-glufosinate by an L-amino acid dehydrogenase (LAAD) enzyme, the aminating is preferably carried out in the presence of an ammonia source.
  • TA transaminase
  • LAAD L-amino acid dehydrogenase
  • the present invention is concerned with a mixture comprising 2- oxo-4-(hydroxy(methyl)phosphinoyl)butyric acid (PPO) according to formula (I)
  • the mixture can be used to produce glufosinate preferably L- glufosinate, by aminating the PPO to L-glufosinate by a transaminase (TA) enzyme, by aminating the PPO to L-glufosinate by an L-amino acid dehydrogenase (LAAD) enzyme, or by chemical conversion.
  • TA transaminase
  • LAAD L-amino acid dehydrogenase
  • the mixture can be used to produce glufosinate, preferably L-glufosinate, by aminating the PPO to L-glufosinate by a transaminase (TA) enzyme or by aminating the PPO to L-glufosinate by an L-amino acid dehydrogenase (LAAD) enzyme.
  • the amination is preferably carried out in the presence of an amine group from one or more amine donors. If the mixture is used to produce glufosinate, preferably L-glufosinate, by aminating the PPO to L-glufosinate by an L-amino acid dehydrogenase (LAAD) enzyme, the amination is preferably carried out in the presence of an ammonia source.
  • TA transaminase
  • LAAD L-amino acid dehydrogenase
  • PPO is the predominant compound among the mixture according to the present invention.
  • the amount of PPO in the mixture according to the present invention is 80% or greater, 85% or greater, 90% or greater, or about 95% or greater, 97% or greater, 98% or greater based on the combined weight of PPO, diol according to formula (Ila) and ketone according to formula (lib).
  • the amount of diol according to formula (Ila) in the mixture according to the present invention is 10% or less, 5% or less, 2.5% or less, or 1% or less based on the combined weight of PPO, and diol according to formula (Ila) and ketone according to formula (lib).
  • the amount of ketone according to formula (lib) in the mixture according to the present invention is 10% or less, 5% or less, 2.5% or less, or 1% or less based on the combined weight of PPO, and diol according to formula (Ila) and ketone according to formula (lib).
  • compositions can optionally occur as dried powders or dissolved in aqueous or nonaqueous carrier and additional chemical species can optionally be present.
  • the composition is prepared and used in an ex vivo environment.
  • HPLC Method The phosphorous containing compounds were separated by an Aminex HPX- 87 H, 300*7.8 mm column. Temperature 30 ° C, Flowrate 0.5 mL/min, Rl Detection, Eluent 5 mM sulfuric acid in water. HPLC retention times: 2-hydroxy-4- (hydroxy(methyl)phosphinoyl)butanol: 16.0 min, PPO 9.7 min,
  • Enzymes were identified from public databases (NCBI, Uniprot). The DNA sequences corresponding to the enzymes were codon-optimized for expression in Escherichia coli (E. coli) and cloned (Twist Bioscience) in pDHE 19.2 vector (DE 19848129). The gene of interest lies under control of a rhamnose inducible promoter (rhaBAD). The synthesized plasmids were used to transform competent cells (Chung, C.T. et al., Proc Natl Acad Sci U S A, 1989, 86, 2172) of the E. coli strain TG10 (WO 2004/050877 Al). The E.
  • coli strain TG10 is a rhaA- -derivate of E. coli TGI (DSMZ 6056) transformed with pHSG575 (Takeshita, S. et al., Gene, 1987, 61, 63) and pAgro4 (pBB541 in Tomoyasu, T. et al., Mol. Microbiol., 2001, 40, 397).
  • GalOx (SEQ ID NO:9) may be cloned and expressed as described in Birmingham, W.R., et al., Nature Communications, 2021, 12, 4946) or WO 2016/150629 Al. The sequences as listed in Table 1 were cloned based on the above-mentioned protocols.
  • E. coli TG10 transformed with the oxidase-containing plasmids were grown in 10 ml LB medium (Bertani, G., J Bacteriol, 1951, 62, 293) supplemented with 100 pg/ml ampicillin, 50 pg/ml spectinomycin, 20 pg/ml chloramphenicol and 12.5 pg/ml tetracyline at 37 ° C for 16 h (200 rpm).
  • This preculture was used to inoculate 100 ml of LB medium supplemented with 100 pg/ml ampicillin, 50 pg/ml spectinomycin, 20 pg/ml chloramphenicol and 12.5 pg/ml tetracyline until the optical density reaches A600 nm of 0.6.
  • 0.2 mM isopropyl-E-D-thiogalactopyranoside, and 0.5 g/L rhamnose were added and incubated further at 22 ° C for 16-18 h (200 rpm).
  • the biomass was harvested by centrifugation at 4000*g for 15 min at 4 C and the pellets were frozen in -20 ° C until further use.
  • Recombinant production of GalOx (SEQ ID NO:10) is described in Birmingham, W.R., et al., Nature Communications, 2021, 12, 4946) or WO 2016/150629 Al.
  • the frozen pellets were thawed in 0.1 M potassium phosphate buffer pH 7.8 (3 mL buffer / g pellet).
  • the cell suspension was distributed in 2 ml vials and lyzed in Homogenisator (Precellys ®, VWR) for 2*30 sec cycles.
  • the cell-free lysate was further centrifuged at 12000*g for 15 min at 4 ° C.
  • the clarified supernatant (cell-free extract) was used for the activity assay.
  • Enzymatic activity was measured at 30 ° C by incubating the cell-free extract (12.5 vol%) in 200 pl of 0.1 M air-saturated potassium phosphate buffer pH 7.8 containing 5 g/L 2- hydroxy-4-(hydroxy(methyl)phosphinoyl)butanol, 0.2 g/L ABTS (2,2’-azino-bis(3- ethylbenzothiazoline-6-sulfonic acid)) and 0.5 g/L HRP (Horse radish peroxidase). The reaction was monitored by measuring the absorbance of ABTSox at 420 nm up to 2 h.
  • HPLC Method Aminex HPX-87 H, 300*7.8 mm column. Temperature 30 ° C, Flowrate 0.5 mL/min, Rl Detection, Eluent 5 mM sulfuric acid in water. HPLC retention times: 2-oxo- 3-butenoic acid 17.3 min, PPO 9.7 min.

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Abstract

L'invention concerne un procédé de préparation d'acide 2-oxo-4-(hydroxy(méthyl)phosphinoyl)butyrique (PPO) de formule (I), comprenant l'oxydation d'un diol de formule (IIa) dans une étape d'oxydation, et/ou une hydroxyméthylcétone selon la formule (IIb).
PCT/EP2025/060006 2024-04-15 2025-04-11 Procédé de préparation d'acide 2-oxo-4-(hydroxy(méthyl)phosphinoyl)butyrique Pending WO2025219237A1 (fr)

Applications Claiming Priority (2)

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EP24170322 2024-04-15
EP24170322.2 2024-04-15

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WO2025219237A1 true WO2025219237A1 (fr) 2025-10-23

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EP0030424B1 (fr) 1979-12-08 1985-02-20 Hoechst Aktiengesellschaft Dérivés d'acide (méthylphosphinyl)-4 oxo-2 butanoique, compositions herbicides les contenant, intermédiaires et procédés pour leur préparation
DE19848129A1 (de) 1998-10-19 2000-04-20 Basf Ag Verfahren zur Herstellung chiraler Carbonsäuren aus Nitrilen mit Hilfe einer Nitrilase oder Mikroorganismen, die ein Gen für die Nitrilase enthalten
WO2004050877A1 (fr) 2002-12-02 2004-06-17 Basf Aktiengesellschaft Systemes d'expression pouvant etre induits par le l-rhamnose
WO2016150629A1 (fr) 2015-03-26 2016-09-29 Basf Se Production biocatalytique de l-fucose
CN106632467A (zh) * 2016-12-15 2017-05-10 石家庄瑞凯化工有限公司 一种草铵膦铵盐的合成方法
WO2017151573A1 (fr) 2016-03-02 2017-09-08 Agrimetis, Llc Procédés de production de l-glufosinate
WO2024051121A1 (fr) 2022-09-08 2024-03-14 浙江新安化工集团股份有限公司 Procédé de préparation d'acide 4-(hydroxyméthylphosphinyl)-2-oxobutyrique

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