Method and intermediate compounds for pregabaline production

FIELD: pharmacology.

SUBSTANCE: invention relates to a method for preparation of a compound of the formula

and intermediates used to implement the method, as well as a method for pregabalin preparation.

EFFECT: method can be implemented on a commercial scale using readily available, safe raw materials and reagents, and without the need for difficult separations.

20 cl, 8 tbl, 41 ex

 



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to biotechnology. Disclosed is a method of producing β-cyclodextrin. The method includes preparing a suspension of maltodextrin, carrying out a ring closure process using a CGTase enzyme preparation in the presence of a trichloroethylene complexant. Further, the method includes removing the complexant by boiling, purifying the obtained product with activated carbon, separating the activated carbon by filtering and evaporating the syrup and crystallisation thereof while stirring and lowering the temperature. Finally, the method includes centrifuging and washing β-cyclodextrin crystals with cold water, drying and packaging.

EFFECT: invention can be used to produce cyclic complexing agents, particularly β-cyclodextrin.

2 dwg

FIELD: chemistry.

SUBSTANCE: group of inventions relates to biotechnology, particularly to mutant O-phosphoserine sulfhydrylase (OPSS) from Mycobacterium smegmatis with an amino acid sequence corresponding to SEQ ID NO: 1 which is devoid of three to seven C-terminal amino acid residues. The inventions also relate to a nucleic acid molecule encoding the mutant OPSS, an expression vector carrying the nucleic acid molecule, and a transformant transformed by the expression vector. In addition, a method is provided for producing cysteine in which O-phospho-L-serine (OPS) is reacted with a sulphide in the presence of the mutant OPSS.

EFFECT: muntant OPSS has improved enzymatic activity and can be used for environmentally friendly production of L-cysteine in conditions through a simple enzymatic conversion reaction; the group of inventions provides high output of L-cysteine.

16 cl, 7 dwg, 20 tbl, 19 ex

FIELD: chemistry.

SUBSTANCE: invention relates to the field of biotechnology. Claimed are version proteins of lysophospholipid-acyltransferase, catalysing a reaction of converting 18:3(n-6)-PL into 18:3(n-6)-CoA and/or DGLA-CoA into DGLA-PL, which have amino acid sequences, at least, by 95% identical to SEQ ID NO:2 and 7, given in the description. In addition, nucleic acids, coding the said proteins, are disclosed. Also claimed are: a recombinant expression vector, containing the said nucleic acids, and a host cell for obtaining a composition of fatty acids, transformed with the said vector. Claimed is the application of the said vector for increasing a quantitative ratio of arachidonic acid (ARA) in the composition of fatty acids in the host. Described is a method of obtaining the composition of fatty acids, which includes cultivation of the host cell for obtaining the composition of fatty acids with the increased quantity of arachidonic acid in comparison with its quantity in the composition of fatty acids, obtained by cultivation of a non-transformed host, and the collection of the composition of fatty acids from cultures of the transformed cell.

EFFECT: invention makes it possible to obtain the composition of fatty acids with an increased content of arachidonic acid.

18 cl, 8 dwg, 8 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method for determination and quantitative estimation of unusually modified glycans, which can be used in analysing glycans. The disclosed method includes the following steps: a) providing a glycan preparation containing unusually modified glycans selected from a group containing sulphated glycans, phosphorylated glycans, polyacetylated sialylated glycans and combinations thereof, where said unusually modified glycans are negatively charged and where said glycan preparation is obtained by separating glycans and sialic acids from a therapeutic glycoprotein composition, where the sialic acids are separated by exposing the therapeutic glycoprotein composition to at least one agent which splits sialic acid residues in conditions which facilitate splitting of sialic acids; b) subjecting the glycan preparation to a chromatographic separation method which separates glycans based on the charge-to-mass ratio, thereby separating said unusually modified glycans; and c) quantitative determination of at least one separated unusually modified glycan using at least one quantitative estimation standard.

EFFECT: novel efficient method which enables to analyse unusually modified glycans.

42 cl, 7 dwg, 2 tbl, 1 ex

Proteins // 2518345

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to biotechnology, particularly to a version of the enzyme lipid acyltransferase with an increased phospholipid transferase activity. The prepared enzyme contains an amino acid motif GDSX, wherein X represents one or more of the following amino acid residues L, A, V, I, F, Y, H, Q, T, N, M or S and a modification of one or more amino acids as compared to the reference enzyme. The given enzyme is used for preparing food stuff, as well as for reducing the content of phospholipids in edible oil.

EFFECT: invention enables providing the effective version of the enzyme with high phospholipid transferase activity.

8 cl, 61 dwg, 1 tbl, 10 ex

FIELD: chemistry.

SUBSTANCE: invention relates to biotechnology and discloses novel diacylglycerol acyltransferase. The invention also relates to a polynucleotide which codes diacylglycerol acyltransferase, an expression vector and a transformant such as yeast or fungus, as well as a method of preparing a composition of lipids or fatty acids using the transformant.

EFFECT: invention enables to obtain a novel enzyme which is suitable for efficient production of lipids and fatty acids.

13 cl, 5 dwg, 2 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: group of inventions relates to biotechnology. Disclosed is a composition for producing a fragrant ester. The composition contains SGNH-acyltranferase, an alcohol substrate containing 2-10 carbon atoms, and an acyl donor which is an ester substrate containing an acyl chain consisting of 2-10 carbon atoms. The alcohol substrate and the acyl donor are selected such that they produce a fragrant ester. Also disclosed is a method of producing a fragrant ester, according to which SGNH-acyltransferase, the alcohol substrate and acyl donor are combined in acyltransferase reaction conditions. Also disclosed is a method for simultaneous production of a bleaching agent, which is a peracid, and a fragrant ester. To this end, the SGNH-acyltransferase, alcohol substrate, acyl donor and aqueous hydrogen peroxide solution are combined in acyltransferase reaction conditions. The disclosed composition is used in detergents for removing stains, which contain at least one triglyceride, and for reducing unpleasant smells.

EFFECT: said SGNH-acyltransferase catalyses transfer of the acyl group from the acyl donor to the alcohol substrate to form a fragrant ester in an aqueous medium.

19 cl, 18 dwg, 9 tbl, 14 ex

FIELD: biotechnologies.

SUBSTANCE: new genes of lysophosphatidic acid acyltransferase were obtained from filamentous fungus Mortierella alpina. Nucleotide sequence coding enzyme was determined, structuring of expression vectors and vector construct by host cell creation containing it was described, and recombinant forms of lysophosphatidic acid acyltransferase coded by new genes were obtained.

EFFECT: higher efficiency.

4 cl, 14 tbl, 6 dwg, 9 ex

FIELD: biotechnologies.

SUBSTANCE: invention proposes use of a composition containing transglycosidase ferment (EC 2.4.1.24) for decomposition of polysaccharide of natural gum. The above polysaccharide of natural gum is a substrate for the above ferment of transglycosidase. A natural gum destruction method is described, which involves contact of transglycosidase ferment with polysaccharide of natural gum for destruction of the above polysaccharide of natural gum. Besides, a cleaning method is proposed, which involves contact of an object contaminated with polysaccharide of natural gum with cleaning composition including transglycosidase ferment; and maintenance of the above object and cleaning composition under conditions sufficient for effective destruction of polysaccharide of natural gum, and thus, cleaning of the above object.

EFFECT: invention allows decomposing natural gums by means of transglycosidase ferment.

19 cl, 7 dwg, 4 ex

FIELD: biotechnologies.

SUBSTANCE: method for inhibition of RNA-polymerase ferment activity is proposed. Inhibition is performed by introduction to a transcriptional system of an inhibitor based on at least one compound containing organic macrocyclic complex with encapsulated ion of transition metal, which has been chosen from the group including 1,8-bis(2-fluorobora)-2,7,9,14,15,20-hexaoxa-3,6,10,13,16,19-hexaasa-4,5,11,12-tetraphenyl-17,18-diamino-bicyclo[6.6.6]eicosa-3,5,10,12,16,18-hexaen(2-) ferrum(2+); 1,8-bis(2-fluorobora)-2,7,9,14,15,20-hexaoxa-3,6,10,13,16,19-hexaasa-4,5,11,12-tetraphenyl-17,18-dimethyl-bicyclo[6.6.6]eicosa-3,5,10,12,16,18-hexaen(2-) cobalt(2+); 1,8-bis(2-phenylbora)-2,7,9,14,15,20-hexaoxa-3,6,10,13,16,19-hexaasa-4,5,11,12,17,18-hexa(methyl thio)-bicyclo[6.6.6]eicosa-3,5,10,12,16,18-hexaen(2-) ruthenium(2+); 1,8-bis(2-fluorobora)-2,7,9,14,15,20-hexaoxa-3,6,10,13,16,19-hexaasa-4,5,11,12-tetraphenyl-17,18-cyclohexanedimercaptylbicyclo[6.6.6]eicosea-3,5,10,12,16,18-hexaen(2-) ferrum(2+); 1,12-bis-(tert-butylbora)-2,11,13,22,23,32-hexaoxa-3,10,14,21,24,31-hexasapentacyclo[11,11.11.04.9015,20025.30]ditri-akonta-3,9,14,20,24,30-hexaen(2-) ferrum(2+).

EFFECT: method provides for inhibition of activity of RNA-polymerase at micromolar concentration of inhibitor and enlarges the range of inhibitors of RNA-polymerase.

22 ex

FIELD: chemistry.

SUBSTANCE: method is realised by heterogeneous catalytic oxidation of carbon by molecular oxygen, selected from group of benzol, n-butane, n-butene, in presence of catalyst, which contains vanadium, phosphorus and oxygen, which includes: (a) maleic acid anhydride absorption from impure mixture of products by absorbing agent, which contains organic solvent, in absorption column; (b) desorption of maleic acid anhydride from absorbing agent, which is obtained at stage (a), enriched by maleic acid anhydride, in desorption column; as well as (c) total or partial return to stage (a) of absorbing agent, depleted at stage (b) by content of maelic acid anhydride, is differ in fact, that (d) total or partial quantity of absorbing agent, depleted on stage (b) by content of maelic acid anhydride, for required sedimentation of fumaric acid is cooled and/or subjected to concentration by evaporating absorbing agent to such degree, that difference between concentration of fumaric acid in reverse flow at output from desorption column c (FA, at output from desorption column) at there existing conditions, expressed in weight p/mln, and balanced concentration of fumaric acid, corresponding to solubility curve, after cooling and/or evaporation of absorbing agent part c (FA, balanced, after cooling/steaming), expressed in weight p/mln, constitutes value larger or equal 250 wt, p/mln, and for sedimentation and separation of fumaric acid applied is reservoir with built-in nozzle elements, and average time of staying in reservoir with built-in nozzle elements constitues from 0.05 to 6 hours; (e) fumaric acid, precipitated in form of solid substance due to operations at stage (d), totally or partially, in continuous or periodic mode is removed from reverse flow of absorbing agent; and (f) depleted by content of fumaric acid absorbing agent from stage (e) totally or partially returns on stage (a).

EFFECT: reduction of formation of fumaric acid sedimentations with obtaining maelic acid anhydride.

12 cl, 3 dwg, 5 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to a method of producing an alkenyl-substituted cyclic anhydride, comprising the following steps: isomerising one or more olefinically unsaturated C6-C28 hydrocarbons, from which at least 30 wt % is alpha-olefin, by contacting said hydrocarbons with a catalyst which contains an alkali metal on a support, and reacting the formed isomerised C6-C28 olefin hydrocarbons with a cyclic anhydride of an unsaturated dicarboxylic acid to form an alkenyl-substituted cyclic anhydride.

EFFECT: invention relates to use of said compound as a paper sizing additive and a method of producing said additive based on the obtained alkenyl-substituted cyclic anhydride.

20 cl, 2 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to a method of producing ketopantolactone, which is widely used in synthesis of pantothenic acid (vitamin B5), as well as other biologically active substances. The method of producing ketopantolactone involves oxidative dehydrogenation of pantolactone under the action of electrochemically generated bromine from a bromide anion source in an electrolysis cell equipped with an anode, a cathode and a stir-bar in the medium of a chlorine-containing organic solvent in a two-phase system containing an organic and an aqueous layer while passing electrical current of 4-6 F per 1 mole pantolactone and stirring the reaction mass at a rate of 1-4 rps at temperature 35-70°C and pH of the medium equal to 0.5-1.5.

EFFECT: simple technology of producing ketopantolactone, avoiding the need to use dangerous (poisonous) and hard to handle molecular bromine, high conversion of the starting pantolactone and high output of the end product which reaches 85%.

4 cl, 12 ex, 1 tbl, 1 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to an improved method of preventing precipitation of fumaric acid when producing maleic acid anhydride comprising the following steps: a) absorption of maleic acid anhydride from the mixture of products obtained as a result of partial oxidation of benzene, olefins having 4 carbon atoms and n-butane, in an organic solvent or water as an absorbent, b) separation of maleic acid anhydride from the absorbent, containing fumaric acid, wherein the absorbent regenerated thus, which contains fumaric acid, is completely or partially catalytically hydrogenated and completely or partially returned to the absorption step (a), wherein fumaric acid is hydrogenated to amber acid.

EFFECT: method enables to prevent precipitation on equipment components and the resulting clogging, cleaning procedures and switching off.

16 cl, 8 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing maleic anhydride in a fluidised bed by oxidising material which contains C4 hydrocarbons with molecular oxygen or oxygen-containing gas in a reactor with a fluidised bed at reactor temperature 325-500°C in the presence of a catalyst capable of working in the fluidised bed, containing mixed oxides of vanadium and phosphorus, wherein the catalyst is prepared as follows: (a) preparation of a catalyst precursor containing mixed vanadium and phosphorus oxide; (b) packing the catalyst precursor; (c) crushing the catalyst precursor to particles whose average size is less than one micrometre in diametre; (d) moulding particles which are capable of working in the fluidised bed, with bulk density greater than or equal to 0.75 g/cm3 from the packed crushed catalyst precursor; and (e) annealing said particles in boiling conditions, where output of the maleic anhydride is increased by adding a compensating catalyst into the reactor with the fluidised bed, wherein said compensating catalyst contains alkyl ether of orthophosphoric acid of formula (RO)3P=O, where R is hydrogen or C1-C4 alkyl and at least one R is C1-C4 alkyl, where the compensating catalyst is prepared by saturating the catalyst obtained according to steps (a) to (e) with alkyl ether of orthophosphoric aid. The invention also discloses a method of improving operation of the mixed vanadium-phosphorus oxide catalyst for producing maleic anhydride from butane in a fluidised bed. The invention also relates to a catalyst capable of working in the fluidised bed, for producing maleic acid by oxidising material which contains C4 hydrocarbons.

EFFECT: invention ensures high output of the end product at low working temperatures.

31 cl, 2 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: method of purifying maleic anhydride involves heating molten initial crude product to 60-65°C and then cooling to 53-54°C and filtering at temperature of 51.5-53°C. Filtration is carried out on a filter with hole size of 0.01-0.05 mm and the molten mass is thermally processed in an atmosphere of dry inert gas or in sealed conditions in an atmosphere of dry inert gas.

EFFECT: high technological effectiveness of the process owing to its short duration and use of lower temperature parametres and higher degree of purification of maleic anhydride.

1 cl, 1 ex

FIELD: chemistry.

SUBSTANCE: described are 2,4,6-phenyl-substituted cyclic ketoenols of formula (I, in which W, X, Y and CKE are given in invention formula. Also described are esters of acylamino acids of formula (II), substituted derivatives of phenylacetic acid of formula (XXIX), (XXVII), (XXXI), which are intermediate compounds for obtaining formula (I) compound.

EFFECT: obtaining herbicidal preparation containing combinations of biologically active substances, including (a), formula (I) compound and (b') improving compatibility with cultural plants mefenpyr-diethyl, with weight ratio 5-1:1-7.7.

9 cl, 46 tbl, 36 ex

FIELD: physics; operation.

SUBSTANCE: invention relates to the chemical industry, particularly to the automatic control systems and can be used for temperature support of the reaction mixture in chemical reactors. The system of automatic temperature profile support in the reactor with distributed constants in maleic anhydride production contains two control systems: cascade automatic control system (ACS) of coolant temperature control in the reactor and ACS of benzene-air mixture fed to the reactor where the correction signal is inleted according to reaction mixture temperature. The correction signal represents the sum of the signals about reaction mixture temperature in the measurement points positioned along the reactor height multiplied to the weight factor determined intuitively or from optimization problem solution. Then the correction signal is compared with assignment signal on the functional generator serving as algebraic adder. The invention allows to increase the temperature support accuracy in the reactor at maleic anhydride production.

EFFECT: increasing of the temperature support accuracy in the reactor.

2 cl, 2 dwg

The invention relates to a method for producing a cyclic anhydride or a nitride of hydrocarbon and oxygen-containing gas in the presence of an appropriate catalyst, in particular to a method of reducing or eliminating the risk of explosion or fire in the headspace of the reactor system, in which there is a formation of the anhydride, or nitrile of hydrocarbon and oxygen

The invention relates to a method for obtaining succinic anhydride used in the production of pharmaceuticals, insecticides, as a hardener of epoxy resins, in analytical chemistry

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing (S)-(+)-3-aminomethyl-5-methylhexanoic acid (pregabalin) of formula (I) The method includes steps (a)-(g). Step (a) includes reacting alkyl ether of cyanoacetic acid CNCH2COOR (A) and isobutyraldehyde to obtain alkyl ether of 2-cyano-4-methylpentanoic acid (B) At step (b) the obtained ether (B) reacts with ethyl ether of alpha-haloacetic acid (Hal=Cl, Br, I) in the presence of a base at 10-90°C in a solvent, such as N,N-dimethyl formamide, tetrahydrofuran, 1,4-dioxane, diemthyl sulphoxide and dimethoxyethane, or without a sovent to form 4-ethyl-1-methyl-2-cyano-2-isobutylsuccinate (C) Step (c) includes hydrolysis of compound (C) under the action of a base, such as an alkali metal hydroxide, at 20-80°C, to obtain 2-cyano-2-isobutylsuccinic acid. Step (d) includes decarboxylation of the obtained 2-cyano-2-isobutylsuccinic acid in the presence of a mineral acid, e.g. sulphuric or hydrochloric acid, in an organic solvent, e.g. ethyl acetate, at 70-80°C to obtain (RS)-3-cyano-5-methylhexanoic acid. Step (e) includes separating enantiomers of the obtained (RS)-3-cyano-5-methylhexanoic acid by forming a corresponding salt with cinchonidine in an organic solvent, such as ethanol, methanol, 1,4-dioxane, ethyl acetate, tetrahydrofuran, 2-methyltetrahydrofuran, dimethoxyethane and diethylene glycol dimethyl ether, at 20-80°C, separating the cinchonidine salt of (S)-3-cyano-5-methylhexanoic acid and additional purification thereof by repeated salt formation in ethyl acetate. At step (f) the cinchonidine salt of (S)-3-cyano-5-methylhexanoic acid is treated with a mixture of ethyl acetate and diluted hydrochloric acid (1:1) at room temperature and the (S)-3-cyano-5-methylhexanoic acid (II) formed is separated from the organic layer. Step (g) includes hydrogenation of the separated optically pure (S)-3-cyano-5-methylhexanoic acid (II), which is catalysed by Raney nickel, to form (S)-(+)-3-aminomethyl-5-methylhexanoic acid (pregabalin) (I). The method is characterised by that at step (a) reaction of the alkyl ether of cyanoacetic acid CNCH2COOR, where R=C1-C4-alkyl, with isobutyraldehyde is carried out under the action of carbon monoxide at pressure of 1-200 atm and temperature of 20-200°C in a polar solvent, such as methanol, ethanol, water, 1,4-dioxane, tetrahydrofuran, acetonitrile, dimethoxyethane and diethylene glycol dimethyl ether, and the catalyst used is a cobalt, nickel, ruthenium or rhodium compound; at step (b) the base used is sodium hydride.

EFFECT: method reduces the number of steps when producing an intermediate, reduces the amount of wastes and improves environmental safety.

5 ex

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