Provided are an immobilized enzyme and an application thereof in continuous production. The immobilized enzyme is a Polyethyleneimine (PEI)-modified immobilized enzyme, and includes: an enzyme, which includes Amine Dehydrogenase (AmDH) and/or Formate Dehydrogenase (FDH); and a carrier, which is a cyanuric chloride-activated amino carrier. The problem in the prior art of poor performance of an immobilized enzyme is solved, the catalytic activity and reusability of the immobilized enzyme are improved, and the immobilized enzyme is suitable for the field of enzyme immobilization.
C12N 11/089 - Enzymes ou cellules microbiennes immobilisées sur ou dans un support organique le support étant un polymère synthétique obtenu autrement que par des réactions faisant intervenir uniquement des liaisons non saturées carbone-carbone
C12M 1/12 - Appareillage pour l'enzymologie ou la microbiologie avec des moyens de stérilisation, filtration ou dialyse
C12N 9/02 - Oxydoréductases (1.), p. ex. luciférase
C12N 9/06 - Oxydoréductases (1.), p. ex. luciférase agissant sur des composés contenant de l'azote comme donneurs (1.4, 1.5, 1.7)
2.
METHOD FOR CONTINUOUSLY SYNTHESIZING N-BOC-2,5-DIHYDROPYRROLE
A method for continuously synthesizing N-Boc-2,5-dihydropyrrole is provided. The method includes the following steps: cis-1,4 dichloro-2 butene is dissolved in an organic solvent, to prepare solution A; urotropine is dissolved in an organic solvent, to prepare solution B; the solution A and solution B are fed into a first continuous reaction device; a product overflow system is transferred to a second continuous reaction device, and concentrated hydrochloric acid is fed into the same; a product overflow system of the second continuous reaction device is transferred to a third continuous reaction device, and potassium carbonate is fed into the same; a product overflow system of the third continuous reaction device is transferred to a fourth continuous reaction device, and Boc acid anhydride solution is fed into the same; and a product of the fourth continuous reaction device is subjected to continuous solid-liquid separation, concentration and distillation, to obtain N-Boc-2,5-dihydropyrrole.
C07D 207/18 - Composés hétérocycliques contenant des cycles à cinq chaînons, non condensés avec d'autres cycles, ne comportant qu'un atome d'azote comme unique hétéro-atome du cycle avec uniquement des atomes d'hydrogène ou de carbone liés directement à l'atome d'azote du cycle comportant une liaison double entre chaînons cycliques ou entre chaînon cyclique et chaînon non cyclique
3.
PREPARATION METHOD FOR ALPHA-AMINO ACID ESTER ACYL TRANSFERASE AND USE THEREOF IN DIPEPTIDE SYNTHESIS
Provided are a preparation method for alpha-amino acid ester acyl transferase, and a use thereof in dipeptide synthesis. A method for dipeptide synthesis comprises: using alpha-amino acid ester acyl transferase to perform a dipeptide synthesis reaction, to obtain a dipeptide; the alpha-amino acid ester acyl transferase has a conserved region with an amino acid sequence as shown in SEQ ID NO: 1. Using the alpha-amino acid ester acyl transferase, a variety of functional dipeptides can be synthesized, a substrate spectrum is wide, and the synthesis efficiency of some enzymes is high; this can be well used for industrial amplification, with low cost and high yield, thus realizing green chemistry.
A preparation method for an L-amino acid ligase and a use thereof in dipeptide synthesis. A dipeptide synthesis method comprises: using an L-amino acid ligase of an amino acid sequence as shown in SEQ ID NO: 1 to perform dipeptide synthesis reaction to obtain a dipeptide. The L-amino acid ligase can be used for synthesis of a plurality of functional dipeptides, has a wide substrate spectrum and high synthesis efficiency, can be well applied to industrial amplification, has low costs and high yield, and realizes real green chemistry.
Provided are a lipase mutant and an application thereof. Specifically, one or more mutations selected from A262H, A338V, V3641, A158PN, and 1159N are generated on the basis of an amino acid sequence as shown in SEQ ID NO: 1; and compared with a parental lipase, a change in the structure and function of a protein occurs in the lipase mutant, and the stereoselectivity is improved, such that a usage amount of an enzyme is decreased to a certain extent, the post-treatment difficulty is reduced, and the lipase mutant is suitable for industrial production.
Provided in the present invention are a preparation method and a purification method for 2,2-dichloropropane. The preparation method comprises: taking acetone and phosphorus pentachloride as substrates, and subjecting same to a chlorination reaction under the catalysis of an acid catalyst, so as to prepare 2,2-dichloropropane, wherein the acid catalyst comprises one or more of an alkali metal halide, an alkaline earth metal halide, boron halide, silicon halide, an aluminum salt, a ferric salt, a copper salt, a zinc salt, a titanium salt, a tin salt, a bismuth salt, an organosilicon halide, an acyl chloride or a protonic acid. The methods can solve the problem of there being difficulties in realizing scaled-up production of 2,2-dichloropropane in the prior art, and are applicable to the field of synthesis of 2,2-dichloropropane.
C07C 17/18 - Préparation d'hydrocarbures halogénés par remplacement par des halogènes d'atomes d'oxygène de groupes carbonyle
C07C 19/01 - Composés acycliques saturés contenant des atomes d'halogène contenant du chlore
B01J 31/02 - Catalyseurs contenant des hydrures, des complexes de coordination ou des composés organiques contenant des composés organiques ou des hydrures métalliques
B01J 27/138 - HalogènesLeurs composés avec des métaux alcalino-terreux, du magnésium, du béryllium, du zinc, du cadmium ou du mercure
B01J 27/135 - HalogènesLeurs composés avec du titane, du zirconium, de l'hafnium, du germanium, de l'étain ou du plomb
Disclosed are a synthesis method for double-stranded RNA and use of an RNA ligase in double-stranded RNA synthesis. The synthesis method comprises the following steps: S1, synthesizing single-stranded RNA fragments; and S2, mixing the single-stranded RNA fragments and linking the single-stranded RNA fragments using the RNA ligase to form the double-stranded RNA. The RNA ligase is an RNA ligase derived from Vibrio phage, Escherichia phage, Klebsiella phage, or the like. By means of applying the technical scheme of the present invention, different nucleotide fragments can be specifically spliced, so that long-fragment nucleotide strands can be synthesized; meanwhile, the linkage of natural nucleotides and non-natural nucleotides can be catalyzed, thus solving the technical problems of synthesizing nucleotide strands at present.
Provided are a transaminase mutant and use. The transaminase mutant comprises (a) a protein having an amino acid sequence as set forth in SEQ ID NO: 1; or (b) a protein, which is subjected to amino acid mutation on at least one of the following sites: V315, I91, V124, Y116, A286, C418, T87, S301, S27, V31, R34, M64, A74, R77, S101, T117, N151, L213, T285, T107 or L449, of the amino acid sequence in (a) and has a transaminase activity function; and (c) a protein having 80% or more homology with an amino acid sequence defined in any one of (a) and (b) and having a transaminase function. The problem of poor activity or tolerance of transaminase in industrial production of catalyzing a large-steric-hindrance chiral amine compound in the prior art is solved.
C12N 15/63 - Introduction de matériel génétique étranger utilisant des vecteursVecteurs Utilisation d'hôtes pour ceux-ciRégulation de l'expression
C12P 13/00 - Préparation de composés organiques contenant de l'azote
C12P 17/12 - Préparation de composés hétérocycliques comportant O, N, S, Se ou Te comme uniques hétéro-atomes du cycle l'azote comme unique hétéro-atome du cycle contenant un hétérocycle à six chaînons
The present invention provides an amidase mutant and use thereof. The amidase mutant comprises (a) a protein having an amino acid sequence set forth in SEQ ID NO: 1; or (b) a protein that is subjected to an amino acid mutation on at least one of the following sites of the amino acid sequence shown in (a): L81, E62, M311, N180, P121, R58, E32, T230, N82, N190, D192, D217, H219, K77, M78, P79, F80, F61, D185, D59, L182, T183, P184, I227, C228, G229, A231, or V232, and has an amidase function; or (c) a protein having more than 80% homology to the amino acid sequence defined in any one of (a) and (b) and having an amidase function. Said mutant can solve the problems of poor amidase stereoselectivity and catalytic activity in the prior art and is suitable for the field of enzyme catalysis.
yyNP shown in SEQ ID NO: 1; the uracil nucleoside phosphorylase comprises a protein which has more than 80% homology with a protein UP shown in SEQ ID NO: 2; and the purine nucleoside phosphorylase comprises a protein which has more than 80% homology with a protein PNP shown in SEQ ID NO: 3, 7 or 8. The present invention can solve the problem in the prior art that there is no biosynthesis method to produce a nucleoside containing a protecting group, and is suitable for the field of enzyme catalysis.
yyNP as shown in SEQ ID NO: 2; the purine nucleoside phosphorylase comprises PNP as shown in SEQ ID NO: 3; the substrate comprises arabinofuranosyluracil and a substrate basic group. The present invention can solve the problem in the prior art that the operation of preparation of an arabinonucleoside by a biosynthesis two-step method is complex, and is applicable to the field of enzyme catalysis.
C12P 19/40 - Nucléosides avec un système cyclique condensé, contenant un cycle à six chaînons, comportant deux atomes d'azote dans le même cycle, p. ex. nucléosides puriques
Provided are an esterase mutant and use thereof. The amino acid sequence of the esterase mutant has a sequence as shown in SEQ ID NO: 1, and sites at which amino acid mutations occur include an N51G site.
Provided are an amino acid dehydrogenase mutant and use thereof. The amino acid sequence of the amino acid dehydrogenase mutant has a sequence as shown in SEQ ID NO: 1, and sites at which amino acid mutations occur include a K144G site.
Provided are a cytochrome P450 enzyme mutant and an application thereof. The enzyme activity and anti-Markov oxidation selectivity of P450 derived from a wild-type strain of Bacillus megaterium undergo protein modification by means of directed evolution, thus improving enzyme activity and selectivity, and developing a series of P450 enzyme mutants that may be used for industrial production.
Provided are a lipase mutant and use thereof. The amino acid sequence of the lipase mutant has a sequence shown in SEQ ID NO: 1, that is, sites at which amino acid mutations occur include a V154L site.
The present invention provides a transaminase mutant and a preparation method for a chiral amine compound. The transaminase mutant comprises: (a) a protein comprising an amino acid sequence represented by SEQ ID NO: 1; or (b) a protein comprising an amino acid sequence represented by SEQ ID NO: 2 or SEQ ID NO: 3; or (c) a protein that undergoes an amino acid mutation at at least one of the following sites of the amino acid sequence in (b): Y89, L380, N86, Y85, T91, P83, K90, S417, S424, F301, G164, T452, and the like, and has a transaminase function; and (d) a protein having homology of more than 80% to the amino acid sequence defined in any one of (a), (b) or (c) and having a transaminase function. The problem of low activity of transaminases in the prior art can be solved. The present invention is suitable for the field of enzyme catalysis.
C12N 15/70 - Vecteurs ou systèmes d'expression spécialement adaptés à E. coli
C12P 13/00 - Préparation de composés organiques contenant de l'azote
C12P 17/12 - Préparation de composés hétérocycliques comportant O, N, S, Se ou Te comme uniques hétéro-atomes du cycle l'azote comme unique hétéro-atome du cycle contenant un hétérocycle à six chaînons
17.
PVA MEMBRANE IMMOBILIZED ENZYME AND PREPARATION METHOD THEREFOR
Described herein are a PVA membrane immobilized enzyme and a preparation method therefor. The PVA membrane immobilized enzyme includes a PVA porous membrane and an enzyme entrapped on the PVA porous membrane. The PVA porous membrane is a three-dimensional structured PVA porous membrane. The enzyme is any one selected from transaminase, D-lactate dehydrogenase, cyclohexanone monooxygenase, ketoreductase, alkene reductase, nitrilase, ammonia lyase, amino acid dehydrogenase, imine reductase, alcohol dehydrogenase, ammonium formate dehydrogenase, glucose 1-dehydrogenase and mutants thereof. The three-dimensional structured PVA porous membrane is used as a carrier to immobilize an enzyme in an entrapment manner. After entrapping and immobilizing the enzyme in the PVA porous membrane, the enzyme is stable, and cannot be easily leached out in the process of use. The PVA porous membrane is suitable for use in continuous flow biochemical catalysis, and has wide applicability to enzymes.
C12N 11/084 - Polymères comportant des unités alcool vinyliques
C12N 11/04 - Enzymes ou cellules microbiennes immobilisées sur ou dans un support organique piégées à l’intérieur du support, p. ex. dans un gel ou dans des fibres creuses
18.
METHOD FOR CONTINUOUSLY SYNTHESIZING N-BOC-2,5-DIHYDROPYRROLE
Disclosed in the present invention is a method for continuously synthesizing N-Boc-2,5-dihydropyrrole. The method comprises the following steps: dissolving cis-1,4 dichloro-2 butene in an organic solvent to prepare solution A; dissolving urotropine in an organic solvent to prepare solution B; beating solution A and solution B into a first continuous reaction device; transferring the product overflow system of the first continuous reaction device to a second continuous reaction device, and beating concentrated hydrochloric acid into same at the same time; transferring the product overflow system of the second continuous reaction device to a third continuous reaction device, and beating potassium carbonate into same at the same time; transferring the product overflow system of the third continuous reaction device to a fourth continuous reaction device, and beating a Boc anhydride solution into same at the same time; and subjecting the product of the fourth continuous reaction device to continuous solid-liquid separation, concentration and distillation to obtain N-Boc-2,5-dihydropyrrole. By using the technical solution of the present invention, the route involving high-risk materials is avoided, and the production capacity and yield are improved in a continuous manner.
C07D 207/20 - Composés hétérocycliques contenant des cycles à cinq chaînons, non condensés avec d'autres cycles, ne comportant qu'un atome d'azote comme unique hétéro-atome du cycle avec uniquement des atomes d'hydrogène ou de carbone liés directement à l'atome d'azote du cycle comportant une liaison double entre chaînons cycliques ou entre chaînon cyclique et chaînon non cyclique avec uniquement des atomes d'hydrogène, des radicaux hydrocarbonés ou des radicaux hydrocarbonés substitués, liés directement aux atomes de carbone du cycle
19.
CATALYST LOADED WITH TEMPO COMPOUND, AND PREPARATION METHOD THEREFOR AND USE THEREOF
Provided are a catalyst loaded with a TEMPO compound, and a preparation method therefor and the use thereof. The catalyst loaded with a TEMPO compound uses a polymer resin as a carrier, wherein the polymer resin is a polystyrene resin containing a chloromethyl or bromomethyl group, and the content of the chloromethyl or bromomethyl group in the polymer resin is 0.5-5.0 mmol g-1. The polymer resin has a polystyrene framework and has a very low swelling degree in an organic solvent; in actual continuous production, the low swelling degree is beneficial for maintaining the rigidity of the resin, and the phenomena of softening, mutual extrusion, the increased pressure (pressure holding) of a reaction device, etc. caused by resin expansion are prevented, such that it is ensured that the resin does not break; and the resin has good tolerance to an oxidizing agent (such as sodium hypochlorite), and does not break and degrade after coming in contact with the oxidizing agent, and thus the cycle life of the loaded catalyst is ensured.
B01J 31/06 - Catalyseurs contenant des hydrures, des complexes de coordination ou des composés organiques contenant des composés organiques ou des hydrures métalliques contenant des polymères
C07C 45/30 - Préparation de composés comportant des groupes C=O liés uniquement à des atomes de carbone ou d'hydrogènePréparation des chélates de ces composés par oxydation avec des composés contenant des atomes d'halogène, p. ex. par hypohalogénation
C07C 201/12 - Préparation de composés nitrés par des réactions ne créant pas de groupes nitro
Provided is a ketoreductase mutant and applications thereof. Compared with an amino acid sequence shown in SEQ ID NO: 1, the amino acid sequence of the ketoreductase mutant includes at least one of the following mutation sites: L198P, S96W/I/L/V, M194L or L1526, herein “/” means “or.” The ketoreductase mutant provides high selectivity and high activity with respect to a substrate ketone, and the application of the mutant in a catalytic reduction reaction of a ketone substrate may increase the production efficiency of a chiral alcohol compound corresponding thereto.
Provided are an immobilized enzyme and the use thereof in continuous production, wherein the immobilized enzyme is a polyethyleneimine-modified immobilized enzyme and includes: an enzyme, which includes an amine dehydrogenase and/or a formate dehydrogenase; and a carrier, which is a cyanuric-chloride-activated amino-type carrier. The problem in the prior art of the performance of an immobilized enzyme being poor is solved, the catalytic activity and reusability of the immobilized enzyme are improved, and the immobilized enzyme is suitable for the field of enzyme immobilization.
Described herein are an immobilized enzyme, and a preparation method therefor and a use thereof. The immobilized enzyme includes activated PEI and an enzyme covalently bonded to the activated PEI, where the enzyme is selected from any one of a transaminase, a ketoreductase, a monooxygenase, an ammonia lyase, an ene-reductase, an imine reductase, an amino acid dehydrogenase and a nitrilase.
C12N 11/089 - Enzymes ou cellules microbiennes immobilisées sur ou dans un support organique le support étant un polymère synthétique obtenu autrement que par des réactions faisant intervenir uniquement des liaisons non saturées carbone-carbone
C12N 11/098 - Enzymes ou cellules microbiennes immobilisées sur ou dans un support organique le support étant un polymère synthétique formé en présence des enzymes ou des cellules microbiennes
C12N 9/04 - Oxydoréductases (1.), p. ex. luciférase agissant sur des groupes CHOH comme donneurs, p. ex. oxydase de glucose, déshydrogénase lactique (1.1)
C12N 9/02 - Oxydoréductases (1.), p. ex. luciférase
C12N 9/06 - Oxydoréductases (1.), p. ex. luciférase agissant sur des composés contenant de l'azote comme donneurs (1.4, 1.5, 1.7)
Disclosed are a modified epoxy resin immobilized enzyme, a preparation method therefor and an application thereof. Herein, the preparation method includes the following steps: modifying an epoxy resin, adding a polyethyleneimine to a modified epoxy resin for further modification, and then adding an enzyme to be immobilized and a glutaraldehyde for immobilization, to obtain the modified epoxy resin immobilized enzyme. The epoxy resin is modified, the polyethyleneimine is added to the modified epoxy resin for the further modification, and an aldehyde group in the resin and an amino group in the polyethyleneimine are covalently bound to each enzyme, then it is activated by the bifunctional reagent glutaraldehyde.
C08G 59/14 - Polycondensats modifiés par post-traitement chimique
C08G 59/16 - Polycondensats modifiés par post-traitement chimique par des acides monocarboxyliques ou par leurs anhydrides, halogénures ou esters à bas poids moléculaire
C08G 59/42 - Acides polycarboxyliquesLeurs anhydrides, halogénures ou esters à bas poids moléculaire
C12N 11/08 - Enzymes ou cellules microbiennes immobilisées sur ou dans un support organique le support étant un polymère synthétique
C12N 11/089 - Enzymes ou cellules microbiennes immobilisées sur ou dans un support organique le support étant un polymère synthétique obtenu autrement que par des réactions faisant intervenir uniquement des liaisons non saturées carbone-carbone
Provided are a lipase mutant and an application thereof. Specifically, one or more mutations selected from A262H, A338V, V364I, A158P/V, and I159N are generated on the basis of an amino acid sequence as shown in SEQ ID NO: 1; compared with parental lipase, a change in the structure and function of a protein occurs in the lipase mutant, and the stereoselectivity is improved, such that the dosage of an enzyme is decreased to a certain extent, the post-treatment difficulty is reduced, and the lipase mutant is suitable for industrial production.
The disclosure discloses a method for an addition reaction of acetylene and a ketone compound. The method includes the following steps: S1, providing a continuous reaction device, wherein the continuous reaction device includes a plurality of bubble tubular reactors being connected with each other through connecting tubes; feeding a raw material solution containing the ketone compound and alkali into the plurality of bubble tubular reactors, and S3, under normal pressure, pumping acetylene from the bottom of the first bubble tubular reactor for the addition reaction. By applying the technical solution of the invention, acetylene reacts with the ketone compound in the plurality of bubble tubular reactors arranged in series, which can ensure the sufficient gas-liquid contact time, and thus making full use of the acetylene gas, improving the utilization rate thereof, effectively reduing the amount of acetylene, reducing costs, and further improving the safety.
C07C 29/38 - Préparation de composés comportant des groupes hydroxyle ou O-métal liés à un atome de carbone ne faisant pas partie d'un cycle aromatique à six chaînons par des réactions augmentant le nombre d'atomes de carbone avec formation de groupes hydroxyle, ces groupes pouvant être produits par l'intermédiaire de dérivés de groupes hydroxyle, p. ex. du dérivé O-métal par réactions avec des aldéhydes ou des cétones
C07C 41/48 - Préparation de composés comportant des groupes
B01J 10/00 - Procédés chimiques généraux faisant réagir un liquide avec des milieux gazeux autrement qu'en présence de particules solidesAppareillage spécialement adapté à cet effet
B01J 19/24 - Réacteurs fixes sans élément interne mobile
B01J 19/00 - Procédés chimiques, physiques ou physico-chimiques en généralAppareils appropriés
The present disclosure provides a preparation method for metformin hydrochloride. The preparation method includes: microwave heating raw materials containing dicyandiamide and dimethylamine hydrochloride, and reacting the two at 100° C. to 160° C. to obtain a product system containing metformin hydrochloride. Microwave heating is adopted to heat the dicyandiamide and the dimethylamine hydrochloride. Compared with a conventional heating mode that requires heat to be gradually transferred from the outside to the inside, microwave heating can directly heat each part inside the reactant, which can make the internal temperature of the reactant more uniform, thereby reducing the generation of impurities.
Provided is an esterase mutant and use thereof. The amino acid sequence of the esterase mutant has the sequence as shown in SEQ ID NO: 1, and sites at which the amino acid mutation occurs comprise an N51G site. The esterase mutant achieves changes of the structure and function of the protein, improves both enzyme specificity and enzyme activity, reduces the usage amount of enzyme, and reduces industrial production costs.
Provided are an amino acid dehydrogenase mutant and an application thereof. The amino acid sequence of the amino acid dehydrogenase has a sequence as shown in SEQ ID NO: 1, and sites at which amino acid mutation occurs comprise a K144G site. According to the amino acid dehydrogenase mutant, changes in protein structure and function are achieved, enzyme activity is improved, the usage amount of amino acid dehydrogenase is reduced, enzyme specificity is correspondingly improved, and costs in industrial production of amino acids are reduced.
Provided is a lipase mutant and an application thereof. The amino acid sequence of the lipase mutant has the sequence shown in SEQ ID NO: 1, that is, the amino acid mutation site comprises a V154L site. The protein structure and function of the lipase mutant are changed, the solubility of the expression of same in E. coli is improved, and the catalytic activity of the enzyme is improved. In practical applications, the dosage of the enzyme is reduced, the reaction volume is reduced, and the difficulty of post-processing is reduced, and same is suitable for industrial production.
Provided are a cytochrome P450 enzyme mutant and an application thereof. The enzyme activity and anti-Markov oxidation selectivity of P450 derived from a wild-type strain of Bacillus megaterium undergo protein modification by means of directed evolution, thus improving enzyme activity and selectivity, and developing a series of P450 enzyme mutants that can be used for industrial production.
Provided are a transaminase mutant and a method for producing a chiral amine using the same. An amino acid sequence of the transaminase mutant is an amino acid sequence obtained by mutation occurred in an amino acid sequence as shown in SEQ ID NO: 1, and the mutation includes at least one of the following mutation sites: position 3, position 5, position 8, position 25, position 32, position 45, position 56, position 59, position 60, position 84, position 86, position 164, position 176, position 178, position 180, position 187, position 197, position 206, position 207, position 242, position 245, position 319 and position 324.
C12P 13/00 - Préparation de composés organiques contenant de l'azote
C12P 17/12 - Préparation de composés hétérocycliques comportant O, N, S, Se ou Te comme uniques hétéro-atomes du cycle l'azote comme unique hétéro-atome du cycle contenant un hétérocycle à six chaînons
Disclosed are a monooxygenase mutant and use thereof. An amino acid sequence of a monooxygenase mutant is an amino acid sequence obtained by mutating an amino acid sequence as shown in SEQ ID NO: 1. Mutation includes at least one of the following mutation sites: site 49, site 60, site 61, site 144, site 145, site 146, site 147, site 167, site 169, site 189, site 246, site 247, site 280, site 284, site 285, site 286, site 287, site 328, site 330, site 332, site 382, site 427, site 428, site 429, site 430, site 431, site 432, site 433, site 434, site 435, site 436, site 438, site 441, site 493, site 494, site 508, site 509, site 510, site 511, site 512, and site 513 sites and the like.
C12N 15/00 - Techniques de mutation ou génie génétiqueADN ou ARN concernant le génie génétique, vecteurs, p. ex. plasmides, ou leur isolement, leur préparation ou leur purificationUtilisation d'hôtes pour ceux-ci
C12N 15/70 - Vecteurs ou systèmes d'expression spécialement adaptés à E. coli
C12N 15/81 - Vecteurs ou systèmes d'expression spécialement adaptés aux hôtes eucaryotes pour champignons pour levures
C12P 17/18 - Préparation de composés hétérocycliques comportant O, N, S, Se ou Te comme uniques hétéro-atomes du cycle contenant plusieurs hétérocycles condensés entre eux ou condensés avec un système carbocyclique commun, p. ex. rifamycine
A synthesis method for a cyclopropane compound. The cyclopropane compound has a structure as represented by general formula (I). The synthesis method comprises: reacting an olefin compound A with ethyl diazoacetate under the catalysis of a supported rhodium catalyst to obtain a cyclopropane compound, wherein the structural formula of the olefin compound A is (aa). The synthesis method features high reaction efficiency, a short time, a yield that can even reach 90% or more, and good repeatability. Moreover, the synthesis method does not require the use of an additive similar to copper halide or acetyl halide, uses a supported rhodium catalyst, and is thus highly environmentally friendly.
C07C 67/343 - Préparation d'esters d'acides carboxyliques par modification de la partie acide de l'ester sans introduction d'un groupe ester par isomérisationPréparation d'esters d'acides carboxyliques par modification de la partie acide de l'ester sans introduction d'un groupe ester par modification de la taille du squelette carboné par augmentation du nombre d'atomes de carbone
C07C 231/12 - Préparation d'amides d'acides carboxyliques par des réactions n'impliquant pas la formation de groupes carboxamide
C07C 253/30 - Préparation de nitriles d'acides carboxyliques par des réactions n'impliquant pas la formation de groupes cyano
C07F 7/18 - Composés comportant une ou plusieurs liaisons C—Si ainsi qu'une ou plusieurs liaisons C—O—Si
C07C 69/743 - Esters d'acides carboxyliques dont un groupe carboxyle est lié à un atome de carbone d'un cycle autre qu'un cycle aromatique à six chaînons d'acides comportant un cycle à trois chaînons avec insaturation en dehors du cycle
C07C 69/757 - Esters d'acides carboxyliques dont un groupe carboxyle est lié à un atome de carbone d'un cycle autre qu'un cycle aromatique à six chaînons dont l'un des groupes OH, O-métal, —CHO, céto, éther, acyloxy, des groupes , des groupes ou des groupes se trouve dans la partie acide
C07C 233/58 - Amides d'acides carboxyliques ayant des atomes de carbone de groupes carboxamide liés à des atomes de carbone de cycles autres que des cycles aromatiques à six chaînons ayant les atomes d'azote des groupes carboxamide liés à des atomes d'hydrogène ou à des atomes de carbone de radicaux hydrocarbonés non substitués
C07C 255/46 - Nitriles d'acides carboxyliques ayant des groupes cyano liés à des atomes de carbone de cycles autres que des cycles aromatiques à six chaînons à des atomes de carbone de cycles non condensés
C07C 69/753 - Esters d'acides carboxyliques dont un groupe carboxyle est lié à un atome de carbone d'un cycle autre qu'un cycle aromatique à six chaînons d'acides polycycliques
C07D 307/54 - Radicaux substitués par des atomes de carbone comportant trois liaisons à des hétéro-atomes, avec au plus une liaison à un halogène, p. ex. radicaux ester ou nitrile
34.
CONTINUOUS SYNTHESIS METHOD FOR ETHYL PIPERIDINE-4-CARBOXYLATE, AND APPLICATION OF CONTINUOUS SYNTHESIS METHOD
The present invention provides a continuous synthesis method for ethyl piperidine-4-carboxylate, and an application of the continuous synthesis method. The continuous synthesis method comprises: dispersing a mixture of ethyl pyridine-4-carboxylate and hydrogen to form small droplets having a particle size of 50 nm to 5 mm as a reaction raw material; and continuously inputting the reaction raw material into a fixed bed reactor for catalytic hydrogenation reaction, and continuously discharging ethyl piperidine-4-carboxylate. According to the forced dispersion process, the reaction raw material can be subjected to high-performance mass transfer in the catalytic hydrogenation reaction process, so that the full reaction degree of the reaction raw material can be improved, the reaction time can be shortened, and yield and purity of ethyl piperidine-4-carboxylate can be improved. Compared with batch reaction, the continuous synthesis method achieves less amount of the reaction raw material in unit time and a small area occupied by a reaction device, and has advantages in heat exchange and in improving pressure bearing of the device, thereby greatly reducing device investment cost and greatly reducing the safety risk caused by use of a large amount of hydrogen gas.
C07D 211/02 - Préparation par cyclisation ou hydrogénation
C07D 211/62 - Atomes de carbone comportant trois liaisons à des hétéro-atomes, avec au plus une liaison à un halogène, p. ex. radicaux ester ou nitrile liés en position 4
35.
CONTINUOUS HYDROGENATION METHOD FOR ETHYL PYRAZINE-2-CARBOXYLATE AND USE THEREOF
Provided is a continuous hydrogenation method for ethyl pyrazine-2-carboxylate. The continuous hydrogenation method comprises: dispersing a mixture of ethyl pyrazine-2-carboxylate and hydrogen to form a gas-liquid mixture containing small liquid drops with sizes of 50 nm to 5 mm, wherein the gas-liquid mixture is used as a reaction raw material; and continuously feeding the reaction raw material into a fixed bed reactor for a catalytic hydrogenation reaction, and continuously discharging ethyl piperazine-2-carboxylate, wherein the fixed bed reactor is divided into at least two temperature control sections along the flow direction of the material, and the temperature of the latter temperature control section is lower than the temperature of the former temperature control section. According to the above forced dispersion process, the reaction raw materials can be subjected to high-performance mass transfer in the catalytic hydrogenation reaction process, the sufficient reaction degree of the reaction raw materials is improved, and the reaction time is shortened. The sectional temperature control along the flow direction of the material of the fixed bed reactor can effectively remove the heat accumulation and control the reaction state in the reactor, and can improve the yield, purity and product performance stability of the target product.
C07D 241/04 - Composés hétérocycliques contenant des cycles diazine-1,4 ou diazine-1,4 hydrogéné non condensés avec d'autres cycles ne comportant pas de liaisons doubles entre chaînons cycliques ou entre chaînons cycliques et chaînons non cycliques
36.
PVA MEMBRANE IMMOBILIZED ENZYME AND PREPARATION METHOD THEREFOR
Provided are a PVA film immobilized enzyme and a preparation method therefor. The PVA membrane immobilized enzyme comprises a PVA porous membrane and an enzyme embedded on the PVA porous membrane. The PVA porous membrane is a three-dimensional structured PVA porous membrane. The enzyme is any one selected from transaminase, D-lactate dehydrogenase, cyclohexanone monooxygenase, ketoreductase, alkene reductase, nitrilase, ammonia lyase, amino acid dehydrogenase, imine reductase, alcohol dehydrogenase, ammonium formate dehydrogenase, glucose 1-dehydrogenase and mutants thereof. The three-dimensional structured PVA porous membrane is used as a carrier to immobilize an enzyme in an embedding manner. The embedding and immobilization process is simple, conditions are mild, and the specific surface area is large. After embedding and immobilizing the enzyme in the PVA porous membrane, the enzyme is stable, and cannot be easily leached out in the process of use. The porous structure of the PVA porous membrane used can better transmit reactants and products, is suitable for use in continuous flow biochemical catalysis, and has wide applicability to enzymes.
A ketoreductase mutant and applications thereof. Compared with the amino acid sequence as represented by SEQ ID NO: 1, the amino acid sequence of the ketoreductase mutant comprises at least one of the following mutation sites: L198P, S96W/I/L/V, M194L or L152G, where "/" means "or." The ketoreductase mutant provides high selectivity and high activity with respect to a substrate ketone, and, application of the mutant in a catalytic reduction reaction of a ketone substrate increases the production efficiency of a chiral alcohol compound corresponding thereto.
Provided are an immobilized enzyme, and a preparation method therefor and the use thereof. The immobilized enzyme comprises activated PEI and an enzyme covalently bonded to the activated PEI, wherein the enzyme is selected from any one of transaminase, ketoreductase, monooxygenase, ammonia lyase, ene-reductase, imine reductase, amino acid dehydrogenase and nitrilase.
C12N 11/089 - Enzymes ou cellules microbiennes immobilisées sur ou dans un support organique le support étant un polymère synthétique obtenu autrement que par des réactions faisant intervenir uniquement des liaisons non saturées carbone-carbone
C12N 11/098 - Enzymes ou cellules microbiennes immobilisées sur ou dans un support organique le support étant un polymère synthétique formé en présence des enzymes ou des cellules microbiennes
Provided is an amino acid dehydrogenase mutant. The amino acid sequence of the mutant is obtained by mutating the amino acid sequence shown in SEQ ID NO:1. The mutation includes at least one of the following mutation sites: 64th, 94th, 133rd, 137th, 148th, 168th, 173rd, 183 rd, 191st, 207th, 229th, 248th, 255th and 282nd sites; or the amino acid sequence of the amino acid dehydrogenase mutant is an amino acid sequence having the mutation sites in the mutated amino acid sequence and having a 80% or more homology with the mutated amino acid sequence. The mutant enzyme activity is more than 50 times higher than that of wild amino acid dehydrogenase, and the enzyme specificity is also correspondingly improved.
Provided is a method for preparing a trifluorohydrocarbyl sulfone compound. The preparation method comprises continuously sending a trifluorohydrocarbyl thioether compound, sodium tungstate dihydrate and a hydrogen peroxide solution to a continuous reactor via a feeding device, and subjecting the trifluorohydrocarbyl thioether compound to an oxidation reaction to obtain a product system containing a trifluorohydrocarbyl sulfone compound, wherein the trifluorohydrocarbyl thioether compound has a structure as represented by structural formula (I), in which R is any one of the following groups: a linear alkyl, a branched alkyl, a substituted aryl, a non-substituted aryl, a substituted heterocyclic aryl, a non-substituted heterocyclic aryl, a non-substituted cyclic alkyl and a substituted cyclic alkyl, and the temperature of the oxidation reaction is 25°C to 50°C. By using continuous feeding, the present application improves the material contact effect, so that the oxidation reaction of the thioether can be performed at a relatively low temperature; in addition, the reduction of the temperature of the oxidation reaction efficiently reduces the decomposition of hydrogen peroxide and reduces the pressure resistance requirement of the continuous reactor.
C07D 213/71 - Atomes de soufre auxquels est lié un second hétéro-atome
C07C 315/02 - Préparation de sulfonesPréparation de sulfoxydes par formation de groupes sulfone ou sulfoxyde par oxydation de sulfures ou par formation de groupes sulfone par oxydation de sulfoxydes
C07C 317/24 - SulfonesSulfoxydes ayant des groupes sulfone ou sulfoxyde et des atomes d'oxygène, liés par des liaisons doubles, liés au même squelette carboné
The present invention provides a continuous preparation method for a 2-amino-pyrrole-3- carboxylate. The preparation method comprises: continuously feeding a chloroacetaldehyde trimer solution into a first continuous reactor to carry out continuous acid catalyzed depolymerization on chloroacetaldehyde trimer to obtain a chloroacetaldehyde solution; and continuously feeding a 3-amino-3-iminopropanoic acid ethyl ester solution, an alkali solution and a chloroacetaldehyde solution into a second continuous reactor for a condensation reaction to obtain the 2-amino-pyrrole-3-carboxylate. The continuous process breaks through the limitation of anhydrous chloroacetaldehyde, and the reaction speed of preparing anhydrous chloroacetaldehyde by using a continuous reaction is faster than that by batches and the yield is higher. When the prepared chloroacetaldehyde solution is directly used in the condensation reaction of the next step, material ratio is more controllable, and the first and second steps are compatible, thereby improving the yield of the 2-amino-pyrrole-3-carboxylate in general. In addition, the continuous process avoids the amplification effect of batches and ensures the high yield in industrial application.
C07D 207/34 - Composés hétérocycliques contenant des cycles à cinq chaînons, non condensés avec d'autres cycles, ne comportant qu'un atome d'azote comme unique hétéro-atome du cycle avec uniquement des atomes d'hydrogène ou de carbone liés directement à l'atome d'azote du cycle comportant deux liaisons doubles entre chaînons cycliques ou entre chaînons cycliques et chaînons non cycliques avec des hétéro-atomes ou avec des atomes de carbone comportant trois liaisons à des hétéro-atomes, avec au plus une liaison à un halogène, p. ex. radicaux ester ou nitrile, liés directement aux atomes de carbone du cycle
C07C 45/60 - Préparation de composés comportant des groupes C=O liés uniquement à des atomes de carbone ou d'hydrogènePréparation des chélates de ces composés à partir de composés hétérocycliques avec l'oxygène comme unique hétéro-atome dans des cycles à six chaînons
C07C 47/14 - Composés saturés comportant des groupes —CHO liés à des atomes de carbone acycliques ou à de l'hydrogène contenant des atomes d'halogène
Provided are a proline hydroxylase and uses thereof. The proline hydroxylase comprises having the amino acid sequence of SEQ ID NO: 2 with the exception of a mutation of one or more amino acids; wherein the mutation of one or more amino acids must comprises E27K, and the mutation of one or more amino acids selected from the group consisting of: H14R, L16N, T25R, F26L, E27K, D30S, S33N, E34N, E34G, E34L, E34S, E34D, Y35W, Y35K, S37W, S37F, S37E, S37N, S37T, S37C, W40F, K41E, D54G, H55Q, S57L, I58T, I58Y, I58A, I58R, I58V, I58S, I58C, K86P, T91A, F95Y, C97Y, I98V, K106V, K106T, K106Q, F111S, K112E, K112R, S154A, K162E, L166M, I118F, I118V, I118R, H119R, H119F, I120V, K123D, K123N, K123Q, K123S, K123I, K123T, T130N, D134G, V135K, N165H, D173G, K209R, I223V and S225A, and having proline hydroxylase activity.
Provided are a continuous gas-liquid reaction device (100) and a continuous gas-liquid reaction system including same. The continuous gas-liquid reaction device (100) comprises: a main reactor, a stirring device and an oscillation source (170), wherein the stirring device is disposed inside the main reactor and extends in the lengthwise direction of the main reactor; and the oscillation source (170) is used for controlling the oscillation frequency of the main reactor. The continuous gas-liquid reaction device (100) is provided with both the stirring device and the oscillation source (170), and under the simultaneous action of the two, axial and radial complex vortexes are formed in the main reactor, and the vortexes appear or disappear continuously as oscillation is performed. Therefore, the flow pattern in the main reactor is more complex, thus enhancing the liquid-liquid mass transfer, and therefore, the reaction is more complete, and the heat transfer effect of the main reactor is also improved. Due to the existence of the oscillation source (170), the risk of bonding blockages occurring during the reaction process can be effectively inhibited by violently and repeatedly scouring a system between a wall of the reactor and the stirring device.
The disclosure discloses a method for an addition reaction of acetylene and a ketone compound. The method includes the following steps: S1, providing a continuous reaction device, wherein the continuous reaction device includes a plurality of bubble tubular reactors being connected with each other through connecting tubes; feeding a raw material solution containing the ketone compound and alkali into the plurality of bubble tubular reactors, and S3, under normal pressure, pumping acetylene from the bottom of the first bubble tubular reactor for the addition reaction. By applying the technical solution of the invention, acetylene reacts with the ketone compound in the plurality of bubble tubular reactors arranged in series, which can ensure the sufficient gas-liquid contact time, and thus making full use of the acetylene gas, improving the utilization rate thereof, effectively reduing the amount of acetylene, reducing costs, and further improving the safety.
C07C 29/42 - Préparation de composés comportant des groupes hydroxyle ou O-métal liés à un atome de carbone ne faisant pas partie d'un cycle aromatique à six chaînons par des réactions augmentant le nombre d'atomes de carbone avec formation de groupes hydroxyle, ces groupes pouvant être produits par l'intermédiaire de dérivés de groupes hydroxyle, p. ex. du dérivé O-métal par réactions avec des aldéhydes ou des cétones avec des composés contenant des liaisons triples carbone-carbone, p. ex. avec des alcynes métalliques
45.
METHOD FOR PERFORMING ADDITION REACTION BETWEEN ACETYLENE AND KETONE COMPOUND
Disclosed in the present invention is a method for performing an addition reaction between acetylene and a ketone compound. The method comprises the following steps: S1, providing a continuous reaction device, the continuous reaction device comprising a plurality of bubble tubular reactors arranged in series; the plurality of bubble tubular reactors being connected to each other by means of a connecting tube; S2, introducing a raw material solution containing the ketone compound and alkaline into the plurality of bubble tubular reactors; and S3, under the normal pressure, bubbling acetylene from the bottom of the first bubble tubular reactor to perform the addition reaction. By applying the technical solution of the present invention, acetylene reacts with the ketone compound in the plurality of bubble tubular reactors arranged in series, which can ensure the sufficient gas-liquid contact time, and thus making full use of the acetylene gas, improving the utilization rate thereof, effectively reducing the amount of acetylene, reducing costs, and further improving the security.
C07C 29/42 - Préparation de composés comportant des groupes hydroxyle ou O-métal liés à un atome de carbone ne faisant pas partie d'un cycle aromatique à six chaînons par des réactions augmentant le nombre d'atomes de carbone avec formation de groupes hydroxyle, ces groupes pouvant être produits par l'intermédiaire de dérivés de groupes hydroxyle, p. ex. du dérivé O-métal par réactions avec des aldéhydes ou des cétones avec des composés contenant des liaisons triples carbone-carbone, p. ex. avec des alcynes métalliques
The invention provides a transaminase mutant and application thereof, wherein the amino acid sequence of the transaminase mutant is formed after mutation of the amino acid sequence as shown in SEQ ID NO: 1, and mutated amino acid sites comprise T7C+S47C sites. The transaminase mutant having the mutation sites can be further prepared into an immobilized enzyme through an immobilization technology, the immobilized enzyme has relatively high activity and high stability, can be recycled for multiple times, and is applicable to continuous flow reaction in a packed bed.
C12P 17/12 - Préparation de composés hétérocycliques comportant O, N, S, Se ou Te comme uniques hétéro-atomes du cycle l'azote comme unique hétéro-atome du cycle contenant un hétérocycle à six chaînons
C12P 17/10 - Préparation de composés hétérocycliques comportant O, N, S, Se ou Te comme uniques hétéro-atomes du cycle l'azote comme unique hétéro-atome du cycle
C12N 11/082 - Enzymes ou cellules microbiennes immobilisées sur ou dans un support organique le support étant un polymère synthétique obtenu par des réactions faisant intervenir uniquement des liaisons non saturées carbone-carbone
C12N 11/00 - Enzymes fixées sur un support ou immobiliséesCellules microbiennes fixées sur un support ou immobiliséesLeur préparation
C12N 11/10 - Enzymes ou cellules microbiennes immobilisées sur ou dans un support organique le support étant un hydrate de carbone
47.
CONTINUOUS SYNTHESIS METHOD FOR 2-FLUOROMALONIC ACID DIESTER COMPOUND
Provided is a continuous synthesis method for a 2-fluoromalonic acid diester compound. The method comprises: using (I) as a raw material, and carrying out continuous decarbonylation reaction in a continuous reaction device to obtain 2-fluoromalonic acid diester compound (II), wherein R and R' respectively represent unbranched or branched alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclic or cyclic alkyl, and R and R' are the same or different. Compared with the traditional kettle reaction, the amount of materials involved in the reaction per unit time is decreased and the high-temperature dangerous area is reduced in the synthesis method, thereby greatly lowering the safety risk.
C07C 67/343 - Préparation d'esters d'acides carboxyliques par modification de la partie acide de l'ester sans introduction d'un groupe ester par isomérisationPréparation d'esters d'acides carboxyliques par modification de la partie acide de l'ester sans introduction d'un groupe ester par modification de la taille du squelette carboné par augmentation du nombre d'atomes de carbone
C07C 69/63 - Esters contenant des atomes d'halogène d'acides saturés
C07C 67/333 - Préparation d'esters d'acides carboxyliques par modification de la partie acide de l'ester sans introduction d'un groupe ester par isomérisationPréparation d'esters d'acides carboxyliques par modification de la partie acide de l'ester sans introduction d'un groupe ester par modification de la taille du squelette carboné
Disclosed is a method for synthesizing Degarelix acetate. The method comprises: S1, carrying out a condensation reaction with the first six amino acids of Degarelix in sequence by using a Rink Amide MBHA resin as a carrier so as to obtain a hexapeptide resin fragment III; S2, carrying out a condensation reaction with the last four amino acids of Degarelix in sequence by using a CTC resin as a carrier so as to obtain a tetrapeptide resin fragment I; S3, cutting the tetrapeptide resin fragment I to obtain a tetrapeptide fragment II; S4, carrying out a condensation reaction on the hexapeptide resin fragment III and the tetrapeptide fragment II under the action of MYMsA and/or MYTsA so as to obtain a whole-peptide resin; S5, cutting the whole-peptide resin to obtain Degarelix; and S6, carrying out acetic acid salt conversion on the Degarelix to obtain Degarelix acetate.
The present invention provides a preparation method for metformin hydrochloride. The preparation method comprises: heating raw materials comprising dicyandiamide and dimethylamine hydrochloride by means of microwave, and making the two react at 100-160°C to obtain a product system comprising metformin hydrochloride. The dicyandiamide and the dimethylamine hydrochloride are heated by means of microwave heating. Compared with a conventional heating method which requires heat to be transferred gradually from the outside to the inside, the microwave heating can directly heat a reactant to all internal parts thereof so as to make the internal temperature of the reactant more uniform, thereby reducing the generation of impurities. Therefore, the synthesis of metformin hydrochloride by means of microwave heating can improve the purity of the metformin hydrochloride, and is suitable for a melting method and a solvent method, thereby greatly reducing the production difficulty, simplifying the technological process, and providing more feasible solutions for industrialization. The preparation method is suitable for a melting method and a solvent method, thereby greatly reducing the production difficulty.
C07C 277/08 - Préparation de la guanidine ou de ses dérivés, c.-à-d. de composés contenant le groupe les atomes d'azote liés par des liaisons simples ne faisant pas partie de groupes nitro ou nitroso de guanidines substituées
C07C 279/26 - X et Y étant des atomes d'azote, c.-à-d. biguanides
Disclosed are transaminase mutants and use thereof. The amino acid sequence of the transaminase mutant is obtained by the mutation of the amino acid sequence as shown in SEQ ID NO: 1, and the mutation at least comprises one of the following mutation sites: the 19-th site, the 41-th site, the 43-th site, the 72-th site, the 76-th site, the 92-th site, the 107-th site, the 125-th site, the 132-th site, the 226-th site, the 292-th site, the 295-th site, the 308-th site, and the 332-th site; and the 19-th site is mutated into a serine, the 41-th site is mutated into a serine, the 43-th site is mutated into an asparagine, a glycine in the 72-th site is mutated into a leucine, etc.; or the amino acid sequence of the transaminase mutant has the mutation sites in the mutanted amino acid sequence, and has more than 80% homology to the mutanted amino acid sequence.
C12P 13/00 - Préparation de composés organiques contenant de l'azote
C12P 17/12 - Préparation de composés hétérocycliques comportant O, N, S, Se ou Te comme uniques hétéro-atomes du cycle l'azote comme unique hétéro-atome du cycle contenant un hétérocycle à six chaînons
Provided are a transaminase mutant and a method for producing chiral amines using the transaminase mutant. The amino acid sequence of the transaminase mutant is an amino acid sequence obtained after mutation occurs to the amino acid sequence shown in SEQ ID NO: 1, and the mutation at least comprises one of the following mutation sites: 3, 5, 8, 25, 32, 45, 56, 59, 60, 84, 86, 164, 176, 178, 180, 187, 197, 206, 207, 242, 245, 319, and 324.
C12P 17/12 - Préparation de composés hétérocycliques comportant O, N, S, Se ou Te comme uniques hétéro-atomes du cycle l'azote comme unique hétéro-atome du cycle contenant un hétérocycle à six chaînons
C12P 17/10 - Préparation de composés hétérocycliques comportant O, N, S, Se ou Te comme uniques hétéro-atomes du cycle l'azote comme unique hétéro-atome du cycle
C12P 13/00 - Préparation de composés organiques contenant de l'azote
Disclosed are a monooxygenase mutant and use thereof. The amino acid sequence of the monooxygenase mutant is an amino acid sequence obtained by mutating the amino acid sequence as shown in SEQ ID NO: 1. The mutation comprises at least one of the following mutation sites: position 49, position 60, position 61, position 144, position 145, position 146, position 147, position 167, position 169, position 189, position 246, position 247, position 280, position 284, position 285, position 286, position 287, position 328, position 330, position 332, position 382, position 427, position 428, position 429, position 430, position 431, position 432, etc. The monooxygenase mutant has the advantage of greatly improved stereoselectivity, and the enzyme activity is also correspondingly increased.
C12N 15/70 - Vecteurs ou systèmes d'expression spécialement adaptés à E. coli
C12N 1/21 - BactériesLeurs milieux de culture modifiés par l'introduction de matériel génétique étranger
C12P 17/04 - Préparation de composés hétérocycliques comportant O, N, S, Se ou Te comme uniques hétéro-atomes du cycle l'oxygène comme unique hétéro-atome du cycle contenant un hétérocycle à cinq chaînons, p. ex. griséofulvine
C12P 17/00 - Préparation de composés hétérocycliques comportant O, N, S, Se ou Te comme uniques hétéro-atomes du cycle
A transaminase mutant and use hereof, the amino acid sequence of the transaminase mutant is an amino acid sequence in which the amino acid sequence as represented by SEQ ID NO: 1 is mutated, the mutated amino acid position being one or more selected from among F89, K193, P243, V234, I262, Q280, V379, R416, A417 and C418. The enzymatic activity and/or stability of the transaminase mutant is improved.
Provided are a proline hydroxylase and uses thereof. The proline hydroxylase comprises (a) a protein having the amino acid sequence as shown in SEQ ID NO: 2; (b) a protein having an amino acid sequence of SEQ HD NO: 2 with a mutation of one or more amino acids and having a proline hydroxylase activity; or (c) a protein retaining the mutation of one or more amino acids as in (b), and having the proline hydroxylase activity and having at least 78% homology with the amino acid sequence of the protein in (b). Protein having the amino acid sequence as shown in SEQ HD NO: 2 and mutants obtained by genetically engineering have higher catalytic specificity or significantly increased catalytic activity when compared to proline hydroxylases in prior art.
Provided is an amino acid dehydrogenase mutant. The amino acid sequence of the mutant is obtained by mutating the amino acid sequence shown in SEQ ID NO: 1. The mutation comprises at least one of the following mutation sites: 64th, 94th, 133th, 137th, 148th, 168th, 173rd, 183th, 191th, 207th, 229th, 248th, 255th, and 282th sites; or the amino acid sequence of the amino acid dehydrogenase mutant is an amino acid sequence having the mutation sites in the mutated amino acid sequence and having a 80% or more homology with the mutated amino acid sequence. The mutant enzyme activity is more than 50 times higher than that of a wild amino acid dehydrogenase, and the enzyme specificity is also correspondingly improved.
Provided are a transaminase mutant and an application thereof. The amino acid sequence of the transaminase mutant is formed after mutation of the amino acid sequence as shown in SEQ ID NO: 1, and mutated amino acid sites comprise a T7C+S47C site. The transaminase mutant having the mutated sites can be further prepared into an immobilized enzyme by means of immobilization technology, the activity and the stability of the immobilized enzyme are relatively high, and the immobilized enzyme can be recycled for a plurality of times, and is applicable to continuous flow reaction in a packed bed.
A metformin hydrochloride synthesis system and a preparation method therefor, the synthesis system comprising a reaction apparatus (20), the reaction apparatus (20) being provided with a feed opening and a reactant discharge opening, and being used for employing a melting method to synthesise metformin hydrochloride, a spiral discharge component being arranged inside the reaction apparatus, and the spiral discharge component being able to discharge reactants from the reactant discharge opening by means of a spiral extrusion method, thereby solving the problems of the high stirring resistance of solid substances and being unable to implement stirring.
C07C 277/08 - Préparation de la guanidine ou de ses dérivés, c.-à-d. de composés contenant le groupe les atomes d'azote liés par des liaisons simples ne faisant pas partie de groupes nitro ou nitroso de guanidines substituées
C07C 279/26 - X et Y étant des atomes d'azote, c.-à-d. biguanides
B01J 19/20 - Réacteurs fixes avec éléments internes mobiles en forme d'hélice, p. ex. réacteurs à vis
A transaminase mutant and an application thereof, the amino acid sequence of the transaminase mutant is an amino acid sequence in which the amino acid sequence as represented by SEQ ID NO: 1 is mutated, the mutated amino acid position being one or more selected from among F89, K193, P243, V234, I262, Q280, V379, R416, A417 and C418. The enzymatic activity and/or stability of the transaminase mutant is improved.
Disclosed are a transaminase mutant and a use thereof. The amino acid sequence of the transaminase mutant is obtained by the mutation of the amino acid sequence as shown in SEQ ID NO: 1, and the mutation at least comprises one of the following mutation sites: position 19, position 41, position 43, position 72, position 76, position 92, position 107, position 125, position 132, position 226, position 292, position 295, position 308 and position 332; and position 19 is mutated into serine, position 41 is mutated into serine, position 43 is mutated into asparagine, and position 72 is mutated into leucine, etc.; or the amino acid sequence of the transaminase mutant has the mutation sites in the mutant amino acid sequence, and has more than 80% homology to the mutant amino acid sequence.
C07D 401/14 - Composés hétérocycliques contenant plusieurs hétérocycles comportant des atomes d'azote comme uniques hétéro-atomes du cycle, au moins un cycle étant un cycle à six chaînons avec un unique atome d'azote contenant au moins trois hétérocycles
Provided are a proline hydroxylase and an application thereof. The proline hydroxylase includes (a) a protein having the amino acid sequence as shown in SEQ ID NO: 2; (b) a protein in which the amino acid sequence as shown in SEQ ID NO: 2 has gone through mutations of one or more amino acids and which has proline hydroxylase activity; or (c) a protein which retains the mutations of one or more amino acids as in (b), which has having has proline hydroxylase activity and which has at least 78% homology with the amino acid sequence of the protein in (b). Proteins having the amino acid sequence as shown in SEQ ID NO: 2 and mutants obtained by genetically engineering the same have higher catalytic specificity or significantly increased catalytic activity when compared to existing proline hydroxylases.
A method for manufacturing aryl nitriles represented by formula I. The method for manufacturing the compound represented by formula I comprises: using an aryl compound represented by formula II as a starting material; for the compound represented by formula II, n = 0 or 1, and X1, X2, X3, and X4 are independently selected from N, S, O, or C; Y is OSO2F, OTf, or OTs; R1, R2, R3 and R4 are independently selected from any one of H, an alkyl group, an aryl group, or a halide. Nitrilization of the aryl compound is performed using a catalytic effect provided by a catalyst, a reducing agent, and a ligand to obtain the class of aryl nitrile compounds.
A method for preparing a crizotinib intermediate, the method comprising: (1) synthesizing a compound 1 and a compound 2 into a compound 3 by means of flow chemical reaction; (2) synthesizing the compound 3 obtained in step (1) and a boric acid vinegar compound 4 into a crizotinib intermediate I by means of flow chemical reaction. The preparation method results in a high yield, and can be used to greatly reduce the energy consumption and costs in the preparation process of crizotinib. The method is environmental friendly, safe and highly automated, and is suitable for large industrial production. The reaction route is as shown in (i), wherein Y is a leaving group, z is an amino protective group, and x is selected from F, Cl, Br and l.
C07D 401/14 - Composés hétérocycliques contenant plusieurs hétérocycles comportant des atomes d'azote comme uniques hétéro-atomes du cycle, au moins un cycle étant un cycle à six chaînons avec un unique atome d'azote contenant au moins trois hétérocycles
C12P 7/22 - Préparation de composés organiques contenant de l'oxygène contenant un groupe hydroxyle aromatiques
The application provides a Diketoreductase (DKR) mutant, its nucleotide coding sequence, and an expression cassette, recombinant vector and host cell containing the sequence, as well as a method for application of the mutant to the preparation of 3R,5S-dicarbonyl compound. An ee value of the obtained 3R,5S-dicarbonyl compound is higher than 99%, and a de value is about 90%. The DKR mutant is a key pharmaceutical intermediate, and particularly provides an efficient catalyst for synthesis of a chiral dicarbonyl hexanoic acid chain of a statin drug.
C12N 9/04 - Oxydoréductases (1.), p. ex. luciférase agissant sur des groupes CHOH comme donneurs, p. ex. oxydase de glucose, déshydrogénase lactique (1.1)
A polymer containing a carboxyl group, a preparation method and an application thereof, a supported catalyst and a preparation method thereof and preparation methods of penem antibiotic intermediate are disclosed. The polymer has high rigidity and hardness, thus the mechanical properties of the polymer is effectively improved. Meanwhile, in the polymer, the carboxyl group is used as a main functional group, and is used as a carrier to prepare, by means of a coordination reaction between the carboxyl group and a heavy metal, a supported metal catalyst which has better connection stability between the metal and the polymer. The above two factors can improve the stability of the supported metal catalyst, such that the catalyst can be recycled without losing the catalytic activity. Meanwhile, loss of a heavy metal active ingredient and production cost can be reduced.
B01J 31/00 - Catalyseurs contenant des hydrures, des complexes de coordination ou des composés organiques
B01J 31/06 - Catalyseurs contenant des hydrures, des complexes de coordination ou des composés organiques contenant des composés organiques ou des hydrures métalliques contenant des polymères
C07D 477/06 - Préparation à partir de composés contenant déjà les systèmes cycliques ou cycliques condensés, p. ex. par déshydrogénation du cycle, par introduction, élimination ou modification de substituants
C08F 12/32 - Monomères ne contenant qu'un seul radical aliphatique non saturé contenant plusieurs cycles
C08F 12/34 - Monomères contenant plusieurs radicaux aliphatiques non saturés
C08F 212/14 - Monomères contenant un seul radical aliphatique non saturé contenant un cycle substitué par des hétéro-atomes ou des groupes contenant des hétéro-atomes
B01J 23/46 - Ruthénium, rhodium, osmium ou iridium
B01J 31/28 - Catalyseurs contenant des hydrures, des complexes de coordination ou des composés organiques contenant en outre des composés métalliques inorganiques non prévus dans les groupes du groupe du platine, du cuivre ou du groupe du fer
C08J 9/00 - Mise en œuvre de substances macromoléculaires pour produire des matériaux ou objets poreux ou alvéolairesLeur post-traitement
C08J 9/14 - Mise en œuvre de substances macromoléculaires pour produire des matériaux ou objets poreux ou alvéolairesLeur post-traitement utilisant des gaz de gonflage produits par un agent de gonflage introduit au préalable par un agent physique de gonflage organique
A transaminase and a use thereof are provided. The transaminase has the amino acid sequences as shown in SEQ ID NO: 2 or 4, or has at least 80% identity to the amino acid sequences as shown in SEQ ID NO: 2 or 4, or has amino acid sequences which are obtained by the substitution, deletion or addition of one or more amino acids and have an the activity of an omega-transaminase with high stereoselective R-configuration catalytic activity, wherein the high stereoselective refers to the content of one of the stereoisomers being at least about 1.1 times that of the other.
C12P 13/00 - Préparation de composés organiques contenant de l'azote
C12P 17/12 - Préparation de composés hétérocycliques comportant O, N, S, Se ou Te comme uniques hétéro-atomes du cycle l'azote comme unique hétéro-atome du cycle contenant un hétérocycle à six chaînons
The present invention provides a process for preparing nilotinib. The preparation method comprises the steps of: performing a carbonylation and amination reaction with respect to compound A and 3-(4-methyl-1H- imidazol-1-yl)-5-(trifluoromethyl) aniline to obtain an aminated product; and performing an R group deprotection treatment on the aminated product to obtain nilotinib. Compound A has a structure shown in formula I, wherein in formula I, the R group is selected from benzyl, -COCF3, -CHO or -CO2R', and the R' group is a C1-C10 alkyl group, a C1-C3 alkoxy group, or a C7-C19 aralkyl group. The preparation method has a short synthesis route, mild reaction conditions, and uses special materials, thereby improving nilotinib yield while reducing process costs.
C07D 401/14 - Composés hétérocycliques contenant plusieurs hétérocycles comportant des atomes d'azote comme uniques hétéro-atomes du cycle, au moins un cycle étant un cycle à six chaînons avec un unique atome d'azote contenant au moins trois hétérocycles
68.
DOUBLE-CARBONYL REDUCTASE MUTANT AND APPLICATION THEREOF
A double-carbonyl reductase mutant and application thereof. An amino acid sequence of the double-carbonyl reductase mutant is the mutant amino acid sequence coded by SEQ ID NO:9, the mutant amino acid sequence has at least two mutation sites: NO:94, NO:151, NO:231, NO:236 and NO:251, and the I mutation of NO:94 is V, A or G; the V mutation of NO:151 is Q, N or S; the F mutation of NO:231 is W, Y or P; the I mutation of NO:236 is L, V or A; the Q mutation of NO:251 is H, R or K; or the amino acid sequence of the double-carbonyl reductase mutant has the mutation sites in the mutant amino acid sequence, and has greater than 90% homology with the mutant amino acid sequence. The enzymatic activity of the double-carbonyl reductase mutant having the mutation sites is improved substantially.
C12N 9/04 - Oxydoréductases (1.), p. ex. luciférase agissant sur des groupes CHOH comme donneurs, p. ex. oxydase de glucose, déshydrogénase lactique (1.1)
Disclosed are a double-carbonyl reductase, a coding gene of same, and an application thereof. The double-carbonyl reductase is provided with one of the following amino acid sequences: 1) the amino acid sequence of SEQ NO. 1; or, 2) an amino acid sequence having a function of stereoselectively reducing formula (I) into formula (II) and derived from SEQ NO. 1 by means of substitution and/or deletion and/or addition of one or multiple amino acids in the amino acid sequence of SEQ NO. 1, where the amino acid sequence derived from SEQ NO. 1 and SEQ NO. 1 have a sequence similarity of 80% or more, R1 is selected from an aryl, an alkyl, a cycloalkyl, an alkyl-substituted aryl, a halogen-substituted aryl, an aralkyl heterocyclyl, a cyclic heteroalkyl or a cyclic heteroalkyl, and R2 is selected from an alkyl, a cycloalkyl, a haloalkyl or a halocycloalkyl. Employment of the double-carbonyl reductase of the present invention allows for one-step reduction of a dione substrate to prepare 3R,5S-dihydroxy compounds of a single optical purity.
Provided are a double-carbonyl reductase, a coding gene of same, and an application thereof. The double-carbonyl reductase is provided with one of the following amino acid sequences: 1) the amino acid sequence of SEQ ID NO: 1; and, 2) an amino acid sequence having a function for stereoselectively reducing formula (I) into formula (II) and derived from SEQ ID NO: 1 by means of substitution and/or deletion and/or addition of one or multiple amino acids in the amino acid sequence of SEQ ID NO: 1, where the amino acid sequence derived from SEQ ID NO: 1 and SEQ ID NO: 1 have a sequence similarity of 80% or more, R1 is selected from an aryl, an alkyl, a cycloalkyl, an alkyl-substituted aryl, a halogen-substituted aryl, an aralkyl heterocyclyl, a cyclic heteroalkyl or a cyclic heteroalkyl, and R2 is selected from an alkyl, a cycloalkyl, a haloalkyl or a halocycloalkyl. Also provided is a use of the double-carbonyl reductase for reducing a dione substrate to prepare 3R,5S-dihydroxy compounds of a single optical purity.
Disclosed are a double-carbonyl reductase, a coding gene of same, and an application thereof. The double-carbonyl reductase is provided with one of the following amino acid sequences: 1) the amino acid sequence of SEQ NO. 1; and, 2), an amino acid sequence having a function of stereoselectively reducing formula (I) into formula (II) and derived from SEQ NO. 1 by means of substitution and/or deletion and/or addition of one or multiple amino acids in the amino acid sequence of SEQ NO. 1, where the amino acid sequence derived from SEQ NO. 1 and SEQ NO. 1 have a sequence similarity of 80% or more, R1 is selected from an aryl, an alkyl, a cycloalkyl, an alkyl-substituted aryl, a halogen-substituted aryl, an aralkyl heterocyclyl, a cyclic heteroalkyl or a cyclic heteroalkyl, and R2 is selected from an alkyl, a cycloalkyl, a haloalkyl or a halocycloalkyl. Employment of the double-carbonyl reductase of the present invention allows for one-step reduction of a dione substrate to prepare 3R,5S-dihydroxy compounds of a single optical purity.
The present invention relates to a preparation method for a chiral intermediate for use in statins, acquired with chloroacetic acid and benzyl alcohol as starting materials via a series of reactions, namely etherification, condensation, substitution, and asymmetric reduction. The preparation method provided in the present invention has a novel route of synthesis, allows an intermediate compound to be introduced conveniently into the chiral center of a glycol via enzyme reduction, and not only is low in costs, but also is reliable in quality. The route of synthesis provided in the present invention uses raw materials of low costs, has an easy to operate process, and provides a final product of great purity and high yield.
Provided is a double-carbonyl reductase mutant, a nucleotide coding sequence thereof and, comprising the sequence, an expression cassette, a recombinant vector, and a host cell, and a method for using the mutant in preparation of 3R,5S-double carbonyl compounds, where the ee values of the acquired 3R,5S-double-carbonyl compounds are greater than 99%, while the de values of same are approximately 90%. The double-carbonyl reductase mutant is a key pharmaceutical intermediate, and specifically provides a high-efficiency catalyst for synthesis of a chiral dihydroxy hexanoic acid chain of statins.
Provided are an intermediate compound for preparing rosuvastatin calcium and a preparation method of the rosuvastatin calcium. The method comprises: using the foregoing intermediate compound as a raw material, and subjecting the raw material to a step of Wittig reaction, a step of protecting group removal and hydrolysis and a step of calcium salt formation, so as to obtain the rosuvastatin calcium. The product, which is prepared from the intermediate compound, can be substantially enhanced in stereoselectivity and also notably improved in purity and yield; in addition, the method for preparing rosuvastatin calcium from the intermediate compound is simple, convenient and low in cost.
Disclosed is a method for preparing sulfobutyl ether-β-cyclodextrin. The method overcomes shortcomings of the prior art; β-cyclodextrin and 1,4-sulfobutyrolactone are used as raw materials, and a proper amount of organic solvent is introduced into an alkaline aqueous solution, so that the solubility of the 1,4-sulfobutyrolactone is increased, and the synthesis rate of the sulfobutyl ether-β-cyclodextrin is improved. Operations, such as ultrasonic dialysis, active carbon decoloration, freezing and drying, are performed on the obtained product solution, so as to obtain the powder product of sulfobutyl ether-beta-cyclodextrin. The method has a stable process, needs a moderate reaction condition, has good selectivity, and needs simple aftertreatment operations; the obtained product has very high purity and yield, thereby providing a new idea and a method for mass production of sulfobutyl ether-β-cyclodextrin.
POLYMER CONTAINING CARBOXYL GROUP, METHOD FOR PREPARING SAME AND USE THEREOF, METHOD FOR PREPARING SUPPORTED CATALYST AND PENEM ANTIBIOTIC INTERMEDIATES
The present invention discloses a polymer containing a carboxyl group, a method for preparing same and a use thereof, and a method for preparing a supported catalyst and a penem antibiotic intermediate. The polymer is made by polymerizing three monomers with different structures. The carboxyl group-containing polymer is a crosslinked polymer, and the polymer chain contains a large number of phenyl rings, and which can improve the rigidity and hardness of the polymer, thus effectively improving the mechanical properties of the polymer. Meanwhile, in the polymer, the carboxyl groups are used as the main functional groups, and are used as a carrier to prepare a supported metal catalyst, by means of a coordination reaction between the carboxyl groups and heavy metals, which has a better connection stability between the metal and the polymer. The above two factors can improve the stability of the supported metal catalyst, such that the catalyst can be recycled without the loss of the catalytic activity. Meanwhile, they are also able to reduce the loss of the heavy metals active ingredients and reduce production costs.
C08F 220/12 - Esters des alcools ou des phénols monohydriques
C08F 220/64 - AcidesLeurs sels métalliques ou leurs sels d'ammonium
C07D 477/06 - Préparation à partir de composés contenant déjà les systèmes cycliques ou cycliques condensés, p. ex. par déshydrogénation du cycle, par introduction, élimination ou modification de substituants
B01J 31/06 - Catalyseurs contenant des hydrures, des complexes de coordination ou des composés organiques contenant des composés organiques ou des hydrures métalliques contenant des polymères
77.
OMEGA-TRANSAMINASE OF R CONFIGURATION AND USE THEREOF
Provided is an omega-transaminase of R-configuration. The omega-transaminase of R-configuration has the amino acid sequences as shown in SEQ ID NO: 2, or has at least 80% identity to the amino acid sequences as shown in SEQ ID NO: 2, or has the amino acid sequences of proteins which have substituted, deleted or added one or more amino acids and have omega-transaminase activity of a high stereoselectivity R-configuration catalytic activity; and does not have the amino acid sequences encoded by the nucleotide sequence as shown in SEQ ID NO: 4. The high stereoselectivity refers to the content of one of the stereoisomers being at least about 1.1 times that of the other. Also provided is a use of omega-transaminase, which can be useful for highly efficient synthesis of a chiral amine of R-configuration with a relatively high chiral purity, and is therefore suitable for the industrial production of the chiral amines.
Provided is a transaminase and a use thereof. The transaminase has the amino acid sequences as shown in SEQ ID NO: 2 or 4, or has at least 80% identity to the amino acid sequences as shown in SEQ ID NO: 2 or 4, or has amino acid sequences which are obtained by the substitution, deletion or addition of one or more amino acids and have an omega-transaminase activity of a high stereoselectivity R-configuration catalytic activity wherein the high stereoselectivity refers to the content of one of the stereoisomers being at least about 1.1 times that of the other. The transaminase can synthesize a chiral amine of R-configuration with a relatively high chiral purity, and is therefore suitable for the industrial use of the synthesis of chiral amines.
C12P 17/12 - Préparation de composés hétérocycliques comportant O, N, S, Se ou Te comme uniques hétéro-atomes du cycle l'azote comme unique hétéro-atome du cycle contenant un hétérocycle à six chaînons
C12P 13/00 - Préparation de composés organiques contenant de l'azote
The present invention relates to a method for preparing a penem antibiotic intermediate. The method comprises the following steps: step 1: preparing an intermediate compound by means of a Mannich reaction; and step 2: converting the intermediate compound into a penem antibiotic intermediate. The method shortens the reaction period, reduces the cost, and reduces environmental pollution, and reaction materials are easily obtained; and the selectivity and the yield of the method are remarkably improved in comparison with the prior art.
C07D 205/08 - Composés hétérocycliques comportant des cycles à quatre chaînons ne contenant qu'un atome d'azote comme unique hétéro-atome du cycle non condensés avec d'autres cycles comportant une liaison double entre chaînons cycliques ou entre chaînon cyclique et chaînon non cyclique avec un atome d'oxygène lié directement en position 2, p. ex. bêta-lactames
80.
METHOD FOR PREPARING CARBAPENEM INTERMEDIATE β-METHYL-ADC-8
A method for preparing a carbapenem intermediate β-methyl-ADC-8, comprising: (1) a reaction of 2-haloacrylate compounds with N-substituted-4-acyloxyazetidinone under the effect of a metal, or a Mannich reaction of a propionate compound with N-substituted-4-acyloxyazetidinone to obtain an α and β racemic mixture of a compound A; (2) an ozonization reaction of the α and β racemic mixture of the compound A to obtain an α and β racemic mixture of a compound B; and (3) a selective hydrolytic reaction in the presence of an additive by controlling the pH value of the reaction system to obtain β-methyl-ADC-8. The general structural formula of the compound A is formula (A), and the structural formula of the compound B is formula (B).
C07F 7/18 - Composés comportant une ou plusieurs liaisons C—Si ainsi qu'une ou plusieurs liaisons C—O—Si
C07D 205/08 - Composés hétérocycliques comportant des cycles à quatre chaînons ne contenant qu'un atome d'azote comme unique hétéro-atome du cycle non condensés avec d'autres cycles comportant une liaison double entre chaînons cycliques ou entre chaînon cyclique et chaînon non cyclique avec un atome d'oxygène lié directement en position 2, p. ex. bêta-lactames
81.
PREPARATION METHOD FOR INTERMEDIATE 4AA OF IMIPENEM DRUGS
Disclosed is a preparation method for an intermediate 4AA of imipenem drugs. The preparation method comprises: making 4-substituted aniline into an intermediate (A); performing epoxidation on L-threonine to produce (2R, 3R)-epoxy butyric acid; enabling the (2R, 3R)-epoxy butyric acid and the intermediate (A) to undergo a coupling reaction, and obtaining an intermediate (B); enabling the intermediate (B) to undergo a cyclization reaction, and obtaining an intermediate (C); enabling the intermediate (C) to undergo a hydroxyl protection reaction, and obtaining an intermediate (D); enabling the intermediate (D) to be oxidized to form an acetoxy group, and enabling an oxidized product to undergo an ozonation reaction, wherein G is H, F, Cl, Br, a methoxy group, oxethyl or an amino group; X is Cl, Br or I; and R is H, straight chain alkyl of C1-C6, cyclopropyl, isopropyl, tert-butyl, a phenyl group, p-chlorophenyl, o-chlorophenyl, p-bromophenyl, o-bromophenyl, p-methoxyphenyl, o-methoxyphenyl or m-methoxyphenyl. According to the preparation method, raw materials are cheap and easy to obtain, reaction conditions are mild, the conversion rate and the yield rate are high, and the preparation method is suitable for industrial production.
Disclosed in the present invention is a continuous production method of 2-MeTHF (2-methyltetrahydrofuran). The method comprises the following steps: inputting gasified furfural and hydrogen into a first reaction area and conducting primary catalytic hydrogenation reaction; inputting gas output by the first reaction area into a second reaction area and conducting secondary catalytic hydrogenation reaction; and condensing gas output by the second reaction area to obtain the 2-MeTHF; the first reaction area is filled with catalyst for reducing aldehyde groups and the second reaction area is filled with catalyst for aromatic saturated hydrogenation. By using low-toxicity, low-cost and easy-to-obtain catalyst to produce high-purity 2-MeTHF through gas-phase continuous reaction under low pressure or low ambient temperature, the traditional technology having the disadvantages of high pressure, great investment and great risk is changed, and the use of high-toxicity precious metals can be reduced. The production technology is simple, the investment is small, the risk is small, the furfural treatment capacity per unit time is large, the yield is high, the purity of the obtained crude product is high and the impurities are easy to separate.
C07D 307/06 - Composés hétérocycliques contenant des cycles à cinq chaînons comportant un atome d'oxygène comme unique hétéro-atome du cycle non condensés avec d'autres cycles ne comportant pas de liaisons doubles entre chaînons cycliques ou entre chaînons cycliques et chaînons non cycliques avec uniquement des atomes d'hydrogène ou des radicaux ne contenant que des atomes d'hydrogène et de carbone, liés directement aux atomes de carbone du cycle
83.
SYNTHESIS METHOD FOR L-HETEROCYCLIC AMINO ACID AND PHARMACEUTICAL COMPOSITION HAVING SAID ACID
A synthesis method for L-heterocyclic amino acid and a pharmaceutical composition thereof are provided. The method comprises: step a.) preparing heterocyclic keto acid, wherein the heterocycle of the heterocyclic keto acid is selected from a five-membered heterocycle, a six-membered heterocycle, a seven-membered heterocycle, an alkyl-substituted five-membered heterocycle, an alkyl-substituted six-membered heterocycle, and an alkyl-substituted seven-membered heterocycle; step b.) mixing the heterocyclic keto acid with ammonium formate, phenylalanine dehydrogenase, formate dehydrogenase and coenzyme NAD+ to generate L-heterocyclic amino acid, wherein the phenylalanine dehydrogenase amino acid sequence is SEQ ID No. 1. The synthesis method allows for a high conversion rate of raw materials and high chiral selectivity.
C12N 15/63 - Introduction de matériel génétique étranger utilisant des vecteursVecteurs Utilisation d'hôtes pour ceux-ciRégulation de l'expression
A61K 31/381 - Composés hétérocycliques ayant le soufre comme hétéro-atome d'un cycle ayant des cycles à cinq chaînons
A61K 31/444 - Pyridines non condenséesLeurs dérivés hydrogénés contenant d'autres systèmes hétérocycliques contenant un cycle à six chaînons avec l'azote comme hétéro-atome du cycle, p. ex. amrinone
A61K 31/4409 - Pyridines non condenséesLeurs dérivés hydrogénés substituées uniquement en position 4, p. ex. isoniazide, iproniazide
A61K 31/4402 - Pyridines non condenséesLeurs dérivés hydrogénés substituées uniquement en position 2, p. ex. phéniramine, bisacodyl
A61K 31/4406 - Pyridines non condenséesLeurs dérivés hydrogénés substituées uniquement en position 3, p. ex. zimeldine
The present invention provides a synthesis method for L-cyclic alkyl amino acid and a pharmaceutical composition having said acid. Said synthesis method comprises: step a.) preparing a cyclic alkyl keto acid or cyclic alkyl keto acid salt having structural formula (I) or structural formula (II), and step b.) mixing cyclic alkyl keto acid or cyclic alkyl keto acid salt with ammonium formate, leucine dehydrogenase, formate dehydrogenase and coenzyme NAD+, and carrying out a reductive amination reaction to generate L-cyclic alkyl amino acid, wherein in structural formula (I), n1≥1, m1≥0, and M1 is H or a monovalent cation, and in structural formula (II), n2≥0, m2≥0, M2 is H or a monovalent cation, and the leucine dehydrogenase amino acid sequence is SEQ ID No. 1. Using a specific leucine dehydrogenase with formate dehydrogenase and coenzyme NAD+ to enable a reductive amination reaction of cyclic alkyl keto acid so as to generate L-cyclic alkyl amino acid allows for a high conversion rate of raw materials and high chiral selectivity.
C12P 17/06 - Préparation de composés hétérocycliques comportant O, N, S, Se ou Te comme uniques hétéro-atomes du cycle l'oxygène comme unique hétéro-atome du cycle contenant un hétérocycle à six chaînons, p. ex. fluorescéine
A61K 31/351 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle non condensés avec un autre cycle
A61K 31/195 - Acides carboxyliques, p. ex. acide valproïque ayant un groupe amino
85.
METHOD FOR SYNTHESIZING SAPROPTERIN DIHYDROCHLORIDE
Disclosed is a method for synthesizing sapropterin dihydrochloride. The present invention reduces a synthesis route of the sapropterin dihydrochloride, and resolves a racemate intermediate or an intermediage having a low antimer isomerism value by using a chiral resolving reagent, thereby obtaining an intermediate having a high antimer isomerism value. Raw materials are cheap and readily available, and the cost is significantly reduced, hence providing an effective scheme for mass industrial production of the sapropterin dihydrochloride.
C07D 475/04 - Composés hétérocycliques contenant des systèmes cycliques ptéridine avec un atome d'oxygène lié directement en position 4 avec un atome d'azote lié directement en position 2
86.
METHOD FOR SYNTHESIZING SAPROPTERIN DIHYDROCHLORIDE
Disclosed is a method for synthesizing sapropterin dihydrochloride. The present invention reduces a synthesis route of the sapropterin dihydrochloride, introduces a tetrahydrofuran solution as a catalyst in an asymmetric synthesis manner, a chiral center of the tetrahydrofuran solution using a samarium catalyst, and obtains a target compound having a high antimer isomerism value by means of selective catalysis. The yield is improved, raw materials are cheap and readily available, and the cost is significantly reduced, hence providing an effective scheme for mass industrial production of the sapropterin dihydrochloride.
C07D 475/04 - Composés hétérocycliques contenant des systèmes cycliques ptéridine avec un atome d'oxygène lié directement en position 4 avec un atome d'azote lié directement en position 2
87.
CONTINUOUS OZONATION REACTION DEVICE AND OPERATING METHOD THEREFOR
A continuous ozonation reaction device comprising a feed inlet (111), a feed distribution unit, one or more single reaction tube(s) (30), a product outlet (171) and gas inlets (131, 173). The first end of the feed distribution unit is connected to the feed inlet (111); the second end of the feed distribution unit is connected to the first end of the one or more single reaction tube(s) (30); the product outlet (171) is connected to the second end of the single reaction tube(s) (30), and the gas inlets (131, 173) convey ozone to the single reaction tube(s) (30). Also provided is an operating method of the continuous ozonation reaction device. The continuous ozonation reaction device realizes continuous large-scale production of ozonation reaction on the premise of ensuring safety.
B01J 8/06 - Procédés chimiques ou physiques en général, conduits en présence de fluides et de particules solidesAppareillage pour de tels procédés avec des particules immobiles, p. ex. dans des lits fixes dans des réacteurs tubulairesProcédés chimiques ou physiques en général, conduits en présence de fluides et de particules solidesAppareillage pour de tels procédés avec des particules immobiles, p. ex. dans des lits fixes les particules solides étant disposées dans des tubes
B01J 19/24 - Réacteurs fixes sans élément interne mobile
B01J 10/00 - Procédés chimiques généraux faisant réagir un liquide avec des milieux gazeux autrement qu'en présence de particules solidesAppareillage spécialement adapté à cet effet
C02F 1/78 - Traitement de l'eau, des eaux résiduaires ou des eaux d'égout par oxydation au moyen d'ozone
brevets
