Provided are a transaminase mutant and an application thereof. The transaminase mutant has an amino acid mutation based on a sequence shown in SEQ ID NO: 1, the amino acid mutation being a single position mutation from among W60Y, Y168A, V379W, V379L, V379M, C418Q and C418W or a combination thereof. The activity, stability, and tolerance to temperature, pH and organic solvents of such transaminase mutants are improved. The present application solves the problem of poor tolerance of extreme environments by transaminase in the prior art, and is suitable for the field of enzyme engineering.
The present invention provides a method for synthesizing a fluorine-containing chiral amine compound. The method comprised: reacting an amino donor with a fluorine-containing dihydroxy ketal compound under a catalysis of a transaminase to generate the fluorine-containing chiral amine compound, wherein the transaminase is derived from a plurality of strains. The transaminase of the present application has substrate specificity on the fluorine-containing dihydroxy ketal compound, and may effectively catalyze this type of the substrate to be converted into the fluorine-containing chiral amine compound. In addition, the transaminase has catalytic activity on a plurality of the fluorine-containing dihydroxy ketal compounds, and is relatively high in reaction selectivity and activity. The method catalyzed by the bio-enzyme is not only short in route, but also high in product yield, and the production using the method reduces cost, organic solvents and three wastes.
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 17/10 - 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 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
3.
Amination Method for Polystyrene-type Resin, and Method for Immobilizing Enzyme Using Aminated Resin
Provided is an amination method for a polystyrene-type resin, and a method for immobilizing an enzyme using an aminated polystyrene-type resin. The amination method includes: in a solvent, a catalyst is used to catalyze a polystyrene-type resin and an enamine salt to perform a Friedel-Crafts alkylation reaction, to obtain an aminated polystyrene-type resin, herein the catalyst is a Lewis acid catalyst. By means of the Friedel-Crafts alkylation reaction, the enamine salt is grafted onto the polystyrene-type resin, and the polystyrene-type resin is aminated. The conditions of the Friedel-Crafts alkylation reaction are easy to control, the post-treatment process is simple, and it is only necessary to remove the catalyst and the unreacted enamine salt by washing. Therefore, the above amination method in the present application has few steps and is simple and easy to implement. Meanwhile, the amination method further avoids the use of a noble metal catalyst, thereby reducing production cost. When the obtained polystyrene resin is used as an enzyme immobilization carrier, good immobilization effect and usability are achieved. This method also provides a new class of enzyme immobilization carriers to the current library.
C08F 8/32 - Introduction d'atomes d'azote ou de groupes contenant de l'azote par réaction avec des amines
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
4.
Enzyme Immobilization Carrier and Preparation Method thereof, Immobilized Enzyme and Preparation Method thereof
The application provides an enzyme immobilization carrier and a preparation method thereof, an immobilized enzyme and a preparation method thereof. The above enzyme immobilization carrier is obtained by an amino modification or a cyanuric chloride modification of super-crosslinked polyvinyl alcohol. The use of the enzyme immobilization carrier provided by the application may effectively improve the stability and reusability of the immobilized enzyme. Moreover, due to the use of the form of enzyme covalent linkage, compared with an embedding method, the preparation method is no need for chemical reagent immersion and the like, it is beneficial to maintain the own activity of the enzyme, and promote the immobilized enzyme to have the better activity while the stability and reusability are kept.
The preparation method for a polypeptide includes the steps of constructing an engineering strain for fusion-expressing a polypeptide gene with a Sumo tag, and inducing the engineering strain for the soluble expression of a polypeptide, obtaining a crude protein containing a polypeptide precursor from the engineering strain by purification, cleaving the crude protein containing the polypeptide precursor by a Ulp1 protease to remove the Sumo tag, and purifying a cleavage product of the Ulp1 protease by a method of acetonitrile combined with heating precipitation or a method of precipitation with hexafluoro isopropanol to obtain the polypeptide.
Provided are transaminase mutants and uses thereof. The transaminase mutant is obtained by one or more amino acid mutations occurring in SEQ ID NO: 2 or is a mutant with a conserved amino acid mutation obtained by taking the sequence SEQ ID NO: 1 of a wild-type CvTA transaminase as a reference. Compared with wild-type transaminases, the catalytic activity of the mutant is improved to different degrees, so that the production efficiency of chiral amine compound synthesis may be improved.
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
C12P 17/14 - Préparation de composés hétérocycliques comportant O, N, S, Se ou Te comme uniques hétéro-atomes du cycle l'azote ou l'oxygène comme hétéro-atome du cycle et dans le même cycle au moins un autre hétéro-atome différent
7.
CONTINUOUS POST-TREATMENT METHOD AND DEVICE FOR PENEM COMPOUND
Provided are a continuous post-treatment method and device for a penem compound. The method includes the following steps: S1, performing continuous extraction on a reaction crude product of a penem compound, to obtain an extraction heavy phase and an extraction light phase; S2, performing continuous solid-liquid separation on the extraction heavy phase, to obtain a liquid phase separation product; S3, performing continuous pH adjustment on the liquid phase separation product until a pH value thereof is 6.1-6.3, to obtain pH-adjusted solution; and S4, performing continuous crystallization treatment on the pH-adjusted solution by a first crystallization solvent, to obtain a penem compound product. The use of the method for the post-treatment of the reaction crude product of the penem compound has the advantages of high treatment speed and high efficiency, and stable material properties and a low deterioration rate during the treatment, and has better control over the yield and purity of a target product.
Provided is a method for synthesizing a chiral amine compound. A transaminase is used to transaminate a ketone substrate under the action of an amino donor, to obtain the chiral amine compound; and the conserved amino acid sequence region of the transaminase at least includes a region 1 (MAGLWCVN) and a region 2 (YNTFFKT). With the transaminase with the specific conserved amino acid sequence region to synthesize a large sterically hindered chiral amine, the enzyme catalytic reaction volume is small, the synthesizing route is short, the product yield is high, a high-cost noble metal is not required for catalysis under the synthesizing conditions, three wastes are reduced, and the production cost is saved.
C12P 17/14 - Préparation de composés hétérocycliques comportant O, N, S, Se ou Te comme uniques hétéro-atomes du cycle l'azote ou l'oxygène comme hétéro-atome du cycle et dans le même cycle au moins un autre hétéro-atome différent
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
9.
METHOD FOR PREPARING OLIGONUCLEOTIDE BY USING RNA LIGASE
Provided is a method for preparing an oligonucleotide by using an RNA ligase. The RNA ligase includes any one or more enzymes of the RNA ligase families Rnl1, Rnl2, Rnl3, and Rnl5, and the oligonucleotide includes natural RNA or non-natural RNA. The method can solve the problem that in the prior art, it is difficult to efficiently synthesize non-natural RNA chains, and the method is suitable for the field of RNA synthesis.
The present invention provides a monooxygenase mutant and use thereof. The monooxygenase mutant comprises (a) a protein having an amino acid sequence set forth in SEQ ID NO: 1; or (b) a protein that undergoes an amino acid mutation at at least one site among W60, Y65, D71, Y77, D163, V166, S178, T179, T199, G200, S201, and R222 of the amino acid sequence from (a) and has monooxygenase functions; and (c) a protein having 80% or more homology with the amino acid sequence defined in any one of (a) and (b) and having monooxygenase functions. The present invention can address the problem of low monooxygenase activity in the prior art and applies to the field of enzyme catalysis.
C12N 15/70 - Vecteurs ou systèmes d'expression spécialement adaptés à E. coli
C12N 1/21 - Bactéries; Leurs milieux de culture modifiés par l'introduction de matériel génétique étranger
C12P 11/00 - Préparation de composés organiques contenant du soufre
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 17/00 - Préparation de composés hétérocycliques comportant O, N, S, Se ou Te comme uniques hétéro-atomes du cycle
The present invention relates to an aminoacyl-tRNA synthase mutant and use thereof. The aminoacyl-tRNA synthase mutant is obtained by means of mutation of an amino acid sequence represented by SEQ ID NO: 19, the mutation at least comprising the following mutation site: I at position 159 is mutated into a hydroxyl-containing amino acid, a basic amino acid or a non-polar amino acid. By means of a method of site-directed mutation, the amino acid sequence is changed, realizing the alteration of the protein structure and function; the mutant has relatively high activity and specificity, so that the mutant can be used for realizing efficient and site-directed introduction of non-natural amino acids in proteins.
A method for enzyme-catalyzed synthesis of a purine nucleoside and a composition. The method utilizes a purine nucleoside phosphorylase and any one of the following enzymes: a pyrimidine nucleoside phosphorylase or a thymidine phosphorylase, which catalyze substrates to synthesize the purine nucleoside; the substrates comprise a substrate nucleoside and a substrate base; the pyrimidine nucleoside phosphorylase comprises PyNP, and PyNP is a protein represented by SEQ ID NO: 1; the thymidine phosphorylase comprises TP, and the TP is a protein represented by SEQ ID NO: 2; the purine nucleoside phosphorylase comprises PNP, and the PNP is a protein represented by SEQ ID NO: 3. The present invention can solve the problem of low yield of purine nucleosides synthesized by means of an enzyme method in the prior art, and is suitable for 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
The present invention provides an immobilized enzyme, a preparation method therefor, and use thereof. The immobilized enzyme comprises an epoxy resin carrier and an enzyme. The enzyme is connected to the epoxy resin carrier by means of a covalent bond. The epoxy resin carrier is LX-109S epoxy resin. The present application uses the LX-109S epoxy resin as the epoxy resin carrier, such that on the basis of the characteristics of the carrier itself, the immobilization effect of the carrier on the enzyme is more stable, and the covalent bond between the carrier and the enzyme is firmly bound, without affecting the activity of the enzyme itself.
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
A continuous amide hydrogenation reduction method. The method comprises the following steps: under the action of a homogeneous catalyst, performing a continuous hydrogenation reduction reaction on an amide and hydrogen in a solvent to obtain a hydrogenation reduction product of the amide, wherein the temperature of the continuous hydrogenation reduction reaction is 100-350 °C, the structural formula of the amide is aa, and the structural formula of the hydrogenation reduction product of the amide is bb.
C07D 209/52 - Composés hétérocycliques contenant des cycles à cinq chaînons condensés avec d'autres cycles, ne comportant qu'un atome d'azote comme unique hétéro-atome du cycle condensés avec un carbocycle condensés avec un cycle autre qu'un cycle à six chaînons
C07D 211/76 - Atomes d'oxygène liés en position 2 ou 6
C07D 211/02 - Préparation par cyclisation ou hydrogénation
C07D 207/267 - Pyrrolidones-2 avec uniquement des atomes d'hydrogène ou des radicaux ne contenant que des atomes d'hydrogène et de carbone, liés directement aux autres atomes de carbone du cycle avec uniquement des atomes d'hydrogène ou des radicaux ne contenant que des atomes d'hydrogène et de carbone, liés directement à l'atome d'azote du cycle
C07D 209/46 - Iso-indoles; Iso-indoles hydrogénés avec un atome d'oxygène en position 1
Provided are a transaminase mutant and use thereof, wherein the transaminase mutant is obtained by mutation of an amino acid sequence set forth in SEQ ID NO: 1, the mutation at least comprising: T291A; or the amino acid sequence of the transaminase mutant has the mutation site in the mutated amino acid sequence, and has 80% or more homology, preferably 85% homology, and more preferably 90% homology to the mutated amino acid sequence. The transaminase mutant expands the substrate spectrum of the enzyme and improves the stereoselectivity, such that the catalytic capability of the enzyme to a large-steric-hindrance substrate is improved. Meanwhile, the stability of the enzyme is enhanced, such that a catalytic reaction can be carried out under the conditions of a high-concentration solvent and a high temperature to produce chiral amine.
Provided are a transaminase mutant and an application thereof. Compared with an amino acid sequence shown in SEQ ID NO:1, an amino acid sequence of the transaminase mutant includes at least one of the following mutation sites: L166, K149, K146, A168, H73, F133, H82, E24, V194, T294, A295, G235 and F236. The mutant of the present invention has the improved catalytic activity for a transammonization reaction of ketone substrates, and is suitable for industrial production of chiral amines.
Provided are a transaminase mutant and use thereof. The transaminase mutant has an amino acid sequence obtained by mutation of an amino acid sequence shown in SEQ ID NO:1, the mutation at least includes one of the following mutation site combinations: T7C+S47C, Q78C+A330C, V137C+G313C, A217C+Y252C and L295C+C328C; or the transaminase mutant has an amino acid sequence which has the mutation sites in the mutated amino acid sequence and has 80% or more identity with the mutated amino acid sequence. The transaminase mutant realizes the change of protein structure and functions, reduces the enzyme amount, increases the enantiomeric excess (ee) value of a product, and reduces the difficulty of post-processing, so that the transaminase mutant may be suitable for industrial production.
Disclosed are a transaminase mutant and the use thereof, wherein the transaminase mutant has a sequence formed after an amino acid mutation occurs in the sequence shown in SEQ ID NO: 1, wherein the site at which the amino acid mutation occurs includes a V242W site. On the basis of transaminase shown in SEQ ID NO: 1, the transaminase mutant undergoes mutation by means of a site-directed mutation method, thereby changing the amino acid sequence of transaminase and achieving changes in protein structure and function, and then the transaminase with the above-mentioned mutation site is obtained by means of a directed screening method. The obtained transaminase has relatively high catalytic activity, specific selectivity, wide substrate spectra and broad industrial prospects.
C12N 1/21 - Bactéries; Leurs milieux de culture modifiés par l'introduction de matériel génétique étranger
C12N 1/19 - Levures; Leurs 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 13/00 - Préparation de composés organiques contenant de l'azote
C12P 17/00 - Préparation de composés hétérocycliques comportant O, N, S, Se ou Te comme uniques hétéro-atomes du cycle
Provided is a method for synthesizing a chiral diamine compound. The synthesizing method includes: converting a substrate represented by Formula I into a chiral diamine compound in Formula I by using a transaminase, herein n=1˜10, an R group represents an alkyl, a cycloalkyl, a heteroatom-containing alkyl, a heteroatom-containing cycloalkyl, a heteroatom-containing aryl, an amide compound residue, or an ether compound residue, and a hetero atom is at least one from among O, S and N; R1 and R2 are the same or not the same, the R1 and R2 are respectively and independently hydrogen, a C1-C3 alkyl, or an amino protecting group; and the transaminases are derived from a plurality of strains.
C12P 13/00 - Préparation de composés organiques contenant de l'azote
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 17/12 - 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 an application thereof. The transaminase mutant has an amino acid mutation based on a sequence shown in SEQ ID NO: 1, the amino acid mutation being a single position mutation from among W60Y, Y168A, V379W, V379L, V379M, C418Q and C418W, or a combination thereof. The activity, stability, and tolerance to temperature, pH and organic solvents of such transaminase mutants are improved. The present invention solves the problem of poor tolerance of extreme environments by transaminase in the prior art, and is suitable for the field of enzyme engineering.
C12N 11/14 - Enzymes ou cellules microbiennes immobilisées sur ou dans un support inorganique
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
21.
NEW CRYSTALLINE FORM OF ERTAPENEM SODIUM AND PREPARATION METHOD THEREFOR
Provided are a new crystalline form of ertapenem sodium and a preparation method therefor. The powder X-ray diffraction diagram of the new crystalline form of ertapenem sodium contains 27 principal characteristic peaks. The ertapenem sodium of the present invention has a rod-like crystalline form with a large particle size, does not easily aggregate and is easier to dry out. Products having high crystallinity and purity may be obtained by a simple drying process. Furthermore, the new crystalline form of the present invention is more stable, and the crystalline form may remain unchanged to a maximum extent during a subsequent washing and drying process, so that the purity of the product may be further improved. In addition, since the new crystalline form of ertapenem sodium of the present invention has a relatively large particle size and good stability, it is easier to produce on a factory scale, so that it is possible to obtain ertapenem sodium products with a high purity and a high yield.
Provided are an esterase mutant and the use thereof. The esterase mutant obtained by means of rational design and several rounds of evolution screening with enzymes on the basis of an amino acid sequence as shown in SEQ ID NO: 1 is changed in terms of protein structure and functions compared with a wild-type esterase; in practical use, the catalytic activity and/or stereoselectivity of the esterase mutant is greatly improved; and when a system contains some organic cosolvents, the esterase mutant still has relatively stable catalytic activity and/or stereoselectivity. In addition, the improvement of the catalytic activity and/or stereoselectivity of the esterase mutant reduces the use amount of the enzyme to a certain extent and reduces the difficulty of post-treatment, and therefore the esterase mutant is suitable for industrial production.
Disclosed are an etelcalcetide intermediate and a method for synthesizing etelcalcetide. The etelcalcetide intermediate is Fmoc-D-Cys(S—S—(N-Boc)-L-Cys(OtBu))-OH. The method for synthesizing the etelcalcetide includes the following steps: using N-Boc-L-Cqs-OtBu as a starting material to generate a primary product of a formula (A) by means of a substitution reaction, herein R is S-Py or Cl; and performing a coupling reaction on the primary product and Fmoc-D-Cys-OH amino acid to obtain Fmoc-D-Cys(S—S—(N-Boc)-L-Cys(OtBu))-OH. The key intermediate is used for synthesizing the etelcalcetide, which may improve the purity and the yield. It is important that the raw materials for synthesizing the key intermediate are cheap and readily available, and the process is simple.
Disclosed are an etelcalcetide intermediate and a method for synthesizing etelcalcetide. The etelcalcetide intermediate is Fmoc-D-Cys(S—S—(N-Boc)-L-Cys(OtBu))-OH. The method for synthesizing the etelcalcetide includes the following steps: using N-Boc-L-Cqs-OtBu as a starting material to generate a primary product of a formula (A) by means of a substitution reaction, herein R is S-Py or Cl; and performing a coupling reaction on the primary product and Fmoc-D-Cys-OH amino acid to obtain Fmoc-D-Cys(S—S—(N-Boc)-L-Cys(OtBu))-OH. The key intermediate is used for synthesizing the etelcalcetide, which may improve the purity and the yield. It is important that the raw materials for synthesizing the key intermediate are cheap and readily available, and the process is simple.
Provided is a ketoreductase mutant and a method for producing chiral alcohol using the same. The ketoreductase mutant has a sequence with amino acid mutations in the sequence shown in SEQ ID NO:1. The mutation sites include at least one of the following positions: 6th position, 21st position, 42nd position, 58th position, 61st position, 76th position, 87th position, 94th position, 96th position, 108th position, 113th position, 117th position, 144th position, 146th position, 147th position, 149th position, 151st position, 152nd, 156th position, 165th position, 177th position, and 198th position.
A preparation method for a polypeptide, the preparation method comprising the following steps: constructing an engineering strain of a Sumo tag fusion expression polypeptide gene, and inducing the engineering strain for the soluble expression of a polypeptide; purifying a crude protein containing a polypeptide precursor from the engineering strain; digesting the crude protein containing the polypeptide precursor by using Ulp1 protease to remove the Sumo tag; purifying a cleavage product of the Ulp1 protease by means of acetonitrile combined with heating precipitation or by using a method for hexafluoroisopropanol precipitation, so as to obtain the polypeptide. Efficient technology based on the soluble recombinant expression of a medicinal polypeptide or a precursor thereof has been established, a simple purification process based on one-step precipitation purification has been established, and further in combination with HPLC purification, a polypeptide purity of more than 97% can be achieved.
Provided is a continuous synthesis method for ethoxymethylenemalononitrile. The method includes the following steps: malononitrile, triethyl orthoformate and acetic anhydride are continuously fed into a continuous reaction device to perform a condensation reaction, to obtain the ethoxymethylenemalononitrile, and in the process of the condensation reaction, the generated ethoxymethylenemalononitrile is continuously discharged; herein, the molar ratio of the malononitrile, the triethyl orthoformate and the acetic anhydride is 1:(0.9-6.0):(2.0-6.0). By adopting the continuous reaction device in the present disclosure, since the amount of materials involved in the reaction per unit time is greatly reduced, a high temperature dangerous area is reduced, and a safety risk is greatly reduced. In addition, through the continuous reactor, the raw materials may be transiently heated to the reaction temperature, so that the decomposition of the raw materials caused by the long-time heating process is avoided, and the yield is significantly improved. Moreover, in the reaction process of the present disclosure, there is no need for a second-class toxic solvent such as a toluene.
C07C 255/15 - Nitriles d'acides carboxyliques ayant des groupes cyano liés à des atomes de carbone acycliques contenant des groupes cyano et des atomes d'oxygène, liés par des liaisons simples, liés au même squelette carboné acyclique non saturé
27.
AMINATION METHOD FOR POLYSTYRENE RESIN, AND METHOD FOR IMMOBILIZING ENZYME USING AMINATED RESIN
Provided are an amination method for a polystyrene resin, and a method for immobilizing an enzyme using an aminated polystyrene resin. The amination method comprises: in a solvent, using a catalyst to catalyze a polystyrene resin and an enamine salt to carry out Friedel–Crafts alkylation reaction to obtain an aminated polystyrene resin, wherein the catalyst is a Lewis acid catalyst. By means of the Friedel–Crafts alkylation reaction, the enamine salt is grafted onto the polystyrene resin, and the polystyrene resin is aminated. The conditions of the Friedel–Crafts alkylation reaction are easy to control, the post-treatment process is simple, and it is only necessary to remove the catalyst and the unreacted enamine salt by washing, such that the amination method has few steps and is simple and easy to implement; meanwhile, the amination method further avoids the use of a noble metal catalyst, thereby reducing the production cost. When the obtained polystyrene resin is used as an enzyme immobilization carrier, a good immobilization effect and the usability are achieved, and an enzyme immobilization carrier library is greatly expanded.
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
28.
ENZYME IMMOBILIZATION CARRIER AND PREPARATION METHOD THEREFOR, IMMOBILIZED ENZYME AND PREPARATION METHOD THEREFOR
Provided are an enzyme immobilization carrier, an immobilized enzyme and a preparation method therefor. The enzyme immobilization carrier is obtained by amino modification or cyanuric chloride modification of hyper-crosslinked polyvinyl alcohol. By utilizing the enzyme immobilization carrier provided by the present invention, the stability and reusability of the immobilized enzyme can be effectively improved. Due to an enzyme covalent linkage form, compared with an embedding method, the method has the advantages that chemical reagent soaking is not needed, the activity of the enzyme is favorably maintained, and the immobilized enzyme is promoted to have better activity while being stable and reusable.
Disclosed are a borohydride reduction stabilizing system and a method for reducing an ester to an alcohol. The borohydride reduction stabilizing system includes: a borohydride reducing agent and a stabilizing agent for stabilizing the borohydride reducing agent. The borohydride reducing agent is sodium borohydride or potassium borohydride. The stabilizing agent is an alkali metal salt of an alcohol. By adding the alkali metal salt of the alcohol, such as sodium alkoxide or potassium alkoxide, on the basis of an existing sodium/potassium borohydride reducing agent, the sodium/potassium borohydride reducing agent may be kept stable without being decomposed under the condition of increased temperature, so that on the one hand, the reducing activity is maintained in a relatively high state, and the condition of excessive use is reduced, and on the other hand, the generation of hydrogen is reduced, and the process risks are reduced.
C07C 29/147 - 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 réduction d'un groupe fonctionnel contenant de l'oxygène de groupes contenant C=O, p.ex. —COOH d'acides carboxyliques ou de leurs dérivés
C07B 41/02 - Formation ou introduction de groupes fonctionnels contenant de l'oxygène de groupes hydroxy ou O-métal
Provided is a method for synthesizing a chiral amine compound. An amino reaction is performed on a ketone substrate by means of a transaminase under the action of an amino donor, and the chiral amine compound is obtained. A conserved amino acid sequence region of the transaminase at least comprises region 1, MAGLWCVN, and region 2, YNTFTKT. By using a transaminase with a specific conserved amino acid sequence region to synthesize the large steric hindrance chiral amine, the enzyme catalytic reaction volume is small, the synthesis route is short, the product yield is high, catalysis by means of a high-cost noble metal is not required under the synthesis condition, the three wastes are reduced, and the production cost is saved.
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
C12P 17/14 - Préparation de composés hétérocycliques comportant O, N, S, Se ou Te comme uniques hétéro-atomes du cycle l'azote ou l'oxygène comme hétéro-atome du cycle et dans le même cycle au moins un autre hétéro-atome différent
Provided are a transaminase mutant and an application thereof. The transaminase mutant is obtained by mutating one or more amino acids in SEQ ID NO: 2 or is a mutant obtained by taking the sequence SEQ ID NO: 1 of wild-type CVTA transaminase as a reference and mutating conserved amino acids therein. Compared with wild-type transaminases, the catalytic activity of the mutant is improved to different degrees, so that the production efficiency of chiral amine compound synthesis can be improved.
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
C12P 17/14 - Préparation de composés hétérocycliques comportant O, N, S, Se ou Te comme uniques hétéro-atomes du cycle l'azote ou l'oxygène comme hétéro-atome du cycle et dans le même cycle au moins un autre hétéro-atome différent
32.
Method and device for continuously synthesizing cyclopropane compounds
The present disclosure discloses a method and a device for continuously synthesizing cyclopropane compounds. The method includes the following steps: continuously performing a synthetic reaction of a diazomethane precursor in a first reactor, the reaction product of the first reactor flowing into a separator for stratification, the organic phase obtained by stratification overflowing into a second reactor, continuously consuming the diazomethane precursor in a second reactor to prepare diazomethane and performing an electron-rich monoolefin cyclopropanation reaction in situ so as to obtain the cyclopropane compound.
C07C 2/86 - Préparation d'hydrocarbures à partir d'hydrocarbures contenant un plus petit nombre d'atomes de carbone par condensation d'un hydrocarbure et d'un non-hydrocarbure
Provided is a preparation process of diazomethane. The preparation process includes: step S1, taking N-methylurea as a raw material to continuously prepare, in a continuous reactor, a first product system containing N-methyl-N-nitrosourea: step S2, performing continuous extraction and continuous back-extraction on the first product system to obtain an N-methyl-N-nitrosourea solution; step S3, enabling the N-methyl-N-nitrosourea solution to continuously react with an alkaline solution in a continuous reactor to obtain a second product system containing the diazomethane; and step S4, performing continuously liquid separation, water freezing and removal on the second product system, to obtain the diazomethane.
An amino acid sequence of the monooxygenase mutant is obtained by mutation of an amino acid sequence shown in SEQ ID NO: 1, and the mutation at least includes one of the following mutation sites: 45-th site, 95-th site, 106-th site, 108-th site, 114-th site, 186-th site, 190-th site, 191-th site, 249-th site, 257-th site, 393-th site, 436-th site, 499-th site, 500-th site, 501-th site, 503-th site, 504-th site, 559-th site, and 560-th site.
Provided in the present invention are a transaminase mutant and use thereof. Compared with an amino acid sequence shown in SEQ ID NO: 1, an amino acid sequence of the transaminase mutant comprises at least one of the following mutation sites: L166, K149, K146, A168, H73, F133, H82, E24, V194, T294, A295, G235 and F236. The mutant of the present invention has an improved catalytic activity for a transammonization reaction of ketone substrates, and is suitable for industrial production of chiral amines.
Provided is a method for synthesizing a chiral diamine compound. The synthesizing method comprises: converting a substrate represented by formula I into a formula I chiral diamine compound by using transaminases, wherein n=1-10, an R group represents an alkyl group, a cycloalkyl group, a heteroatom-containing alkyl group, a heteroatom-containing cycloalkyl group, a heteroatom-containing aryl group, an amide compound residue, or an ether compound residue, and a hetero atom is at least one from among O, S and N; R1 and R2 are the same or not the same, the R1 and R2 are respectively and independently hydrogen, C1-C3 alkyl groups, or amino protecting groups; and the transaminases are derived from a plurality of strains, Said transaminases all have a relatively high reaction selectivity and activity on various substrates represented by formula 1. By catalyzing and synthesizing a chiral diamine compound by using said biological enzyme, not only is the substrate scope wider, but the route also short and product yield high, thus greatly reducing production costs and reducing the production of an organic solvent and the three wastes.
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
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
The present invention provides a synthesis method for a fluorine-containing chiral amine compound. The synthesis method comprises: reacting an amino donor with a fluorine-containing dihydroxy ketal compound under the catalysis of transaminase to generate a fluorine-containing chiral amine compound, wherein the transaminase is derived from a plurality of strains. The transaminase of the present application has substrate specificity on the fluorine-containing dihydroxy ketal compound, can effectively catalyze the substrate to be converted into the fluorine-containing chiral amine compound, has catalytic activity on multiple fluorine-containing dihydroxy ketal compounds, and is relatively high in reaction selectivity and activity. The bio-enzyme catalytic synthesis method is not only short in route, but also high in product yield, the production cost is greatly reduced, and the production of organic solvents and three wastes is reduced.
C07C 319/20 - Préparation de thiols, de sulfures, d'hydropolysulfures ou de polysulfures de sulfures par des réactions n'impliquant pas la formation de groupes sulfure
C07C 323/25 - Thiols, sulfures, hydropolysulfures ou polysulfures substitués par des halogènes, des atomes d'oxygène ou d'azote ou par des atomes de soufre ne faisant pas partie de groupes thio contenant des groupes thio et des atomes d'azote, ne faisant pas partie de groupes nitro ou nitroso, liés au même squelette carboné ayant les atomes de soufre des groupes thio liés à des atomes de carbone acycliques du squelette carboné le squelette carboné étant acyclique et saturé
C07C 211/29 - Composés contenant des groupes amino liés à un squelette carboné ayant des groupes amino liés à des atomes de carbone acycliques d'un squelette carboné non saturé contenant au moins un cycle aromatique à six chaînons le squelette carboné étant substitué de plus par des atomes d'halogène ou par des groupes nitro ou nitroso
C07C 231/12 - Préparation d'amides d'acides carboxyliques par des réactions n'impliquant pas la formation de groupes carboxamide
C07C 233/78 - Amides d'acides carboxyliques ayant des atomes de carbone de groupes carboxamide liés à des atomes de carbone de cycles aromatiques à six chaînons ayant l'atome d'azote d'au moins un des groupes carboxamide lié à un atome de carbone d'un radical hydrocarboné substitué par des groupes amino avec le radical hydrocarboné substitué lié à l'atome d'azote du groupe carboxamide par un atome de carbone acyclique
C07C 213/02 - Préparation de composés contenant des groupes amino et hydroxy, amino et hydroxy éthérifiés ou amino et hydroxy estérifiés liés au même squelette carboné par des réactions impliquant la formation de groupes amino à partir de composés contenant des groupes hydroxy ou des groupes hydroxy éthérifiés ou estérifiés
C07C 217/26 - Composés contenant des groupes amino et hydroxy éthérifiés liés au même squelette carboné ayant des groupes hydroxy éthérifiés et des groupes amino liés à des atomes de carbone acycliques du même squelette carboné le squelette carboné étant acyclique et saturé ayant un seul groupe hydroxy éthérifié et un seul groupe amino liés au squelette carboné, qui est substitué de plus par des atomes d'halogène ou par des groupes nitro ou nitroso
C07C 211/15 - Composés contenant des groupes amino liés à un squelette carboné ayant des groupes amino liés à des atomes de carbone acycliques d'un squelette carboné saturé acyclique le squelette carboné étant substitué de plus par des atomes d'halogène ou par des groupes nitro ou nitroso
C07C 211/35 - Composés contenant des groupes amino liés à un squelette carboné ayant des groupes amino liés à des atomes de carbone de cycles autres que des cycles aromatiques à six chaînons d'un squelette carboné saturé contenant uniquement des cycles non condensés
C07D 307/33 - Atomes d'oxygène en position 2, l'atome d'oxygène étant sous la forme céto ou énol non substituée
C07D 235/14 - Radicaux substitués par des atomes d'azote
C07D 213/38 - Radicaux substitués par des atomes d'azote liés par des liaisons simples comportant uniquement de l'hydrogène, ou des radicaux hydrocarbonés, liés à l'atome d'azote substituant
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
38.
METHOD FOR CONTINUOUSLY SYNTHESIZING TAZOBACTAM INTERMEDIATE
Provided is a method for continuously synthesizing a tazobactam intermediate. The devices used in the continuous synthesis method comprise: a continuous reaction device and a heat exchange device, the heat exchange device being used to adjust the reaction temperature of the continuous reaction device. The method comprises: continuously delivering penicillane sulfoxide diphenylmethyl ester and 2-mercaptobenzothiazole into a continuous reaction device for a ring-opening reaction, and continuously discharging a tazobactam intermediate; the temperature of the ring-opening reaction is 80-160℃, the material retention time is 10-100 min, and the reaction pressure is 0-10 MPa. By using the heat exchange device and the continuous reaction device, raw materials can instantly be heated to a predetermined reaction temperature, and a product system after reaction can instantly be reduced to a specific temperature. By precisely controlling the reaction temperature and reaction time, the generation of isomers due to the temperature of a reaction being excessive or reaction time being prolonged in a kettle-type process can be effectively prevented. Moreover, the selectivity and yield of a reaction are significantly improved, and scaled-up production can be easily achieved.
C07D 417/12 - Composés hétérocycliques contenant plusieurs hétérocycles, au moins un cycle comportant des atomes de soufre et d'azote comme uniques hétéro-atomes du cycle, non prévus par le groupe contenant deux hétérocycles liés par une chaîne contenant des hétéro-atomes comme chaînons
The present invention provides an ethoxy methylene malononitrile continuous synthesis method. The method comprises the following steps: malononitrile, triethyl orthoformate, and acetic anhydride are continuously introduced into continuous reaction equipment for a substitution reaction to obtain ethoxy methylene malononitrile, and during the process of the substitution reaction, the generated ethoxy methylene malononitrile is continuously discharged, wherein the molar ratio of malononitrile, triethyl orthoformate, and acetic anhydride is 1:(0.9-6.0):(2.0-6.0). In the present invention, by using the continuous reaction equipment, the amount of materials participating in the reaction per unit time is greatly reduced, and therefore, a high-temperature hazardous area is reduced, and the safety risk is greatly reduced. Moreover, a continuous reactor can instantly heat raw materials to a reaction temperature, thereby avoiding the decomposition of the raw materials caused by a long-term temperature rising process, and thus the yield is significantly improved. Moreover, in the reaction process of the present invention, a class II toxic solvent such as methylbenzene is not required.
C07C 253/30 - Préparation de nitriles d'acides carboxyliques par des réactions n'impliquant pas la formation de groupes cyano
C07C 255/15 - Nitriles d'acides carboxyliques ayant des groupes cyano liés à des atomes de carbone acycliques contenant des groupes cyano et des atomes d'oxygène, liés par des liaisons simples, liés au même squelette carboné acyclique non saturé
C07C 255/16 - Nitriles d'acides carboxyliques ayant des groupes cyano liés à des atomes de carbone acycliques contenant des groupes cyano et des atomes d'oxygène, liés par des liaisons simples, liés au même atome de carbone d'un squelette carboné acyclique
40.
ETELCALCETIDE INTERMEDIATE AND METHOD FOR SYNTHESIZING ETELCALCETIDE
Disclosed are an etelcalcetide intermediate and a method for synthesizing etelcalcetide. The etelcalcetide intermediate is Fmoc-D-Cys(S-S-(N-Boc)-L-Cys(OtBu))-OH. The method for synthesizing etelcalcetide comprises the following steps: using N-Boc-L-Cys-OtBu as a starting material to generate a primary product of formula (A) by means of a substitution reaction, wherein R is S-Py or Cl; and performing a coupling reaction on the primary product and Fmoc-D-Cys-OH amino acid to obtain Fmoc-D-Cys(S-S-(N-Boc)-L-Cys(OtBu))-OH. The key intermediate is used for synthesizing etelcalcetide, which can improve the purity and the yield. It is important that the raw materials for synthesizing the key intermediate are cheap and readily available, and the process is simple.
C07C 319/22 - Préparation de thiols, de sulfures, d'hydropolysulfures ou de polysulfures d'hydropolysulfures ou de polysulfures
C07C 323/59 - Thiols, sulfures, hydropolysulfures ou polysulfures substitués par des halogènes, des atomes d'oxygène ou d'azote ou par des atomes de soufre ne faisant pas partie de groupes thio contenant des groupes thio et des groupes carboxyle liés au même squelette carboné ayant les atomes de soufre des groupes thio liés à des atomes de carbone acycliques du squelette carboné le squelette carboné étant substitué de plus par des atomes d'azote, ne faisant pas partie de groupes nitro ou nitroso avec des groupes amino liés au squelette carboné avec des groupes amino acylés liés au squelette carboné
C07K 7/06 - Peptides linéaires ne contenant que des liaisons peptidiques normales ayant de 5 à 11 amino-acides
C07K 1/06 - Procédés généraux de préparation de peptides utilisant des groupes protecteurs ou des agents d'activation
C07K 1/04 - Procédés généraux de préparation de peptides sur des supports
Provided are a transaminase mutant and application thereof. The transaminase mutant has an amino acid sequence obtained by mutation of the amino acid sequence shown in SEQ ID NO:1, the mutation at least comprises one of the following mutation site combinations: T7C+S47C, Q78C+A330C, V137C+G313C, A217C+Y252C and L295C+C328C; or the transaminase mutant has an amino acid sequence which has the mutation sites in the mutanted amino acid sequence and has 80% or more homology with the mutanted amino acid sequence. The transaminase mutant realizes change of protein structure and functions, reduces the enzyme amount, increases the ee value of the product, and reduces the difficulty of post-processing, so that the transaminase mutant can be suitable for industrial production.
Provided are a continuous post-treatment method and device for a penem compound. The method comprises the following steps: S1, performing continuous extraction on a reaction crude product of a penem compound to obtain an extraction heavy phase and an extraction light phase; S2, performing continuous solid-liquid separation on the extraction heavy phase to obtain a liquid phase separation product; S3, performing continuous pH adjustment on the liquid phase separation product until the pH value is 6.1-6.3 to obtain a pH-adjusted solution; and S4, performing continuous crystallization treatment on the pH-adjusted solution by using a first crystallization solvent to obtain a penem compound product. The use of the method for post-treatment of a reaction crude product of a penem compound has the advantages of high treatment speed and high efficiency, and stable material properties and a low deterioration rate during treatment, and has better control over the yield and purity of a target product.
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.
A continuous preparation method for benzyl zinc halide and derivatives thereof. In the continuous preparation method, a reaction, in which the zinc atom is directly inserted into a carbon-halide bond, is performed using a continuous reactor, wherein the continuous reactor comprises a heating section and a cooling section communicated with each other, the cooling section is located above the heating section, and the cooling section has a product overflow port. The continuous preparation method comprises: separately feeding a liquid reaction material and zinc powder into the heating section, continuously, the zinc powder being continuously fed into the heating section from above the heating section, and the liquid reaction material being continuously fed into the heating section from the lower part of the heating section; and performing a reaction, in which the zinc atom is directly inserted into a carbon-halide bond, in the heating section to obtain a product system, the product system flowing out of the continuous reactor from the product overflow port, wherein the liquid reaction material comprise a halide, and the halide has structural formula I. In the continuous preparation method, zinc powder does not accumulate in the continuous reactor so that the risk of material spout is avoided, thus facilitating the application of the continuous preparation method in large-scale production.
A continuous preparation method for benzyl zinc halide and derivatives thereof. In the continuous preparation method, a reaction, in which the zinc atom is directly inserted into a carbon-halide bond, is performed using a continuous reactor, wherein the continuous reactor comprises a heating section and a cooling section communicated with each other, the cooling section is located above the heating section, and the cooling section has a product overflow port. The continuous preparation method comprises: separately feeding a liquid reaction material and zinc powder into the heating section, continuously, the zinc powder being continuously fed into the heating section from above the heating section, and the liquid reaction material being continuously fed into the heating section from the lower part of the heating section; and performing a reaction, in which the zinc atom is directly inserted into a carbon-halide bond, in the heating section to obtain a product system, the product system flowing out of the continuous reactor from the product overflow port, wherein the liquid reaction material comprise a halide, and the halide has structural formula I. In the continuous preparation method, zinc powder does not accumulate in the continuous reactor so that the risk of material spout is avoided, thus facilitating the application of the continuous preparation method in large-scale production.
Provided are a segmentable integrated solid catalytic continuous reaction apparatus and continuous reaction system; the segmentable integrated solid catalytic continuous reaction apparatus comprises: n cylinders (1), the cylinders (1) being detachably fixedly connected from bottom to top; n support structures (3), each support structure (3) being arranged at the lower end of the inner cavity of each cylinder (1) in a one-to-one correspondence, the inner cavities of adjacent cylinders (1) being connected by means of through-holes of the support structures (3); n heat exchangers (2), each heat exchanger (2) being arranged in the inner cavity of each cylinder (1) in a one-to-one correspondence; and a filler (6), arranged in the inner cavity of each cylinder (1); the continuous reaction system comprises one or a plurality of serially connected segmentable integrated solid catalytic continuous reaction apparatuses.
B01J 8/04 - Procédés chimiques ou physiques en général, conduits en présence de fluides et de particules solides; Appareillage pour de tels procédés avec des particules immobiles, p.ex. dans des lits fixes le fluide passant successivement à travers plusieurs lits
47.
METHOD AND APPARATUS FOR CONTINUOUS SYNTHESIS OF CYCLOPROPANE COMPOUNDS
Disclosed in the present invention are a method and an apparatus for continuous synthesis of cyclopropane compounds. The method comprises the following steps: the synthesis reaction of a diazomethane precursor is carried out continuously in a first reactor; the reaction product in the first reactor flows into a separator to perform stratification; the organic phase obtained by stratification overflows into a second reactor; in the second reactor, the diazomethane precursor is continuously consumed to prepare diazomethane, and an electron-rich monoolefin cyclopropanation reaction is performed in situ to obtain cyclopropane compounds. By applying the technical solution of the present invention, automatic control can be achieved, the transfer of high-risk materials can be reduced, and the risk of pipeline transfer of diazomethane solution can be prevented, so that production safety is effectively improved. Moreover, the apparatus is simple, so that the investment in the apparatus is reduced. The production of diazomethane and the cyclopropanation of olefins can be safely and quantitatively implemented simultaneously.
C07C 2/86 - Préparation d'hydrocarbures à partir d'hydrocarbures contenant un plus petit nombre d'atomes de carbone par condensation d'un hydrocarbure et d'un non-hydrocarbure
C07C 13/04 - Hydrocarbures monocycliques ou leurs dérivés hydrocarbonés acycliques à cycle à trois chaînons
A borohydride reduction stabilizing system and a method for reducing an ester to an alcohol. The borohydride reduction stabilizing system comprises: a borohydride reducing agent and a stabilizing agent for stabilizing the borohydride reducing agent. The borohydride reducing agent is sodium borohydride or potassium borohydride. The stabilizing agent is an alkali metal salt of an alcohol. By adding the alkali metal salt of an alcohol, such as sodium alkoxide or potassium alkoxide, on the basis of an existing sodium/potassium borohydride reducing agent, the sodium borohydride/potassium reducing agent can be kept stable without being decomposed under the condition of increased temperature, so that on the one hand, the reducing activity is maintained in a relatively high state, and the condition of excessive use is reduced, and on the other hand, the generation of hydrogen is reduced, and the process risks are reduced.
C07B 41/02 - Formation ou introduction de groupes fonctionnels contenant de l'oxygène de groupes hydroxy ou O-métal
C07C 29/147 - 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 réduction d'un groupe fonctionnel contenant de l'oxygène de groupes contenant C=O, p.ex. —COOH d'acides carboxyliques ou de leurs dérivés
C07C 31/125 - Alcools monohydroxyliques acycliques contenant de cinq à vingt-deux atomes de carbone
C07C 201/12 - Préparation de composés nitrés par des réactions ne créant pas de groupes nitro
C07C 205/19 - Composés contenant des groupes nitro liés à un squelette carboné le squelette carboné étant substitué de plus par des groupes hydroxy ayant des groupes nitro liés à des atomes de carbone de cycles aromatiques à six chaînons et des groupes hydroxy liés à des atomes de carbone acycliques
C07C 213/00 - Préparation de composés contenant des groupes amino et hydroxy, amino et hydroxy éthérifiés ou amino et hydroxy estérifiés liés au même squelette carboné
C07C 215/08 - Composés contenant des groupes amino et hydroxy liés au même squelette carboné ayant des groupes hydroxy et des groupes amino liés à des atomes de carbone acycliques du même squelette carboné le squelette carboné étant saturé et acyclique avec un seul groupe hydroxy et un seul groupe amino liés au squelette carboné
C07C 215/20 - Composés contenant des groupes amino et hydroxy liés au même squelette carboné ayant des groupes hydroxy et des groupes amino liés à des atomes de carbone acycliques du même squelette carboné le squelette carboné étant saturé le squelette carboné étant saturé et contenant des cycles
C07C 215/28 - Composés contenant des groupes amino et hydroxy liés au même squelette carboné ayant des groupes hydroxy et des groupes amino liés à des atomes de carbone acycliques du même squelette carboné le squelette carboné étant non saturé et contenant des cycles aromatiques à six chaînons
Provided are a ketoreductase mutant and a method for producing chiral alcohol using the ketoreductase mutant. The ketoreductase mutant has a sequence with amino acid mutations in the sequence shown in SEQ ID NO:1. The mutation sites comprise at least one of the following positions: 6th position, 21st position, 42nd position, 58th position, 61st position, 76th position, 87th position, 94th position, 96th position, 108th position, 113th position, 117th position, 144th position, 146th position, 147th position, 149th position, 151st position, 152nd, 156th position, 165th position, 177th position, and 198th position.
The present invention provides a process of preparing diazomethane. The process comprises: step S1, using N-methylurea as a raw material to continuously prepare a first product system containing N-methyl-N-nitrosourea in a continuous reactor; step S2, extracting and back-extracting the first product system continuously to obtain a N-methyl-N-nitrosourea solution; step S3, continuously reacting the N-methyl-N-nitrosourea solution with an alkali solution in a continuous reactor to obtain a second product system containing diazomethane; and step S4, continuously performing liquid separation and water removal by freezing on the second product system to obtain the diazomethane. A 2-methyltetrahydrofuran solution of MNU is obtained through a completely continuous reaction and posttreatment by using N-methylurea as a raw material, and then an anhydrous diazomethane solution is directly obtained through a completely continuous reaction and posttreatment. Water is removed by a freezing technology, and use of an expensive semipermeable membrane or liquid-liquid separator is avoided, so that the cost is lower.
C07C 245/14 - Composés diazo, c. à d. composés ayant les valences libres de groupes N2 attachées au même atome de carbone ayant des groupes diazo liés à des atomes de carbone acycliques d'un squelette carboné
51.
Monooxygenase mutant, preparation method and application thereof
The present application relates to the technical field of genetic engineering, and provides a monooxygenase mutant, a preparation method and application thereof. The monooxygenase mutant has any one of the amino acid sequences shown in (I) and (II): (I) an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO. 1; and (II) an amino acid sequence obtained by modifying, substituting, deleting, or adding one or several amino acids to the amino acids at 23 to 508 positions of the amino acid sequence shown in SEQ ID NO. 1, the substituting referring to a substitution of 1 to 34 amino acids, wherein the mutant has the activity of monooxygenase.
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 are a monooxygenase mutant and an application thereof. The amino acid sequence of the monooxygenase mutant is a mutated version of the amino acid sequence shown in SEQ ID NO: 1. The mutation comprises a mutation at at least one of the following sites: 45, 95, 106, 108, 114, 186, 190, 191, 249, 257, 393, 436, 499, 500, 501, 503, 504, 559, and 560.
Provided is a method for the alcoholysis of an amide. The method comprises subjecting an amide-containing compound to alcoholysis under alkaline conditions using an epoxy compound as an accelerant of alcoholysis, the method comprising: mixing the amide-containing compound, the epoxy compound, a pH adjuster and a solvent to form an alkaline reaction system, the pH of the alkaline reaction system being 7.5-9.5; reacting the alkaline reaction system at 50° C. ˜150° C. to subject the amide-containing compound to alcoholysis.
C07C 67/20 - Préparation d'esters d'acides carboxyliques par conversion d'un groupe contenant de l'azote dans un groupe ester à partir d'amides ou de lactames
55.
MONOOXYGENASE MUTANT, PREPARATION METHOD THEREFOR AND APPLICATION THEREOF
The present invention relates to the technical field of genetic engineering, and provides a monooxygenase mutant, a preparation method therefor and an application thereof. The monooxygenase mutant has any one of the amino acid sequences shown in (I) and (II): (I) an amino acid sequence having at least 80% identity with the amino acid sequence shown in SEQ ID NO. 1; and (II) an amino acid sequence obtained by modifying, substituting, deleting, or adding one or several amino acids to the amino acids at 23-508 positions of the amino acid sequence shown in SEQ ID NO. 1, the substitution referring to a substitution of 1-34 amino acids, wherein the mutant has the activity of monooxygenase.
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 is a method for the alcoholysis of an amide. The method comprises subjecting an amide-containing compound to alcoholysis under alkaline conditions using an epoxy compound as an accelerator. The method described above is easy to operate; furthermore, for post-treatment, a pure product can be obtained only by means of a simple conventional separation step. Furthermore, due to the fact that the epoxy compound has a low cost, the production operation costs and the risk and cost of the treatment of three wastes can be greatly reduced. In addition, during use, the above-mentioned method has mild reaction conditions, is compatible with a variety of different substituents and functional groups, can achieve a good yield for amides of various structural types, and has a wide range of applicable substrates. That is, the present invention provides an environmentally-friendly, economical and practical efficient method for converting an amide into a more useful ester. The above-mentioned alcoholysis reaction of the present application is not affected by impurities in a C-H activation reaction system in the last step, thus saving an intermediate purification step, and the two steps of the reactions, i.e., C-H activation and amide alcoholysis, can be linked.
C07C 67/20 - Préparation d'esters d'acides carboxyliques par conversion d'un groupe contenant de l'azote dans un groupe ester à partir d'amides ou de lactames
C07C 69/00 - Esters d'acides carboxyliques; Esters de l'acide carbonique ou de l'acide formique halogéné
C07C 51/06 - Préparation d'acides carboxyliques, de leurs sels, halogénures ou anhydrides à partir d'amides d'acides carboxyliques
C07C 213/04 - Préparation de composés contenant des groupes amino et hydroxy, amino et hydroxy éthérifiés ou amino et hydroxy estérifiés liés au même squelette carboné par réaction d'ammoniac ou d'amines avec des oxydes d'oléfines ou des halohydrines
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 5/10 - Cellules modifiées par l'introduction de matériel génétique étranger, p.ex. cellules transformées par des virus
C12N 15/63 - Introduction de matériel génétique étranger utilisant des vecteurs; Vecteurs; Utilisation d'hôtes pour ceux-ci; Régulation de l'expression
62.
Polymer containing carboxyl group, preparation method and application thereof, supported catalyst and preparation methods thereof and preparation methods of penem antibiotic intermediate
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 alvéolaires; Leur post-traitement
C08J 9/14 - Mise en œuvre de substances macromoléculaires pour produire des matériaux ou objets poreux ou alvéolaires; Leur 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
65.
Method for preparing sulfobutyl ether-β-cyclodextrin
A method for preparing sulfobutyl ether-β-cyclodextrin. β-cyclodextrin and 1,4-sulfobutyrolactone are used as raw materials, and a proper amount of an organic solvent is introduced into an alkaline aqueous solution, so that the solubility of the 1,4-sulfobutyrolactone is increased, and the synthesis yield of the sulfobutyl ether-β-cyclodextrin is improved. Operations including ultrasonic dialysis, active carbon decoloration, freeze-drying and so on are performed on the obtained product solution, so as to obtain a powder product of the sulfobutyl ether-beta-cyclodextrin.
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.
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.
C12N 15/63 - Introduction de matériel génétique étranger utilisant des vecteurs; Vecteurs; Utilisation d'hôtes pour ceux-ci; Régulation de l'expression
C12N 5/10 - Cellules modifiées par l'introduction de matériel génétique étranger, p.ex. cellules transformées par des virus
C12N 1/15 - Champignons; Leurs milieux de culture modifiés par l'introduction de matériel génétique étranger
C12N 1/19 - Levures; Leurs milieux de culture modifiés par l'introduction de matériel génétique étranger
C12N 1/21 - Bactéries; Leurs milieux de culture modifiés par l'introduction de matériel génétique étranger
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.
C12N 15/63 - Introduction de matériel génétique étranger utilisant des vecteurs; Vecteurs; Utilisation d'hôtes pour ceux-ci; Régulation de l'expression
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 - Acides; Leurs 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
75.
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
78.
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
79.
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
81.
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 vecteurs; Vecteurs; Utilisation d'hôtes pour ceux-ci; Régulation 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 condensées; Leurs 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 condensées; Leurs dérivés hydrogénés substituées uniquement en position 4, p.ex. isoniazide, iproniazide
A61K 31/4402 - Pyridines non condensées; Leurs dérivés hydrogénés substituées uniquement en position 2, p.ex. phéniramine, bisacodyl
A61K 31/4406 - Pyridines non condensées; Leurs 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
83.
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
84.
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
85.
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 solides; Appareillage 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 solides; Appareillage 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
