Provided are an enzyme immobilization carrier and a preparation method therefor, an immobilized enzyme and a preparation method therefor, and use thereof. The enzyme immobilization carrier comprises a resin matrix and a divinyl sulfone group modified on the resin matrix by means of a covalent bond. In order to realize the directed immobilization of an enzyme, the divinyl sulfone group is loaded on the resin matrix by means of the covalent bond. In a subsequent enzyme immobilization reaction, by using specific binding of the divinyl sulfone group to a histidine tag, the divinyl sulfone group in the enzyme immobilization carrier is connected to a specific amino acid residue in an enzyme molecule by means of a covalent bond, without reacting with an active group in the enzyme molecule, thereby effectively avoiding excessive influence of the enzyme immobilization carrier on enzyme conformation, and thus retaining a high catalytic activity of the enzyme. Compared with a traditional metal chelating type resin-enzyme molecule binding mode, the present invention shows better immobility.
C12N 9/04 - Oxydoréductases (1.), p.ex. luciférase agissant sur des groupes CHOH comme donneurs, p.ex. oxydase de glucose, déshydrogénase lactique (1.1)
C12P 7/22 - Préparation de composés organiques contenant de l'oxygène contenant un groupe hydroxyle aromatiques
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 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
2.
Ketoreductase mutant and method for producing chiral alcohol
Disclosed are a ketoreductase mutant and a method for producing a chiral alcohol. The ketoreductase mutant has an amino acid sequence obtained by the mutation of the amino acid sequence shown in SEQ ID NO: 1, and the mutation includes a mutation siteK200H. In the present disclosure, the mutant obtained by mutation takes a ketone compound as a raw material, the chiral alcohol may be efficiently produced by stereoselective reduction, and the stability is greatly improved, which is suitable for popularization and application to the industrial production of the chiral alcohol.
An amino acid sequence of the transaminase mutant is an amino acid sequence obtained by a mutation of an amino acid sequence is shown in SEQ ID NO: 1. The mutation occurred at least one of the following mutation sites: G17V, L36P, Q40H, G69Y, H70T, L73A, V77G, V77S, V77T, A78I, Y130M, Y130V, Y130T, N132I, N132T, K141S, K142S, K142T, R143P, G144F, G144W, G144Y, E145D, E145S, E145G, K146R, L148A, L148I and the like.
The present disclosure provides a device for continuously preparing 2,6-dihydroxybenzaldehyde and use thereof. The device includes a first continuous reaction unit for hydroxy protection reaction, a second continuous reaction unit for lithiation and hydroformylation, and a third continuous reaction unit for deprotection reaction that are connected in series. The third continuous reaction unit includes: a first columnar continuous reactor, connected to the second continuous reaction unit and used for deprotection of the lithiated hydroformylated product while performing liquid separation to obtain an organic phase containing 2,6-dihydroxybenzaldehyde and an aqueous phase. When the device is applied in the preparation of 2,6-dihydroxybenzaldehyde, reaction time is shortened and the intermediate purification treatment is no longer required. Therefore, compared with batch process, the present disclosure can greatly save equipment cost and post-processing cost, and greatly improve the production efficiency, more beneficial to the industrial scale-up production of 2,6-dihydroxybenzaldehyde.
B01J 19/18 - Réacteurs fixes avec éléments internes mobiles
C07C 41/54 - Préparation de composés comportant des groupes par des réactions donnant des groupes par addition de composés à des liaisons non saturées carbone-carbone
C07C 45/50 - Préparation de composés comportant des groupes C=O liés uniquement à des atomes de carbone ou d'hydrogène; Préparation des chélates de ces composés par réaction avec le monoxyde de carbone par synthèse oxo
C07C 45/64 - Préparation de composés comportant des groupes C=O liés uniquement à des atomes de carbone ou d'hydrogène; Préparation des chélates de ces composés par des réactions ne créant pas de groupe C=O par introduction de groupes fonctionnels contenant de l'oxygène lié uniquement par liaison simple
5.
KETOREDUCTASE MUTANT AND METHOD FOR PRODUCING CHIRAL ALCOHOL
Disclosed are a ketoreductase mutant and a method for producing a chiral alcohol. The ketoreductase mutant has a sequence with amino acid mutations in the sequence shown in SEQ ID NO:1. The mutation sites comprise K200H. In the present invention, the mutant obtained by mutation takes a ketone compound as a raw material, a chiral alcohol can be efficiently produced by stereoselective reduction, and the stability is greatly improved, which is suitable for popularization and application to the industrial production of the chiral alcohol.
Disclosed in the present invention are a transaminase mutant and a use thereof. The amino acid sequence of the transaminase mutant is an amino acid sequence obtained by mutating an amino acid sequence shown as SEQ ID NO: 1, and the mutation at least comprises one of the following mutation sites: G17V, L36P, Q40H, G69Y, H70T, L73A, V77G, V77S, V77T, A78I, Y130M, Y130V, Y130T, N132I, N132T, K141S, K142S, K142T, R143P, G144F, G144W, G144Y, E145D, E145S, E145G, K146R, L148A, L148I, etc. The transaminase mutant of the present invention obtains a catalytic activity on a carbonyl substrate.
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.
The present invention provides a device for continuously preparing 2,6-dihydroxybenzaldehyde and an application thereof. The device comprises a first continuous reaction unit for hydroxyl protection reaction, a second continuous reaction unit for lithiation hydroformylation reaction, and a third continuous reaction unit for protective group removal reaction which are sequentially connected in series, wherein the third continuous reaction unit comprises a first columnar continuous reactor which is connected to the second continuous reaction unit and used for performing liquid separation while performing protective group removal treatment on a lithiation hydroformylation product to obtain an organic phase containing the 2, 6-dihydroxybenzaldehyde and a water phase. When the device is applied to the preparation of the 2, 6-dihydroxybenzaldehyde, the reaction time is shortened, and intermediate purification treatment is not needed, so that compared with a batch process, the equipment cost and the post-treatment cost can be greatly saved, the production efficiency is greatly improved, and the industrialized enlarged production of the 2, 6-dihydroxybenzaldehyde is more facilitated.
B01J 19/00 - Procédés chimiques, physiques ou physico-chimiques en général; Appareils appropriés
B01J 19/18 - Réacteurs fixes avec éléments internes mobiles
B01J 19/24 - Réacteurs fixes sans élément interne mobile
B01J 4/00 - Dispositifs d'alimentation; Dispositifs de commande d'alimentation ou d'évacuation
C07C 45/64 - Préparation de composés comportant des groupes C=O liés uniquement à des atomes de carbone ou d'hydrogène; Préparation des chélates de ces composés par des réactions ne créant pas de groupe C=O par introduction de groupes fonctionnels contenant de l'oxygène lié uniquement par liaison simple
C07C 47/565 - Composés comportant des groupes —CHO liés à des atomes de carbone de cycles aromatiques à six chaînons contenant des groupes hydroxyle tous les groupes hydroxyle étant liés au cycle
C07C 41/54 - Préparation de composés comportant des groupes par des réactions donnant des groupes par addition de composés à des liaisons non saturées carbone-carbone
C07C 43/303 - Composés comportant des groupes les atomes de carbone de l'acétal étant liés à des atomes de carbone acycliques
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.
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
15.
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
18.
DOUBLE-CARBONYL REDUCTASE MUTANT AND APPLICATION THEREOF
A double-carbonyl reductase mutant and application thereof. An amino acid sequence of the double-carbonyl reductase mutant is the mutant amino acid sequence coded by SEQ ID NO:9, the mutant amino acid sequence has at least two mutation sites: NO:94, NO:151, NO:231, NO:236 and NO:251, and the I mutation of NO:94 is V, A or G; the V mutation of NO:151 is Q, N or S; the F mutation of NO:231 is W, Y or P; the I mutation of NO:236 is L, V or A; the Q mutation of NO:251 is H, R or K; or the amino acid sequence of the double-carbonyl reductase mutant has the mutation sites in the mutant amino acid sequence, and has greater than 90% homology with the mutant amino acid sequence. The enzymatic activity of the double-carbonyl reductase mutant having the mutation sites is improved substantially.
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
27.
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
30.
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
31.
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
33.
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
35.
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
36.
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
37.
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
