Provided in the present invention is a preparation method for a siRNA for inhibiting PCSK9 gene expression. The siRNA in the preparation method is a double-stranded RNA consisting of a sense strand and an antisense strand which are complementarily paired. The preparation method comprises: mixing a sense strand substrate, an antisense strand substrate and an RNA ligase, using the RNA ligase for catalyzing the sense strand substrate and the antisense strand substrate to be connected by means of a phosphodiester bond, and obtaining a sense strand and an antisense strand, so as to obtain the siRNA. The sense strand substrate can form the sense strand, and the antisense strand substrate can form the antisense strand. The sense strand is a nucleic acid sequence as shown in SEQ ID NO: 45, and the antisense strand is a nucleic acid sequence as shown as SEQ ID NO: 46. The solution solves the problem in the prior art of low purity of the siRNA, and is applicable in the field of medicine biosynthesis.
Provided in the present invention are a preparation method for a non-natural RNA and a product. The preparation method for the non-natural RNA comprises: connecting the 3' end of a substrate donor with the 5' end of a substrate receptor by using an RNA ligase to form a phosphodiester bond, wherein the connection does not need a template chain, and the non-natural RNA is prepared. The substrate donor and/or the substrate receptor comprise one or more non-natural nucleotides. The 5' end of the substrate receptor is a phosphoric acid group; and the 3' end of the substrate donor is a hydroxyl group. The RNA ligase comprises any one or more enzymes in RNA ligase family Rnl1 and Rnl2. The solution solves the problem in the prior art of non-natural RNA being difficult to prepare using enzyme catalysis, and the method is suitable for the field of RNA synthesis.
Provided are a tRNA and a biosynthesis method therefor. The biosynthesis method for the tRNA comprises: using an RNA ligase to connect 3' ends and 5' ends of different substrates to form phosphodiester bonds, and forming the tRNA, wherein the number of the substrates is greater than or equal to 2, and the RNA ligase comprises any one or more of RNA ligase family Rnl1, Rnl2, Rnl3 and Rnl5. The present invention can solve the problem in the prior art of low tRNA synthesis yields, and is suitable for the field of tRNA synthesis.
Provided are a gRNA and a biosynthesis method therefor, suitable for the field of gRNA synthesis. The biosynthesis method comprises: connecting the 3' end and the 5' end of different substrates by using an RNA ligase to form a phosphodiester bond, so as to form a gRNA. The gRNA comprises natural gRNA or non-natural gRNA. The number of the substrates is greater than or equal to 2. The connection site of the substrate is located at any one or more positions in the stem-loop structure complementary region, the stem-loop structure annular region or a linker region between the stem-loop structures of the gRNA, and base complementary pairing can be carried out in a substrate or among substrates to form a secondary structure of the gRNA; wherein the RNA ligase comprises any one or more enzymes in the RNA ligase family 1, 2 or 3. The solution solves the problem in the prior art of low purity of synthesized gRNA.
Provided are an RNA containing a thioester bond and a preparation method therefor. The method comprises: connecting a 3' hydroxyl group of a substrate with a 5' thiophosphoric acid by using an RNA ligase to form an RNA containing a thioester bond. The 5' thiophosphoric acid comprises a thio-modified 5' phosphoric acid. The thio-modification comprises P-OH of 5' phosphoric acid or the oxygen atom in P=O being replaced by a sulfur atom, correspondingly becoming P-SH or P=S. The RNA ligase comprises any one or more enzymes in RNA ligase family 1, 2 or 3; in particular being one or more of the RNA ligase as shown in SEQ ID NO: 1-22 etc.
The present invention provides a method for preparing a polyethylene glycol-glycerol derivative and an intermediate thereof. The method comprises: performing an esterification reaction on a starting material comprising polyethylene glycol and a sulfonyl chloride resin to give a first product system comprising the intermediate of the polyethylene glycol-glycerol derivative. At least one end group of the polyethylene glycol is hydroxyl, and the sulfonyl chloride resin is a polystyrene resin containing a sulfonyl chloride group. By utilizing the solid-phase characteristics of the sulfonyl chloride resin as a resin macromolecule, the product system comprising the intermediate of the polyethylene glycol-glycerol derivative can be prepared by means of a solid-phase synthesis method. In the resultant product system, the intermediate of the polyethylene glycol-glycerol derivative can be easily separated by a solid-liquid separation method and used for subsequent reactions, which greatly simplifies the separation and purification procedures and can acquire the target product with high yield and purity. All of the reagents used in the preparation process can be recycled, which greatly improves the cost-efficiency.
C08G 81/02 - Composés macromoléculaires obtenus par l'interréaction de polymères en l'absence de monomères, p. ex. polymères séquencés au moins un des polymères étant obtenu par des réactions ne faisant intervenir que des liaisons non saturées carbone-carbone
C08G 65/32 - Polymères modifiés par post-traitement chimique
C08G 65/331 - Polymères modifiés par post-traitement chimique avec des composés organiques contenant de l'oxygène
7.
PHOTOCHEMICAL SYNTHESIS METHOD FOR HETEROARYL AMINE COMPOUND
Provided is a photochemical synthesis method for a heteroaryl amine compound. The photochemical synthesis method comprises: step S1, mixing raw materials comprising a heteroaryl nitro compound, a solvent, and a photocatalyst to obtain a mixture; and step S2, carrying out a photocatalytic reduction reaction to the mixture under lighting conditions to obtain a product system containing a heteroaryl amine compound. The photochemical synthesis method implements the photocatalytic reduction of various different heteroaryl nitro compounds under lighting conditions, so as to obtain higher yields of heteroaryl amine compounds. The photocatalyst is an existing commonly used catalyst, has no strict requirements on equipment, is easy to recycle, and reduces safety risks and catalyst costs of heteroaryl amine compounds. The whole reaction process of photocatalysis does not need the addition of any metal reagent and reducing agent, features a high reaction conversion rate and easy-operate post-treatment, and is thus safer and more environmentally friendly.
The present invention provides a continuous synthesis method for a 2-chloropyrimidine-4-formic acid compound. The 2-chloropyrimidine-4-formic acid compound has the structure as shown in formula I: (I), in formula I, R1and R2are independently selected from hydrogen, alkoxy, aryl, benzyl or fluorine. The synthesis method comprises the following steps: S1, under the action of a non-noble metal catalyst, a compound A and a methyl Grignard reagent B being continuously methylated to obtain a compound C, wherein the compound A is (II), the compound C is (III), R1and R2 have the same definitions as above, and the non-noble metal catalyst is one or more of an iron salt, a cobalt salt and a nickel salt; and S2, carrying out continuous oxidation reaction on the compound C under the action of oxygen, an oxidation catalyst and an additive to obtain the 2-chloropyrimidine-4-formic acid compound. The 2-chloropyrimidine-4-formic acid compound is synthesized by using the process provided by the present invention, which can give consideration to cost, yield, environmental protection and the like.
Provided are a proline hydroxylase and uses thereof. The proline hydroxylase comprises having the amino acid sequence of SEQ ID NO: 2 with the exception of a mutation of one or more amino acids; wherein the mutation of one or more amino acids must comprises E27K, and the mutation of one or more amino acids selected from the group consisting of: H14R, L16N, T25R, F26L, E27K, D30S, S33N, E34N, E34G, E34L, E34S, E34D, Y35W, Y35K, S37W, S37F, S37E, S37N, S37T, S37C, W40F, K41E, D54G, H55Q, S57L, I58T, I58Y, I58A, I58R, I58V, I58S, I58C, K86P, T91A, F95Y, C97Y, I98V, K106V, K106T, K106Q, F111S, K112E, K112R, S154A, K162E, L166M, I118F, I118V, I118R, H119R, H119F, I120V, K123D, K123N, K123Q, K123S, K123I, K123T, T130N, D134G, V135K, N165H, D173G, K209R, I223V and S225A, and having proline hydroxylase activity.
Provided are a 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.
The application provides a Diketoreductase (DKR) mutant, its nucleotide coding sequence, and an expression cassette, recombinant vector and host cell containing the sequence, as well as a method for application of the mutant to the preparation of 3R,5S-dicarbonyl compound. An ee value of the obtained 3R,5S-dicarbonyl compound is higher than 99%, and a de value is about 90%. The DKR mutant is a key pharmaceutical intermediate, and particularly provides an efficient catalyst for synthesis of a chiral dicarbonyl hexanoic acid chain of a statin drug.
C12N 9/04 - Oxydoréductases (1.), p. ex. luciférase agissant sur des groupes CHOH comme donneurs, p. ex. oxydase de glucose, déshydrogénase lactique (1.1)
A polymer containing a carboxyl group, a preparation method and an application thereof, a supported catalyst and a preparation method thereof and preparation methods of penem antibiotic intermediate are disclosed. The polymer has high rigidity and hardness, thus the mechanical properties of the polymer is effectively improved. Meanwhile, in the polymer, the carboxyl group is used as a main functional group, and is used as a carrier to prepare, by means of a coordination reaction between the carboxyl group and a heavy metal, a supported metal catalyst which has better connection stability between the metal and the polymer. The above two factors can improve the stability of the supported metal catalyst, such that the catalyst can be recycled without losing the catalytic activity. Meanwhile, loss of a heavy metal active ingredient and production cost can be reduced.
B01J 31/00 - Catalyseurs contenant des hydrures, des complexes de coordination ou des composés organiques
B01J 31/06 - Catalyseurs contenant des hydrures, des complexes de coordination ou des composés organiques contenant des composés organiques ou des hydrures métalliques contenant des polymères
C07D 477/06 - Préparation à partir de composés contenant déjà les systèmes cycliques ou cycliques condensés, p. ex. par déshydrogénation du cycle, par introduction, élimination ou modification de substituants
C08F 12/32 - Monomères ne contenant qu'un seul radical aliphatique non saturé contenant plusieurs cycles
C08F 12/34 - Monomères contenant plusieurs radicaux aliphatiques non saturés
C08F 212/14 - Monomères contenant un seul radical aliphatique non saturé contenant un cycle substitué par des hétéro-atomes ou des groupes contenant des hétéro-atomes
B01J 23/46 - Ruthénium, rhodium, osmium ou iridium
B01J 31/28 - Catalyseurs contenant des hydrures, des complexes de coordination ou des composés organiques contenant en outre des composés métalliques inorganiques non prévus dans les groupes du groupe du platine, du cuivre ou du groupe du fer
C08J 9/00 - Mise en œuvre de substances macromoléculaires pour produire des matériaux ou objets poreux ou alvéolairesLeur post-traitement
C08J 9/14 - Mise en œuvre de substances macromoléculaires pour produire des matériaux ou objets poreux ou alvéolairesLeur post-traitement utilisant des gaz de gonflage produits par un agent de gonflage introduit au préalable par un agent physique de gonflage organique
A transaminase and a use thereof are provided. The transaminase has the amino acid sequences as shown in SEQ ID NO: 2 or 4, or has at least 80% identity to the amino acid sequences as shown in SEQ ID NO: 2 or 4, or has amino acid sequences which are obtained by the substitution, deletion or addition of one or more amino acids and have an the activity of an omega-transaminase with high stereoselective R-configuration catalytic activity, wherein the high stereoselective refers to the content of one of the stereoisomers being at least about 1.1 times that of the other.
C12P 13/00 - Préparation de composés organiques contenant de l'azote
C12P 17/12 - Préparation de composés hétérocycliques comportant O, N, S, Se ou Te comme uniques hétéro-atomes du cycle l'azote comme unique hétéro-atome du cycle contenant un hétérocycle à six chaînons
The present invention provides a process for preparing nilotinib. The preparation method comprises the steps of: performing a carbonylation and amination reaction with respect to compound A and 3-(4-methyl-1H- imidazol-1-yl)-5-(trifluoromethyl) aniline to obtain an aminated product; and performing an R group deprotection treatment on the aminated product to obtain nilotinib. Compound A has a structure shown in formula I, wherein in formula I, the R group is selected from benzyl, -COCF3, -CHO or -CO2R', and the R' group is a C1-C10 alkyl group, a C1-C3 alkoxy group, or a C7-C19 aralkyl group. The preparation method has a short synthesis route, mild reaction conditions, and uses special materials, thereby improving nilotinib yield while reducing process costs.
C07D 401/14 - Composés hétérocycliques contenant plusieurs hétérocycles comportant des atomes d'azote comme uniques hétéro-atomes du cycle, au moins un cycle étant un cycle à six chaînons avec un unique atome d'azote contenant au moins trois hétérocycles
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.
C12N 9/04 - Oxydoréductases (1.), p. ex. luciférase agissant sur des groupes CHOH comme donneurs, p. ex. oxydase de glucose, déshydrogénase lactique (1.1)
Disclosed are a double-carbonyl reductase, a coding gene of same, and an application thereof. The double-carbonyl reductase is provided with one of the following amino acid sequences: 1) the amino acid sequence of SEQ NO. 1; or, 2) an amino acid sequence having a function of stereoselectively reducing formula (I) into formula (II) and derived from SEQ NO. 1 by means of substitution and/or deletion and/or addition of one or multiple amino acids in the amino acid sequence of SEQ NO. 1, where the amino acid sequence derived from SEQ NO. 1 and SEQ NO. 1 have a sequence similarity of 80% or more, R1 is selected from an aryl, an alkyl, a cycloalkyl, an alkyl-substituted aryl, a halogen-substituted aryl, an aralkyl heterocyclyl, a cyclic heteroalkyl or a cyclic heteroalkyl, and R2 is selected from an alkyl, a cycloalkyl, a haloalkyl or a halocycloalkyl. Employment of the double-carbonyl reductase of the present invention allows for one-step reduction of a dione substrate to prepare 3R,5S-dihydroxy compounds of a single optical purity.
Provided are a double-carbonyl reductase, a coding gene of same, and an application thereof. The double-carbonyl reductase is provided with one of the following amino acid sequences: 1) the amino acid sequence of SEQ ID NO: 1; and, 2) an amino acid sequence having a function for stereoselectively reducing formula (I) into formula (II) and derived from SEQ ID NO: 1 by means of substitution and/or deletion and/or addition of one or multiple amino acids in the amino acid sequence of SEQ ID NO: 1, where the amino acid sequence derived from SEQ ID NO: 1 and SEQ ID NO: 1 have a sequence similarity of 80% or more, R1 is selected from an aryl, an alkyl, a cycloalkyl, an alkyl-substituted aryl, a halogen-substituted aryl, an aralkyl heterocyclyl, a cyclic heteroalkyl or a cyclic heteroalkyl, and R2 is selected from an alkyl, a cycloalkyl, a haloalkyl or a halocycloalkyl. Also provided is a use of the double-carbonyl reductase for reducing a dione substrate to prepare 3R,5S-dihydroxy compounds of a single optical purity.
Disclosed are a double-carbonyl reductase, a coding gene of same, and an application thereof. The double-carbonyl reductase is provided with one of the following amino acid sequences: 1) the amino acid sequence of SEQ NO. 1; and, 2), an amino acid sequence having a function of stereoselectively reducing formula (I) into formula (II) and derived from SEQ NO. 1 by means of substitution and/or deletion and/or addition of one or multiple amino acids in the amino acid sequence of SEQ NO. 1, where the amino acid sequence derived from SEQ NO. 1 and SEQ NO. 1 have a sequence similarity of 80% or more, R1 is selected from an aryl, an alkyl, a cycloalkyl, an alkyl-substituted aryl, a halogen-substituted aryl, an aralkyl heterocyclyl, a cyclic heteroalkyl or a cyclic heteroalkyl, and R2 is selected from an alkyl, a cycloalkyl, a haloalkyl or a halocycloalkyl. Employment of the double-carbonyl reductase of the present invention allows for one-step reduction of a dione substrate to prepare 3R,5S-dihydroxy compounds of a single optical purity.
The present invention relates to a preparation method for a chiral intermediate for use in statins, acquired with chloroacetic acid and benzyl alcohol as starting materials via a series of reactions, namely etherification, condensation, substitution, and asymmetric reduction. The preparation method provided in the present invention has a novel route of synthesis, allows an intermediate compound to be introduced conveniently into the chiral center of a glycol via enzyme reduction, and not only is low in costs, but also is reliable in quality. The route of synthesis provided in the present invention uses raw materials of low costs, has an easy to operate process, and provides a final product of great purity and high yield.
Provided is a double-carbonyl reductase mutant, a nucleotide coding sequence thereof and, comprising the sequence, an expression cassette, a recombinant vector, and a host cell, and a method for using the mutant in preparation of 3R,5S-double carbonyl compounds, where the ee values of the acquired 3R,5S-double-carbonyl compounds are greater than 99%, while the de values of same are approximately 90%. The double-carbonyl reductase mutant is a key pharmaceutical intermediate, and specifically provides a high-efficiency catalyst for synthesis of a chiral dihydroxy hexanoic acid chain of statins.
Provided are an intermediate compound for preparing rosuvastatin calcium and a preparation method of the rosuvastatin calcium. The method comprises: using the foregoing intermediate compound as a raw material, and subjecting the raw material to a step of Wittig reaction, a step of protecting group removal and hydrolysis and a step of calcium salt formation, so as to obtain the rosuvastatin calcium. The product, which is prepared from the intermediate compound, can be substantially enhanced in stereoselectivity and also notably improved in purity and yield; in addition, the method for preparing rosuvastatin calcium from the intermediate compound is simple, convenient and low in cost.
Disclosed is a method for preparing sulfobutyl ether-β-cyclodextrin. The method overcomes shortcomings of the prior art; β-cyclodextrin and 1,4-sulfobutyrolactone are used as raw materials, and a proper amount of organic solvent is introduced into an alkaline aqueous solution, so that the solubility of the 1,4-sulfobutyrolactone is increased, and the synthesis rate of the sulfobutyl ether-β-cyclodextrin is improved. Operations, such as ultrasonic dialysis, active carbon decoloration, freezing and drying, are performed on the obtained product solution, so as to obtain the powder product of sulfobutyl ether-beta-cyclodextrin. The method has a stable process, needs a moderate reaction condition, has good selectivity, and needs simple aftertreatment operations; the obtained product has very high purity and yield, thereby providing a new idea and a method for mass production of sulfobutyl ether-β-cyclodextrin.
POLYMER CONTAINING CARBOXYL GROUP, METHOD FOR PREPARING SAME AND USE THEREOF, METHOD FOR PREPARING SUPPORTED CATALYST AND PENEM ANTIBIOTIC INTERMEDIATES
The present invention discloses a polymer containing a carboxyl group, a method for preparing same and a use thereof, and a method for preparing a supported catalyst and a penem antibiotic intermediate. The polymer is made by polymerizing three monomers with different structures. The carboxyl group-containing polymer is a crosslinked polymer, and the polymer chain contains a large number of phenyl rings, and which can improve the rigidity and hardness of the polymer, thus effectively improving the mechanical properties of the polymer. Meanwhile, in the polymer, the carboxyl groups are used as the main functional groups, and are used as a carrier to prepare a supported metal catalyst, by means of a coordination reaction between the carboxyl groups and heavy metals, which has a better connection stability between the metal and the polymer. The above two factors can improve the stability of the supported metal catalyst, such that the catalyst can be recycled without the loss of the catalytic activity. Meanwhile, they are also able to reduce the loss of the heavy metals active ingredients and reduce production costs.
C08F 220/12 - Esters des alcools ou des phénols monohydriques
C08F 220/64 - AcidesLeurs sels métalliques ou leurs sels d'ammonium
C07D 477/06 - Préparation à partir de composés contenant déjà les systèmes cycliques ou cycliques condensés, p. ex. par déshydrogénation du cycle, par introduction, élimination ou modification de substituants
B01J 31/06 - Catalyseurs contenant des hydrures, des complexes de coordination ou des composés organiques contenant des composés organiques ou des hydrures métalliques contenant des polymères
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 vecteursVecteurs Utilisation d'hôtes pour ceux-ciRégulation de l'expression
A61K 31/381 - Composés hétérocycliques ayant le soufre comme hétéro-atome d'un cycle ayant des cycles à cinq chaînons
A61K 31/444 - Pyridines non condenséesLeurs dérivés hydrogénés contenant d'autres systèmes hétérocycliques contenant un cycle à six chaînons avec l'azote comme hétéro-atome du cycle, p. ex. amrinone
A61K 31/4409 - Pyridines non condenséesLeurs dérivés hydrogénés substituées uniquement en position 4, p. ex. isoniazide, iproniazide
A61K 31/4402 - Pyridines non condenséesLeurs dérivés hydrogénés substituées uniquement en position 2, p. ex. phéniramine, bisacodyl
A61K 31/4406 - Pyridines non condenséesLeurs dérivés hydrogénés substituées uniquement en position 3, p. ex. zimeldine
The present invention provides a synthesis method for L-cyclic alkyl amino acid and a pharmaceutical composition having said acid. Said synthesis method comprises: step a.) preparing a cyclic alkyl keto acid or cyclic alkyl keto acid salt having structural formula (I) or structural formula (II), and step b.) mixing cyclic alkyl keto acid or cyclic alkyl keto acid salt with ammonium formate, leucine dehydrogenase, formate dehydrogenase and coenzyme NAD+, and carrying out a reductive amination reaction to generate L-cyclic alkyl amino acid, wherein in structural formula (I), n1≥1, m1≥0, and M1 is H or a monovalent cation, and in structural formula (II), n2≥0, m2≥0, M2 is H or a monovalent cation, and the leucine dehydrogenase amino acid sequence is SEQ ID No. 1. Using a specific leucine dehydrogenase with formate dehydrogenase and coenzyme NAD+ to enable a reductive amination reaction of cyclic alkyl keto acid so as to generate L-cyclic alkyl amino acid allows for a high conversion rate of raw materials and high chiral selectivity.
C12P 17/06 - Préparation de composés hétérocycliques comportant O, N, S, Se ou Te comme uniques hétéro-atomes du cycle l'oxygène comme unique hétéro-atome du cycle contenant un hétérocycle à six chaînons, p. ex. fluorescéine
A61K 31/351 - Composés hétérocycliques ayant l'oxygène comme seul hétéro-atome d'un cycle, p. ex. fungichromine ayant des cycles à six chaînons avec un oxygène comme seul hétéro-atome d'un cycle non condensés avec un autre cycle
A61K 31/195 - Acides carboxyliques, p. ex. acide valproïque ayant un groupe amino
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 solidesAppareillage pour de tels procédés avec des particules immobiles, p. ex. dans des lits fixes dans des réacteurs tubulairesProcédés chimiques ou physiques en général, conduits en présence de fluides et de particules solidesAppareillage pour de tels procédés avec des particules immobiles, p. ex. dans des lits fixes les particules solides étant disposées dans des tubes
B01J 19/24 - Réacteurs fixes sans élément interne mobile
B01J 10/00 - Procédés chimiques généraux faisant réagir un liquide avec des milieux gazeux autrement qu'en présence de particules solidesAppareillage spécialement adapté à cet effet
C02F 1/78 - Traitement de l'eau, des eaux résiduaires ou des eaux d'égout par oxydation au moyen d'ozone
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