535 results about "Enantiomeric excess" patented technology

The invention relates to a bimetallic catalyst for synthetizing vertical structure regular makrolon through catalyzing and activating carbon dioxide to be copolymerized with internal compensation alkyleneoxide. The catalyst is a dual four-tooth or dual three-tooth Schiff alkali complex, of which two metal centers are connected through a biphenyl skeleton. Under the action of single or nucleophilicity co-catalyst, the catalyst can be used for catalyzing the carbon dioxide efficiently to be copolymerized with the internal compensation alkyleneoxide under mild condition and lower concentration of the catalyst to prepare the makrolon, the makrolon can be regulated when the catalyst efficiency is 104-106g polymer/mole catalyst and the polymer molecular weight is between 103 and 105, the makrolon can be regulated when the molecular weight distribution is less than 2 and the vertical structure regularity is between 60-100%, an alternate structure exceeds 98% and the makrolon can be degraded into a small molecular compound. The product selectivity and structure selectivity of the polymer compounds of the catalyst system using a chiral ligand are all above 98%, the enantiomer excess value of the mellow obtained by degradation reaches as high as 99%, so that the bimetallic catalyst provides a broad prospect for industrial application.

The invention relates to a method for preparing (S)-(4-chlorphenyl)-(pyridine-2-yl)-methanol by utilizing microbial catalysis, and belongs to the technical field of biological catalysis. According to the method, 4-chlorphenyl-(pyridine-2-yl)-ketone is subjected to asymmetrical reduction by utilizing kluyveromycessp (CCTCCM 2011385) whole cells to synthesize the (S)-(4-chlorphenyl)-(pyridine-2-yl)-methanol. The method comprises the following steps of: sieving a microbe which has high-stereoselectivity carbonyl reductase activity on a prochiral ketone substrate, determining a series of conditions of asymmetrical reduction reaction, such as reaction temperature, pH, the concentration of cells, the concentration of the substrate and reaction time and additives (including various secondary solvents, polyethyleneglycol (PEG), phosphates and the like), wherein the enantiomer excess value and yield of the (S)-(4-chlorphenyl)-(pyridine-2-yl)-methanol serving as a product can reach 86.7 percent e.e and 92.1. The product is separated and extracted initially by silicagel column chromatography, so that the purity of the separated product is 99.2 percent, and the extraction yield is 56.7 percent.

The invention discloses a method for synthesizing and refining salt of esomeprazole. According to the method, 2-sulfydryl-5-methoxyl-1H-benzimidazole is used as an initiative raw material for reaction, and a reaction condition is optimized, so that reaction is performed under a mild condition, and the content of impurities in the product is reduced effectively. After the synthesized product is refined further, the purity and enantiomer excess of the product are over 99 percent, so that the effect and safety of administration are improved.

The invention discloses application of alcohol dehydrogenase with amino acid sequence disclosed as SEQ ID NO:2 in preparing ethyl (R)-4-chloro-3-hydroxy butyrate from ethyl 4-chloroacetoacetate by asymmetric reduction. By using alcohol dehydrogenase with amino acid sequence disclosed as SEQ ID NO:2 as a catalyst, ethyl 4-chloroacetoacetate as a substrate and NADH (nicotinamide adenine dinucleotide) as a cofactor, asymmetric reduction is carried out to prepare the ethyl (R)-4-chloro-3-hydroxy butyrate. The invention applies the alcohol dehydrogenase with amino acid sequence disclosed as SEQ ID NO:2 in preparing ethyl (R)-4-chloro-3-hydroxy butyrate from ethyl 4-chloroacetoacetate by asymmetric reduction for the first time, and has favorable effect. The enzyme activity is up to 5.6 U/mg, the yield of the substrate is up to 94%, and the enantiomeric excess value of the product is 100%. The yield is high, and the production cost is greatly lowered.

This invention belongs to pharmacy field, it relates optical pure mei pu ta fen and its preparation method and application. Racemation mei pu ta fen is splited by optical pure tartaric acid evolving object to get optical pure monomer, enantiomeric excess testing is done through capillary electrophoresis method, their e.e.valude are both excess 99 percent. Laevorotation and dextrorotation mei put a fen absolute configuration is decided by single crystal X-diffraction method as S and R. the R(+)mei pu ta fen has srong activity in analgesia activity testing, but S(-)mei pu ta fen has more stronger activity in acetylcholine esterase restrain activity testing, analgesic medicine and senile dementia medicine can be further prepared.

The invention discloses an application of carbonyl reductase with the amino acid sequence as shown in SEQ ID NO:2 to prepare (S)-4-chloro-3-hydroxybutanoic ethyl ester by asymmetric reduction of 4-chloracetyl ethyl acetate. The carbonyl reductase with the amino acid sequence as shown in SEQ ID NO:2 is taken as a catalyst, the ethyl 4-chloracetyl ethyl acetate is taken as a substrate, and NADPH is taken as a cofactor, and the (S)-4-chloro-3-hydroxybutanoic ethyl ester is prepared by the asymmetric reduction. The carbonyl reductase with the amino acid sequence as shown in SEQ ID NO:2 is applied to preparing the (S)-4-chloro-3-hydroxybutanoic ethyl ester by the asymmertric reduction of the 4-chloroacetyl ethyl acetate for the first time, which produces good effect; the yield of the substrate is up to 95%, and the enantiomer excess value of the product is 100%, the yield is high, and the production cost is greatly reduced.

The invention belongs to the technical field of organic synthesis, and provides a novel method for preparing a chiral alpha-hydroxy-beta-dicarbonyl compound by using quinine C-2' derivative as a catalyst. The quinine C-2' derivative, of which the amount is 0.5-50 mol%, is used as the catalyst to react with a substrate and an oxidizer in an inert reaction solvent to prepare the chiral alpha-hydroxy-beta-dicarbonyl compound, wherein the maximum yield is 99%, and the maximum enantiomeric excess value is 98%. The inert solvent comprises halohydrocarbon, aromatic hydrocarbon, alkane and the like. The oxidizer is common organic peroxide. The ratio of the oxidizer to the beta-dicarbonyl compound is 1-20, and the reaction temperature is -70 to 50 DEG C. The organic peroxide or oxydol can be used as the oxidizer to respectively obtain two alpha-hydroxylation products in different configuration.

The invention discloses a method for preparing (R)-2-hydroxy-4-phenyl ethyl butyrate by catalyzing recombinant carbonyl reductase, which belongs to the technical field of biological engineering. The method comprises the following steps of: cloning gene segments of carbonyl reductase (IolS) and glucose dehydrogenase (GDH) from bacillus subtilis CGMCC NO.1.1508, expressing an IolS gene and a GDH gene in series by adopting a dual-starter method to construct a recombinant plasmid pET24a-G-T7-I, and introducing the plasmid into escherichia coli BL21(DE3); and under the condition of not adding or adding a small amount of NADP+cofactors, performing biotransformation by taking a cell-free extract of the escherichia coli recombinant plasmid as a catalyst, 2-oxo-4-phenyl ethyl butyrate as a substrate and glucose as a substrate to obtain (R)-2-hydroxy-4-phenyl ethyl butyrate, wherein the enantiomeric excess value of the product is higher than 99.5 percent. In the method, IolS and GDH are co-expressed, so that efficient regeneration of an intra-cellular cofactor NADP(H) is realized, production cost is lowered, and a good industrial application prospect is achieved.

A catalysis system used by a method for synthesizing chiral cyclic amine through catalyzing asymmetric hydrogenation of quinolin-3-amine by iridium is a chiral diphosphine complex of iridium. A reaction is carried out under the following conditions: the temperature is 25-70DEG C; a solvent is a toluene/tetrahydrofuran mixed solvent (V/V=3:1); the pressure is 2-14atm; a ratio of a substrate to a catalyst is 25:1; and the catalyst is a (1,5-cyclooctadiene)iridium chloride dimer and chiral diphosphine ligand complex. A corresponding chiral cyclic amine derivative is prepared from quinolin-3-amine, and the enantiomeric excess value can reach 94%. The method has the advantages of simple and practical operation, easily available raw material, high enantioselectivity, good yield, and green, atom-economic and environmentally-friendly reaction.

The invention discloses a method for asymmetric synthesis of levorotation menthol. The method comprises the following steps: citral is taken as an initial raw material, a dihydropyridine derivant is taken as a negative hydrogen source, chiral amine serves as a chiral auxiliary agent for catalytic and asymmetric hydrogenization synthesis of dextrorotation citronellal, the dextrorotation citronellal is catalyzed by Lewis acid for ring-closing synthesis of levorotation isopulegol, and the levorotation isopulegol is subject to catalytic hydrogenation to finally produce the levorotation menthol. The total yield of the levorotation menthol produced by adopting the method is larger than 60 percent, and the ee (enantiomeric excess) value is larger than 90 percent. The method has the characteristics of mild reaction conditions, simple synthetic process, simplicity in catalyst preparation, convenience in catalyst recovery and the like and is suitable for large-scale industrial production of levorotation menthol.

The present invention provides a process for stereoselectively reducing 2-[3-[3-[2-(7-chloro-2-quinolinyl)ethenyl]-phenyl]-3-oxopropyyl]benzoic-acid methyl ester, to produce to produce methyl 2-[3-(S)-[3-[2-(7-chloro-2-quinolinyl)-ethenyl]phenyl]-3-hydroxypropyl]benzoate, and a process for producing montelukast or a salt thereof. The present invention further provides a process for purifying methyl 2-[3-(S)-[3-[2-(7-chloro-2-quinolinyl)-ethenyl]phenyl]-3-hydroxypropyl]benzoate. The reduction process of the present invention uses a chiral reagent and can produce the desired reduction product in high enantiomeric excess (ee).

The invention discloses a method for biologically preparing (S)-4-chloro-3-hydroxy butyric acid ethyl ester with recombinant escherichia coli expressed ketoreductase and application thereof in preparing (S)-4-chloro-3-hydroxy butyric acid ethyl ester through asymmetric reduction of 4-chloroacetoacetic acid ethyl ester. The recombinant escherichia coli for expressing the gene of the ketoreductase (KRED) is coupled with glucose dehydrogenase (GDH) so that the escherichia coli cell is recombined into a catalyst; efficient preparation of (S)-4-chloro-3-hydroxy butyric acid ethyl ester through asymmetric reduction of 4-chloroacetoacetic acid ethyl ester in a single water phase is realized no matter in the presence of or in the absence of coenzyme NAD(P)H; and the molar transformation rate is higher than 92% and the enantiomer excess (e.e.) of the product is 100%.

PCT No. PCT/GB97/00023 Sec. 371 Date Jul. 2, 1998 Sec. 102(e) Date Jul. 2, 1998 PCT Filed Jan. 6, 1997 PCT Pub. No. WO97/25330 PCT Pub. Date Jul. 17, 1997The subject invention concerns a process for the preparation of enantiomerically-enriched galanthamine from racemic galanthamine, and a process for increasing the enantiomeric excess of enantiomerically-enriched galanthamine, by direct crystallization of galanthamine salts.

The invention relates to a method for synthesizing chiral beta-acetenyl ketone by catalytic intermolecular decarboxylation from beta-ketonic acid and a propargyl compound. A chiral copper catalyst adopted in the invention is synthesized in stiu from a copper salt and a chiral P,N,N-tridentate ligand in various polar solvents and nonpolar solvents. According to the invention, various chiral beta-acetenyl ketone compounds with substituent groups can be synthesized conveniently, and can obtain a percent enantiomeric excess as high as 95%. The method in the invention is advantaged by operational simplicity, available raw materials, wide substrate application range, high enantioselectivity, and the like.

The invention discloses a method for synthesizing a chiraltetrahydro naphthalenederivate through asymmetric hydrogenation on isoquinoline by means of an iridium catalyst. A catalysis system applied in the method is a chiral bi-phosphine complex of metal iridium. The reaction is carried out under the conditions that the temperature is 25-60 DEG C; the volume ratio of tetrahydrofuran to dichloromethane in a solvent, namely a mixed solvent of tetrahydrofuran and dichloromethane is 1:1; the pressure is 13-50 Mpa; the ratio of a substrate to a catalyst is 50:1; the catalyst is a coordination compound of a (1,5-cyclooctadiene) iridium chloridedipolymer and a chiral bi-phosphine ligand. The corresponding chiral 1-position or 3-position substituted tetrahydro naphthalenederivate through hydrogenation on isoquinoline, and the enantiomeric excess of the derivate can reach 96%. The method is simple and practical in operation, raw materials are easy to obtain, the enantioselectivity is high, the yield is high, the reaction has atom economy, and the environment is friendly.

The invention discloses nitrilase from brassica rapa, encoding genes and an application of the encoding genes to the preparation of pregabalin chiral intermediate (S)-3-cyan-5-methylhexanoic acid through biocatalysis, and an amino acid sequence of the nitrilase is shown as SEQ ID NO:1. The invention provides novel nitrilase for preparing the (S)-3-cyan-5-methylhexanoic acid with high region and high stereoselectivity through hydrolysis, the concentration of hydrolysis substrates of the nitrilase can reach more than 1 M, and an ee (enantiomeric excess) value is kept more than 99 percent. The pregabalin important chiral intermediate (S)-3-cyan-5-methylhexanoic acid can be prepared through the nitrilase; a preparation method of the (S)-3-cyan-5-methylhexanoic acid has the advantages of high atom economy, mild conditions, environmental friendliness and the like and has high industrial application potential.

The invention discloses an application of aldo-keto reductase in catalytic generation of (R)-4-chlorine-3-hydroxy ethyl butyrate. With aldo-keto reductase of which an amino acid sequence is as shown in SEQ ID NO:2 as a catalyst, with 4-ethyl acetoacetate as a substrate and NADPH as a cofactor, the (R)-4-chlorine-3-hydroxy ethyl butyrate is prepared by asymmetric reduction. The aldo-keto reductase of which the amino acid sequence is as shown in SEQ ID NO:2 is applied to the 4-ethyl acetoacetate to prepare the (R)-4-chlorine-3-hydroxy ethyl butyrate in an asymmetric reduction manner for the first time, so that a good effect is obtained; the enzyme activity can be up to 8.1U/mg; the conversion ratio of the aldo-keto reductase on the substrate can be up to 99.8%; the enantiomer excess value of the product is greater than 995; the yield is high; and the production cost is greatly reduced.

The invention discloses a method for performing the asymmetric catalytic hydrogenation of ketone-derived N-alkylimine. In the method disclosed by the invention, the catalytic hydrogenation of the ketone-derived N-alkylimine is performed in the presence of a chiral catalyst formed by a chiral diamine ligand and a transitional metal to obtain a chiral amine product with high yield and high enantioselectivity. The enantiomeric excess of a chiral amine product formed by the hydrogenation of an acyclic N-alkylimine substrate may reach 98 percent ee; and the enantiomeric excess of a chiral amine product formed by the hydrogenation of an exocyclic N-alkylimine substrate may reach over 99 percent ee. The method disclosed by the invention realizes the asymmetric catalytic hydrogenation of ketone-derived N-alkylimine with high enantioselectivity, and the obtained chiral amine product is an important medicinal and material intermediate and has a bright actual application prospect.

The invention discloses a method for asymmetrically reducing a carbonyl compound by biocatalysis in a water/ion liquid biphasic system, which belongs to the biochemical engineering technical field. The method takes a selective strain producing carbonyl reductase as a starting strain, and prochiral ketone as a substrate to perform reducing preparation of corresponding chiral alcohol in the water/ion liquid biphasic system; the method comprises the following steps that: Aureobasidium pullulans CGMCC No.1244 is used to catalyze 4-chloro-acetoacetic acid ethyl ester to perform the asymmetrical reduction preparation of (S)-4-chloro-3-hydroxybutyric acid ethyl ester, and Saccharoinyces uvarum ATCC 26602 is used to catalyze 4,4,4-trifluoroacetoacetate to perform the asymmetrical reduction preparation of (R)-4, 4, 4-trilfluoro-3-hydroxybutyrate. The method shows the advantages of no toxicity, no smell, difficult volatilization, good biocompatibility, no environmental pollution, simple product separation, easy recovery, repeated use and so on, of ion liquid. At the same time, the method improves the transformation rate, the concentration and an enantiomeric excess value of a reaction product, and quickens the process of the reaction.

The invention provides a method for synthesizing derivatives of chiral tetrahydroquinoline by catalyzing asymmetric hydrosilylation with iridium. In the method, a used catalytic system is a chiral duplex phosphorus complex generated in situ. The reaction can be performed under the following conditions: a room temperature; a tetrahydrofuran solvent; a chlorizated cyclooctadiene iridium metallic precursor; and a chiral duplex phosphorus ligand chiral ligand. The method for preparing the catalyst comprises the following steps of: stirring the metallic precursor of iridium and the chiral duplex phosphorus ligand in the tetrahydrofuran at room temperature, adding the simple substance of iodine, stirring the mixture, and finally adding quinoline substrates, triethyl silicon hydrogen and water. By the hydrosilylation of quinoline, the corresponding derivatives of chiral tetrahydroquinoline are obtained, and the enantiomeric excess of the derivatives reaches 93 percent. The method has the advantages of easy and practical operation, readily available raw materials, high antipodal selectivity, high yield, no use of dangerous articles such as hydrogen gas and the like, safety and reliability; in addition, the reaction is environment-friendly.

The invention belongs to the technical fields of organic synthesis and provides a novel method for asymmetric alpha-hydroxylation of a photo-oxygenation beta-dicarbonyl compound based on a C-2' phase transfer catalyst.The beta-dicarbonyl compound, the cinchona alkaloid C-2' phase transfer catalyst and an organic photosensitizer are stirred in a solvent, alkali is added, strong stirring reaction is performed in the air under the condition of visible light, the reaction temperature is 50-70 DEG C, the reaction time is 1-4 hours, and a chiral alpha-hydroxyl-beta-dicarbonyl compound with the yield no lower than 70% and the enantiomeric excess selectivity no lower than 60% ee is obtained; derivatization is conducted on a cheap cinchona alkaloid C-2' potential easy to obtain a series of chiral phase transfer catalysts having higher catalytic activity, molecules are successively oxidized into an oxidant, and the asymmetric alpha-hydroxylation of the photo-oxygenation beta-dicarbonyl compound is achieved.The method has good substrate applicability and environmental friendliness.