31results about How to "High optical purity" patented technology

The invention relates to the field of novel medical compounds, in particular to a chiral synthesis method of epigalanthamine hydrobromide which is a key impurity of galanthamine hydrobromide. An intermediate easy for industrial production is used as a raw material, and epigalanthamine hydrobromide is synthesized in one step through a chiral reducing agent. The synthesis method utilizes intermediates in the existing industrial production process, has the advantages of simple steps, low reagent cost, high yield, high optical purity of the product and the like, and greatly facilitates preparation of impurities of galanthamine and further development of a pharmaceutical analysis method of galanthamine.

This invention provides an imine reductase mutant, its preparation method, and its application in the catalytic preparation of dextromethorphan intermediates. The imine reductase mutant is an imine reductase with an amino acid mutation, comprising the amino acid sequence shown in SEQ ID NO:1. The amino acid mutation type includes any one or a combination of at least two of I122T, D212A, or G228R. By introducing a mutation into the imine reductase, this invention significantly improves the enzyme's activity and stereoselectivity, enabling the high-yield synthesis of the dextromethorphan intermediate (S)-1-(4-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline under mild conditions, greatly reducing production costs and making it suitable for industrial production.

The invention discloses a piperidine compound crystal form and a preparation method thereof. The invention provides a crystal form A of compounds 1-13, which uses Cu-K alpha radiation, and an X-ray powder diffraction pattern represented by a 2 theta angle has diffraction peaks at 6.42 degrees + / -0.20 degrees, 11.80 degrees + / -0.20 degrees, 17.46 degrees + / -0.20 degrees, 18.18 degrees + / -0.20 degrees, 18.58 degrees + / -0.20 degrees and 19.34 degrees + / -0.20 degrees. According to the preparation method of the compound 1-13, the compound 1-13 with the single stereo configuration is obtained, and then the compound 1 with the single stereo configuration is obtained. The chemical purity and optical purity of the compound 1 are improved, the production cost is greatly reduced, and the production scale is greatly enlarged, so that the method is more suitable for industrial production. # imgabs0 #

The invention discloses a chiral alpha-alkenyl substituted carboxylic ester compound and an asymmetric preparation method thereof, and the chiral alpha-alkenyl substituted carboxylic ester compound is an optically active compound with a structure as shown in the following formula I, and comprises a stereoisomer with the same chemical general formula, in the formula, * represents a chiral carbon atom; ar is an aromatic ring or a substituted aromatic ring; r1, R2, R3, R4 and R5 are respectively and independently selected from hydrogen, halogen, alkyl or alkoxy of C1-10, aryl and trifluoromethyl; r6 is independently selected from H, C1-10 alkyl or alkoxy, aryl or substituted aryl, and a substituent group of the substituted aryl is selected from halogen and C1-10 alkyl. According to the invention, the chiral alpha-alkenyl substituted carboxylic ester compound is accurately and rapidly synthesized with high yield, high stereoselectivity and gram-level scale. The preparation method is simple, and has biomedical practicability and industrial application prospects.

The invention discloses a production process for blue glass, and relates to the technical field of blue glass production. The process comprises the following steps: S1, raw material pretreatment: respectively grinding and drying a basic glass raw material, a coloring agent and a functional additive, and then mixing in sequence; s2, melting the mixture in a primary melting furnace in a reducing atmosphere, and adding a reducing agent; s3, transferring the primarily molten glass liquid into a main furnace, and stirring and clarifying in a nitrogen-oxygen mixed protective gas environment; s4, cooling the clarified glass liquid, and continuously stirring and homogenizing; according to the preparation method, the basic raw materials, the coloring agent and the functional additive are accurately proportioned, and control steps of staged mixing, reducing atmosphere melting, multi-stage clarification and homogenization, float forming and the like are combined, so that synergistic improvement of high optical purity and excellent mechanical performance is realized. In the process, the purity, the granularity, the charging sequence and the thermal regulation of the raw materials are strictly controlled, so that the component uniformity and the product consistency are guaranteed.

The present invention discloses a novel chiral ligand, a metal chelate, a plurality of unnatural amino acids, a method for synthesizing maraviroc and a key intermediate thereof. The present invention selects (R)-2-methylproline as a starting material, utilizes nickel chelate to induce asymmetric splitting to obtain (S)-β 3 ‑amino acid, and (S)‑3‑amino‑3‑phenylpropionic acid as a key intermediate to synthesize maraviroc with high yield and ee value of more than 98.2%. The method of the invention has a wide source of raw materials, mild synthesis process conditions, easy control, and high optical purity of the product.

The application discloses a lysine cyclodeaminase, mutants, recombinant genetically engineered bacteria and application thereof. The amino acid sequence of the lysine cyclodeaminase is shown as SEQ ID NO. 1. The lysine cyclodeaminase mutants include: mutants I61V, I94V, I233V and A235S obtained by taking the lysine cyclodeaminase with the amino acid sequence shown as SEQ ID NO. 1 as a template and respectively mutating the 61st, 94th, 233rd and 235th positions, a mutant I233V / A235S obtained by iterative saturation mutation of the 233rd and 235th positions, and mutants I94V / I233V / A235S and I61V / I94V / I233V / A235S obtained by hot combination mutation. The lysine cyclodeaminase and the mutants thereof obtained according to the application have high enantiomeric selectivity and activity, and can catalyze L-lysine to generate optically pure L-piperidinecarboxylic acid.

The invention belongs to the technical field of production of L-lactic acid, and particularly relates to a production method of lactic acid, which comprises the following steps: carrying out filter pressing on lactic acid fermentation liquor, filtering by a nanofiltration membrane, concentrating in a concentrator to obtain lactic acid concentrated liquor, evaporating the lactic acid concentrated liquor in a vacuum wiped-film drum evaporator, and distilling and purifying in a molecular distillation purifier to obtain the L-lactic acid. The separation of lactic acid and other trace impurities is realized, high-quality lactic acid is obtained, the optical purity of the L-lactic acid is 99.2% or above, a large amount of organic impurities and inorganic salts are removed firstly, then molecular distillation purification is used for further purification, the efficient purification of the L-lactic acid is realized, and the optical purity and the yield of the L-lactic acid product are remarkably improved.

The invention relates to the technical field of organic chemistry, and particularly discloses an alpha hydroxyl beta keto ester compound and an asymmetric hydrogenation preparation method thereof.The asymmetric hydrogenation preparation method comprises the steps that in the presence of a chiral ligand f-phamidol and a metal precursor complex catalyst, a compound shown in the structural formula I reacts with hydrogen to obtain a key chiral intermediate II compound, and the key chiral intermediate II compound is subjected to asymmetric hydrogenation to obtain the alpha hydroxyl beta keto ester compound. According to the method, the specific chiral tetradentate phosphine ligand and metal iridium are adopted to form the catalyst to be applied to asymmetric hydrogenation of ketone, the reaction obtains excellent reaction activity under the condition of high conversion number, and the method has the advantages that the raw materials are cheap and easy to obtain, the operation steps are simple, the yield is high, and the method is suitable for industrial production. And the method has the advantages of high catalytic efficiency, high yield, high product enantioselectivity and the like.

The invention relates to the technical field of chemical production, in particular to a method for synthesizing high-purity L-lactide. The molecular sieve is used as the carrier, the metal oxide is used as the active component, and the L-lactic acid is used as the raw material, so that the raw material cost is low, the preparation process is simple, the reaction condition is mild, the equipment investment is low, and the optical purity of the reaction product L-lactide is high; and the prepared catalyst has the advantages of good stability, small pollution to the product, easy recovery after the reaction is finished, and the prepared catalyst is especially suitable for the synthesis of catalyzing lactic acid to directly polymerize lactide, is easy to separate after the reaction is finished, and is a heterogeneous catalyst with a significant selective polymerization effect.

The invention discloses a method for synthesizing S-fluorobutyric acid amide from (R)-2-alkyl sulfonylbutyrate, which belongs to the field of organic chemical synthesis. The method comprises: the S-fluorobutyric acid amide is prepared from a compound R-1; wherein the compound R-1 is obtained by treating a compound R-2 with a compound 1; and wherein R 1 It is a C1-C6 alkyl group, and R is selected from a C1-C6 alkyl group, a C1-C6 haloalkyl group, a phenyl group, or a phenyl group independently selected from a C1-C6 alkyl group or substituted with a halogen. The present invention uses (R)-2-hydroxybutyric acid produced by large-scale microbial fermentation as a raw material, and prepares compound R-2 through esterification reaction and sulfonylation reaction. The key chiral intermediate R-1 is obtained by a classical SN2 substitution reaction in which intermediate 1 and compound R-2 undergo a configuration flip. After the preparation of R-1, S-fluorobutyric acid is prepared, which has low cost, low pollution, good safety, high yield, and excellent optical purity.

The invention provides a preparation method of ((1R, 3S)-3-hydroxycyclopentyl) tert-butyl carbamate, which comprises the following steps: (1) mixing (R)-3-oxocyclopentane carboxylic acid with alkali, diphenyl azide phosphate and tert-butyl alcohol for reaction to obtain an intermediate; and (2) mixing the intermediate with a chiral catalyst and borane for reaction to obtain ((1R, 3S)-3-hydroxycyclopentyl) tert-butyl carbamate. The preparation method provided by the invention has the advantages of cheap and easily available raw materials, simple process operation, safe and controllable production and high optical purity of the target product, and can meet the requirements of industrial production.

The invention discloses a preparation method of esomeprazole: in a solvent, omeprazole sulfide is used as a starting raw material, D-diethyl tartrate and 2-ethyl-1-hexyl titanium are used as inducing agents, and phthaloyl peroxide is asymmetric oxidized to obtain high-yield esomeprazole, wherein the ee% is above 99.6%, the peroxide impurity "sulfone" is less than 0.032%, no titanium residue is present, and the method is suitable for industrial production.

This invention, entitled "A Method for Preparing Milobalin Benzylsulfonic Acid," belongs to the field of organic synthesis technology. The technical problem to be solved is to improve the yield and purity of Milobalin Benzylsulfonic Acid, while ensuring convenient, environmentally friendly, and safe operation. The key technical points are: a method for preparing Milobalin Benzylsulfonic Acid, comprising the following steps: S1, using Formula 1 as a raw material, an esterification reaction is carried out to obtain Formula 2; S2, using Formula 1 as a raw material, a TL100L lipase reaction is used to obtain Formula 3; or using Formula 2 as a raw material, a CALB lipase hydrolysis is used to obtain Formula 3; S3, using Formula 3 as a raw material, an ammonolysis reaction is carried out under the action of a catalyst to obtain Formula 4; S4, using Formula 4 as a raw material, a Hoffmann reaction is carried out to obtain Formula 5; S5, using Formula 5 as a raw material, a salt-forming reaction is carried out with benzylsulfonic acid to obtain the final product.

This invention discloses a method for preparing (S)-nicotine and its intermediates. Specifically, this invention discloses a method for preparing a compound as shown in Formula 3, which includes the following steps: the compound as shown in Formula 4 and an amino donor undergo an amino-transfer reaction as described below under the action of a transaminase to prepare the compound as shown in Formula 3. The transaminase is a transaminase purchased from Shangke Biopharmaceutical Co., Ltd., which is selected from one or more of the following enzymes: enzyme with catalog number ES-ATA-105, enzyme with catalog number ES-ATA-109, enzyme with catalog number ES-ATA-118, enzyme with catalog number ES-ATA-121, and enzyme with catalog number ES-ATA-123.

The invention discloses a method for preparing fenerenone from a fenerenone raceme and refining and crystallizing an intermediate. Chirally substituted tartaric acid ester is adopted to prepare an intermediate, namely, a non-nepetenone diastereomer salt III, and then the non-nepetenone diastereomer salt III is subjected to alkali dissociation to prepare the non-nepetenone (IIa). According to the invention, by adding a refining and crystallizing method of the intermediate fenerenone diastereomer salt (III), the ee value obtained by the prepared intermediate fenerenone diastereomer salt (III) is higher than 99.5%, and the e.e value in a fenerenone bulk drug further prepared on the basis is basically 100%; a resolving agent tartrate is not detected in the free fenerenone enantiomer, product loss and three-waste generation caused by multiple dissociation are avoided, the production and manufacturing cost is greatly reduced, the product prepared by the method is high in yield and low in three-waste pollution, the preparation process is extremely simple to operate, the reaction condition is mild, the production cost is saved, and the method is suitable for industrial production. The method is suitable for industrial production.

The invention discloses a chiral dicarbonyl compound and an asymmetric preparation method thereof, and the chiral dicarbonyl compound is an optical active compound with a structure as shown in the following formula I, and comprises a stereoisomer with the same chemical general formula: # imgabs0 # in the formula: * represents a chiral carbon atom; n is 0, 1 or 2; ar is an aromatic ring or a substituted aromatic ring; r1, R2, R3, R4 and R5 are respectively and independently selected from hydrogen, halogen, C1-10 alkyl or alkoxy; r6 is independently selected from a C1-10 alkyl group or an aryl group; and R7 is independently selected from C1-10 alkyl groups or aryl groups. According to the invention, a micromolecular chiral isothiourea catalyst is applied to catalyze electrochemical asymmetric alkylation reaction as a key step, and the chiral dicarbonyl compound is accurately and rapidly synthesized with high yield, high stereoselectivity and gram-level scale. The preparation method is simple, and has biomedical practicability and industrial application prospects.

The present application relates to the technical field of delta-lactone synthesis, in particular to a high-purity delta-lactone synthesis method, comprising the following steps: using potassium carbonate to catalyze Michael addition reaction of the active methylene functional group of dimethyl malonate and the alpha, beta-alkenyl functional group of 1-octene-3-ketone to generate intermediate product I; intermediate product I generates decarboxylation reaction under the catalysis of boric acid to generate intermediate product II; chiral ligand supported nickel catalyst catalyzes asymmetric hydrogenation reaction of the delta-carbonyl functional group of intermediate product II to generate chiral delta-hydroxyl functional group, and ester exchange reaction of the chiral delta-hydroxyl functional group and the ester functional group of intermediate product II to generate chiral delta-decalactone. The present application designs and synthesizes four chiral ligand supported nickel catalysts on one hand, and designs a new route capable of synthesizing chiral delta-decalactone with high optical purity on the other hand.

The invention belongs to the technical field of biological catalysis, and particularly relates to a method for preparing (R)-citronellal through whole-cell catalysis. According to the preparation technology of the (R)-citronellal through whole-cell catalysis, escherichia coli is used as a fermentation strain, a selected induction substrate is added in the fermentation process, and expression of key enzymes synthesized by the interior of thalli and the (R)-citronellal is enhanced in microorganisms through induction and metabolic engineering means; and coenzyme factors are added in the thallus catalytic conversion process to synthesize (R)-citronellal, so that enzyme with high catalytic efficiency and specificity can be generated, and the substrate conversion rate, yield and optical purity ee value can be remarkably improved.

The invention relates to a high-selectivity synthesis method of (3S, 4R)-3-(N-benzyl-N-cyclopropyl) aminomethyl-4-hydroxypyrrolidine-1-carboxylic acid benzyl ester, 1-benzyl-3-tert-butyl-4-oxopyrrolidine-1, 3-dicarboxylate is subjected to selective reduction reaction in the presence of a chiral catalyst to obtain (3S, 4S)-3-tert-butyl-4-hydroxypyrrolidine-1, 3-dicarboxylate, and the (3S, 4R)-3-(N-benzyl-N-cyclopropyl) aminomethyl-4-hydroxypyrrolidine-1, 3-dicarboxylate is subjected to high-selectivity synthesis to obtain (3S, 4R)-3-(N-benzyl-N-cyclopropyl) aminomethyl-4- The preparation method comprises the following steps: firstly, preparing (3S, 4R)-3-((benzyl (cyclopropyl) amino) methyl)-4-((aryl formyl) oxy) pyrrolidine-1-carboxylic acid benzyl ester, then sequentially carrying out acid-catalyzed hydrolysis, condensation reaction with cyclopropylamine, reduction reaction and substitution reaction, then carrying out Mitsunobu reaction with para-substituted aryl formic acid to obtain (3S, 4R)-3-((benzyl (cyclopropyl) amino) methyl)-4-((aryl formyl) oxy) pyrrolidine-1-carboxylic acid benzyl ester, and hydrolyzing under base catalysis to obtain a target compound. The synthesis method has the advantages of high yield and high selectivity, and is expected to be used for industrial production.

The application discloses a synthesis method of chiral amino alcohol compounds. The synthesis method of the chiral amino alcohol compounds comprises the following steps: in the presence of a carbonyl reductase and a coenzyme, a carbonyl compound shown as formula II is subjected to a reduction reaction shown as formula I in an organic solvent and a buffer solution to obtain a conversion solution containing the chiral amino alcohol compound shown as formula I. 1 The application uses a racemic aziridine chiral compound as a starting material, and through enzyme reaction of recombined carbonyl reductase, a single configuration chiral amino alcohol is efficiently synthesized, an important intermediate with a high de value is obtained, and production cost is reduced.

The invention discloses a chiral dienyl substituted carboxylic ester compound and an asymmetric preparation method thereof, the chiral dienyl substituted carboxylic ester compound is an optical active compound with a structure as shown in the following formula I, and comprises a stereoisomer with the same chemical general formula: # imgabs0 # in the formula: * represents a chiral carbon atom; the substituent R is selected from hydrogen, C1-10 alkyl or aryl; ar is an aromatic ring or a substituted aromatic ring; r1, R2, R3, R4 and R5 are respectively and independently selected from hydrogen, halogen, C1-10 alkyl or alkoxy; r6 is independently selected from a C1-10 alkyl group or an aryl group; and R7 is independently selected from C1-10 alkyl groups or aryl groups. According to the invention, a chiral isothiourea catalytic electrochemical synthesis system is applied, and the chiral dialkenyl substituted carboxylic ester compound is accurately and rapidly synthesized with high yield, high stereoselectivity and gram-level scale. The preparation method is simple, and has biomedical practicability and industrial application prospects.

The invention discloses a synthesis method of chiral cyclic ether, chiral cyclic ether and application thereof, and the synthesis method comprises the following step: in the presence of a catalyst, reacting a compound as shown in a structural formula I with hydrogen to obtain the chiral cyclic ether as shown in a structural formula II. The synthesis method is simple in reaction system, easy to operate and high in economic benefit.

The invention discloses a mutant double-enzyme catalyst, application and an (S)-vitrin synthesis method, and relates to the technical field of bioengineering.Methylglyoxal reductase GRE2 (A) of candida glabrata and phosphite dehydrogenase PTDH of methylotrophicus are used as sources for modification, mutants of the candida glabrata and the phosphite dehydrogenase PTDH are screened, and the mutant double-enzyme catalyst is obtained. The key residues influencing the enzymatic properties of the initial methylglyoxal reductase and the phosphite dehydrogenase are determined, and the methylglyoxal reductase mutant and the phosphite dehydrogenase mutant with high activity are obtained at the same time. The two mutants with the highest utilization efficiency have a good catalytic effect in a reaction for catalyzing beta-acetone xyloside to prepare (S)-bose in a 22T reaction system, the overall catalytic efficiency is improved by about 43%, and the cost is reduced by about 8%.

This invention provides a novel crystalline form of phenelzine optically active intermediate IIa and its preparation method. The powder X-ray diffraction pattern of this novel crystalline form has the following characteristic diffraction angles: 8.89°, 12.78°, 19.33°, 21.43°, 22.05°, 26.77°, and 27.01°, with an error range of ±0.2° for the diffraction angle 2θ values. This invention also provides a method for preparing this novel crystalline form and its pharmaceutical applications, including its use in the preparation of phenelzine, and even its use as a chiral resolving agent in the preparation of phenelzine.

The invention discloses an N, P, O tridentate chiral ligand based on a ferrocene skeleton, and the N, P, O tridentate chiral ligand shows excellent enantioselectivity and diastereoselectivity in a Sonogashira coupling reaction. The chiral ligand can effectively control the stereochemistry of the reaction and significantly improve the optical purity of the product, and has excellent reaction yield.

The invention discloses an axially chiral thioimine compound and a preparation method and application thereof.The preparation method comprises the steps that sulfenamide, cyclic diaryl iodonium salt, copper tetraacetonitrile hexafluorophosphate, metal center chiral cobalt (III) complex anions, lithium acetate and dichloromethane react for 36 hours at the temperature of minus 10 DEG C under the protection of nitrogen, and the axially chiral thioimine compound is obtained. The axially chiral thioimine compound is obtained through separation and purification; the axial chiral sulfur imine compound prepared by the invention has a potential application of being used as a novel chiral ligand precursor, and can realize efficient synthesis of a series of axial chiral sulfur ligands.

This invention discloses an alcohol dehydrogenase derived from *Rhodotorula toruloides* and its application in the asymmetric reduction of 1-(2-chlorophenyl)-2-(1,2,3,4-tetrazol-2-yl)ethane-1-one to (R)-1-(2-chlorophenyl)-2-(1,2,3,4-tetrazol-2-yl)ethane-1-ol. The alcohol dehydrogenase can catalyze substrate conversion reactions at concentrations greater than 400 g / L, with a conversion rate >99.9% and a product ee value >99.5%. The reaction rate is fast, easily controlled, and the catalytic level is significantly improved compared to previous reports, demonstrating great potential for industrial application.

The application discloses a preparation method of brivaracetam, and the brivaracetam is synthesized through four steps from (R)-4-propylpyrrol-2-one and ethyl 2-bromobutyrate as raw materials. The preparation method of the application does not need to use a resolving agent for chiral resolution, and a hydrolytic enzyme is selected to perform stereoselective hydrolysis, so that the method has high yield, simple post-treatment and low cost, and is a process route more suitable for industrial production. The application further discloses a preparation method of a brivaracetam intermediate.

The application discloses an organic quaternary phosphonium salt microcrystal flexible X-ray scintillation screen and a preparation method and application thereof, and belongs to the technical field of organic photoelectric functional materials. The organic radiation luminescent material is prepared from triphenylphosphine and iodomethane as raw materials through a quaternary phosphonium reaction to obtain methyltriphenylphosphonium iodide crystals, and then the methyltriphenylphosphonium iodide crystals are ground, sieved, compounded with a PVA aqueous solution and drop-coated and dried to obtain the flexible X-ray scintillation screen. The preparation method has the advantages of mild reaction conditions, simple synthesis, cheap raw materials and easy product purification, and provides a new idea for preparing an organic scintillator. The PVA aqueous solution is doped with methyltriphenylphosphonium iodide microcrystals to prepare the scintillation screen, the prepared scintillation screen has the advantages of bright radiation luminescence, high imaging resolution, low detection limit, bendability and curlability, and successfully realizes static, curved surface and dynamic X-ray imaging.