24 results about "Kinetic resolution" patented technology

The invention provides a method for regulating and controlling dynamic kinetic resolution of spiral polycyclic aromatic hydrocarbon based on an inorganic chiral surface and application, and the method comprises the following steps: S1, rotating a substrate clockwise or anticlockwise, and depositing an inorganic material on the substrate by adopting a physical vapor deposition method to obtain an inorganic chiral nano material layer; wherein the contact angle between the inorganic material and N, N-dimethylformamide is less than 22 degrees, and the deposition angle and the normal direction of the substrate form an angle of 86 degrees or 0 degree; s2, dissolving spiral polycyclic aromatic hydrocarbon molecules needing to be split into N, N-dimethylformamide to obtain a solution; then dropwise adding to the surface of the inorganic chiral nano material layer to obtain a sample; and S3, annealing the sample at 40-50 DEG C, and obtaining the homochiral aggregate after the solvent is completely evaporated. The technical scheme provided by the invention is high in controllability, strong in universality and good in stability, and can be used for efficiently preparing chiral compounds with specific configurations.

The application discloses a kind of S-delta-substituted caprolactam chemical / enzyme series preparation method, and the specific preparation method is: 1-substituted high allyl amine occurs dynamic kinetic resolution reaction with acrylic ester compound under the catalysis of alkaline protease (special treatment) and generates S-acryl (1-substituted high allyl) amine, then the product occurs intramolecular olefin metathesis under the catalysis of Grubbs reagent and finally generates S-delta-substituted caprolactam shown in formula (1), wherein, substituent R is phenyl, halogenated phenyl or C2-C12 alkyl.The application has mild reaction condition, is conducive to reducing the equipment requirement of preparation process, improves synthesis safety and economy;Secondly, the reaction course of the method is simple, and single configuration S-delta-substituted caprolactam can be obtained by one-pot reaction, with very high atom economy.

This invention discloses a method for the kinetic resolution of oxaspirone via organocatalytic hydrogenolysis. Using chiral phosphate CPA as a catalyst, Hantzsch ester as a hydrogen source, and racemic oxaspirone 2,4-dien-6-one rac-1 as a substrate, a series of axially chiral biaryl phenolic compounds 2 are synthesized via asymmetric hydrogenolysis, and the central chiral oxaspirone 1 is recovered. This invention offers advantages such as simple and practical operation, readily available raw materials, high resolution coefficient, and good enantioselectivity. Some of the axially chiral biaryl products have structures similar to axially chiral cannabinol, possessing potential medicinal value.

The application belongs to the technical field of medicine and chemical industry, and particularly discloses a synthesis method of chiral epichlorohydrin.The chiral Salen Co(II) is in-situ oxidized, and then is reacted with TsOH or PhSO3H to obtain a catalyst Salen Co(III) OTs or Salen Co(III) SO3Ph, which is used to catalyze the asymmetric kinetic resolution of racemic epichlorohydrin and TsOH or PhSO3H at a certain temperature, and chiral epichlorohydrin is obtained at a high yield.In addition, the reaction raw material and the catalyst can be recycled and reused.

The invention belongs to the technical field of chiral resolution of organic compounds, and particularly discloses a method for obtaining 1S, 5R-pinanol by chiral carboxylic acid-mediated dynamic kinetic resolution of trans-pinanol, which comprises the following steps: dissolving trans-pinanol, chiral carboxylic acid and a solid acid catalyst in a solvent, stirring at a proper temperature, and reacting to obtain the 1S, 5R-pinanol. The method comprises the following steps: carrying out selective esterification reaction on trans-pinyl hydrate to generate a chiral ester intermediate, carrying out rapid racemization on unreacted trans-pinyl hydrate, after the reaction is finished, filtering and recovering a solid acid catalyst, carrying out reduced pressure rectification on filtrate, separating a product chiral ester and recovering a solvent, and further hydrolyzing the chiral ester in an alkaline system to obtain optically pure 1S, 5R-pinyl hydrate, and recovering the chiral carboxylic acid. The optically pure 1S, 5R-pinyl hydrate is prepared in a green and efficient manner by utilizing the catalytic synergistic effect of chiral carboxylic acid and solid acid, and the method has the advantages of high enantioselectivity, high raw material utilization rate, good process adaptability and good industrial application prospect.

This invention discloses a method for synthesizing ferrocene-isoquinoline and ferrocene-dihydroisoquinoline planar chiral compounds, belonging to the field of asymmetric catalysis technology. Using chiral phosphoric acid (CPA) as a catalyst, 1,4-dihydropyridine compound (HEH) as a hydrogen source, and racemic ferrocene-isoquinoline derivative (+ / -)-1 and ditert-butyl dicarbonate as substrates, two types of planar chiral ferrocene compounds are synthesized through asymmetric transfer hydrogenation resolution. The enantiomeric excess of the ferrocene-isoquinoline planar chiral compounds can reach 95%, while the enantiomeric excess of the ferrocene-dihydroisoquinoline carboxylic acid tert-butyl ester planar chiral compounds can reach 89%, with a resolution coefficient (S value) reaching 50. This invention achieves the hydrogenation kinetic resolution of ferrocene-isoquinoline compounds, is simple to operate, uses commercially available catalysts, operates under mild reaction conditions, and exhibits good resolution effects, showing excellent application prospects.

The application belongs to the technical field of medicine synthesis, and particularly relates to an alpha-methenyl-gamma-butyrolactone compound and an asymmetric kinetic resolution synthesis method thereof. The compound provided by the application is shown as formula I. The application provides a simple, efficient and alpha-methenyl-gamma-butyrolactone compound synthesis method. The series of compounds prepared have good antitumor activity and good application prospect.

The invention relates to the technical field of biological engineering and biological catalysis, in particular to an alcohol dehydrogenase mutant and application thereof. The invention discloses an alcohol dehydrogenase mutant CpAR2-M5 (F85A / T125S / F192L / E209A / I213F). The corresponding amino acid sequence of the alcohol dehydrogenase mutant CpAR2-M5 is shown as SEQ ID No. 3. The invention also discloses a preparation method of the alcohol dehydrogenase mutant CpAR2-M5. The S-configuration axial chiral biaryl dimethyl carbinol compound can be applied to dynamic kinetic resolution asymmetric reduction of the biaryl dimethyl carbinol compound so as to prepare the S-configuration axial chiral biaryl dimethyl carbinol compound, the highest yield can reach 95%, the highest stereoselectivity can reach 99% ee, and a green, efficient and high-stereoselectivity synthesis strategy is provided for subsequent synthesis of the compound.

The application belongs to the field of bioengineering and biocatalysis technology, and particularly relates to an alcohol dehydrogenase mutant and application thereof. The application discloses an alcohol dehydrogenase mutant CcPAR-M1 (V158L), and an amino acid sequence of the mutant is shown as SEQ ID No. 3. The mutant can be used for catalyzing asymmetric reduction reaction of a biaryl aldehyde substrate through dynamic kinetic resolution to generate R an axially chiral biaryl dimethanol compound. By using the biocatalytic system disclosed in the application, the highest yield of the target product can reach 96%, and the enantiomeric excess value can reach 99% ee at most. The method provides a green, efficient and excellent stereoselective biocatalytic strategy for construction of the axially chiral biaryl dimethanol compound.

This invention discloses a method for resolving racemic mixtures based on dynamic kinetics, belonging to the field of catalysis technology. The method includes the following steps: taking a proton-selective permeable membrane and pretreating it; using the pretreated proton-selective permeable membrane to separate the aqueous phase and organic phase for reaction, thereby resolving the racemic mixture; wherein the aqueous phase is an acid solution, and the organic phase contains at least the racemic mixture, an acyl donor, an enzyme, and an organic solvent, and the racemic mixture is a racemic mixture of a chiral secondary alcohol or its derivative. This invention utilizes a proton-selective permeable membrane as a racemic catalyst applied to the dynamic kinetic resolution process, solving the problem of incompatibility between racemic catalysts and enzyme catalysts in conventional dynamic kinetic resolution techniques. This method has advantages such as a simple reaction system, easy process control, environmental friendliness, simple post-processing, and low cost.

The application discloses a preparation method of a chiral phthalic ester prodrug and relates to the technical field of organic chemical synthesis. In the application, isothiourea is used as a Lewis base catalyst, and acyl chloride is used as an acylating agent, so that an acylation dynamic kinetic resolution process of racemic 3-hydroxyisobenzofuran-1(3H)-one (hereinafter referred to as phthalide) is realized, thereby forming a chiral phthalic ester with good to excellent yield and enantioselectivity and natural products and drugs containing the structure.

The invention provides a method for constructing a planar chiral [2, 2] paracyclophane compound by activating asymmetric carbon-hydrogen bonds under the catalysis of cobalt, which comprises the following steps: under the action of a cobalt catalyst and a chiral assistant, carrying out asymmetric C-H activation reaction on aryl hydrazone and racemic 4-ethynyl-[2, 2] paracyclophane, and carrying out kinetic resolution on the racemic 4-ethynyl-[2, 2] paracyclophane to obtain the planar chiral [2, 2] paracyclophane compound. After the reaction is finished, separation is carried out to obtain planar chiral 4-ethynyl-[2, 2] paracyclophane and a planar chiral 4-isoquinoline-[2, 2] paracyclophane compound; the invention further develops a research technology for catalyzing C-H activation by a cheap transition metal, and expands a synthetic strategy of the planar chiral [2, 2] paracyclophane compound; the reaction substrate is wide in adaptability, and the product is high in stereoselectivity; the multi-planar chiral [2, 2] paracyclophane compound is synthesized, the synthesis method is simple and convenient, the atom economy is good, and the synthesis efficiency is high.

An imine reductase mutant and the use thereof in the preparation of a tofacitinib chiral amine building block. By means of an enzymatically coupled coenzyme regeneration system, the imine reductase mutant can efficiently catalyze racemic 1-benzyl-4-methylpiperidin-3-one as a substrate to undergo dynamic kinetic resolution and asymmetric reductive amination, so as to accurately synthesize a tofacitinib chiral amine building block (3R,4R)-1-benzyl-N-4-dimethylpiperidin-3-amine. Compared with conventional resolution methods, the technology has the significant advantages of simple operation, mild reaction conditions, environmental friendliness, high product yield, low cost, etc., and exhibits excellent application prospects in the synthesis of tofacitinib chiral amine intermediates.

The invention discloses a method for synthesizing an axially chiral isoquinoline naphthalene compound based on nickel / light concerted catalysis, and belongs to the field of organic chemical synthesis. According to the present invention, the racemic isoquinoline naphthalene derivative is subjected to kinetic resolution, such that the target axial chiral isoquinoline naphthalene compound is synthesized with high yield and high enantioselectivity; according to the method, an isoquinoline naphthalene derivative and carboxylic acid are taken as raw materials and react under the action of a nickel catalyst, a chiral oxazoline ligand, a photosensitizer and alkali through visible light irradiation, so that efficient synthesis of a target product and efficient recovery of the raw materials are realized. Further, the axially chiral compound can be converted into a corresponding N-oxide catalyst through an oxidation reaction. The catalyst shows excellent catalytic activity and stereoselectivity in an asymmetric allylation reaction. The method has the advantages of mild reaction conditions, simplicity and convenience in operation, wide substrate applicability, high enantioselectivity, good atom economy and the like, and has an important industrial application prospect.

This invention discloses a method for the deracemization of benzyl sulfoxide catalyzed by a dual-enzyme catalyst. The method includes the following steps: a) culturing and expressing genetically engineered bacteria producing cyclohexanone monooxygenase and sulfoxide reductase separately in LB medium, collecting the bacterial cells by centrifugation, and resuspending the cells in PBS buffer to obtain bacterial suspensions; b) mixing the two bacterial suspensions obtained in step a), racemic benzyl sulfoxide, DTT, and D-glucose, and reacting with shaking at 30°C; c) after the reaction is complete, extracting multiple times with an organic solvent, combining the organic phases, drying with anhydrous sodium sulfate, filtering, and recovering the solvent to obtain the target product. This invention achieves the deracemization of benzyl sulfoxide through dual-enzyme catalysis, resulting in a product with high optical purity and low raw material cost. The dynamic kinetic resolution method in aqueous solution is simple to operate, with mild reaction conditions, environmentally friendly operation, high substrate conversion rate, and good stereoselectivity.

The invention discloses a method for synthesizing chiral fluorine-containing quaternary carbon unsaturated ketone through ruthenium catalytic transfer hydrogenation kinetic resolution, the fluorine-containing quaternary carbon unsaturated ketone is used as a reaction substrate 1, a chiral dinitrogen ligand of ruthenium is used as a catalyst, the chiral fluorine-containing quaternary carbon unsaturated ketone 1 'is synthesized through asymmetric transfer hydrogenation kinetic resolution, and the selectivity factor can reach 214.4. The method is simple and practical to operate, excellent in enantioselectivity and diastereoselectivity and wide in substrate range, and the reaction is green, atom-economical and environment-friendly.

The application provides a synthesis method of a key intermediate of florfenicol, and particularly relates to a preparation method of (1R,2R)-2-amino-1-(4-methylsulfonyl)phenyl-1,3-propanediol. The application utilizes the selectivity of ketoreductase to the substrate carbonyl ortho position chirality, realizes dynamic kinetic resolution (DKR) while reducing the carbonyl group to obtain a pure chiral compound, and then reduces the chiral compound to obtain a target product. The method is simple in process, high in selectivity, and greatly improves the product yield.

The invention discloses a preparation method of a fenerenone raw material. The preparation method comprises the following steps: (1) carrying out condensation reaction on 4-formyl-3-methoxybenzonitrile and 3-oxobutyric acid-2-cyanoethyl ester to obtain a first intermediate; (2) carrying out cyclization reaction on the first intermediate and 4-amino-5-methylpyridone to obtain a second intermediate; (3) ethylating the second intermediate to obtain a third intermediate; (4) performing hydrolysis reaction on the third intermediate to obtain a fourth intermediate; (5) carrying out ammonolysis reaction on the fourth intermediate to obtain a finelrenone raceme; and (6) performing chiral resolution to obtain the fenerenone. According to the invention, a tubular reactor is adopted for cyclization reaction, ethylene glycol diethyl ether is adopted to replace low alcohol as a solvent, and processes such as dynamic kinetic resolution under catalysis of beta zeolite and ammonium iodide are adopted, so that the content of sensitive impurities in the material is greatly reduced, and the quality level of the product is greatly improved; the market competitiveness of the product is improved, the yield of the product is improved, and the production cost of the product is reduced.

The invention discloses a method for preparing (1R, 2S)-2, 6-dimethyl-1H-indene-1-amine, and relates to the technical field of synthesis of herbicide indaziflam. The invention relates to a high-temperature-resistant and high-pressure-resistant polyester resin, which is prepared from the following components in parts by weight: 26.1 to 63.0 parts of Ritter reaction component and 42.0 to 123.5 parts of hydrolysis reaction component, and the Ritter reaction component is prepared from the following components in parts by weight: 10.0 parts of (1S, 2S)-2, 6-dimethyl-1-hydroxyindane, 10.0 to 40.0 parts of cyanide, 0.1 to 2.0 parts of acid catalyst and 5.0 to 10.0 parts of Ritter reaction solvent. According to the method disclosed by the invention, the Ritter reaction and the acid-promoted hydrolysis two-step reaction are matched, and the (1S, 2S)-2, 6-dimethyl-1-hydroxyindane, the cyanide, the preferable acid catalyst NTPA and the L-camphorsulfonic acid are matched; the preparation method solves the problems of difficulty in chiral control, mixing of multi-configuration isomers and low target product yield which is generally lower than 65% in an azide method and a dynamic kinetic resolution method in the existing preparation method, does not generate redundant chiral isomers, can directly meet the requirements of products such as indaziflam and the like as downstream herbicides on high-purity chiral intermediates, avoids a subsequent complex resolution process, and is suitable for industrial production. And the downstream production efficiency is improved.

The invention discloses a method for preparing chiral alkynyl phosphine oxide through palladium-catalyzed asymmetric cross-coupling reaction, which is characterized in that racemization secondary phosphine oxide and chloro alkyne are used as raw materials, and asymmetric construction of a C (sp)-P bond is realized in a kinetic resolution mode. The reaction conditions are mild, the yield is up to 90% or above, and the ee value can also reach 90% or above. The chiral alkynyl phosphine is prepared through the asymmetric palladium catalysis reaction, raw materials are cheap and easy to obtain, reaction conditions are mild, experimental operation is simple, the yield is high, the chiral maintaining effect is good, the method is an economical and efficient synthesis route, a new route is provided for synthesis of chiral alkynyl phosphine oxide, and the method can be suitable for industrial production.

The present invention relates to a process for the preparation of chiral alpha-amino acids using a protease enzyme in combination with catalytic amounts of an aldehyde for the racemization of an unwanted isomer in a miniemulsion system.

The application discloses a method for catalytically synthesizing optically pure (S)-alpha-fluorophenylacetate compounds by P450 enzymes and belongs to the technical field of biological catalysis and chiral synthesis. In view of the problem that (S)-configuration fluorine-containing compounds are difficult to synthesize, the method uses alpha-fluorophenylacetate derivatives as substrates, uses a P450 BM3 mutant (F87V-L188G-R47L-Y51F) obtained through directional evolution as a catalyst, and performs an oxidative defluorination reaction in the presence of a coenzyme regeneration system to obtain a target product through kinetic resolution. The optically pure (S)-alpha-fluorophenylacetate compound has an optical purity ee>96% and can be used for preparing chiral fluorine-containing medical intermediates.

The present invention provides engineered carboxyesterase enzymes having improved properties as compared to a naturally occurring wild-type carboxyesterase enzymes, as well as polynucleotides encoding the engineered carboxyesterase enzymes, host cells capable of expressing the engineered carboxyesterase enzymes, and methods of using the engineered carboxyesterase enzymes in hydrolysis reactions.

The application discloses a preparation method of a telaprevir intermediate and telaprevir, wherein compound 6 and compound 9 or compound 13 are subjected to 2-step reaction or 3-step reaction respectively to obtain compound 15; and 1-phenyl-3-hexanone is used as an initial raw material to obtain compound 20, i.e., telaprevir, through a Reformatsky reaction, hydrolysis, kinetic resolution, condensation, cyclization, asymmetric allylation reaction, reduction and sulfonamidation reaction. The synthesis route is short and efficient, simple to operate, safe and easy to obtain raw materials, and the reaction condition is mild, the reaction yield is high, the reaction steps and synthesis cost are reduced, and the method is more suitable for industrial production.