102 results about "Chiral resolution" patented technology

The invention relates to the technical field of enzyme engineering, in particular to an acylase mutant and a biosynthesis method of (R)-2-aminobutanol.The acylase mutant comprises at least one of mutation of the following sites relative to wild type acylase with the amino acid sequence being SEQ ID NO: 1: T106, A625 and S413. The acylase mutant disclosed by the invention is used for synthesizing (R)-2-aminobutanol through biological catalysis, and the reaction route is as follows: the catalytic efficiency of a product is remarkably improved by the mutant, and the ee value of a chiral product is improved; according to the synthesis method, the problem of chiral resolution in the prior art is solved, the production cost is reduced, and pollution is reduced.

The invention provides a synthesis method of a selective THRbeta agonist key intermediate compound as shown in the formula (II). The synthesis method has the advantages of cheap and easily available raw materials, simple and efficient process, no need of SFC chiral resolution, high yield, controllable quality and cost, and huge industrialization prospect.

The invention provides a preparation method of an omariglitazone intermediate, which comprises the following steps: by taking p-halogenated benzaldehyde as a raw material, carrying out aldol condensation reaction, hydrolysis, decarboxylation, reduction, ring closing and the like to obtain an intermediate as shown in a formula 9, carrying out catalytic reaction, reduction reaction, ring closing and the like to obtain an intermediate as shown in a formula 13, and finally hydrolyzing to obtain a target product omariglitazone intermediate A. According to the invention, links of precious metal use and chiral resolution (key steps influencing cost and yield) in the prior art are avoided, and a method for synthesizing a single configuration through a chemical method is adopted, so that the yield is greatly improved, and the production cost is greatly reduced; meanwhile, a synthesis route is broken through, a target product is synthesized through cheap initial materials, and post-treatment is simpler and more controllable.

The invention relates to a synthesis method of milobalin or acid salt thereof, and belongs to the technical field of medicine synthesis. In order to solve the problem that chiral resolution needs to be adopted in the prior art, the invention provides a synthesis method of miloabalin or an acid salt thereof, which comprises the following steps: under the action of an organic strong base, carrying out Michael addition reaction on a compound shown as a formula III and acetonitrile in a non-polar organic solvent at a low temperature of-50 DEG C or below to obtain an intermediate product; under the alkaline condition, the intermediate product is subjected to an oxidation reaction and a hydrolysis reaction under the action of an oxidizing agent, after the reaction is finished, an intermediate product is obtained through acidification, and the intermediate product is subjected to a high-temperature decarboxylation reaction in an aprotic solvent to obtain a compound of a formula VI; and carrying out Hofmann degradation reaction on the compound of formula VI to obtain the compound of formula I miloabalin or miloabalin acid salt. The method has the advantages of high stereoselectivity, no need of chiral resolution operation, avoidance of the problem of large material loss caused by resolution, high chiral purity and high yield.

The invention belongs to the technical field of biosynthesis, and particularly relates to a method for preparing chiral alcohol through asymmetric reduction of large steric hindrance rigid ketone based on aldehyde ketoreductase and a mutant thereof. Comprising the following steps: adding a recombinant Escherichia coli wet cell for expressing aldehyde ketoreductase, a recombinant Escherichia coli wet cell for expressing formate dehydrogenase, a buffer solution, a substrate, a cosolvent, ammonium formate and coenzyme into a reaction container, reacting at a certain temperature, and after the reaction is completed, extracting, separating and carrying out rotary evaporation to obtain a product alcohol. The biological catalysis method is mild in reaction condition, environmentally friendly and high in regioselectivity and stereoselectivity, chiral resolution and heavy metal residues in products are avoided, and the defects of a chemical method are exactly overcome.

The present application relates to the technical field of organic synthesis, and particularly relates to a method for preparing (+)-crispine A by means of biological enzyme resolution. First, 6,7-dimethoxy-3,4-dihydroisoquinoline-2-oxide is subjected to 1,3-dipolar cycloaddition with allyl alcohol to obtain a first compound; then the first compound is added into a sulfonylation reagent and zinc powder to obtain a racemate second compound through a three-step continuous series reaction of primary alcohol sulfonylation, nitrogen-oxygen bond cleavage and ring formation; then the second compound is mixed with vinyl acetate and biological enzyme, and chiral resolution is carried out under the action of the biological enzyme to obtain a third compound with right-handed optical rotation and a fourth compound with left-handed optical rotation; finally, the third compound is mixed with an alkaline reagent and a sulfonylation reagent, and then secondary alcohol sulfonylation is carried out to obtain a fifth compound with right-handed optical rotation; the fifth compound is mixed with a deoxidizing reagent to carry out deoxidation reaction, and (+)-crispine A is prepared. The method is simple, green and environmentally friendly, and can be produced in large quantities.

This invention provides a method for preparing chiral epoxy compounds, chiral β-lactones, and polyhydroxyalkanoates. The method involves three steps: chiral resolution of the epoxy compound, carbonylation of the chiral epoxy compound to prepare a chiral β-lactone, and ring-opening polymerization of the β-lactone. Using this method, polyhydroxyalkanoates with good tensile strength and toughness, as well as a wide processing window, can be prepared. This invention has advantages such as simple steps, low raw material costs, and no need to introduce a second monomer, making it easy to scale up production.

This invention belongs to the field of organic synthesis technology and relates to a precursor of an obisec key intermediate and a method for preparing the key intermediate. The method involves a [4+2] cycloaddition reaction of 4-trifluoromethylaniline, propionaldehyde, and N-vinylformamide under the catalysis of chiral phosphoric acid, yielding the obisec key intermediate precursor with high enantioselectivity. N -((2) R 4 S )-2-ethyl-6-trifluoromethyl-1,2,3,4-tetrahydroquinoline-4-yl)formamide; subsequently, the key intermediate of obisetri can be obtained through a deprotection reaction under acidic conditions. The method provided by this invention uses a small amount of chiral catalyst and commercially available reagents to efficiently obtain the key intermediate of obisetri in just two steps. R 4 S )-2-ethyl-6-trifluoromethyl-1,2,3,4-tetrahydroquinoline-4-amine; under mild conditions without the need for chiral resolution, the utilization of starting materials is greatly improved, thereby significantly increasing the yield of the target product and the economic efficiency of the process.

The present application relates to ticagrelor intermediates and a preparation method thereof, wherein a halogenated group of compound VI is removed by a deacidifying agent to open a ring, process conditions are simple, and operation is easy; meanwhile, a chiral center in a molecule is constructed by using a transaminase to prepare compound VII from compound VI, conditions are more mild, chiral selectivity is better, raw material utilization is improved, chiral separation or chiral reduction process is avoided, and industrialized production is more beneficial. The disclosed technical scheme can be connected with a process for preparing compound VII from D-ribose as a starting material, forming a process for preparing target compound ticagrelor intermediate compound VII from compound I (D-ribose) as a raw material, synthesizing compound II by reacting with methanol, then synthesizing compound III by sulfonylization of compound II, then synthesizing compound IV by halogen substitution of compound III, and further opening a ring, closing a ring, and catalyzing by a transaminase.

The present invention relates to the technical field of circularly polarized luminescent material preparation, and in particular to a spirochiral tetradentate platinum(II) complex-based circularly polarized luminescent material based on pyridine-carbazole-phenylcarbene and a derivative structure thereof, and an application thereof. The provided complex molecule autonomously induces, by means of a remote stereocenter-containing fragment in chirally substituted pyridine, an entire tetradentate ligand to coordinate with a metal ion in a less sterically hindered manner, so as to form an optically pure spirochiral metal complex-based circularly polarized luminescent material. Such spirochiral metal complex-based circularly polarized luminescent material does not require chiral resolution, has high molecular thermodynamic stability, and has important applications in circularly polarized light-emitting components.

The application discloses a synthesis method of a casein kinase 1 epsilon inhibitor chiral intermediate, and comprises the following steps: dissolving compound 1 and a phosphine reagent L1 in a reaction solvent, adding azodicarboxylic ester, and ending the reaction; adding compound 2, and continuing the reaction until the reaction is completed; adding an acid, ending the reaction, and obtaining a compound shown in formula (I) through post-treatment of a reaction solution; and the route has the effects of no need of chiral resolution, high yield and stable process.

The present invention provides a method for chiral resolution of Trolox. The present disclosure relates to a method for producing a solid salt of a compound of formula I, wherein an amide-based solvent is added to a sample, which contains a compound of formula I, while being assumed to contain a compound of formula II, in the presence of an optical resolution agent:Formula I: (R)-6-hydroxy-2, 5, 7, 8-tetramethylchroman-2-carboxylic acid (hereinafter referred to R Trolox)Formula II: (S)-6-hydroxy-2, 5, 7, 8-tetramethylchroman-2-carboxylic acid (hereinafter referred to S Trolox).

The invention discloses an alpha-carbonyl gamma-chiral methyl carboxylate compound and an analogue thereof as well as a preparation method and application of the alpha-carbonyl gamma-chiral methyl carboxylate compound. The alpha-carbonyl gamma-chiral methyl carboxylate compound comprises a compound as shown in a formula I or a formula II, wherein R1 is selected from H, phenyl, t-butyloxycarboryl or meta-position cyano substituted phenyl; r2 is selected from H, alkyl with 1-6 carbon atoms, hydroxyl, tertiary butyl, benzyl or benzhydryl. According to the alpha-carbonyl gamma-chiral methyl carboxylate compound provided by the invention, ester groups with different steric hindrances are selected, so that a Dieckmann condensation reaction with high regioselectivity is realized under a low-temperature condition; the product obtained by the reaction does not need to be subjected to chiral resolution to obtain a single component, the purification step is simplified, and the method is suitable for being widely used in actual production.

This invention discloses a method for preparing melogabalin or its salts. The method involves resolution using a specific chiral resolving agent, S-tetrahydrofuran-2-carboxylic acid, followed by alkalization and hydrolysis to obtain melogabalin. Optionally, it may react with an acid to form a salt. The melogabalin or its salts prepared by this method have high optical purity, high resolution yield, require no complex additional post-processing steps, can be industrially produced, and are inexpensive.

The invention provides atomoxetine hydrochloride and a preparation method thereof, and relates to the technical field of medicinal chemistry and organic synthesis. The method provided by the invention comprises the following steps: adopting acetophenone, methylamine hydrochloride and a formaldehyde aqueous solution as raw materials, carrying out Mannich reaction to construct a beta-amino carbonyl skeleton, reducing carbonyl into hydroxyl by adopting sodium borohydride, then reacting with di-tert-butyl dicarbonate to form an amino protecting group, adopting o-methylphenol as a raw material, and preparing the beta-amino carbonyl skeleton. The method comprises the following steps: adding p-toluenesulfonic acid monohydrate and a (2-hydroxybenzyl) phosphine oxide catalyst to construct an ether bond through a Mitsunobu reaction, then removing a t-butyloxycarboryl protecting group, and carrying out chiral resolution and salinization reaction by using S-mandelic acid to obtain atomoxetine hydrochloride. The method of dropwise adding the formaldehyde aqueous solution in batches and controlling the reaction temperature is adopted, so that the generation of impurities can be reduced, and the yield is effectively improved; the p-toluenesulfonic acid monohydrate and the (2-hydroxybenzyl) phosphine oxide catalyst capable of participating in catalytic circulation are used for catalyzing the Mitsunobu reaction, the economic principle is met, and the purity and the yield of the product are greatly improved.

The invention provides a method for chiral resolution of (trans)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxylic acid. The method comprises the steps of: (a) treating (trans)-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxylic acid with a chiral base selected from the list consisting of: quinine, R )-1-cyclohexylethan-1-amine, S )-1-cyclohexylethan-1-amine and L )-leucinamide, in an organic solvent to form a suspension, (b) separating the desired enantiomer and diastereomeric salt of the chiral base from the suspension, and (c) optionally, treating the separated diastereomeric salt with an acid to obtain the desired enantiomer of 2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxylic acid.

The application discloses an alcohol dehydrogenase mutant and application thereof in enzymatic synthesis of a loratadine intermediate. A plurality of alcohol dehydrogenase mutants are developed, and a loratadine chiral intermediate is obtained through an enzyme catalytic synthesis method based on the mutants, wherein the reaction condition is mild, the environment is friendly, the reaction has high regional selectivity and stereoselectivity, the reaction conversion rate is high, the chiral purity of the product is high, the enzyme consumption is low, the preparation cost is low, the method is suitable for industrial production, the method avoids the problems of difficult chiral resolution and heavy metal residue in a product in a conventional method, and the method makes up for the deficiencies of a traditional chemical method.

The invention relates to a preparation method of a diamine chiral resolving agent. The method comprises the following steps: by taking chiral alpha-amino acid as a raw material, reacting the chiral alpha-amino acid with (Boc) 2O and alkali in a solvent to obtain Boc-protected amino acid; in a solvent, the Boc-protected amino acid and secondary amine are subjected to catalysis of a condensing agent and alkali to obtain Boc amino-protected secondary amide; dissolving the Boc amino protected secondary amide in an organic solvent, and removing a Boc protecting group under an acidic condition to obtain chiral alpha-amino secondary amide; and reducing the chiral alpha-amino secondary amide into amine under the action of a reducing agent to obtain chiral amino secondary amine, namely the target product diamine chiral resolving agent. The chiral alpha-amino acid required by the preparation method is cheap and easy to obtain, the operation is simple, the obtained chiral diamine resolving agent is novel in structure, the variety of alkaline resolving agents is enriched, and the chiral diamine resolving agent is applied to resolution of racemic propionic acid compounds such as non-steroidal anti-inflammatory drugs ibuprofen and flurbiprofen and has practicability.

The invention discloses an enantioselective reverse micelle extraction and resolution method of a phenylethanolamine raceme drug. According to the method, an enantioselective reversed micelle formed by a carbamyl amino acid chiral surfactant in a non-aqueous solvent is used as a chiral recognition agent, the enantioselective reversed micelle and one enantiomer of a phenylethanolamine raceme drug aqueous solution are preferentially subjected to specific recognition and selectively extracted to an organic phase, and the other enantiomer is left in the aqueous phase; therefore, chiral resolution is realized. The resolution method of the phenylethanolamine racemate drug has the characteristics that the resolution process is simple, the chiral surfactant can be recycled and reused, the cost is low, the method is green and environment-friendly, and the requirement of large-scale resolution is met.

The present invention relates to the technical field of drug synthesis, and specifically relates to a method for preparing elacestrant and an intermediate thereof. The method comprises: 1) subjecting compound A1 and 4-bromo-3-nitroanisole as raw materials to a Suzuki coupling reaction to obtain compound A2; 2) subjecting compound A2 to catalytic hydrogenation and debenzylation reactions to obtain compound A3; 3) subjecting compound A3 to an acetylation reaction under the action of an acetylation reagent to obtain compound A4; 4) subjecting compound A4 to a reduction reaction to obtain compound A5; 5) subjecting compound A5 to chiral resolution to obtain compound A6; 6) subjecting compound A6 to reductive amination with N-ethyl-2-(4-formylphenyl)acetamide to obtain compound A7; and 7) subjecting compound A7 to reaction under the action of a reducing agent to obtain elacestrant. The method for preparing elacestrant and an intermediate thereof, as provided by the present invention, has the characteristics of short synthesis route, high yield, and high purity.

The invention discloses a high performance liquid chromatography (HPLC) detection method for enantiomers in moxifloxacin hydrochloride with high separation degree, and belongs to the technical field of medicine detection. The method aims at solving the problems that in the prior art, the leading edge of a main component peak is serious, and the detection accuracy and good peak pattern under the conditions of high separation degree and low content are difficult to meet at the same time, and the adoption of an expensive chiral chromatographic column is avoided. According to the detection method, chiral resolution is realized on a conventional high performance liquid chromatograph by adopting a reversed-phase chromatographic column (such as terminated octadecylsilane chemically bonded silica as a filler). According to the core technical scheme, the unique mobile phase composition is as follows: a water phase contains 0.54 g / L of zinc acetate and 1.17 g / L of L-valine, 1ml of diethylamine is creatively added, and the pH value is adjusted to 5.6 by using dilute sulfuric acid; and an organic phase adopts a methanol-ethanol mixed solution (15: 8) with a specific ratio. And finally, mixing the water phase and the organic phase according to the volume ratio of 77: 23. Under optimal chromatographic conditions (the column temperature is 40 DEG C and the detection wavelength is 295 nm), the method can realize efficient separation between moxifloxacin hydrochloride and enantiomers, the separation degree is greater than 4.5, and the detection accuracy of trace isomers can be realized. A methodological verification result shows that the method is high in sensitivity (the detection limit is 0.0096%, and the quantitation limit is 0.024%), and has a good linear relationship (a correlation coefficient rgt; and the accuracy is good (the recovery rate is between 80.0% and 120.0%). The method can be used for qualitative and quantitative analysis of the moxifloxacin hydrochloride bulk drug and enantiomers in the moxifloxacin hydrochloride preparation.

The present invention relates to a process for the preparation of highly pure enantiomer of Fezolinetant, and in particular highly pure (R)-Fezolinetant. The invention also relates to chiral resolution by acid for the preparation of highly pure R-Fezolinetant. Additionally, the invention relates to a process for preparing intermediates useful for the preparation of (R)-Fezolinetant, their uses and a process for preparing (R)-Fezolinetant. In particular, the intermediate (R)-3-methylpiperazin-2-one is prepared by reductive amination with an imine reductase from Myxococcus stipitatus and ethylene diamine and ethyl pyruvate.

The application discloses a modified corn protein zein chiral separation membrane and belongs to the technical field of functional high polymer materials. The modified corn protein zein chiral separation membrane is prepared by the following steps: 1) mixing and stirring nano corn protein zein, chiral resolution material and an ethanol solution, adding acid to adjust the pH to 5-10, and then performing ultrasonic oscillation, and then flowing the solution on a film preparation plate to form a nano membrane material; the chiral resolution material is polysaccharide or a supramolecular compound; 2) drying and peeling the nano membrane material to obtain the modified corn protein zein chiral separation membrane. The modified corn protein zein chiral separation membrane provided by the application has high separation performance when applied to the separation of racemic compounds.

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.

The invention discloses a preparation method and application of a liquid chromatography filler for chiral resolution of a fenugreek lactone derivative, glycidyl is used as a derivatization reagent for the first time, beta-cyclodextrin is continuously modified in the reaction process, so that the beta-cyclodextrin is modified, the adsorption capacity of the beta-cyclodextrin is changed, and the adsorption capacity of the beta-cyclodextrin is changed. According to the preparation method disclosed by the invention, the beta-cyclodextrin derivative bonded with glycidyl is bonded to the silica gel microspheres by using isocyanatopropyltriethoxysilane as a silane coupling agent, and the finally obtained (R)-OH-CSP or OH-CSP can be used for splitting the fenugreek lactone derivative enantiomer, and meanwhile, the separation degree is relatively high.

The invention provides a fenerenone intermediate, a preparation method thereof and a method for preparing fenerenone from the intermediate. According to the method disclosed by the invention, the chiral intermediate of the fenerenone is prepared by adopting an efficient asymmetric hydrogenation process, the intermediate does not need a traditional chiral resolution step, the fenerenone can be directly prepared, the enantioselectivity is improved, and the conversion rate is greatly improved; meanwhile, by optimizing the utilization efficiency of the catalyst, the dosage of the catalyst is remarkably reduced. The catalytic efficiency is improved while the cost is reduced, and the process has good amplified production potential.

The application provides a kind of spiro compound and its application, the structure of the spiro compound is as shown in formula I or formula II, the spiro compound is used for the preparation of spiro compound, and the preparation method comprises the following steps: (1) compound I is subjected to alkylation reaction to obtain compound II;(2) compound II is reacted with benzylamine compound to obtain compound III;(3) compound III is reduced to obtain compound IV;(4) compound IV is mixed with debenzyl reagent to obtain compound V, and then chiral resolution obtains the target spiro compound.The preparation method provided by the application is simple in process operation, raw materials are cheap and easy to obtain, the yield is high, and the process avoids the use of hydrogen and metal catalyst in the debenzyl process through specific process design, greatly reduces the safety and environmental problems, and also reduces the production cost.

This invention discloses an enzymatically catalytic synthesis method for a chiral intermediate of dzoxadamine. Using methyl acetoacetate as a substrate, buffer, substrate, alcohol dehydrogenase, formate dehydrogenase, ammonium formate, and coenzyme are added to a reaction vessel. The reaction is carried out at 20–40°C for 2–24 hours. After extraction, separation, and rotary evaporation, the chiral intermediate (R)-3-hydroxybutyrate methyl ester is obtained. The alcohol dehydrogenase is a mutant of ADH1 derived from Rollstonella, and the amino acid sequence of ADH1 is shown in SEQ ID No. 1. This invention offers mild reaction conditions, high stereoselectivity, and environmental friendliness. It also boasts high conversion rate, high chiral purity, low enzyme dosage, tolerance to high substrate concentrations, and low preparation cost, making it suitable for industrial production. Furthermore, it avoids chiral resolution and heavy metal residues in the product, overcoming the shortcomings of chemical methods.

The invention relates to the technical field of preparation of circularly polarized luminescent materials, in particular to a circularly polarized luminescent material of a central chirality remote induction spiral chirality four-tooth ring metal platinum (II) complex and application of the circularly polarized luminescent material of the central chirality remote induction spiral chirality four-tooth ring metal platinum (II) complex. The spiral chiral metal complex molecule can autonomously induce the whole tetradentate ligand to coordinate with metal ions in a mode of small steric hindrance through a remote central chiral fragment in chiral substituted pyridine; a thermodynamically stable and optically pure P-configuration spiral chiral four-tooth ring metal platinum (II) complex circularly polarized light luminescent material with a metal ion as a center is diastereoselectively formed, and a strong circularly polarized light luminescent signal is shown; the spiral chiral metal complex circular polarization luminescent material does not need chiral resolution, has high molecular thermodynamic stability, and has important application in circular polarization luminescent elements.

The application belongs to the field of pharmaceutical chemistry, and discloses a preparation method of a PARP inhibitor intermediate. The preparation method provided by the application does not involve the steps of noble metal catalytic coupling and chiral resolution, has low requirements on equipment, is simple to operate, is beneficial to industrial production, and when the amino protecting group is a trifluoroacetic acid group, the yield of the ring closure reaction is significantly improved.