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150 results about "Chiral resolution" patented technology

Chiral resolution in stereochemistry is a process for the separation of racemic compounds into their enantiomers. It is an important tool in the production of optically active drugs. Other terms with the same meaning are optical resolution and mechanical resolution.

Chiral resolution method and application of 3-aryl substituted glutaric acid monoester compound

The invention provides a chiral resolution method and application of a 3-aryl substituted glutaric acid monoester compound, and the method comprises the following steps: taking a substance as shown in a formula I as a starting raw material, and carrying out alcoholysis to obtain a racemic intermediate as shown in a formula IV; and splitting the intermediate shown in the formula IV, and then dissociating to obtain the compound shown in the formula III, which has a single spatial configuration and an ee value of more than 99%. A cyclic anhydride substrate with a symmetrical structure is used and reacts with alcohol to obtain racemic 3-aryl substituted glutaric acid monoester, a target configuration with high chiral purity is obtained by screening some resolution reagents and solvents and performing salifying resolution on the 3-aryl substituted glutaric acid monoester, the operation is simple, the resolution reagents are easily available in the market and can be recycled, and the method is suitable for industrial production. The method has the advantages that an expensive chiral catalyst or a harsh enzyme catalysis condition is avoided, the reaction cost is reduced, amplified production is facilitated, the ee value of a target configuration can be increased to 99% or above, and the method is an economic and environment-friendly technical route which is simple in post-treatment and convenient for amplified production.
Owner:HANGZHOU ALLSINO CHEM

Acylase mutant and biosynthesis method of (R)-2-aminobutanol

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.
Owner:SUQIAN COLLEGE

Synthesis method of selective THRbeta agonist key intermediate

PendingCN121039107AOrganic compounds purification/separation/stabilisationEther/acetal/ketal group formation/introductionCombinatorial chemistryAgonist
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.
Owner:HAISCO PHARMACEUTICAL GROUP CO LTD

Preparation method of omariglitazone intermediate

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.
Owner:HANGZHOU NUOAO BIOMEDICAL TECH CO LTD

Synthesis method of miloabalin or acid salt thereof

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.
Owner:ZHEJIANG EAST ASIA PHARM CO LTD

Synthesis method of chiral polyaniline nano material and application of chiral polyaniline nano material in amino acid chiral crystallization

The invention discloses a synthesis method of a chiral polyaniline nano material and application of the chiral polyaniline nano material in amino acid chiral crystallization. The preparation method comprises the following steps: ultrasonically dissolving unichiral tartaric acid, an aniline monomer and N-phenyl p-phenylenediamine in water, adding a certain volume of an ammonium persulfate aqueous solution to initiate polymerization, centrifuging after complete reaction to obtain a polyaniline-tartaric acid (PANI-TA) chiral nano material, and carrying out ammonia water dedoping and hydrochloric acid solution re-doping to obtain a polyaniline-hydrochloric acid (PANI-HCl) chiral nano material. And finally, respectively adding the polyaniline-hydrochloric acid chiral nano-material into a supersaturated leucine, alanine or tryptophan aqueous solution to induce chiral crystallization, wherein the result shows that the polyaniline-hydrochloric acid chiral nano-material can induce one configuration of amino acid to crystallize more quickly and the other configuration of amino acid with enantiomeric excess remains in the solution. The chiral polyaniline nano material prepared by the method avoids introduction of other chiral molecules in chiral crystallization, is beneficial to separation of products, has the advantages of simplicity in operation, low cost and the like, and has a wide application prospect in the field of chiral resolution.
Owner:YANGZHOU UNIV

Method for preparing chiral alcohol through asymmetric reduction of large steric hindrance rigid ketone based on aldehyde ketone reductase and mutant thereof

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.
Owner:杭州微远生物科技有限公司

A method for preparing (+)-crispine A by enzymatic resolution

ActiveCN117946105BOrganic synthesisBond cleavage
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.
Owner:SHANGHAI INST OF TECH

Process for the preparation of chiral epoxides, chiral beta-lactones and polyhydroxyalkanoates

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.
Owner:SHANGHAI ZHONGHUA TECH CO LTD

Synthesis method of atavapam

The invention provides a synthesis method of atavapam, which comprises the following steps: carrying out nucleophilic addition-elimination reaction on commercially available raw materials and 4-methyl-3-trifluoromethylaniline under alkaline conditions, carrying out Suzuki coupling reaction under the action of a catalyst, carrying out pressurized hydrogenation, and carrying out chiral resolution, thereby obtaining the atavapam. And condensing with 2-fluoro-6-methyl benzoyl chloride under an alkaline condition, and further removing a Boc protecting group under an acidic condition to finish synthesis of the atavapam. According to the invention, a convergent synthesis process is adopted, tedious synthesis steps in the original process are shortened, and post-treatment is simpler and more controllable.
Owner:HANGZHOU NUOAO BIOMEDICAL TECH CO LTD

Process for the preparation of a key intermediate precursor of obiseplimab and a key intermediate

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.
Owner:TAIZHOU UNIV

Ticagrelor intermediates and processes for their preparation

ActiveCN115537433BOrganic chemistry methodsFermentationHalogenChiral selectivity
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.
Owner:CHONGQING PUYOU BIOPHARMA CO LTD

Acylated hydroxypropyl-beta-cyclodextrin derivatization chiral stationary phase as well as preparation method and application thereof

The invention discloses an acylated hydroxypropyl-beta-cyclodextrin derivatization chiral stationary phase as well as a preparation method and application thereof. The preparation method comprises the following steps: sequentially reacting hydroxypropyl-beta-cyclodextrin with a 3-isocyanate propyltriethoxysilane coupling agent and an anhydride derivatization reagent by utilizing a one-pot method, and then reacting with activated silica gel microspheres to prepare a target material; the acylated hydroxypropyl-beta-cyclodextrin derivative chiral stationary phase prepared by the invention has good chiral resolution capability compared with an aryl carboxylic acid compound with relatively large steric hindrance, and is suitable for reversed-phase high performance liquid chromatography conditions, and the stability of a chromatographic column is good.
Owner:ZHEJIANG UNIV OF TECH

Spirochiral tetradentate platinum(II) complex-based circularly polarized luminescent material and application thereof

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.
Owner:ZHEJIANG UNIV OF TECH +1

A method for preparing a chiral intermediate of a drug for treating ocular hypertension

ActiveCN118580192BOrganic chemistryBulk chemical productionBeckmann rearrangementHydroxylamine
The invention discloses a preparation method of a chiral intermediate (S)-3-methyl-1-tert-butoxycarbonyl-1,4-diazepane for treating ocular hypertension, relating to the technical field of pharmaceutical chemicals. The invention comprises the following steps: using 1-benzyl-3-methylpiperidin-4-one as a starting raw material, performing chiral resolution to obtain an intermediate 1, performing an addition-elimination reaction on the intermediate 1 and hydroxylamine hydrochloride to obtain an intermediate 2, performing a Beckmann rearrangement reaction on the intermediate 2 to obtain an intermediate 3, performing an amino deprotection reaction on the intermediate 3 to obtain an intermediate 4, performing an amino protection reaction on the intermediate 4 and di-tert-butyl dicarbonate to obtain an intermediate 5, and performing a decarbonylation reaction on the intermediate 5 to obtain the (S)-3-methyl-1-tert-butoxycarbonyl-1,4-diazepane. The preparation method has the characteristics of readily available raw materials, a simple process and a high product yield, and is suitable for the industrial production of the (S)-3-methyl-1-tert-butoxycarbonyl-1,4-diazepane.
Owner:ANHUI HERYI CHEM

A method for synthesizing a chiral intermediate of casein kinase 1 epsilon inhibitor

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.
Owner:HEALZEN THERAPEUTICS CO LTD

Optically resolved Trolox intermediate and method for producing same

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).
Owner:PTC THERAPEUTICS INC

Alpha-carbonyl gamma-chiral methyl carboxylate compound and analogue thereof, and preparation method and application of alpha-carbonyl gamma-chiral methyl carboxylate compound and analogue thereof

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.
Owner:ZHONGSHAN INST FOR DRUG DISCOVERY SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI

A central chirality-induced helical chirality tetradentate cyclometalated platinum(II) complex, electronic device and application

The present invention relates to the technical field of the preparation of circularly polarized luminescent materials, and particularly relates to a central chirality-induced helical chirality tetradentate cyclometalated platinum(II) complex, an electronic device and applications thereof. The central chirality-induced helical chirality tetradentate cyclometalated platinum(II) complex provided by the present invention has a general formula structure as shown in formula (I) or (I'), wherein (I) and (I') are enantiomers of each other: the helical chiral metal complex molecule can autonomously induce the entire tetradentate ligand to coordinate with metal ions in a manner with small steric hindrance through the central chiral fragment L<supgt;a< / supgt; in the tetradentate ligand, forming an optically pure helical chiral metal complex circularly polarized luminescent material. There is no need for chiral resolution, and it has high chemical stability, and has important applications in circularly polarized luminescence elements.
Owner:ZHEJIANG UNIV OF TECH +1

A process for the preparation of meloxicam benzene sulfonic acid using s-tetrahydrofuran-2-carboxylic acid

PendingCN122301712AMeloxicamBenzene
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.
Owner:JIANGXI KERUI PHARM CO LTD

Amino chiral metabolite resolution reagent and application thereof

The invention provides an amino chiral metabolite resolution reagent and application thereof, and belongs to the technical field of biochemistry. The compound TPP-R-BSA and TPP-S-BSA reagents provided by the invention contain triphenylphosphine groups with positive charges and a chiral center structure, and can be used for performing mass spectrum labeling on amino functional group chiral compounds. According to the present invention, the chiral resolution of 13 chiral amino compounds can be simultaneously performed under the neutral condition for the first time, and the mild degree of the derivatization is significantly higher than the mild degree of the existing chiral derivatization reagent; according to the reagent, an analysis method which is mild in amino functional group chiral compound resolution, high in sensitivity and high in selectivity can be established by utilizing a liquid chromatography-mass spectrometry detection technology. And an effective and reliable mass spectrum chiral derivatization reagent is provided for the resolution research of amino functional group chiral metabolites and the screening of chiral biomarkers.
Owner:YANBIAN UNIV

A method for preparing aminoacetonitrile compounds and intermediates thereof

The present invention discloses a method for preparing an aminoacetonitrile compound and an intermediate thereof, belonging to the technical field of pharmaceutical synthesis. The aminoacetonitrile compound is a compound of formula (I). The method for preparing the compound of formula (I) of the present invention uses 1-(tert-butyldimethylsilyloxy)-2-acetone as a starting material 1, and obtains a high-purity chiral intermediate 2 under the action of a chiral catalyst. The chiral intermediate 2 is subjected to a condensation reaction with p-trifluoromethylthiobenzoyl chloride to obtain an intermediate 3, which is then subjected to a deprotection and substitution reaction to obtain the compound of formula (I). Finally, the compound of formula (I) is recrystallized from a solvent to obtain a fine product. In the method for preparing the compound of formula (I) of the present invention, a chiral catalyst is used to efficiently obtain the key chiral intermediate, avoiding the chiral resolution process. The reagents used are all low-toxic or non-toxic, environmentally friendly, and the reaction conditions are simple. The prepared compound of formula (I) has a high yield and purity, and the product quality is stable, making it suitable for industrial production.
Owner:TIANJIN RINGPU BIO TECHNOLOGY CO LTD

Tomoxetine hydrochloride and preparation method thereof

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.
Owner:FUZHOU MEDICAL COLLEGE OF NANCHANG UNIV

A process for the chiral resolution of trans-2,2-dichloro-3-(3-chloro-4-fluorophenyl)cyclopropane-1-carboxylic acid

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.
Owner:INTERVET INT BV

Alcohol dehydrogenase mutants and their use in enzymatic synthesis of loratadine intermediates

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.
Owner:杭州微远生物科技有限公司

Preparation method of diamine chiral resolving agent

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.
Owner:YUNNAN INST OF MATERIA MEDICA +1

Resolution method of phenylethanolamine racemate drug

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.
Owner:CENT SOUTH UNIV

Method for preparing elacestrant and intermediate thereof

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.
Owner:CHONGQING HUABANGSHENGKAI PHARM CO LTD

Liquid chromatography detection method for enantiomers in moxifloxacin hydrochloride with high separation degree

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.
Owner:CHONGQING PHARMACEUTICAL VALLEY PHARMACEUTICAL CO LTD

Application of carbonyl reductase and mutant thereof in preparation of atomoxetine chiral intermediate

The invention discloses carbonyl reductase and application of a mutant thereof in preparation of a atomoxetine chiral intermediate. The carbonyl reductase and the mutant thereof have a sequence as shown in SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 or 33. According to the carbonyl reductase disclosed by the invention, the reaction conversion rate of the carbonyl reductase for generating (S)-3-chlorobenzene propanol from 3-chloropropiophenone reaches 99%, the optical purity is greater than 99%, and the carbonyl reductase shows excellent catalytic effect and conversion efficiency. The method based on the enzyme and the mutant is mild in reaction condition and environmentally friendly, has high regioselectivity and stereoselectivity, avoids chiral resolution and heavy metal residues in products, makes up for the defects of chemical methods, and has wide application prospects and high market value.
Owner:杭州微远生物科技有限公司