183 results about "Chiral resolution" patented technology

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.

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.

A method for synthesizing mirogabalin besilate. The method comprises the following steps: subjecting a chiral ketene and cyanoacetate to a condensation reaction under the action of ammonium acetate to obtain an unsaturated cyano ester, then subjecting the unsaturated cyano ester and nitromethane to a condensation reaction to obtain a nitro ester, subjecting the nitro ester to high-temperature de-esterification to obtain a chiral nitronitrile, then subjecting same to nitroreduction to obtain a chiral aminonitrile, subsequently hydrolyzing the chiral aminonitrile to obtain a mirogabalin free alkali, and finally salifying the mirogabalin free alkali and benzenesulfonic acid to obtain mirogabalin besilate. In the present invention, a chiral cyclobutane quaternary carbon center is stereoscopically and specifically constructed to obtain a chiral nitro ester having a single stereoscopic configuration, thereby preventing chiral isomer waste generated by chiral isomer resolution, such that chiral column separation or chiral resolution is not required, the production cost is significantly reduced, and the residue of heavy-metal titanium in a product and environmental pollution caused by solid waste heavy-metal titanium are also prevented.

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 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.

The invention provides a method for chiral resolution of a fluoxazole amide enantiomer. A high performance liquid chromatography-mass spectrometry technology is adopted to separate the fluoxazole amide enantiomer, a chromatographic column is a polysaccharide derivative chiral chromatographic column, a mobile phase A is an organic solvent, a mobile phase B is 0.05-0.1% formic acid water, the volume ratio of the mobile phases A to the mobile phase B is 60: 40-100: 0, gradient elution is performed, the column temperature is 30-35 DEG C, and the flow velocity is 0.3-0.6 mL / min. The invention provides a method for effectively splitting the chiral fluoxazole amide enantiomer, and the method has the advantages of high sensitivity, simplicity in operation, high separation speed and the like.

The present invention provides a method for determining isomers in carfilzomib and its preparations by reverse phase liquid chromatography, and belongs to the technical field of drug analysis. The present invention adopts high performance liquid chromatography to determine isomers in carfilzomib and its preparations, and the chromatographic conditions are as follows: chromatographic column: octylsilane bonded silica gel as filler; mobile phase: sulfobutyl-β-cyclodextrin sodium aqueous solution-acetonitrile as mobile phase. The chromatographic column used in the present invention is a conventional chromatographic column, which is inexpensive and has a longer life; the chiral separation agent added to the mobile phase has a lower cost than special chiral reagents. Through systematic methodological verification, the results show that the method of the present invention has good specificity, sensitivity, accuracy, repeatability, durability, etc., and is suitable for the detection of chiral isomers in carfilzomib and its preparations.

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.

The present invention relates to the technical field of drug intermediate synthesis, and particularly relates to a preparation method of posaconazole starting material SM3. CeCl3·7H2O and sodium borohydride are added to compound POS-1 for an asymmetric reduction reaction to obtain compound POS-2. Compound POS-2 reacts with 3,5-bis(trifluoromethyl)benzenesulfonyl chloride to obtain compound POS-3. Hydrazine hydrate attacks from the back of compound POS-3 with a larger steric hindrance to undergo an SN2 reaction to obtain a stereoselectively specific compound POS-4. Compound POS-4 then reacts with ethyl formate and forms a salt with oxalic acid to obtain the product posaconazole starting material SM3. By means of asymmetric reduction of carbonyl groups and selective nucleophilic substitution, the present invention effectively avoids the chiral resolution step, thereby reducing the content of isomeric impurities. The prepared product not only has a high ee value, but also the yield is significantly improved, thereby greatly reducing the production cost.

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.

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 invention relates to the technical field of chiral resolution, in particular to a solvent activated cyclodextrin membrane for chiral separation and a preparation method and application thereof.The preparation method comprises the steps that beta-CD and CDI are mixed in DMSO and stirred at the room temperature in inert gas, then excessive EDA is added, continuous stirring is conducted, and a mixed solution is obtained; performing vacuum concentration, washing, precipitating, filtering, repeating for multiple times, and drying to obtain a white powdery compound; activating through an organic solvent, washing and drying to obtain solvent activated cyclodextrin; the method comprises the following steps: dissolving cyclodextrin in deionized water to obtain a water-phase solution, and preparing the solvent-activated cyclodextrin membrane by taking an n-hexane solution of trimesoyl chloride as an organic-phase solution through a free interface polymerization method. Compared with the prior art, the cyclodextrin membrane prepared by the invention has a good separation effect on various amino acids, overcomes the problem of single resolution object of a chiral membrane in the prior art, and has important significance on design and preparation of a chiral separation membrane.

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 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.

The invention belongs to the field of bioengineering and food technology, and discloses a method for enzymatic resolution of chiral substances, including the following steps: (1) preparing an enzyme solution with a lipase concentration of 1-3000 U / mL, and adding a soluble salt, a hydrophilic solvent and a hydrophobic solvent to the enzyme solution to form a three-liquid phase system; the hydrophobic solvent contains esters or amide compounds composed of racemic chiral compounds; (2) subjecting the three-liquid phase system to enzyme-catalyzed reaction under stirring condition; after the reaction is completed, standing or centrifuging the three-liquid phase system to divide it into three layers, which are a upper liquid layer, a middle liquid layer and a lower liquid layer from top to bottom. The optically pure chiral product after hydrolysis is mainly rich in the middle liquid layer or the lower liquid layer, while the upper liquid layer product is another ester or amide product containing an optically pure chiral product. The method has the advantages of low energy consumption, high raw material utilization rate, and mild reaction conditions, and solves the problems of low chiral resolution efficiency, poor chiral selectivity, low recovery rate, and difficulty in industrialization in the existing enzymatic method.

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 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.

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.

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.

The invention discloses a high-yield synthesis method of elxalidone, and relates to the technical field of drug synthesis. 1-chloro-2-(trifluoromethyl) benzene and 4-(methylsulfonyl) aniline are used as initial raw materials; according to the present invention, the isaprorenone is obtained through the Grignard reaction, the addition reaction, the bromination reaction, the condensation reaction, the substitution reaction, the cyclization reaction, the reduction reaction, the substitution reaction and the chiral resolution, and the synthesis method has advantages of low raw material cost, short route, high yield and the like, and can be used for the quantitative production of the isaprorenone.

The invention provides a method for chiral resolution of a cyflumetofen enantiomer. The cyflumetofen enantiomer in a cyflumetofen test solution is separated by adopting an ultrahigh liquid chromatography, a stationary phase is a polysaccharide derivative chiral chromatographic column, a mobile phase A is an organic solvent, a mobile phase B is deionized water, the mobile phase B is subjected to gradient elution according to a volume percentage ratio of 15-5% within 0-5 minutes, and the mobile phase B is subjected to gradient elution according to a volume percentage ratio of 15-5% within 5-10 minutes. The mobile phase B is subjected to isocratic elution according to the volume percent of 5%, the column temperature is 35 DEG C, and the flow velocity is 0.7 mL / min; a detector is adopted for determination, and cyflumetofen chiral monomer fractions are collected in a fraction collector. The invention provides the cyflumetofen chiral enantiomer which can be effectively separated and can be used for preparing a certain scale, the method overcomes the defects in the prior art, and the method has the characteristics of mild and simple operation conditions, high sensitivity, high separation speed, high purity of the separated monomer, green and environment-friendly mobile phase and the like.

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 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.

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.