109 results about "Enantiomeric excess" patented technology

The invention discloses a p-nitrophenyl ethyl esterase mutant with high enantioselectivity as well as a construction method and application of the p-nitrophenyl ethyl esterase mutant. The p-nitrophenyl ethyl esterase mutant is obtained by mutating an amino acid sequence of wild p-nitrophenyl ethyl esterase pnbA as shown in SEQ ID NO.1 according to one or a combination of more of the following modes: leucine at the 273rd site is mutated into aspartic acid, phenylalanine at the 314th site is mutated into histidine, and leucine at the 362nd site is mutated into arginine. The mutant pnbA-L273D / F314H / L362R provided by the invention shows optimal catalytic performance (E = 47.16) for racemization-acetic acid pinyl hydrate, the enantiomeric excess value of the mutant is 95.13%, the conversion rate of 1S, 5R-acetic acid pinyl hydrate is 90.42%, the enantioselectivity of the mutant is obviously higher than that of a wild type, and the mutant has great application potential in biological catalytic synthesis of monocyclic monoterpenoid chiral alcohols.

The present invention relates to a process for the preparation of (6R)-6-(2-(N-(4-(2- (ethylamino)ethyl)benzyl)-N-ethylamino)-4-methoxyphenyl)-5,6,7,8-tetrahydro nap- hthalen-2-ol dihydrochloride (1) and its novel intermediates thereof. Elacestrant dihydrochloride (1) The present invention further relates to a process for the preparation of intermediates of formula (3), formula (4), formula (4a), formula (5), formula (5a), formula (6), formula (6a), formula (7), formula (7a), formula (9) and formula (10). with enantiomeric excess greater than 50%.

The invention discloses an AxSDR (Adenosine Diphosphate Dehydrogenase Regulator) gene of an Algaea xinjiangensis source enzyme, a recombinant bacterium containing the gene and an application of the recombinant bacterium and the AxSDR gene of the Algaea xinjiangensis source enzyme. The nucleotide sequence of the enzyme AxSDR gene is as shown in SEQ ID NO. 1; the amino acid sequence of the enzyme protein coded by the enzyme AxSDR gene is SEQ ID NO. 2. The AxSDR gene is used for constructing a recombinant plasmid, and then the recombinant plasmid is introduced into E.coli BL21 (DE3) to obtain a gene recombinant bacterium containing the gene. Enzyme protein coded by the AxSDR gene or recombinant bacteria containing the gene can catalytically reduce 1500 mmol / L of m-trifluoromethyl acetophenone to prepare a chiral compound (R)-1-(3-trifluoromethyl phenyl) ethanol, conversion of a high-concentration (282g / L) substrate is achieved, the reaction lasts for 11 hours, the product yield is 99.6%, and the enantiomer excess value is 99% or above.

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 present invention provides a method for detecting and identifying molecular chirality based on a composite plasmon chiral nanostructure. The present invention constructs a composite plasmon chiral nanostructure using chiral nanofibers and gold nanorods as basic components, and achieves molecular chirality recognition and detection through plasmon chiral optical amplification. The excellent plasmon circular dichroism optical properties of the composite nanostructure can convert the host-guest chiral recognition interaction occurring at the fiber interface into an asymmetric plasmon chiral optical amplification signal. This technology can detect and identify the chiral enantiomers of amino acid molecules in about 1 minute, with a sensitivity of 10 ‑6 mol / L. This structure can also be used for quantitative analysis of molecular enantiomeric excess (ee), with a detection sensitivity of ±0.05. Furthermore, given that the chiral host-guest complexes involved in this technology are primarily based on hydrogen bonding interactions, the chiral fiber host can be used as a universal substrate for the detection of chiral amino acid molecules.

To provide a process for forming arylcyclopropylcarboxylic acids useful for forming molecules having insecticidal applications against pests in the phyla Arthropoda, Mollusca, and Nematoda.SOLUTION: There is provided an enantiomerically enriched preparation of the compound (R2, R4) - 3 - (3, 5-bis (trifluoromethyl) phenyl) - 2, 2-dichlorocyclopropane-1-carboxylic acid in a heterogeneous S3a, wherein CF3 and R3 are; R2, and R5 are H; and R7 and R8 are Cl; wherein the enantiomeric excess of the (R, R) - enantiomer of the is greater than 80%, greater than 90% or greater than 95%. 1R 3R S3a. Also provided are pesticidal formulations comprising said enantiomerically enriched preparations.SELECTED DRAWING: None

Provided are a transaminase mutant and use thereof. The transaminase mutant has an amino acid sequence obtained by mutation of an amino acid sequence shown in SEQ ID NO:1, the mutation at least includes one of the following mutation site combinations: T7C+S47C, Q78C+A330C, V137C+G313C, A217C+Y252C and L295C+C328C; or the transaminase mutant has an amino acid sequence which has the mutation sites in the mutated amino acid sequence and has 80% or more identity with the mutated amino acid sequence. The transaminase mutant realizes the change of protein structure and functions, reduces the enzyme amount, increases the enantiomeric excess (ee) value of a product, and reduces the difficulty of post-processing, so that the transaminase mutant may be suitable for industrial production.

The application discloses an iridium complex, a preparation method thereof and application of the iridium complex in synthesis of chiral piperidines, and the preparation method of the iridium complex comprises the following steps: adding an indole compound, an iridium compound and an alkali into a first solvent, heating and stirring at 40-80 DEG C, lowering to room temperature after reaction, filtering, reducing pressure distillation, and separating by silica gel column chromatography to obtain the iridium complex; under the cooperation of the iridium complex as a catalyst and chiral phosphoric acid, 1,5-diol compounds and amine compounds can be directly reacted to obtain a series of chiral piperidine compounds, the method has the advantages of high reaction efficiency, simplicity and high yield, and the enantiomeric excess value of the chiral piperidine prepared by using the iridium catalyst is not less than 83%.

The present invention relates to a compound selected from (R)-(+)-5-(p-cyanophenyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyridine and a pharmaceutically acceptable salt thereof, and in particular to the phosphate salt of (R)-(+)-5-(p-cyanophenyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyridine, both having preferably an enantiomeric excess of the (R) form higher than or equal to 97%. Furthermore, the present invention relates to pharmaceutical compositions comprising the same, their use as a medicament and in methods of treatment of diseases and disorders in humans including women of child bearing potential and pediatric patients in which aldosterone over-exposure contributes to the deleterious effects of said diseases or disorders, as well as processes for preparing said inventive compounds.

The invention discloses a chiral compound quantification method based on an enantiomer internal standard, and belongs to the technical field of testing. According to the method, chiral distinguishing and enantiomer excess (ee) determination are carried out based on a diastereoisomerization strategy and ion mobility mass spectrometry, and absolute quantitative analysis of chiral compounds can be realized with extremely high flux by adding an enantiomer internal standard; the method can realize dual quantitative analysis of absolute concentration and stereocomposition of the chiral compound only by depending on mobility dimension, is successfully applied to high-throughput screening of yield and stereoselectivity of an enzyme catalytic reaction, can avoid interference of a matrix effect and an ion inhibition effect, and has the advantages of high analysis speed, high accuracy, simplicity, convenience and rapidness.

The invention discloses a plant source leuco-anthocyanidin dioxygenase mutant and application thereof in synthesis of chiral drug intermediates, and belongs to the technical field of enzymology engineering. According to the invention, leuco-anthocyanidin dioxygenase (LDOX) derived from arabidopsis thaliana is modified through site-specific mutagenesis, an F304L / T239S double mutant (LDOXLS) is obtained, the (R)-phenylglycine analogue can be synthesized with the yield of 1.69 g / L, the yield of 81% and the enantiomeric excess ratio of 97: 3, and different substituent derivatives of the (R)-phenylglycine analogue can be generated. Compared with the traditional method, the method for synthesizing the (R)-phenylglycine analogue and the derivative thereof by using the enzyme has the advantages of wider substrate range, higher stereoselectivity, more environment-friendly requirement, simplicity and convenience in operation and the like.

Disclosed is a process for asymmetric cis-dihydroxylation ("AD") of styrene and conjugated dienes to produce cis-glycols of styrene and conjugated dienes or tetrols of conjugated dienes in high yields (i.e. Yields > = 30%) and high enantioselectivity (i.e. Enantiomeric excess > = 60%). The process uses an iron-based catalyst, such as one or more Fe (II) complexes, etc., as a catalyst. The process generally includes: (i) maintaining the reaction mixture at a temperature sufficient to form a product for a period of time, where the reaction mixture contains styrene or conjugated diene, one or more iron-based catalysts, an oxidizing agent, and a solvent, and where the product contains a cis-diol or tetraol.

The present disclosure provides methods of preparing a compound of Formula (I): wherein R1, R2, and R3 are as defined as set forth in the application. In one embodiment, a compound of Formula (I) is prepared in >95% chemical purity and >95% enantiomeric excess.

This invention discloses a highly enantioselective hydrated pinol esterase mutant, its construction method, and its applications, belonging to the field of enzyme engineering technology. The hydrated pinol esterase mutant provided by this invention is obtained through a high-throughput screening method based on fluorescence conjugation from Bacillus subtilis. Bacillus subtilis The hydrated pinyl esterase was obtained by single-point or combined mutations of leucine at position 273, phenylalanine at position 314, leucine at position 362, and methionine at position 193 in its amino acid sequence. Among them, mutant M4 exhibited the best catalytic performance for racemic pinyl acetate hydrate, with an enantiomeric excess of 99.35% (1...). S 5 R The conversion rate of 1-acetic acid hydrated pinyl esterase was 83.90%. The hydrated pinyl esterase mutant provided by the invention catalyzes (1) S 5 R Pinyl acetate hydrate has high enzyme activity. ee p High value, high conversion rate.

The present invention discloses a method for asymmetric transfer hydrogenation synthesis of chiral flavanol compounds by dynamic kinetic resolution, and the catalyst used is a chiral ruthenium diamine complex. Through this method, asymmetric transfer hydrogenation of flavanone derivatives can be realized, and optically pure flavanol compounds containing three consecutive chiral centers can be obtained in high yield (the enantiomeric excess can reach 99%, and the diastereomeric ratio can reach >20:1). The present invention has high enantioselectivity and diastereoselectivity, is simple and easy to operate, the catalyst is commercially available, the reaction conditions are mild, the energy consumption is low, it is environmentally friendly and has good yield, and gram-scale experiments can be realized without loss of activity and enantioselectivity.

The preparation method of the iridium complex comprises the following steps: adding an indole compound, an iridium compound and alkali into a first solvent, heating and stirring at 40-80 DEG C, after the reaction is finished, cooling to room temperature, filtering, carrying out reduced pressure distillation, and carrying out silica gel column chromatography separation to obtain the iridium complex; the iridium complex is used as a catalyst, under the combined action of the iridium complex and chiral phosphoric acid, the purpose that a 1, 5-diol compound and an amine compound directly react to obtain a series of chiral piperidine compounds can be achieved, and the method has the advantages of being high in reaction efficiency, simple, convenient and high in yield; and the enantiomer excess value of the chiral piperidine prepared by adopting the iridium catalyst is not less than 83%.

This invention discloses a palladium-catalyzed asymmetric hydrogenation method for synthesizing chiral dihydrocoumarin from tetrasubstituted olefins. The method uses a chiral bisphosphine complex of palladium as a catalyst and a tetrasubstituted olefin as a substrate to synthesize chiral dihydrocoumarin via asymmetric hydrogenation. This invention employs a homogeneous palladium catalytic system to achieve asymmetric hydrogenation of tetrasubstituted olefins with high yield, high enantioselectivity (up to 99% enantiomeric excess), and high diastereoselectivity (diastereomer ratio >20:1), producing chiral dihydrocoumarin. The method is simple and practical, the catalyst is commercially available, the reaction conditions are mild, energy consumption is low, and it is environmentally friendly.

The invention relates to a preparation method of (S)-flurbiprofen with high optical purity. The method comprises the following steps: by taking racemic flurbiprofen as a raw material, reacting with a resolving agent in a solvent to obtain optically pure diastereomer salt; the obtained diastereomer salt is recrystallized and purified by a solvent, so that the optical purity is further improved; acidifying the purified diastereomer, and filtering or extracting with an organic solvent to obtain a crude product (S)-flurbiprofen; and completely dissolving the crude product (S)-flurbiprofen with a benign solvent, adding pure water, and recrystallizing to obtain the (S)-flurbiprofen with high optical purity. The resolving agent required by the preparation method is novel, cheap and easy to obtain, the resolving effect is good, the enantiomeric excess is greater than or equal to 98.0%, the yield is high, the cost is low, the operation is simple, step-by-step amplification from the 10 g level to the hectogram level to the kilogram level is completed, the process is reproducible, and the amplification feasibility is realized.

The invention discloses a carbonyl reductase mutant and application thereof, and belongs to the technical field of biology. The carbonyl reductase mutant is obtained by mutation of at least one amino acid of the 198 site, the 213 site and the 215 site of an amino acid sequence shown in SEQ ID NO.1. The invention further provides a coding gene of the carbonyl reductase mutant, a recombinant vector containing the coding gene of the mutant, a genetic engineering bacterium containing the coding gene of the mutant, and a preparation method of the carbonyl reductase mutant. The invention also discloses an application of the carbonyl reductase mutant in preparation of (S)-3-hydroxy-3-phenyl ethyl propionate through biological catalytic synthesis. Compared with a wild type carbonyl reductase, the novel carbonyl reductase mutant KlSDRV198A / N213D / T215K provided by the invention has better stereoselectivity and thermal stability, the specific enzyme activity reaches 91.67 U / mg and is improved by 975.6% compared with the wild type carbonyl reductase, and the enantiomer excess value gt of the product (S)-3-hydroxy-3-phenyl ethyl propionate is higher than that of the wild type carbonyl reductase. The yield is 99% which is higher than that of a wild type by 66.7%, and the method has good industrial application potential.

The present invention relates to a method for obtaining fezolinetant which allows said product to be obtained with a high purity and enantiomeric excess by means of using trifluoromethanesulfonic acid. The present invention also relates to the trifluoromethanesulfonic acid salt of fezolinetant and to the use of said salt in obtaining fezolinetant.

The invention provides a hydantoinase mutant, a related product of the hydantoinase mutant and application of the hydantoinase mutant in production of a medical intermediate (R)-3-(carbamylmethyl)-5-methylhexanoic acid or an analogue and a downstream product of the (R)-3-(carbamylmethyl)-5-methylhexanoic acid. Compared with wild-type hydantoinase, the hydantoinase mutant disclosed by the invention has remarkably improved catalytic activity, and can stably maintain a high enantiomeric excess value (ee value) in the process of catalytically synthesizing (R)-3-(carbamylmethyl)-5-methylhexanoic acid. Therefore, by adopting the hydantoinase mutant disclosed by the invention, the production of high-purity R-3-(carbamylmethyl)-5-methylhexanoic acid or the analogue thereof can be realized in a low-cost and high-efficiency manner, so that the hydantoinase mutant has outstanding application value and wide industrialization prospect.

The invention relates to the technical field of biochemical engineering, in particular to a method for preparing a chiral beta-trifluoromethyl nitro compound through enzymatic high-enantioselective reduction, which successfully realizes efficient biological catalytic conversion of a beta-trifluoromethyl nitroolefin substrate under the synergistic effect of an NADPH (Nicotinamide Adenine Dinucleotide Phosphate) coenzyme system by adopting olefin reductase GluER and a variant thereof. The technology has excellent catalytic efficiency, and the substrate conversion rate is as high as 90%; absolute stereoselectivity is achieved, and the product enantiomer excess value (e.e) is 99% or above; a reaction system is simple, conditions are mild (normal temperature and normal pressure), and green chemical requirements are met. Compared with a traditional chemical synthesis method, a biological catalysis path shows remarkable advantages in the aspects of atom economy, environmental friendliness and optical purity of a product, and an innovative solution is provided for synthesis of chiral fluorine-containing drugs.

The present invention relates to a composition for use in the treatment of a disease or condition in which the disease or condition is preferably a disease or condition in which overexposure of aldosterone causes a symptom of the disease or condition, comprising a compound which is a compound of (R)-(+)-5-(p-cyanophenyl)-5, 6, 7, 8-tetrahydroimidazo [l, l]-1, 3, 4-triazole-1-yl)-1, 3, 4-triazole-1-yl)-1, 3, 4-triazole-1-yl)-1, 3, 4-triazole-1-yl, 1, 3, 4-triazole-1-yl. The present invention relates to a composition for the preparation of a pharmaceutical composition, preferably (R)-(+)-5-(p-cyanophenyl)-5, 6, 7, 8-tetrahydroimidazolium [l, 5-a] pyridine or a pharmaceutically acceptable salt thereof, said compound preferably being (R)-(+)-5-(p-cyanophenyl)-5, 6, 7, 8-tetrahydroimidazolium [l, 5-a] pyridine dihydric phosphate, said compound in the (R) form having an enantiomeric excess (ee) of 99% or more, said composition being administered once a day to a patient in need thereof for at least eight weeks.

The invention provides a method for asymmetric organic catalytic synthesis of spiro [indole-3, 4-b] pyridine. The invention discloses a method for preparing an optically active spiro [indole-3, 4 '-pyrrole [3, 4-b] pyridine] derivative, which comprises the following steps of: mixing substituted isatin with a structure as shown in a formula 2, cyanoacetate with a structure as shown in a formula 3, 3-aminomaleimide with a structure as shown in a formula 4, chiral cinchona alkali and a Takemoto type catalyst in an organic solvent, and reacting to obtain the optically active spiro [indole-3, 4'-pyrrole [3, 4-b] pyridine] derivative with a structure as shown in a formula 5. The invention relates to a 1, 4-b] pyridine] derivative. According to the method, the high-optical-purity spiro [indole-3, 4 '-pyrrole [3, 4-b] pyridine] derivative can be obtained, the maximum enantiomeric excess value of the derivative reaches 99%, the yield is good (74%-91%), and it is determined that the absolute configuration of a target compound is S through an X-single crystal diffraction experiment.

This invention discloses a rhodium-catalyzed asymmetric dearomatization cyclization method for synthesizing chiral dihydropyridine spirocyclic compounds, belonging to the field of asymmetric catalytic synthesis technology. The method uses a rhodium chiral bisphosphine complex and a base as the catalytic system, and alkynylpyridine salts and arylboronic acids as substrates to synthesize chiral dihydropyridine spirocyclic compounds through asymmetric dearomatization cyclization. The synthesis process of this invention is simple to operate, uses inexpensive and readily available reactants, operates under mild reaction conditions (not exceeding 60°C), exhibits high reactivity and enantioselectivity, complete reaction, specific products, and convenient separation, and can obtain pure products with high enantiomeric excess (up to 98%), showing excellent application prospects.

The invention discloses a transaminase mutant, a preparation method of the transaminase mutant and application of the transaminase mutant in synthesis of (R)-1-Boc-3-aminopiperidine. The mutant is a protein variant obtained through site-specific mutagenesis on the basis of an amino acid sequence as shown in SEQ ID NO: 1. When the mutant provided by the invention is used for catalyzing asymmetric amination of 1-Boc-3-piperidone to synthesize (R)-1-Boc-3-aminopiperidine, the catalytic activity and stereoselectivity are obviously improved, and the conversion rate and the enantiomeric excess value of the product are both greater than 99%. The mutant is clear in coding gene, easy to prepare through a recombinant expression system, simple in process, mild in condition and suitable for industrial production of (R)-1-Boc-3-aminopiperidine.

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

The invention relates to a chiral amino alcohol compound containing a carbamate structure and a preparation method thereof, the compound is an N-substituted 1, 2-chiral amino alcohol compound, and the structural formula of the compound is as shown in formula (I): # imgabs0. Under the catalysis of a non-C2 symmetric azaspiropyrrolidine oxazoline chiral ligand, cuprous acetate and potassium iodide, the chiral amino alcohol compound containing the carbamate structure is synthesized into a chiral amino alcohol compound containing the carbamate structure, and the chiral amino alcohol compound containing the carbamate structure and the preparation method of the chiral amino alcohol compound containing the carbamate structure are synthesized into the chiral amino alcohol compound containing the carbamate structure. According to the method, serinol and a derivative thereof are desymmetrical by using isocyanate, a higher enantiomer excess value (82%-97%) is obtained, a series of N-substituted 1, 2-chiral amino alcohol compounds with carbamate structures are prepared with higher yield, and the method has better scientific significance and application prospects.

Fezolinetant preparation procedure. The present invention relates to a process for obtaining fezolinetant that allows for the production of said product with high purity and enantiomeric excess through the use of trifluoromethanesulfonic acid. The present invention also relates to the trifluoromethanesulfonic acid salt of fezolinetant and to the use of said salt in the production of fezolinetant.