35 results about "Enantiomeric excess" patented technology

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

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.

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.

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 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 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.

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.

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.

The invention discloses a method for synthesizing levosalbutamol and a precursor thereof through three-enzyme cascade catalysis, and belongs to the technical field of biological engineering. The invention designs a new route for efficiently biologically synthesizing the levosalbutamol and the precursor thereof by taking cheap 5-[2-[(1, 1-dimethylethyl) amino] acetyl]-2-hydroxybenzaldehyde as a substrate through three-enzyme cascade catalysis of benzyl alcohol dehydrogenase, carbonyl reductase and glucose dehydrogenase. When the substrate concentration is 100 mM, the yield of the levosalbutamol reaches 98%, and the enantiomeric excess (ee) is greater than 99%. In addition, according to the route, 5-bromoacetyl-2-hydroxybenzaldehyde can be used as a substrate, and the levosalbutamol precursor can be efficiently synthesized through three-enzyme cascade catalysis. Compared with the existing method for mainly producing the levosalbutamol and the precursor thereof, the method disclosed by the invention has the advantages that the production cost is obviously reduced, the synthesis efficiency and the chiral purity of the product are improved, and the method has a wide application prospect.

The invention relates to a composition of δ-decalactone comprising at least one compound chosen from the group A and / or at least one compound chosen from the group B, said composition comprising an excess of enantiomer (R) over enantiomer (S), the enantiomeric excess of enantiomer (R) over enantiomer (S) being at least 85%, preferably at least 90%, more preferably at least 95%, more preferably at least 98%, and more preferably at least 99%.

The present disclosure generally relates to improved synthesis of fused bicyclic Raf inhibitor enantiomers of formula (I), (Ia), (Ib), (II), (IIa), or (IIb), or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof, with high enantiomeric excess (% ee). The disclosure also relates to method of using the compound of formula (I), (Ia), (Ib), (II), (IIa), or (IIb), or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof, for treating diseases such as cancer, including colorectal cancer.

The invention discloses a method for enantioselective synthesis of NH-aziridine, which comprises the following steps: in the presence of a chiral phosphoric acid catalyst, reacting alpha-cyano heterocyclic conjugated olefin as shown in a formula (I) with N-acyloxyhydroxylamine in an organic solvent to obtain NH-aziridine as shown in a formula (II), according to the present invention, the method can be smoothly performed in the inert organic solvent at the temperature of-40-25 DEG C, the substrate can suitably cover pyridine, quinoline, benzimidazole, benzothiazole, benzoxazole and other N-heteroaromatic rings, the product yield is high, and the enantiomeric excess (ee) can be up to 99%. Inorganic additives (such as magnesium oxide) may be optionally added during the reaction to increase yield on individual substrates without affecting enantioselectivity. The method avoids the traditional multi-step sequence of nitrogen protection first and then deprotection, and has the advantages of economical steps, mild conditions, feasible amplification and the like.

The invention discloses a method for producing a clopidogrel intermediate through biological catalysis chiral resolution, which comprises the following steps: screening an esterase mutant capable of efficiently resolving the clopidogrel intermediate (R, S)-2-(2-chlorphenyl)-2-(2-thiophene ethylamino) methyl acetate through molecular modification to obtain (S)-2-(2-chlorphenyl)-2-(2-thiophene ethylamino) methyl acetate; according to the present invention, the biocatalysis activity and the stereoselectivity are high, the reaction efficiency is improved, the position of the biocatalysis step in the whole synthesis route is beneficial to the improvement of the efficiency of other chemical steps, the overall conversion rate, the enantiomer excess value and the product purity, and the production cost can be significantly reduced. In addition, the method also has the common advantages of enzymatic synthesis, such as simplicity and convenience in implementation and operation, greenness and environmental protection, easiness in product separation and the like.

The invention discloses a preparation method and application of a series of novel chiral polydentate amino alcohol ligands. The synthesis method comprises the following steps: preparing primary alcohol type chiral amino alcohol by taking L-amino alcohol and 2-halogenated heteroaromatic ring as raw materials and carrying out nucleophilic substitution reaction in one step; the tertiary alcohol type chiral amino alcohol is prepared by taking L-leucine as a raw material, and sequentially carrying out methyl esterification, Buchwald-Harwig cross-coupling reaction and phenyl magnesium bromide addition reaction to synthesize the tertiary alcohol type chiral amino alcohol. The method disclosed by the invention is simple in process, mild in reaction condition, cheap and easily available in raw materials, easy in product separation and purification and high in yield; and the prepared chiral polydentate amino alcohol ligand can be applied to identification of camphorsulfonic acid enantiomers and determination of enantiomer excess (ee value).

The application discloses a method for synthesizing indoline derivatives through palladium-catalyzed asymmetric hydrogenation, and belongs to the technical field of organic synthesis. The method uses indole derivatives as reaction substrates, uses a chiral diphosphine palladium complex as a catalyst, and uses a Bronsted acid as an additive to synthesize indoline derivatives through asymmetric hydrogenation. The chiral diphosphine ligand is one of (S)-MeO-Biphep, (S)-SynPhos, (S)-SegPhos, (S)-BINAP and (S)-JosiPhos; the metal precursor of palladium is palladium trifluoroacetate; and the Bronsted acid is methyl sulfonic acid, p-toluenesulfonic acid, trifluoroacetic acid, D-camphorsulfonic acid or L-camphorsulfonic acid. The hydrogenation of specific indole derivatives can obtain corresponding chiral indoline derivatives, and the enantiomeric excess of the chiral indoline derivatives can reach 97%. The method is simple and practical, has high enantioselectivity, has good yield, and has green atom economy and environmental friendliness.

The invention discloses a pinyl hydrate esterase mutant with high enantioselectivity as well as a construction method and application of the pinyl hydrate esterase mutant, and belongs to the technical field of enzyme engineering. The pinyl hydrate esterase mutant provided by the invention is obtained by carrying out single-point mutation or combined mutation on the 273 site leucine, the 314 site phenylalanine, the 362 site leucine and the 193 site methionine of a pinyl hydrate esterase amino acid sequence derived from bacillus subtilis through a high-throughput screening method based on fluorescence coupling. Wherein the mutant M4 shows the best catalytic performance for racemization-acetic acid pinyl hydrate, the enantiomer excess value of the mutant M4 is 99.35%, and the conversion rate of the (1S, 5R)-acetic acid pinyl hydrate is 83.90%. The pinyl hydrate esterase mutant provided by the invention is high in enzyme activity of catalyzing (1S, 5R)-acetic acid pinyl hydrate, high in eep value and high in conversion rate.

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

This invention discloses an R-type transaminase mutant and its applications, relating to the field of biocatalysis technology. The amino acid sequence of the R-type transaminase of this invention is shown in SEQ ID NO.7, the nucleotide sequence of the encoding gene is shown in SEQ ID NO.1, and the amino acid sequences of the R-type transaminase mutant are shown in SEQ ID NO.2-SEQ ID NO.6. This invention also provides the application of the R-type transaminase mutant in the asymmetric synthesis of chiral amine compounds. The R-type transaminase of this invention has a maximum sequence similarity of only about 80% with existing R-type transaminases. It provides a method for the enzymatic synthesis of chiral intermediates, with simple reaction steps, mild reaction conditions, and a single-step reaction to reduce and amination 1-naphthyl acetone to a high optical purity (…). R )-1-(1-naphthyl)-ethylamine, with a conversion rate of over 90% and an ee value (enantiomer excess) greater than 99%.

The present invention relates to processes with an improved enantiomeric excess of the desired enantiomer of the dengue viral replication inhibitor 2-(4-chloro-2-methoxyphenyl)-2- ((3-methoxy-5-(methylsulfonyl)phenyl)amino)-1-(5-(trifluoro-methoxy)-1H-indol-3-yl)ethan-1-5 one, to polymorphic forms and solvates of (S)-2-(4-chloro-2 methoxyphenyl)-2-((3-methoxy-5- (methylsulfonyl)phenyl)amino)-1-(5-(trifluoromethoxy)-1H-indol-3-yl)ethan-1-one (Compound A), to pharmaceutical compositions comprising said forms, to processes for preparing said forms, and the use of these forms.

The invention relates to the technical field of organic synthesis chemistry and asymmetric catalysis, in particular to an amino acid-derived N, N, N-tridentate ligand and a preparation method and application thereof.The ligand has the structure shown in the general formula (I) or comprises an acyl / sulfonyl unit part and an amino acid-derived diamine unit, wherein R1 is selected from substituted or unsubstituted aryl, heteroaryl, alkyl or styryl, and the diamine unit is derived from natural or artificial amino acid. The ligand is wide in source, simple and convenient to synthesize, diverse in structure, low in price and easy to obtain, can be coordinated with a copper catalyst to be used for catalyzing S-functionalization and other asymmetric free radical reactions of sulfenamide, shows excellent catalytic activity and enantioselectivity, has the yield of 80% or above and the enantiomeric excess (ee) value of 90% or above, and is suitable for industrial production. The quinine alkaloid ligand overcomes the defects of single structure, high price and difficulty in modification of the existing quinine alkaloid ligand.

The present invention relates to a composition for use in the treatment of a disease or disorder, wherein said disease or disorder is preferably a disease or disorder in which aldosterone overexposure contributes to the symptoms of said disease or disorder, said composition comprises a compound which is (R)-(+)-5-(p-cyanophenyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyridine or a pharmaceutically acceptable salt thereof, wherein preferably said compound is (R)-(+)-5-(p-cyanophenyl)-5,6,7,8-tetrahydroimidazolium[1,5-a]pyridine dihydrogen phosphate, and wherein said compound has an enantiomeric excess (ee) of the (R) form higher than or equal to 99%, and wherein said composition is administered once daily for at least eight weeks to a patient in need thereof.

This invention discloses an Ecu0554 esterase mutant with significantly improved enantioselectivity and stability, its construction method, and its applications. The Ecu0554 esterase mutant provided by this invention exhibits excellent stereoselectivity for racemic pinene acetate hydrate, with an enantiomeric excess value of 99%, (1 S 5 R The conversion rate of 1-acetic acid hydrate pinyl ester was 81.42%. The half-life (~225 min) of the mutant A163I / L273Y / F314Y / L362R at 51 °C was approximately 45 times that of the mutant L273Y / F314Y / L362R. The Ecu0554 esterase mutant provided by this invention catalyzes (1 S 5 R )-Pinyl acetate hydrate ee High value, high conversion rate, high thermal stability, suitable for producing high-value chiral intermediates (1 S 5 R Application prospects of )-hydrated pinol and similar monocyclic monoterpenoids.

The present invention relates to a novel method for synthesizing L-BDHU and related starting materials and intermediate compounds from (7?J-2,2-dimethyl-1,3-dioxolane-4-carboxylate (7) in only 7 steps. The invention eliminates the expensive chiral purification of L-dioxolane (11), resulting in an enantiomerically enriched compound (ee > 99%). The optically pure compound 11 is utilized to construct L-BHDU (15) and its monophosphate drug precursor (POM-L-BHDU, 22). New synthetic methods and new intermediate compounds represent additional embodiments of the present invention.

The invention discloses a method for preparing (S)-1-Boc-3-aminopiperidine, and belongs to the technical field of biological catalysis. According to the method, transaminase containing an amino acid sequence as shown in SEQ ID NO: 1 or a homologous variant of the transaminase is used as a catalyst, and the (S)-1-Boc-3-aminopiperidine is prepared by catalyzing an asymmetric amination reaction of 1-Boc-3-piperidone in the presence of an amino donor and a cofactor. According to the method, efficient catalysis of the reaction is realized by using specific transaminase, the highest conversion rate can reach 96.8%, the product has extremely high optical purity, and the enantiomeric excess value is greater than 99%. The synthesis route provided by the invention is mild in condition, simple and convenient to operate and environment-friendly, and a reliable scheme is provided for industrial production of (S)-1-Boc-3-aminopiperidine after 100-gram-level process verification.

The invention discloses an amine dehydrogenase mutant and application thereof in preparation of a chiral compound, and relates to the field of biology. The amine dehydrogenase mutant provided by the embodiment of the invention has mutation at any one or more sites of the 179th site, the 202 site, the 223rd site, the 224th site, the 226th site, the 227th site and the 242th site of a wild type amino acid sequence, has high activity and high enantioselectivity, has the enzyme catalysis efficiency obviously superior to that of a parent enzyme and the existing amine dehydrogenase, and can be used for preparing the amino acid sequence of the amino acid sequence of the amino acid sequence of the amino acid sequence of the amino acid sequence of the amino acid sequence of the amino acid sequence of the amino acid sequence of the amino acid sequence. The R-3-aminobutanol has the advantages of high yield and high enantiomeric excess (ee value), and provides a high-performance biocatalyst and an industrial application foundation for efficient asymmetric synthesis of R-3-aminobutanol, and the high-concentration substrate can be catalyzed by the R-3-aminobutanol has the advantages of high yield and high enantiomeric excess (ee value).

This invention provides a hydantoin mutant, related products, and their application in the production of the pharmaceutical intermediate (R)-3-(carbamoylmethyl)-5-methylhexanoic acid or its analogues and downstream products. Compared with wild-type hydantoin, the hydantoin mutant of this invention exhibits significantly enhanced catalytic activity, and can stably maintain a high enantiomeric excess (ee value) during the catalytic synthesis of (R)-3-(carbamoylmethyl)-5-methylhexanoic acid. Therefore, using the hydantoin mutant of this invention, high-purity R-3-(carbamoylmethyl)-5-methylhexanoic acid or its analogues can be produced in a low-cost and high-efficiency manner, thus possessing outstanding application value and broad industrialization prospects.

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. The present invention relates to a process for the preparation of amorphous solid dispersion 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). with at least one pharmaceutically acceptable excipient. and its novel intermediates thereof. Elacestrant dihydrochloride (1) The present invention further relates to a process for the preparation of intermediates of formula (D), formula (E1), formula (H1) & Elacestrant sulfate (2) with enantiomeric excess greater than 50%.