64 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 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 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.

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 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 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.

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 preparation method of dexmedetomidine hydrochloride. First, 2', 3'-dimethylacetophenone is used as raw material. Under Lewis acid catalysis, chlorination reaction occurs with dimethylchlorosilane to synthesize 1-(1-chloroethyl)-2,3-dimethylbenzene. Then, under chiral catalyst catalysis, cross-reduction coupling reaction occurs with 4-iodoimidazole, and finally salification is performed to obtain dexmedetomidine hydrochloride with an enantiomeric excess of up to 99%. The method has the advantages of easy availability of raw materials, simple operation, mild reaction conditions, short synthesis route, high yield, good stereoselectivity, and good economic and social benefits.

The invention discloses a method for preparing D-lysine hydrochloride through enzyme catalysis cascade reaction, and belongs to the technical field of biochemistry. The method comprises the following steps: by taking L-lysine hydrochloride as a substrate, carrying out racemization reaction through racemase to prepare DL-lysine, then carrying out decarboxylation on the L-lysine in a reaction solution under the action of decarboxylase to generate pentamethylene diamine, and finally extracting to obtain the D-lysine hydrochloride. The reaction liquid is extracted and purified to obtain a high-purity D-lysine hydrochloride product, and the conversion rate of the decarboxylase to the L-lysine reaches 99% or above. After decoloration, rotary evaporation, alcohol washing and drying, the purity of the D-lysine hydrochloride product is detected to be more than 99%, the enantiomeric excess value ee is 100%, and the yield reaches the theoretical value 85% or above of the D-lysine hydrochloride. The method provided by the invention has the characteristics of high conversion rate and high yield, and is easy to industrialize.

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 discloses a sensor for rapidly detecting excessive lactic acid enantiomers in urine based on a semiconductor SERS (Surface Enhanced Raman Scattering) technology. The method comprises the following steps: step 1, synthesizing a ZIF-8 nanocrystal precursor; step 2, synthesis of a ZIF-8 / ZnS nano material; and step 3, preparing the ZIF-8 / ZnS / 4-MPY chiral recognition sensor. And 4, detecting the enantiomer excess value of the lactic acid enantiomer in the urine. The sensor for directly detecting excessive lactic acid enantiomers in urine based on the semiconductor SERS technology has the advantages of being low in cost, easy and convenient to operate, sensitive in detection and the like, is particularly suitable for clinical preliminary screening of intestinal diseases, and has wide application prospects. The fitting peak area of shoulder peaks with Raman shifts of 1004 and 1024 cm <-1 > and excessive lactic acid enantiomers in urine show an extremely high linear relationship.

The invention discloses an R-type transaminase mutant and application, and relates to the technical field of biological catalysis. The amino acid sequence of the R-type transaminase is shown as SEQ ID NO.7, the nucleotide sequence of the coding gene is shown as SEQ ID NO.1, and the amino acid sequence of the R-type transaminase mutant is shown as SEQ ID NO.2-SEQ ID NO.6. The invention further provides application of the R-type transaminase mutant in asymmetric synthesis of chiral amine compounds. The maximum sequence similarity of the R-type transaminase and the existing R-type transaminase is only about 80%, the method for synthesizing the chiral intermediate through the biological enzyme method is provided, the reaction steps are simple, the reaction conditions are mild, 1-acetophenone can be reduced and aminated into (R)-1-(1-naphthyl)-ethylamine with high optical purity only through one-step reaction, the conversion rate is up to 90% or above, and the method is suitable for industrial production. The ee value (enantiomeric excess) is greater than 99%.

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).