85 results about "Stereoselectivity" patented technology

The application relates to a chiral NSiN ligand based on a phenyloxazoline skeleton, a preparation method and application thereof, wherein the chiral NSiN ligand is prepared from a chiral phenyloxazoline bromide with R or S configuration through lithiation and silylation. The chiral NSiN ligand can be used in transition metal catalyzed asymmetric synthesis, and is used in catalyzing an allylic sulfonylation reaction with a cobalt catalyst, and shows high reaction activity and high stereoselectivity.

The application discloses a kind of using cobalt catalyst by unreported double migration coupling strategy, realizes migration asymmetric nitrogen hetero Nozaki-Hiyama-Kishi (aza-NHK) reaction, and the selective preparation α-chiral (E)-allyl amine starting from simple and easy to obtain ortho halogen phenyl ethylene or corresponding E / Z-alkyl bromide or its mixture belongs to the field of organic chemistry and medicinal chemistry.The application under the action of metal cobalt source, ligand, organic additive, inorganic additive etc., makes cyclic sulfonamide and ortho alkenyl substituted aryl halide or alkenyl halide react in organic solvent, to obtain a series of polysubstituted olefins with excellent regioselectivity, stereoselectivity and good yield, which can be used as active drug molecules and important synthetic intermediates.The application uses cheap transition metal cobalt as catalyst, and uses ortho alkenyl substituted aryl iodine and cyclic sulfonamide as raw material, and the reaction condition is warm, simple operation, and good functional group compatibility.

The present invention provides a carbonyl reductase mutant, preparation method and use thereof, and a preparation method of ethyl (R)-6-hydroxy-8-chlorooctanoate. The carbonyl reductase mutant is a carbonyl reductase with amino acid mutation; the carbonyl reductase comprises an amino acid sequence as set forth in SEQ ID NO: 2; the amino acid mutation includes E101V, F214R or E101V / F214R. In the present invention, by introducing mutations on the basis of the original carbonyl reductase sequence, the enzyme activity is improved, the stereoselectivity is improved, and ethyl (R)-6-hydroxy-8-chlorooctanoate can be obtained with high yield and high purity under relatively mild conditions, which reduces the production cost and is suitable for industrial production.

The present invention relates to a process for stereoselective polyene cyclization to produce tricyclic compounds of formula (I), wherein X is CH2or C=O, comprising reacting a compound of formula (II), wherein X is CH2or C=O and wherein the curved line indicates the E- or Z-configuration, in the presence of a catalytic amount of a Bronsted acid having an acidic sulfonamide moiety.(I)(II)

The application relates to the technical field of biotechnology, in particular to a dopamine reuptake inhibitor intermediate synthesis enzyme mutant and application, and amino acid sequences are shown in SEQ ID NO: 7-SEQ ID NO: 12. The stereoselectivity of asymmetric reduction catalysis of the dopamine reuptake inhibitor intermediate precursor is improved, the R-type dopamine reuptake inhibitor intermediate with high chirality purity is obtained, and the synthesis efficiency of the dopamine reuptake inhibitor intermediate is improved.

This invention provides the ketone reductase RasADH-E189D and its applications. The RasADH-E189D enzyme was obtained through site-directed mutagenesis, and its amino acid sequence is shown in SEQ ID NO.4. RasADH-E189D can efficiently and stereoselectively catalyze the asymmetric reduction reaction of aryl-substituted alkenyl 3,5-dicarbonyl esters, thereby preparing high-purity chiral aryl-substituted alkenyl β-hydroxy esters, which has important application value in the field of chiral drug synthesis.

The application discloses an ammonia lyase mutant, a recombinant bacterium and application of the ammonia lyase mutant in preparation of aromatic L-amino acid, and relates to the technical field of bioengineering and enzyme catalysis. Compared with a wild-type ammonia lyase, the ammonia lyase mutant comprises any one of the following mutations: M152A and / or L149G, and the amino acid sequence of the wild-type ammonia lyase is shown as SEQ ID NO. 1. The application provides the ammonia lyase mutant with higher enzyme activity and catalytic efficiency than the wild type, which can catalyze preparation of aromatic L-amino acid with high selectivity, high stability and high conversion rate. The ammonia lyase mutant has high stereoselectivity, avoids tedious chiral separation, and can directly obtain a medical-grade high-purity product. The method for preparing aromatic L-amino acid provided by the application can reduce the cost of materials, does not need a cosolvent and other reagents, simplifies the preparation process of aromatic L-amino acid, and has good industrial application potential.

This invention provides an imine reductase mutant, its preparation method, and its application in the catalytic preparation of dextromethorphan intermediates. The imine reductase mutant is an imine reductase with an amino acid mutation, comprising the amino acid sequence shown in SEQ ID NO:1. The amino acid mutation type includes any one or a combination of at least two of I122T, D212A, or G228R. By introducing a mutation into the imine reductase, this invention significantly improves the enzyme's activity and stereoselectivity, enabling the high-yield synthesis of the dextromethorphan intermediate (S)-1-(4-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline under mild conditions, greatly reducing production costs and making it suitable for industrial production.

This invention provides methods for the synthesis of cannabidiol and its analogues, as well as related compounds, formulations, and methods of use. [Solution] Methods are provided for the synthesis of oliveitol, oliveitol analogs, cannabidiol (CBD), CBD analogs, and other cannabinoids. One method uses phloroglucinol or phloroglucinol analogs as starting materials. The synthesis is stereospecific, efficient, selective, cost-effective, and THC((-)-trans-Δ 9 There is little to no possibility of generating (tetrahydro-cannabinol) or any other psychoactive by-products. Shortened synthesis is also provided, as well as new cannabinoids, pharmaceutical formulations, and methods of use.

This invention relates to the field of pharmaceutical intermediates, and in particular to a method for synthesizing chiral indane. The method uses indane as a raw material, synthesizes an oxime, then an enamine, and subsequently synthesizes the trans-chiral indane via an asymmetric hydrogenation reaction using a ruthenium chiral bisphosphine catalyst, achieving high yield and high stereoselectivity. The advantages of this invention are: in the asymmetric hydrogenation reaction of the enamine, the trans-chiral indane is obtained with a content greater than 97%, an ee of 95%, and a yield greater than 90%; the catalyst is readily available; the operation is simple; the raw materials are readily available; there is minimal pollution from waste; and energy consumption is low, making it suitable for industrial production.

The application discloses a selenoglycoside compound and a synthesis method, and aims at a series of technical defects in the existing selenoglycoside synthesis technology, such as high reagent toxicity, strong irritability, poor stability, harsh reaction conditions, complicated operation, insufficient stereoselectivity, poor substrate universality and difficulty in industrial application, and provides a green and efficient selenoglycoside compound synthesis method with strong universality, which has remarkable beneficial technical effects. The core reaction substrate adopted in the application is a glycosyl selenosulfonate and a (hetero) aryl boronic acid, both of which are conventional reagents easy to obtain, have no irritating odor, and have excellent chemical stability and environmental tolerance, thereby avoiding the use of high-toxicity, high-irritability and low-stability reagents such as diselenide, selenol and glycosyl stannane in the traditional synthesis process from the source, greatly reducing the safety control cost and three-waste treatment pressure in the synthesis process, and meeting the development requirements of green chemistry.

The application relates to application of a transaminase mutant in synthesis of a key chiral intermediate D-4,4'-diphenylalanine of sacubitril valsartan sodium salt (LCZ696), and belongs to the technical field of biocatalytic synthesis.The mutant is a quadruple mutant of the amino acid sequence shown in SEQ ID NO:1, the amino acid sequence of the transaminase mutant is shown in SEQ ID NO:3, and the corresponding amino acid sequence is shown in SEQ ID NO:4.Compared with a wild-type transaminase parent, the unit enzyme activity is increased by about 30 times under the condition of ensuring the chiral purity of a product, the transaminase has very high stereoselectivity and conversion rate, the industrial production cost of sacubitril and LCZ696 can be further reduced, and the transaminase has good industrial application value.

This invention belongs to the field of polymer materials technology, specifically relating to a production process for ultra-high molecular weight polyethylene (UHMWPE). By optimizing the catalyst system and polymerization process, this invention improves the performance and production stability of UHMWPE. A co-catalyst composed of alkylaluminum and organosiloxane modifiers, acting synergistically with external electron donors, significantly enhances catalyst activity and stereoselectivity, resulting in a more stable polymerization process, higher molecular weight and narrower molecular weight distribution, and significantly enhanced mechanical properties. The multi-stage polymerization process achieves precise control of the polymerization process through segmented temperature control, coupled with a dual-circulation heat removal system to effectively remove reaction heat, avoid localized overheating, and ensure a uniform and stable product structure. An integrated solvent recovery and molecular sieve drying system enables efficient recycling of hexane, controlling moisture content to ≤5ppm, preventing catalyst poisoning, ensuring stable continuous production, and overall improving the process's economy and reliability.

This invention discloses a chiral monophosphine ligand, its preparation method, and its application in asymmetric synthesis. The ligand preparation method involves mixing an N,N',1,2-tetrasubstituted ethane-1,2-diamine compound, phosphorus trichloride, triethylamine, and solvent under a nitrogen or argon atmosphere at -80 to -70°C, and reacting at 60 to 80°C for 6 to 8 hours. The resulting reaction mixture is then cooled to room temperature, and an alcohol, phenol, or Grignard reagent is added dropwise, reacting at 60 to 80°C for 8 to 12 hours. The resulting mixture is then post-treated to obtain the chiral monophosphine ligand. The application involves stirring a nickel catalyst, a chiral monophosphine ligand, a solvent, a diene, and an aldehyde under an argon or nitrogen atmosphere at a specified temperature for 12 to 15 hours. The mixture is then post-treated to obtain the target product. This method utilizes widely available and inexpensive raw materials, and the operation is simple, achieving high stereoselectivity and enantioselectivity in the synthesis of alcohol compounds containing chiral conjugated dienes through a one-step reaction.

The application discloses an alcohol dehydrogenase mutant and application thereof in enzymatic synthesis of a loratadine intermediate. A plurality of alcohol dehydrogenase mutants are developed, and a loratadine chiral intermediate is obtained through an enzyme catalytic synthesis method based on the mutants, wherein the reaction condition is mild, the environment is friendly, the reaction has high regional selectivity and stereoselectivity, the reaction conversion rate is high, the chiral purity of the product is high, the enzyme consumption is low, the preparation cost is low, the method is suitable for industrial production, the method avoids the problems of difficult chiral resolution and heavy metal residue in a product in a conventional method, and the method makes up for the deficiencies of a traditional chemical method.

The present application relates to the technical field of pharmaceutical intermediates, and in particular to a synthesis method of chiral indanamine, which comprises the following steps: taking indanone as a raw material, using a chiral biphosphine catalyst of ruthenium to synthesize chiral indanamine in a cis form with high yield and high stereoselectivity, and then obtaining chiral indanamine in a trans form through a transposition process.The reaction process is as follows: the chiral indanamine in the trans form has a content of greater than 99%, 98% ee and a total yield of greater than 90%, the catalyst is convenient and easy to obtain, the operation is simple, the raw material is easy to obtain, the three-waste pollution is small, the energy consumption is low, and the method is suitable for industrial production.

This invention discloses an R-type α-fluoroimine reductase mutant, its preparation method, and its applications. The wild-type imine reductase is derived from *Xanthomonas aeruginosa*. Luteolibacter luteus By using directed evolution to modify its active site, an imine reductase mutant with high activity, stereoselectivity, and high yield of 4-methoxy-N-(2,2,2-trifluoro-1-phenylethyl)aniline was obtained. The mutation is at least one of S237T, I241L, or R248L. This invention achieves efficient synthesis of (R)-4-methoxy-N-(2,2,2-trifluoro-1-phenylethyl)aniline from inexpensive (Z)-2,2,2-trifluoro-N-(4-methoxyphenyl)-1-phenylethylimine, which is beneficial for the industrial synthesis and application of (R)-4-methoxy-N-(2,2,2-trifluoro-1-phenylethyl)aniline.

This invention relates to the field of chemical synthesis technology, and more specifically to a method for synthesizing N-glycosides from unprotected sugars. The method is characterized by dissolving an unprotected glycosyl donor, acceptor, and base in water or a mixture of water and an organic solvent at temperatures ranging from -78°C to 25°C, adding a promoter, and reacting to obtain the corresponding glycoside. This invention synthesizes a series of DMC analogs, which are previously unreported and are novel compounds. These analogs can mediate the glycosylation of unprotected sugars with a base as the acceptor, and can also specifically bind to the 9-N position of the acceptor. This method avoids the complex operations of upper and lower protecting groups, and the glycosylation reaction product exhibits high stereoselectivity, significantly reducing the complexity and cost of glycosylation synthesis.

The application belongs to the technical field of biochemical synthesis, and particularly relates to a high stereoselectivity amino-cleaving enzyme and a synthesis method of (S)-3-aminobutyronitrile and a salt thereof. The high stereoselectivity amino-cleaving enzyme is selected from the amino acid sequences shown in SEQ ID NO. 6-8. The synthesis method comprises: performing an enzyme catalytic reaction on crotonic acid in the presence of the high stereoselectivity amino-cleaving enzyme to obtain (S)-3-aminobutyric acid with a chiral purity e.e. of 99.5% or more; reacting (S)-3-aminobutyric acid with di-tert-butyl dicarbonate, and then reacting with ammonium bicarbonate, and further performing dehydration and deprotection to obtain (S)-3-aminobutyronitrile hydrochloride. The application combines chemical method and enzyme method, avoids the use of highly toxic substances, is safe and efficient, improves the economic benefits in the industrialization process, and the overall route reflects the value of green chemical synthesis.

The application provides a synthesis method of chondroitin polysaccharide ABW90-1 and / or chondroitin polysaccharide ABW50-1, and relates to the technical field of polysaccharide preparation.The synthesis method provided by the application adopts a fructose 6-position picoloyl group as a guiding group, highly stereoselectively constructs beta-(2 to 6)-D-furan fructose and internal beta-(2 to 1)-D-furan fructose glycosidic bonds through a glycoside unit transfer strategy mediated by hydrogen bonds, and efficiently prepares chondroitin polysaccharide ABW90-1 and chondroitin polysaccharide ABW50-1.The synthesis method provided by the application has the advantages of simplicity, high efficiency, high target product yield and high purity, and has reference significance for the synthesis of other types of sucrose oligosaccharides.

This invention belongs to the fields of organic catalysis and asymmetric catalysis, and relates to a bichiral synergistic nitrogen heterocyclic carbene-oxynitrile adduct catalyst, its preparation method, and its application. The catalyst is composed of a nitrogen heterocyclic carbene unit and an oxynitrile unit, wherein both the nitrogen heterocyclic carbene and oxynitrile moieties can incorporate chiral structural units, thereby constructing a synergistic chiral environment composed of two chiral sources within the overall catalyst structure. This structural design allows for a more refined stereoselectivity control during the catalytic reaction, thereby enhancing the catalyst's stereoinductive ability in asymmetric catalytic reactions. The catalyst is prepared through a modular synthesis process, which involves fewer steps and is safe and simple to operate, and the catalyst structure is easily modulated. Applying this catalyst to acyl rearrangement reactions enables effective control of the reaction's stereoselectivity, thereby efficiently synthesizing various indolones or benzofuranones containing a chiral quaternary carbon center at the C3 position.

This invention discloses a chemical-biological fusion method for cholesterol synthesis. Using plant-derived 21-hydroxy-20-methylpregn-4-en-3-one, also known as bis(2-hydroxy-2-yl)-3-one (BA), as a raw material, cholesterol is synthesized through a four-step reaction involving sulfonation, acetylation, enzymatic hydrolysis and reduction, and Grignard coupling. Addressing the drawbacks of traditional animal-derived cholesterol, which carries unpredictable risks of pathogenic bacteria and viruses, this invention uses plant-derived steroidal raw material BA to synthesize cholesterol. This method not only offers high safety, avoiding the risk of pathogenic bacteria and viral infections, but also utilizes the tandem catalysis of esterase and carbonyl reductase during synthesis, along with coenzyme regeneration, to obtain key intermediates with high stereoselectivity and in a safe and clean manner. This significantly shortens the cholesterol synthesis route, increases efficiency, simplifies operation, minimizes solvent recycling losses, reduces waste, and allows for mild reaction conditions. This method is safe, economical, and suitable for industrial production.

The application discloses an alcohol dehydrogenase mutant and application thereof in preparation of cis-4-propylcyclohexanol. The mutant is obtained by substituting at least one amino acid in three positions of an amino acid sequence shown in SEQ ID No. 1, i.e. the 43th, 271th and 282th positions. The 43th phenylalanine (F) is substituted into valine (V) or serine (S), the 271th isoleucine (I) is substituted into valine (V) or phenylalanine (F), and the 282th phenylalanine (F) is substituted into valine (V). The wild-type alcohol dehydrogenase gene is subjected to directional evolution modification, and the alcohol dehydrogenase mutant has higher catalytic activity and higher stereoselectivity than the wild-type alcohol dehydrogenase, so that the cis-4-propylcyclohexanol is efficiently and highly stereoselectively generated.

This invention provides an enzymatic method for the preparation of R-3-aminobutyric acid (GABA), belonging to the field of biochemistry. Using crotonic acid as a substrate and a recombinant aspartate enzyme mutant as a biocatalyst, an enzymatic reaction is carried out under suitable temperature and pH control to efficiently and stereoselectively prepare the product R-3-aminobutyric acid. This method utilizes *E. coli* as a host for heterologous expression of recombinant aspartate enzyme. The whole cells of the expression host are used as crude enzyme for the enzymatic reaction. After extraction and purification, high-purity R-3-aminobutyric acid is obtained, with a conversion rate exceeding 99% and a product purity >99% and >99.9% ee. This method features high conversion and high yield, and is easily industrialized.

This invention discloses an enzymatically catalytic synthesis method for a chiral intermediate of dzoxadamine. Using methyl acetoacetate as a substrate, buffer, substrate, alcohol dehydrogenase, formate dehydrogenase, ammonium formate, and coenzyme are added to a reaction vessel. The reaction is carried out at 20–40°C for 2–24 hours. After extraction, separation, and rotary evaporation, the chiral intermediate (R)-3-hydroxybutyrate methyl ester is obtained. The alcohol dehydrogenase is a mutant of ADH1 derived from Rollstonella, and the amino acid sequence of ADH1 is shown in SEQ ID No. 1. This invention offers mild reaction conditions, high stereoselectivity, and environmental friendliness. It also boasts high conversion rate, high chiral purity, low enzyme dosage, tolerance to high substrate concentrations, and low preparation cost, making it suitable for industrial production. Furthermore, it avoids chiral resolution and heavy metal residues in the product, overcoming the shortcomings of chemical methods.

The invention relates to a catalytic system comprising the metallic components of formulas R1R2Mg and Ca(AR'y)2(L)x, in which: - each of R1 and R2 represents, independently of each other, a C1-C10 aliphatic radical, substituted or unsubstituted, or a C6-C20 aromatic radical, substituted or unsubstituted; - A denotes a nitrogen atom (N) or an oxygen atom (O); - y is 2 when A is N and y is 1 when A is O; - each R' represents, independently of each other, a C1-C10 aliphatic radical, substituted or unsubstituted, a C6-C20 aromatic radical, substituted or unsubstituted, a silyl radical, substituted or unsubstituted, a C1-C10 aliphatic radical substituted by at least one silyl radical, substituted or unsubstituted, or a C6-C20 aromatic radical substituted by at least one silyl radical. substituted or not, - L represents a ligand, - x is a number from 0 to 4.The use of this catalytic system for the anionic polymerization of conjugated dienes allows the obtaining of diene polymers with high trans content.

The application relates to an imine reductase mutant and application thereof, the amino acid sequence of the imine reductase mutant is an amino acid sequence obtained by mutation on the basis of the sequence shown in SEQ ID NO. 1, imine is used as a substrate, a high (S) stereoselective imine reductase VpIR is obtained by screening an imine reductase library, a high catalytic efficiency and high selectivity imine reductase mutant is obtained by mutation on a key site of the enzyme molecule, and the application potential of the enzyme in industrial application is expanded.