103 results about "Chiral amine" patented technology

The invention discloses a chiral amine reagent and a preparation method thereof as well as a method for analyzing and splitting a chiral drug, the chiral amine reagent is APMA # imgabs0 # or d5-APMA # imgabs1 #, and the configuration of a carbon atom connected with an amino group on a piperidine ring in the structural formula is an S configuration. The APMA and d5-APMA provided by the invention can be used for analysis and detection of chiral drugs, 3-aminocyclohexyl-phenyl methane ketone (APMA) and the d5-APMA in a stable isotope form thereof are independently or jointly used as a pair of isotope labeling reagents and are subjected to condensation reaction with the chiral drugs to obtain derivatives, enantiomers of the chiral drugs can be effectively split, and the chiral drugs can be analyzed and detected. And an easy-to-ionize group is introduced, so that the mass spectrum response in an ESI positive ion mode is greatly improved.

The invention provides a transaminase mutant and application of the transaminase mutant in chiral amine synthesis. According to the transaminase derived from Mycobacterium sp. Provided by the invention, in a 1 mL reaction system for catalyzing N-Boc-3-piperidone to generate N-Boc-3-aminopiperidine, the 24-hour conversion rate is 95%, and the e.e. Value of the product is greater than 99%. On the basis, the invention further provides a series of mutants of the transaminase, the relative enzyme activity of the mutants reaches 153%-293%, and the catalytic activity of the transaminase is further improved. Wherein the 34-hour conversion rate of the optimal transaminase mutant is increased to 90% or above under the condition of 120g / L substrate concentration in a 10mL reaction system, and the e.e. Value of the product is greater than 99%. The production technology has the advantages of high catalytic activity, easiness in fermentation, environment friendliness and the like, and has good development and application values.

The invention relates to a method for preparing (S)-chiral amine through asymmetric catalysis of imine reductase, and belongs to the technical field of biological pharmacy. Comprising the following steps that imine reductase catalyzes imine to be subjected to a reductive hydrogenation reaction under the conditions of coenzyme and a coenzyme regeneration system, and the (S)-chiral amine compound is generated. According to the method, imine reductase is utilized to catalyze imine asymmetric reduction to prepare the innovative drug (S)-chiral amine compound, and compared with a traditional chemical synthesis method, the method has the advantages of being high in reaction efficiency, good in stereoselectivity, mild in reaction condition, environmentally friendly and the like, and is a method meeting the green production requirement.

The invention relates to an organic crystalline piezoelectric material based on chiral 4-bromophenylethylamine hydrochloride, which is synthesized by using hydrochloric acid as an anion and protonated (R / S)-4-bromophenylethylamine as a cation according to the stoichiometric ratio of (R / S)-4-bromophenylethylamine to hydrochloric acid of 1: 1. The invention provides an organic crystalline piezoelectric material based on chiral 4-bromophenylethylamine hydrochloride and a preparation method, and provides a two-dimensional hydrogen bond network construction strategy based on protonated chiral amine: protonated (R / S)-4-bromophenylethylamine cations are used as structural elements, chloride ions are used as charge balance bodies, and the chiral 4-bromophenylethylamine hydrochloride is prepared by precisely regulating the interaction of intermolecular hydrogen bonds. Constructing a two-dimensional hydrogen bond network with high orientation; by enhancing ordered arrangement of molecular dipoles and optimizing a lattice strain-polarization response collaborative mode, breakthrough improvement of piezoelectric performance is successfully realized, and a new normal form is provided for developing high-performance organic piezoelectric materials.

The invention discloses a reductive aminase mutant and application of the reductive aminase mutant in synthesis of chiral alkylated benzyl propylamine. The invention relates to a mutant protein of carbonyl reductase, which is characterized in that the mutant protein has one or more alternative mutations in sites 85, 87, 128, 134, 162, 197, 219, 234 and 235 on the basis of an amino acid sequence as shown in SEQ ID NO: 1. On the basis of analysis of the crystal structure of reductive aminase M5 in the early stage, stereoselective transformation is carried out through site-specific mutagenesis, combinatorial mutation and the like, an efficient mutant for synthesizing an alkylated benzyl propylamine S-enantiomer is obtained, and a series of chiral amines with the selectivity larger than 99% S are synthesized with different amine donors such as benzyl acetone and benzylamine as substrates. And the method has important significance on industrial green synthesis of the chiral amine.

The present invention discloses a transaminase and its use in preparing optically pure chiral amines. The amino acid sequence of the transaminase of the present invention has one or more mutations at positions 65, 318, 399, 419, 426, 465, and 466 compared to SEQ ID NO: 1, wherein the mutation is an addition, deletion, or substitution of an amino acid residue. The present invention also discloses a nucleic acid molecule encoding the transaminase, a nucleic acid construct comprising the nucleic acid molecule, a recombinant vector, and a host cell. The present invention also discloses an enzyme preparation comprising the transaminase of the present invention. The present invention also discloses a method for preparing chiral amines using the transaminase. In the industrial production process of optically pure chiral amines, the enzyme provided by the present invention has advantages such as substrate specificity, enantiomeric selectivity, and high conversion rate. The method for preparing optically pure chiral amines provided by the present invention has high reaction efficiency, stereoselectivity, and yield.

The invention provides an R-type transaminase mutant and application thereof, and compared with an amino acid sequence of wild-type transaminase as shown in SEQ ID NO.1, the mutant has mutation of a 62nd site, a 152nd site and a 155th site. The mutant has high catalytic activity and excellent stereoselectivity on a heterocyclic ketone substrate, and can be used for efficiently preparing R-configuration heterocyclic chiral amine.

The embodiment of the invention discloses an imine reductase mutant as well as a coding gene and application thereof, and belongs to the technical field of genetic engineering and biosynthesis, and the similarity between the amino acid sequence of the imine reductase mutant and the amino acid sequence of wild type imine reductase is 90%-99.9%. Wherein the amino acid sequence of the wild type imine reductase is as shown in SEQ ID NO. 1. According to the imine reductase mutant provided by the invention, the catalytic activity, optical selectivity and stability of the imine reductase mutant during synthesis of chiral amine compounds can be improved.

A Pseudomonas putida ω-aminotransferase gene with broad substrate spectrum and an application thereof are provided. According to the disclosure, codon optimization is carried out on an ω-transaminase gene, and the nucleotide sequence of the ω-transaminase gene is shown in SEQ ID NO: 1. The crude enzyme solution, crude enzyme powder and pure enzyme of ω-aminotransferase prepared from ω-aminotransferase gene can be used as an enzyme preparation to catalyze the transamination reaction of substrates to prepare chiral amino alcohols and chiral amines. The substrate spectrum of the recombinant ω-transaminase obtained by the disclosure is broad, and 15 kinds of chiral amino alcohols and chiral amines with high added value are asymmetrically catalyzed and synthesized; in particular, 4-hydroxy-2-butanone is catalyzed to produce pharmaceutical intermediate (R)-3-amino-1-butanol.

The present disclosure provides engineered transaminase polypeptides useful for the synthesis of chiral amine compounds under industrially relevant conditions. The disclosure also provides polynucleotides encoding the engineered transaminase polypeptides, host cells capable of expressing the engineered transaminases, and methods of using the engineered transaminases for the production of chiral amine compounds.

Provided are a method for preparing (R)-ketorolac and use thereof. The method includes the following steps: step 1, preparing ketorolac; and step 2, subjecting the ketorolac to resolution to obtain the (R)-ketorolac, the resolution being selected from the group consisting of chiral amine resolution and enzyme resolution.

The invention provides a method for preparing chiral amine by catalyzing asymmetric hydrogenation of aromatic imine through a manganese / chiral ferrocene P, N, N ligand. The manganese precursor and ligand adopted by the method are easy to obtain, the reaction condition is mild, the operation is simple, the target chiral amine compound can be obtained with high yield and high stereoselectivity, and continuous large-scale preparation can be realized. The catalyst system is high in activity, the molar ratio of imine to the catalyst can reach 100000: 1, and the catalyst has a very good industrial application prospect.

The invention discloses an imine reductase mutant and an application of the imine reductase mutant in synthesis of vibeglone. The invention discloses an imine reductase mutant, which is characterized in that on the basis of an imine reductase mutant IR-13-M5, the imine reductase mutant has the following mutations: M203P-F269W-I149G-S241Q-L200T-G268Q, M203P-F269W-I149G-L200T, M203P-F269W-I149G-S241Q-L200T, M203P-F269W-I149G-S241Q-L200T or M203P-F269W-I149G-L200T-G268Q, and the imine reductase mutant has the following mutations: M203P-F269W-I149G The mutant can be used for asymmetric catalytic synthesis of an S-selective chiral amine product vibeglone, the conversion rate reaches 78%, the stereoselectivity reaches up to 99%, and the mutant has a good industrial application prospect.

The present invention discloses a rapid synthesis method for axially chiral aromatic amine compounds using metal-free catalysis. 1-substituted tetrahydro-2-naphthalenone and a cheap and readily available chiral amine are used as raw materials. Axial chiral aromatic amines are prepared by reaction under the action of a catalyst, and a wide range of substrates can be selected. Compared with traditional synthesis methods, the method of the present invention uses metal-free catalysis, has the advantages of simple conditions, convenient operation, relatively high yield, low environmental pollution, and ease of industrial production. The synthesis method of the present invention can simultaneously obtain two axially chiral aromatic amine compounds, and the yield range is 20%-70%.

The invention provides an improved engineered phenylalanine ammonia lyase which can be used for preparing a chiral amine compound, in particular for asymmetrically synthesizing L-2-chloro-phenylalanine. Compared with a wild-type enzyme corresponding to SEQ ID NO: 2, the engineered phenylalanine ammonia lyase polypeptide has better activity and / or stability, can be used for asymmetrically preparing chiral amine compounds with extremely high stereoselectivity, particularly can be used for more efficiently catalyzing o-chloro-cinnamic acid to prepare L-2-chloro-phenylalanine, can accept various ammonia donors, and can be used for preparing the chiral amine compounds. Such as ammonium carbonate, ammonia water and ammonium chloride.

The invention discloses a universal covalent organic framework material with spiral chiral morphology and a synthesis method thereof. The covalent organic framework material with spiral chiral morphology is generated by introducing a chiral amine precursor and multilateral aromatic aldehyde molecules to realize imine condensation under an acid catalysis condition. By changing the molecular chirality of the used chiral amine precursor, the regulation and control of the spiral direction of the chiral morphology of the finally obtained covalent organic framework material can be realized. According to the method, the covalent organic framework material with high crystallinity, large specific surface area and uniform spiral morphology can be synthesized under the catalysis of various solvents and various acids. The method has good synthesis universality, and the synthesized covalent organic framework material with the spiral chiral morphology has good chiral optical properties.

This invention provides a method for preparing chiral N-tert-butylsulfonamide compounds. The method uses N-tert-butylsulfonylimide as a starting material, employs Mn(CO)₅Br and a chiral PNN ligand as catalysts, and an alcohol as a solvent. A hydrogenation reaction occurs in this homogeneous catalytic system, yielding axially chiral diaryl nitrophenol compounds in high yield (99%) and with high ee values ​​(>99%). This reaction has the advantages of high efficiency, mild conditions, and environmental friendliness. The obtained chiral N-tert-butylsulfonamide can be deprotected with a sulfonyl protecting group to obtain the corresponding chiral primary amine.

The present invention discloses an imine reductase mutant, a recombinant genetic engineering bacterium and their application in the synthesis of (R)-2-methylpyrrolidine. The imine reductase mutant uses the wild-type imine reductase IR23 with the amino acid sequence shown in SEQ ID NO.1 as a template, and the mutant V249T obtained by mutating valine at position 249, and the mutant V249T / W224F obtained by mutating valine at position 249 and tryptophan at position 224. Through the molecular modification method of semi-rational design, the present invention significantly improves the ability of imine reductase to catalyze the formation of the corresponding cyclic amine from the cyclic imine 2-methylpyrroline. When the mutant V249T / W224F catalyzes 2-methylpyrroline, the substrate conversion rate is 93.3%, which is increased by 49.8% compared with the wild type. The present invention effectively improves the ability of imine reductase to asymmetrically synthesize chiral amines, which is of great significance for the green catalytic synthesis of chiral amine compounds.

The invention discloses a circular polarization organic laser material and a preparation method and application thereof, and the preparation method of the circular polarization organic laser material comprises the following steps: taking chiral amine, rare earth chloride and hydrochloric acid as raw materials, placing the raw materials in a solvent, and heating for reaction to obtain a precursor solution; after drying the precursor solution, dissolving again to obtain a transparent solution; and putting the open container filled with the transparent solution into a closed container filled with an anti-solvent, and growing the zero-dimensional perovskite structure luminescent material A4BX7 single crystal by utilizing the diffusion of the anti-solvent. The chiral ligand is introduced into the hybrid perovskite, a chiral environment is successfully introduced into an inorganic perovskite system, chiral transfer is realized, and the prepared circular polarization organic laser material has good circular polarization organic laser properties and high fluorescence quantum yield.

The application discloses a method for synthesizing chiral 1,3-disubstituted tetrahydroisoquinoline by using a chemical enzyme cascade system and belongs to the technical field of bioengineering. The application establishes a method for preparing chiral 1,3-disubstituted tetrahydroisoquinoline by using an enzyme cascade catalysis. Simple non-chiral ketone is used as a raw material, a transaminase obtained through screening is used to generate a chiral amine, a B-N cyclization reaction is used to obtain a chiral imine, and finally, an imine reductase is used to generate 1,3-disubstituted tetrahydroisoquinoline. The method has a high yield, can be close to 100%, has excellent diastereoselectivity and enantioselectivity, the de value and the ee value are close to 99%, and has good application value and prospect.

The present invention discloses a novel chiral aminoamide-selenoether ligand having a chemical structure shown in Formula 1: wherein X represents selenium; R 1 represents any one of hydrogen, methyl, and benzyl; R 2 represents an aryl or alkyl group. The complex formed by the ligand and copper trifluoromethanesulfonate has good catalytic activity for asymmetric Friedel-Crafts alkylation reactions. A method for preparing the novel chiral aminoamide-selenoether ligand is provided, comprising reacting phenylselenol with chiral 2,3-diphenylaziridine under nitrogen protection to obtain an aminoselenoether intermediate, and then dehydrating and condensing the aminoselenoether intermediate with an amino acid to obtain the target ligand. The preparation method is simple and has a high ligand yield.

The invention provides an omariglitazone intermediate, a preparation method thereof and a method for preparing an omariglitazone key intermediate, and relates to the technical field of organic chemistry. The omarignelone intermediate provided by the invention has a structure as shown in a formula VIII; the omariglitazone intermediate is easy to obtain and can be conveniently prepared by taking benzaldehyde as a starting raw material, a chiral chromatographic column does not need to be used for preparation of the omariglitazone intermediate, a key chiral center of the omariglitazone intermediate is constructed by catalyzing a cheap chiral amine catalyst through an asymmetric Knoevenagel-Michael addition reaction, and the preparation method is simple and convenient. According to the omariglitazone intermediate, industrial production of the omariglitazone key intermediate (the structure as shown in the formula I) is easy to realize, and the production cost is reduced. The invention provides a method for preparing an omariglone key intermediate (a structure shown in a formula I), the omariglone key intermediate can be prepared from the omariglone intermediate through a nitro reduction reaction, a Jappp-Klingemann reaction and an indole synthesis reaction, and the method is suitable for industrial production. A formula VIII and a formula I are shown in the description.

The invention provides an omega transaminase mutant as well as a preparation method and application thereof, and relates to the technical field of gene engineering, the mutant is obtained by mutating wild-type omega transaminase with an amino acid sequence as shown in SEQ ID NO.1 at the 80th site, the 96th site, the 129th site, the 170th site and the 205th site. The enzyme catalytic activity, the stereoselectivity and the organic solvent tolerance are improved; in biological catalysis application, the raw material conversion rate reaches 100%, the concentration of the product in a catalytic system reaches up to 200g / L, and the ees value is 100%; the obtained omega transaminase can be subjected to soluble expression in a cell supernatant, can be subjected to large-scale production through microbial fermentation, and is mild in reaction condition, simple and convenient in operation process and more suitable for industrial production. The technical problem that in the prior art, bio-enzyme with certain chiral amine construction capacity cannot be produced on a large scale due to weak stereoselectivity, low conversion rate and poor organic solvent tolerance is solved.

The invention relates to a chiral rare earth supramolecular spirochete complex as well as a preparation method and application thereof, in particular to a chiral rare earth supramolecular spirochete complex as well as a preparation method and application thereof. The invention aims to solve the problems that the existing luminescent rare earth-based supramolecular material for chiral amine sensing is complicated in treatment process, relatively weak in material stability and difficult to be converted into a device. According to the chiral rare earth supramolecular spiral luminescent probe disclosed by the invention, due to a secondary spiral structure generated by ligand chirality, the chiral rare earth supramolecular spiral luminescent probe has specific recognition capability of chiral amine in space, and two enantiomers of the chiral amine can be accurately distinguished by detecting the change of a glm value; moreover, the chiral rare earth supramolecular spiral body can be dissolved in various organic solvents and can be converted into devices more easily, so that the preparation process is simplified, the synthesis cost is low, and the possibility of large-scale industrial application is achieved.

The application relates to a chiral triazole-oxazoline compound and a preparation method and application thereof, and belongs to the technical field of organic synthesis. The chiral triazole-oxazoline compound has the structural formula: the preparation method comprises the steps of click reaction, triazole N2 substitution reaction, Suzuki coupling, triazole ester hydrolysis, amidation with a chiral amine alcohol and dehydration condensation. After a chiral triazole-oxazoline compound and a palladium salt compound are added to generate a catalyst in situ, asymmetric addition of aryl boronic acid on a carbon-carbon double bond of a prochiral organic compound is carried out to prepare a chiral organic compound. The application has the advantages of low raw material cost, few synthesis steps, low experiment site requirement, relatively mild reaction conditions and simple operation for preparing the novel triazole-oxazoline compound.

The invention discloses an application of amide hydrolase in preparation of chiral amines. The invention provides a preparation method of a compound II, which comprises the following steps: in a solvent, in the presence of an enzyme, a compound I is subjected to a hydrolysis reaction as shown in the following formula to obtain the compound II, and the enzyme has an amino acid sequence as shown in SEQ ID NO: 1. The amide hydrolase with the amino acid sequence as shown in SEQ ID NO: 1 can selectively hydrolyze an L-configuration substrate to obtain an L-configuration amino acid, has a good conversion rate, and is wide in applicable substrate range. # imgabs0 #

The invention discloses a method for preparing a chiral amine compound through asymmetric hydrogenation of ruthenium catalyzed imine. The chiral ruthenium catalyst is a chiral metal ruthenium complex prepared by reacting metal ruthenium salt with a chiral phosphine-phosphoramidite ester ligand and chiral diamine in a solvent and carrying out column chromatography. Compared with other chiral amine synthesis methods, the method provided by the invention has the characteristics of cheap catalyst, easy preparation of chiral ligand, mild reaction conditions, simple operation, high yield and enantioselectivity and the like, and can be applied to large-scale preparation of chiral amine compounds. The method is also suitable for synthesis of the key intermediate of the herbicide (S)-metolachlor, the yield can reach 92%, the enantioselectivity can reach 90%, and the method has good industrial application prospects.

Disclosed herein are engineered polypeptides having improved imine reductase (IRED) activity, the nucleotides that encode said engineered polypeptides, and methods for using said engineered polypeptides in a reduction of an imine to a chiral amine.

The present invention relates to novel reductive aminase (RedAm) enzymes and methods of producing chiral amines, achiral amines or a N1-((1R,2S)-2 phenyl cyclopropyl)cyclohexane-1,4-diamine compound and derivatives thereof by a reductive amination reaction catalysed by an enzyme of the invention. Also provided are nucleic acid molecules encoding the novel enzymes, expression vectors comprising said nucleic acid molecule and host cells comprising said nucleic acid molecules or said expression vectors. The present invention also provides a solid support upon which an enzyme of the invention is immobilised, and a reaction chamber comprising an enzyme of the invention, for example for use in a reductive amination method.

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%.