70 results about "Chiral amine" patented technology

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 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.

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.

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 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 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 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 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 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%.

This invention discloses the application of chiral amines in the analysis and / or resolution of chiral amino acids, and a method for analyzing and / or resolving chiral amino acids. The method for analyzing and / or resolving chiral amino acids using chiral amines includes the following steps: using chiral amines... d One or two of 5-APPM and APPM are used as labeling reagents to react with chiral amino acids to obtain derivatives; the derivatives are then detected by LC-MS; wherein, the carbon atom on the pyrrole ring of the chiral amine has an R configuration. This invention relates to APPM and its deuterated stable isotope form. d 5-APPM can undergo a specific condensation reaction with chiral amino acids, and the resulting derivative contains easily ionized groups, thereby enhancing the mass spectrometry signal response and improving detection sensitivity in electrospray ionization (ESI) positive ion mode. This invention also achieves efficient separation of chiral amino acid enantiomers on conventional chromatographic columns.

The invention provides a biosynthesis method of an esdoxaban tosylate chiral intermediate. According to the preparation method, 3-cyclohexene-1-carboxylic acid methyl ester is taken as a starting raw material, and a target intermediate is finally obtained through carboxylesterase resolution, hydrolysis, hydroxylation, dehydrogenation oxidation, transamination reaction, amidation and Boc2O reaction in sequence. According to the method, high-selectivity carboxylesterase is used for realizing chiral resolution; p450 oxidase with excellent regioselectivity and stereoselectivity is utilized to realize specific hydroxylation of a C-H bond under a mild condition, and a traditional process depending on a highly toxic chemical oxidant is overturned; then, clean oxidation is realized through alcohol dehydrogenase, and a way is laid for subsequent reaction; most importantly, the transaminase is adopted to directly construct the chiral amine, so that the use of a high-risk reagent sodium azide is thoroughly avoided, and major potential safety hazards are eliminated from the source; and finally, green amidation is realized by virtue of lipase, and an acyl chloride method for generating corrosive wastewater is replaced.

The present application provides an amine dehydrogenase, which is obtained by mutating an amino acid dehydrogenase as shown in SEQ ID NO. 1, and the mutation comprises at least one mutation in the amino acids at positions 293, 69, 115 and 262 of SEQ ID NO. 1. The present application also provides the use of the amine dehydrogenase in preparing chiral amines. By means of protein engineering, the present application modifies the amino acid dehydrogenase catalyzing amino acid substrates into an amine dehydrogenase (AmDH) with ketone and aldehyde as substrates. The amine dehydrogenase of the present application has high reductive amination activity, and can be applied in the process of catalyzing transamination of hydroxy ketone and prochiral ketone compounds to prepare chiral amines, including but not limited to 3-hydroxy-D-tyrosine. The high catalytic activity, high yield and 99%+ stereoselectivity meet the requirements, and the present application has the advantages of green and efficient, low cost and high optical purity of products, and is one of the most ideal reactions for the synthesis of chiral amines.

The present application relates to engineered biocatalysts and methods for the synthesis of chiral amines. The present disclosure provides engineered transaminase polypeptides useful for the production of amines, polynucleotides encoding engineered transaminase, host cells capable of expressing engineered transaminase, and methods of using engineered transaminase to prepare compounds useful for the production of active agents.

The invention discloses an asymmetric synthesis method of a letemovir key intermediate and application of the intermediate in preparation of letemovir, and belongs to the technical field of medicinal chemistry. The synthesis method comprises the following steps: taking a compound I or an organic acid salt thereof as a raw material, taking a binaphthyl-derived chiral amine salt II as a catalyst, and carrying out intramolecular asymmetric conjugate addition to obtain a compound III. According to the present invention, the key intermediate is further adopted to synthesize letemovir, and compared with the reported scheme, the strategy greatly improves the letemovir synthesis efficiency and the atom utilization rate, reduces the generation of three wastes, reduces the cost by more than 30%, and provides the new idea for the industrial production of letemovir.

The invention discloses a chiral metal halide optical waveguide material and a preparation method thereof, and relates to the technical field of optical waveguide materials, and the preparation method of the chiral metal halide optical waveguide material comprises the steps that chiral amine, metal halide, a reducing agent and acid are mixed and heated till solid is dissolved; and cooling and crystallizing to obtain the chiral metal halide optical waveguide material. The optical waveguide material with CPL emission and optical waveguide transmission functions is prepared, the material can efficiently generate circular polarization luminescence, and low-loss and directional optical waveguide transmission of CPL is achieved.

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%.

This invention belongs to the field of medicinal chemistry, specifically relating to a method for synthesizing ivcarboxylate. The specific technical solution includes: a method for synthesizing ivcarboxylate, comprising: reductive amination of a chiral amine with a benzyl-protected nitrogen atom with a pyrrolidone, followed by catalytic hydrogenation to remove the protecting group, thereby obtaining ivcarboxylate. The preparation method provided by this invention has a short synthetic route, relatively mild preparation conditions, and great application potential.

The application discloses a chiral 6-hydroxypyridine oxazoline compound, a preparation method and application. The chiral 6-hydroxypyridine oxazoline compound is synthesized by using 1-cyanopyridine containing a substituent group and chiral 2-aminethanol as starting materials, and a series of novel chiral 6-hydroxypyridine oxazoline compounds are synthesized. The preparation method disclosed by the application has the advantages that the starting materials are easily obtained on the market or are easy to prepare, the cost of preparing target molecules is reduced, the synthetic route is simple and efficient, the reaction condition is mild and the operation is simple, chemical waste generated in preparation is reduced, the target molecule 6-hydroxypyridine oxazoline is a kind of novel chiral compound, has a potential application prospect of assisting transition metal catalytic asymmetric synthesis, the types of substituents of the starting materials are rich, the requirement of a synthesis strategy on the diversity of target molecules is met, and the product can be used to prepare more complex molecules through functional group transformation.

The present disclosure provides engineered transaminase polypeptides for the production of amines, polynucleotides encoding the engineered transaminases, host cells capable of expressing the engineered transaminases, and methods of using the engineered transaminases to prepare compounds useful in the production of active pharmaceutical agents.

The present application provides a kind of thermostable transaminase or its mutant and its application in preparing chiral amine compound.The amino acid sequence of the thermostable transaminase is selected from any one of the following:(1) the amino acid sequence shown as SEQ ID NO:1;(2) the amino acid sequence shown as SEQ ID NO:1 is derived by substitution, deletion or addition of one or more amino acids and has transaminase activity;(3) the amino acid sequence shown as SEQ ID NO:1 has at least 95% identity and has transaminase activity.The present application also improves the catalytic activity and stability of the transaminase from thermophilic microorganism by modification, thereby improving the catalytic efficiency and being suitable for the preparation process of chiral amine.

The present invention discloses an ω-transaminase ancestral enzyme mutant and application for efficiently catalyzing the synthesis of (R)-chiral amine compounds, relating to the field of molecular biology technology. Obtained by mutation of the ancestral enzyme Ancata-101 of the ω-transaminase from Aspergillus terreus, the amino acid sequence of the ω-transaminase mutant is shown in SEQ ID NO.6. Compared with the ancestral enzyme, the ω-transaminase ancestral enzyme mutant has significantly improved activity on non-natural substrates 1-acetylnaphthalene, N-tert-butyloxycarbonyl-3-piperidone or 3-oxopyrrolidine-1-carboxylic acid tert-butyl ester.