25 results about "Prochirality" patented technology

The invention relates to the technical field of biology, in particular to an L-amino acid synthesis system and application. According to the L-amino acid synthesis system and application provided by the embodiment of the invention, in the presence of coenzyme NAD < + >, isopropanol is catalyzed by isopropanol dehydrogenase to generate acetone, and NAD < + > is reduced into coenzyme NADH; in the presence of coenzyme NADH, the leucine dehydrogenase mutant utilizes NH3 generated by ammonia water volatilization to perform asymmetric reductive amination on a prochiral alpha-keto acid compound, the NADH is oxidized into NAD +, the catalytic efficiency of asymmetric reductive amination of the leucine dehydrogenase mutant on the prochiral alpha-keto acid compound is improved, the circulating speed of the coenzyme NADH and NAD + is increased, and the catalytic activity of the leucine dehydrogenase mutant on the prochiral alpha-keto acid compound is improved. The catalytic efficiency of asymmetric reductive amination of the leucine dehydrogenase is favorably improved.

The invention discloses a carbonyl reductase mutant as well as a preparation method and application thereof, and belongs to the technical field of gene engineering and enzyme engineering. According to the invention, wild-type carbonyl reductase of Stachybotrys chlorohallonata is taken as an evolution template, and a plurality of mutants with catalytic activity, thermal stability and substrate spectrum obviously superior to those of the wild-type carbonyl reductase are obtained through an enzyme engineering technology. The carbonyl reductase mutant can catalyze various prochiral carbonyl compounds to obtain chiral alcohol with high stereoselectivity (ee is greater than 99%). The carbonyl reductase mutant provides a novel, efficient and environment-friendly technical route for industrial production of chiral alcohol products, and has very high industrial application potential.

The invention relates to the technical field of biology, in particular to a carbonyl reductase mutant, a gene, an engineering bacterium and application. The amino acid sequence of the carbonyl reductase mutant is shown as SEQ ID NO: 1, the catalytic efficiency of asymmetric reductive hydrogenation of prochiral ketone compounds is improved, the stereoselectivity of chiral hydroxyl compounds formed through catalysis is improved, and the synthesis efficiency of (S)-1-(5-fluoro-2-iodophenyl) ethanol is improved.

The invention discloses an ethanol dehydrogenase mutant and an application of the ethanol dehydrogenase mutant in synthesis of symmetric chiral diol. The ethanol dehydrogenase mutant is obtained by carrying out single mutation or multiple mutations on amino acids at 74th, 187th, 210th, 211th and 352th sites of an ethanol dehydrogenase amino acid sequence as shown in SEQ ID NO.2 from Candida orbiculata Co. The invention further discloses a preparation method of the ethanol dehydrogenase mutant, and the preparation method comprises the following steps: carrying out single mutation or multiple mutations on the amino acids at the 74th, 187th, 210th, 211th and 352th sites of the ethanol dehydrogenase amino acid sequence as shown in SEQ ID NO.2. Alcohol dehydrogenase is utilized to catalyze prochiral symmetric diketone to synthesize symmetric chiral diol, the method is high in substrate concentration, high in stereoselectivity, mild in reaction, simple in operation process, environment-friendly and more suitable for industrial amplification production, and the problems that in the prior art, the substrate concentration is not high, the reaction condition is violent, the reaction process is complex and difficult to control, and the production cost is low are solved. And the method is not environment-friendly enough, and the like.

The invention relates to the technical field of catalysts, in particular to a chiral diphosphine ligand modification-based ruthenium-carbon hydrogenation catalyst as well as a preparation method and application thereof. The method comprises the following steps: preparing a nitrogen-containing defect carbon carrier; loading ruthenium and reducing; pre-coating the confinement by using an ionic liquid A; introducing a chloride ion template microenvironment; carrying out coordination with a chiral diphosphine ligand; weak coordination anion sizing is realized through the treatment of bis (trifluoromethanesulfonyl) imide silver; and finally introducing chiral ionic liquid B to construct an outer network. The catalyst realizes high enantioselective conversion of a prochiral substrate while maintaining high hydrogenation activity through a multi-layer chiral microenvironment synergistic effect, is excellent in cycling stability, and solves the technical problem that the activity and selectivity of a heterogeneous chiral catalyst are difficult to consider at the same time.

The application discloses a five-membered ring containing alkynyl or triazole functional group P The chiral phosphine oxide compound is obtained through Domino Heck-Sonogashira cascade reaction by taking a prochiral tertiary phosphine oxide compound containing a double ethylene group and phenylacetylene as raw materials, transition metal palladium catalyst and chiral TADDOL phosphoramidite ligand under the protection of inert gas P The chiral phosphine oxide compound has a product yield of 96% and an enantioselectivity ee value of 99%, and a diastereoselectivity dr value of greater than 20:1. The application adopts an asymmetric desymmetrization strategy, uses a Heck reaction to start and a Sonogashira reaction to end a cascade reaction, simultaneously constructs P The chiral and quaternary carbon chiral center has mild reaction conditions, simple operation and good substrate universality, provides a compound skeleton with diversity, and is successfully applied to a palladium-catalyzed asymmetric allyl substitution reaction as a chiral ligand.

The invention discloses an ethanol dehydrogenase mutant, engineering bacteria and application in synthesis of a sinobamate intermediate, the ethanol dehydrogenase mutant is utilized to catalyze prochiral ketone (B) to synthesize chiral alcohol (A), the method is high in substrate concentration, simple and convenient in post-treatment step and more suitable for industrial large-scale production, and the problems that in the prior art, the substrate concentration is not high, and the yield is high are solved. Post-treatment is complicated, and the like.

The invention comprises chiral aminophosphine ligands of the formula I, iridium catalysts containing the chiral aminophosphine ligands of the formula I, of the formula II or III;, and the use of the iridium catalysts in the asymmetric hydrogenation of a compound, containing at least one prochiral keto group preparation and the formation of chiral alcohols.

The invention relates to a chiral ferrocene skeleton PNNO tetradentate ligand and application thereof in asymmetric hydrogenation reaction. The ligand has the advantages of simple synthesis, good stability, high selectivity and the like. A metal complex of the ligand shows very excellent catalytic activity and extremely high enantioselectivity in an asymmetric hydrogenation reaction of ketone, can efficiently catalyze reduction of prochiral ketones such as aryl alkyl ketone, heteroaryl alkyl ketone, aryl (hetero) aryl ketone, aliphatic ketone and the like into corresponding chiral alcohol, and has huge industrial application potential.

In one aspect, the disclosure relates to axially chiral cannabinoid analogs and methods of making the same. In one aspect, several tetracyclic scaffolds can be prepared from O-propargyl vinyl coumarins in good yields. In a further aspect, these tetracyclic scaffolds can be treated with a reductant to form the axially chiral cannabinoid analogs. In another aspect, the axially chiral cannabinoid analogs are shelf stable and maintain a three-dimensional structure during storage, enabling superior recognition of biological targets such as cannabinoid receptors. Also disclosed herein are prochiral cannabinoid analogs that can be synthesized from axially chiral cannabinoid analogs.

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 relates to the technical field of biology, in particular to a coenzyme circulation system and application. According to the coenzyme circulation system and application provided by the embodiment of the invention, in the presence of coenzyme NAD < + >, ammonium formate is catalyzed by formate dehydrogenase to generate NH3, and NAD < + > is reduced into coenzyme NADH; in the presence of coenzyme NADH, the leucine dehydrogenase mutant utilizes generated NH3 to carry out asymmetric reductive amination on a prochiral alpha-keto acid compound, the NADH is oxidized into NAD +, the catalytic efficiency of asymmetric reductive amination of the leucine dehydrogenase mutant on the prochiral alpha-keto acid compound is improved, the circulating speed of the coenzyme NADH and the NAD + is increased, and the catalytic activity of the leucine dehydrogenase mutant on the prochiral alpha-keto acid compound is improved. The catalytic efficiency of asymmetric reductive amination of the leucine dehydrogenase is favorably improved.

The invention discloses a method for biocatalytically synthesizing optically pure 2R-fluorocarboxylic acids and 2R-hydroxycarboxylic acids, and belongs to the field of bioengineering technology. Using α-fluoro acid and / or α-fluoro acid derivatives as substrates, using fluoroacetic acid dehalogenase mutants K181M, K181S, W185G, K181M-W185Y, K181S-W185A, K181S-W185C, K181S-W185G, K181S-W185V as biocatalysts, hydrolysis and defluorination obtain chirally pure 2R-fluorocarboxylic acids and 2R-hydroxycarboxylic acids and derivatives thereof. The present invention has strong stereoselectivity and simple steps, and solves the problems of low optical purity, low yield and environmental pollution that are widely present in the synthesis of chiral compounds. In addition, the inventive method amplifies the reaction system to gram-level experiments using whole cells as catalysts, obtains products with higher yields and ee values, has low cost, low energy consumption, and is suitable for industrial production.

This application relates to the field of biotechnology, and more particularly to a leucine dehydrogenase mutant and its applications. The leucine dehydrogenase mutant and its applications provided in this application are obtained by screening wild-type leucine dehydrogenase for mutations, resulting in a leucine dehydrogenase mutant with the amino acid sequence shown in SEQ ID NO: 1 or SEQ ID NO: 2. This mutant exhibits improved catalytic efficiency and thermal stability for the asymmetric reductive amination of prochiral α-keto acid compounds, which is beneficial for improving the synthesis efficiency of L-amino acids.

A mutant transaminase and its use in the preparation of a sitagliptin intermediate are provided. The mutant is obtained by substituting tyrosine at position 74 with proline, glutamic acid at position 228 with aspartic acid, leucine at position 254 with alanine, and methionine at position 290 with threonine in the amino acid sequence shown in SEQ ID NO: 2. The sitagliptin intermediate or sitagliptin ester is prepared using wet thallus or a pure enzyme obtained by fermentation and culture of genetically modified bacteria containing a gene encoding the mutant transaminase as a biocatalyst, and using a ketone precursor of the sitagliptin intermediate or a prochiral carbonyl compound as a substrate. The overall yield is approximately 82%, and the ee value of the product can reach up to 99%.

The invention relates to the technical field of organic synthesis, and provides an asymmetric carbon-hydrogen bond boronation reaction catalyst and a preparation method of chiral dicyclobutane. A catalyst composed of a chiral boron-based ligand and an iridium salt is adopted to catalyze an asymmetric carbon-hydrogen bond boronation reaction of prochiral dicyclobutane, in a reaction system, the iridium salt and the chiral boron-based ligand are combined to form a complex, the complex reacts with B2pin2 to form an active intermediate, and the active intermediate is separated from the chiral boron-based ligand to form the chiral dicyclobutane. Then the iridium center and a carbon-hydrogen bond of a 3-substituted dicyclobutane-1-formamide compound are subjected to an asymmetric oxidative addition reaction to form an iridium-carbon bond, then reduction elimination is carried out, and the target product chiral dicyclobutane is generated. The reaction condition for constructing the chiral dicyclobutane is mild, the selectivity is high, the enantioselectivity is 95% or above, the substrate universality is wide, and chiral dicyclobutane compounds of different structures can be synthesized.

The invention discloses a method for preparing chiral lactam from prochiral ketone, and belongs to the technical field of chemical synthesis. According to the method, chlorobenzene or toluene or a chlorobenzene / diethyl ether mixed solution is used as a solvent, under the action of a chiral catalyst, prochiral cyclic ketone and sulfonyl hydroxylamine are subjected to a desymmetrical nitrogen atom insertion reaction at-78 DEG C to 25 DEG C, high-stereoselectivity chiral lactam is prepared in one step, and the reaction time is 2-8 h. The method has the advantages that the raw materials are low in price and easy to obtain, the chiral catalyst is commercially available and small in dosage, the product has excellent stereoselectivity, post-treatment is simple and convenient, and a novel green and economical way with wide industrial application prospects is provided for synthesis of chiral drugs and fine chemicals.

The present invention discloses a transaminase mutant and application thereof in preparation of sitagliptin intermediates, the transaminase mutant is obtained by substitution of tyrosine with proline at position 74, substitution of glutamic acid with aspartic acid at position 228, substitution of leucine with alanine at position 254 and substitution of methionine with threonine at position 290 of the amino acid sequence shown in SEQ ID NO: 2. The present invention uses wet cells or a purified transaminase as a biocatalyst and a sitagliptin precursor ketone or a prochiral carbonyl compound as a substrate to prepare a sitagliptin intermediate or a sitagliptin ester intermediate; the total yield of the method reaches about 82%, and e.e. value of the product reaches 99%.

The present application relates to the technical field of catalyst, in particular to a ruthenium carbon hydrogenation catalyst based on chiral diphosphine ligand modification and its preparation method and application. The method comprises the following steps: preparing a nitrogen-defect-containing carbon carrier; loading ruthenium and reducing; pre-coating a confinement layer by using ionic liquid A; introducing a chloride ion template microenvironment; coordinating with a chiral diphosphine ligand; achieving weakly coordinated anion shaping by treating with bis(trifluoromethanesulfonyl) imide silver; and finally introducing chiral ionic liquid B to construct an outer network. The catalyst realizes high enantioselective conversion of prochiral substrates through the synergistic effect of multi-level chiral microenvironments while maintaining high hydrogenation activity, and has excellent cycle stability, solving the technical problem that the activity and selectivity of non-homogeneous chiral catalysts are difficult to balance.

The invention is applicable to the technical field of enzyme engineering, and provides a carbonyl reductase mutant as well as a preparation method and application thereof, the carbonyl reductase mutant is used for asymmetrically and specifically catalyzing a prochiral carbonyl compound to generate corresponding chiral alcohol; the carbonyl reductase mutant takes the sequence of the carbonyl reductase polypeptide as a starting sequence, and compared with the sequence of the carbonyl reductase polypeptide, the carbonyl reductase mutant contains one or more residue differences; the amino acid sequence of the carbonyl reductase polypeptide is as shown in SEQ ID NO. 2 in the sequence table. The enzyme activity of the carbonyl reductase mutant obtained by carrying out site-directed mutagenesis on the carbonyl reductase is far higher than that of the carbonyl reductase which is not mutated; the carbonyl reductase mutant can be used for specifically catalyzing a prochiral carbonyl compound into a chiral product of a required Ritlecitinib medical intermediate, so that the carbonyl reductase mutant has a wide application value and a very strong practical value in the synthesis application of a medicament Ritlecitinib for treating alopecia areata.

The invention belongs to the technical field of organic synthesis, and particularly discloses a preparation method of a chiral silacyclopentane derivative with a silicon-containing stereocenter. Under the action of a chiral catalyst, 2-mercaptobenzothiazole is used for carrying out ring-opening desymmetry on a prochiral 3-silacyclopentene epoxy compound, and the reaction has good yield and enantiomer selectivity. The method overcomes the defects in the aspect of synthesis of chiral silacyclopentane reported in previous literatures: a stoichiometric chiral lithium amide reagent is needed under anhydrous and anaerobic conditions, and a greatly excessive nucleophilic reagent is needed due to relatively low reaction activity. The method is mild in reaction condition, free of metal and high in reaction activity, and the structure comprises a silicon three-dimensional center.

The present application relates to a preparation method of chiral homomorpholine-5-methanoic acid and fluorenylmethoxycarbonyl derivatives thereof, and mainly solves the technical problem that there is no industrial synthesis method for chiral homomorpholine-5-methanoic acid at present. The preparation method comprises the following steps: condensing benzyloxyethyloxyethyl bromide and 2-acetylamino malonic acid diethyl ester, hydrolyzing to obtain compound I, and enzymatically separating to obtain compound II and compound III; after Boc protection and methyl ester of compound II, debenzyl, sulfonylation, iodination, obtaining protected compound V, after deprotection, ring formation under alkaline conditions to obtain compound VII, and finally Fmoc protection to obtain compound VIII. The whole process is a conventional reaction, does not need fine operation, does not need deep low temperature reaction, does not need expensive palladium coupling reagent or flammable and explosive metal organic reagent, and can be mass produced.

The present invention discloses an ω-transaminase mutant and its application. The ω-transaminase mutant is obtained by single-point or multi-point mutations of tryptophan at position 54 and arginine at position 411 in the amino acid sequence of the wild-type ω-transaminase shown in SEQ ID NO.1. Compared with the wild-type ω-transaminase, the ω-transaminase mutant of the present invention has a high catalytic efficiency for catalyzing prochiral ketones to generate chiral amines. Among them, the conversion yield of the mutant R411A for 4-(trifluoromethyl)acetophenone is 2.39 times that of the wild-type ω-transaminase, and the enantiomeric excess (ee) of the obtained product > 99.9%.

The application discloses an ethanol dehydrogenase mutant and application thereof in synthesis of symmetrical chiral diols, wherein the ethanol dehydrogenase mutant is obtained by single mutation or multiple mutations of amino acids at positions 74, 187, 210, 211 and 352 in the amino acid sequence of ethanol dehydrogenase shown in SEQ ID NO. 2 from Candida orthopsilosis Co. The application utilizes ethanol dehydrogenase to catalyze synthesis of symmetrical chiral diols from prochiral symmetrical diketones, and the method has the advantages of high substrate concentration, high stereoselectivity, mild reaction, simple operation process and environmental friendliness, is more suitable for industrial scale production, and solves the problems in the prior art, such as low substrate concentration, severe reaction condition, relatively complex reaction process difficult to control, many by-products and environmental unfriendliness.