25 results about "Chiral selectivity" patented technology

The invention relates to the technical field of organic synthesis, in particular to a method for constructing Orforglipron tetrahydropyran ring chirality through enzyme catalysis, which comprises the following steps: step S1, taking SM1 as a raw material, and carrying out hydrolysis resolution in a solvent, a buffer salt system and enzyme catalysis to obtain a chiral pure intermediate INT-1; step S2; performing ring closing on the INT-1 through Grignard reaction to synthesize a lactone intermediate; s3, carrying out Diball-H reduction, quenching, dichloromethane extraction and anhydrous sodium sulfate drying on the INT-4, and then reducing the INT-4 by using triethyl silane to obtain an intermediate INT3; step S4, coupling the INT-3 in the presence of a catalyst and a ligand to obtain an intermediate INT-4; step S5, carrying out deprotection and salification on the INT-4 to obtain an intermediate INT5; s6, closing an indole ring from INT5 to obtain a compound of which the general formula is A; chirality is constructed through enzyme catalysis, isomer impurities do not need to be split and separated through SFC when the chirality is constructed, the loss is reduced, the yield is increased, and a target product is obtained with high chiral selectivity; meanwhile, the cost is relatively reduced, and the cost is saved.

The present invention relates to the technical field of organic synthesis, and specifically relates to a method for constructing the chirality of a pyran ring in Orforglipron by means of enzymatic catalysis, the method comprising the following steps: step S1, by using SM1 and SM2 as starting materials, carrying out a reaction under the action of a palladium catalyst and a ligand to obtain INT-1; step S2, under the catalysis of Pd / C, subjecting INT-1 to double bond hydrogenation reduction to obtain INT-2; step S3, in the presence of a solvent, a buffer salt system and enzymatic catalysis, subjecting INT-2 to hydrolysis and resolution to obtain a chirally pure intermediate INT-3; step S4, subjecting INT-3 to a Grignard reaction for cyclization, so as to synthesize a lactone intermediate INT-4; and step S5, subjecting INT-4 to reduction by means of Dibal-H, quenching same, performing extraction with dichloromethane, drying same with anhydrous sodium sulfate, and then performing reduction by means of triethylsilane to obtain a compound of general formula A. In the present invention, the chirality is constructed by means of enzymatic catalysis without the need of SFC resolution for separating isomeric impurities during the construction of the chirality, thereby reducing losses and improving yield, obtaining the target product at high yield and high chiral selectivity, and further saving expenses and reducing costs.

The application belongs to the technical field of antitumor drugs, and particularly relates to an AuNRs@L / D-Ag2S QDs complex, a preparation method and application thereof. Sodium polystyrene sulfonate is electrostatically adsorbed on AuNRs to obtain 1-PSS-AuNRs; polyallylamine hydrochloride is electrostatically adsorbed on 1-PSS-AuNRs to obtain 2-PAH-AuNRs; polyallylamine hydrochloride is electrostatically adsorbed on 2-PAH-AuNRs to obtain a non-chiral nanomaterial; and the non-chiral nanomaterial is covalently crosslinked with L / D-Ag2S QDs to obtain the AuNRs@L / D-Ag2S QDs complex. The application combines the efficient photo-thermal conversion characteristics of AuNRs with the chiral-dependent targeting and potential fluorescence imaging ability of chiral Ag2S quantum dots by constructing a complex structure, so that a novel nanodiagnostic and therapeutic agent with efficient photo-thermal performance and chiral selectivity is obtained.

The invention belongs to the field of medical intermediate compounds and organic synthesis, and particularly relates to a key intermediate of lotinib and a preparation method thereof, the preparation method comprises the following steps: (1) in an organic solvent, organic alkali, 2-cyanoethyl 5-acetyl-3-methylthiophene-2-carboxylic ester and 2, 2, 2-trifluoro-1-(3, 4, 5-trichlorobenzene) ethanone react to obtain an intermediate 1; (2) dehydrating the intermediate 1 into double bonds to obtain an intermediate 2; and (3) reacting the intermediate 2 with a ligand to obtain the key intermediate of lotinib. The intermediate is used for synthesizing lotinib. The preparation method provided by the invention has the advantages of extremely high chiral selectivity, mild conditions and stable yield, can be suitable for amplified production, and provides a new technology suitable for industrial production for the key intermediate of lotinia.

The present application relates to ticagrelor intermediates and a preparation method thereof, wherein a halogenated group of compound VI is removed by a deacidifying agent to open a ring, process conditions are simple, and operation is easy; meanwhile, a chiral center in a molecule is constructed by using a transaminase to prepare compound VII from compound VI, conditions are more mild, chiral selectivity is better, raw material utilization is improved, chiral separation or chiral reduction process is avoided, and industrialized production is more beneficial. The disclosed technical scheme can be connected with a process for preparing compound VII from D-ribose as a starting material, forming a process for preparing target compound ticagrelor intermediate compound VII from compound I (D-ribose) as a raw material, synthesizing compound II by reacting with methanol, then synthesizing compound III by sulfonylization of compound II, then synthesizing compound IV by halogen substitution of compound III, and further opening a ring, closing a ring, and catalyzing by a transaminase.

The invention provides an amidase mutant and application thereof in preparation of (S)-penthiopyrad, and belongs to the technical field of gene engineering and enzyme catalysis. Compared with amidase with an amino acid sequence as shown in SEQ ID No.1, the amidase mutant disclosed by the invention comprises one or more site mutations as follows: alanine at the 132 site is mutated into leucine; serine at the 205th site is mutated into glycine; the alanine at the 211 site is mutated into glycine. Compared with wild amidase, the amidase mutant disclosed by the invention has the advantages that the enzyme activity and stereoselectivity are obviously improved; the preparation method based on the mutant is mild in process and simple and convenient to operate, and the obtained (S)-penthiopyrad has excellent chiral selectivity and product optical purity, conforms to the development trend of green pesticide creation and has important industrial application value.

This application discloses a polarization-independent chiral selective reflection and multidimensional optical field modulation device and method, relating to the fields of integrated photonics and micro / nano optics. The device includes: a geometrically phased liquid crystal layer, a transparent capping layer, a chiral metasurface array layer, a dielectric substrate layer, and a total reflection layer; wherein, the chiral metasurface array layer can break the in-plane mirror symmetry and exhibit chiral selective reflection characteristics in the target wavelength band. The geometrically phased liquid crystal converts the polarization state of arbitrary incident light into orthogonal left-handed and right-handed circularly polarized light. The chiral metasurface array layer selectively reflects one type of circularly polarized light while absorbing another type of circularly polarized light with the opposite chirality. The reflected circularly polarized light exits through the geometrically phased liquid crystal, achieving two-way phase modulation. This invention achieves geometrically phase modulation by four times the rotation angle of liquid crystal molecules, and has the advantages of compact structure, low crosstalk, low cost, and easy integration with semiconductor processes.

The invention provides a chiral electrochemical sensor based on beta-cyclodextrin / cerium-doped copper-based metal organic framework / carboxylated multi-walled carbon nanotube (beta-CD / Ce-doped Cu-MOF / MWCNTs-COOH), a preparation method of the chiral electrochemical sensor, and a detection method for carrying out chiral recognition on an ofloxacin enantiomer by using the sensor. According to the chiral electrochemical sensor, a glassy carbon electrode is used as a substrate, a composite conducting layer of a carboxylated multi-walled carbon nanotube (MWCNTs-COOH) and a cerium-doped copper-based metal organic framework (Ce-doped Cu-MOF) is modified firstly, and then a beta-cyclodextrin (beta-CD) chiral recognition layer is modified on the surface through an electrochemical polymerization method. According to the design, the electro-catalytic activity of the Ce-doped Cu-MOF, the high conductivity of the MWCNTs-COOH and the chiral selectivity of the beta-CD are integrated, so that a synergistic enhancement effect is generated. By utilizing the sensor and combining a linear sweep voltammetry (LSV), high-sensitivity and high-selectivity detection of levofloxacin can be realized. The method has the advantages of being simple in instrument, easy and convenient to operate, rapid in detection, high in sensitivity, high in selectivity, good in stability and the like, is suitable for rapid analysis of levofloxacin in pharmaceutical preparations, food and environmental samples, and has wide application prospects in the fields of drug quality control and safety monitoring.

The present invention provides a paroxysmal hemoglobinuria indication drug ipropam key intermediate synthesis method, and relates to the technical field of ipropam, the method comprises: taking p-bromobenzaldehyde as an initial raw material, adopting an organic catalyst to obtain an intermediate 03, carrying out protection group removal on the intermediate 03, carrying out automatic ring closing to obtain an intermediate 04, and carrying out post-treatment to obtain the paroxysmal hemoglobinuria indication drug ipropam key intermediate. Reducing the intermediate 04 with sodium borohydride to obtain a single cis-configuration intermediate 05, then carrying out a chiral flip reaction and hydrolysis to remove p-nitrobenzoic acid, then carrying out an etherification reaction with diethyl sulfate to obtain an intermediate 08, reducing amide of the intermediate 08 with sodium borohydride and boron trifluoride diethyl etherate to obtain an intermediate 09, then carrying out an acetylation reaction to protect amino, and finally carrying out a reaction to obtain the chiral cis-configuration intermediate 03. Cuprous cyanide is subjected to a cyanation reaction and a hydrolytic esterification reaction to obtain the ipropam key intermediate TM. The method is low in raw material price, high in chiral control selectivity, easy in reaction condition control and low in equipment requirement, avoids column chromatography and other operations, and is more suitable for industrial production.

The invention discloses a pair of one-driving-two binocular different-display ultrathin AR glasses based on geometric phase optical integration, which comprises an optical engine module and a waveguide display module, and is characterized in that the optical engine module comprises a display chip and a collimation optical system, and the display area of the display chip is divided into a first sub-image area and a second sub-image area; the waveguide display module comprises a polarization sensitive diffraction coupling element, a first waveguide display lens and a second waveguide display lens, the polarization sensitive diffraction coupling element adopts a geometric phase element, and diffracts and splits a collimation linear polarized light beam into + 1 level and-1 level diffracted light with opposite rotation directions; image information carrying the two sub-image areas is coupled into the corresponding waveguide display lenses, and chiral selective coupling out is achieved through the polarizer holographic grating. The binocular different display function can be achieved only through a single light engine module, the size, weight, power consumption and cost of the system are reduced, and meanwhile the problem that consistency calibration of a left-eye optical system and a right-eye optical system in a double-light-engine scheme is difficult is solved.

The invention relates to the technical field of asymmetric hydrogenation, and particularly discloses a preparation method of a nebivolol intermediate, the nebivolol intermediate is prepared by adopting asymmetric hydrogenation reaction, the method has remarkable technical advantages, extremely high catalytic activity is realized by selecting a catalytic system composed of a specific chiral phosphine ligand and rhodium salt, and the method is suitable for industrial production. According to the present invention, the molar ratio (S / C) of the substrate to the catalyst is as high as 30,000, the production cost is significantly reduced, the process has characteristics of excellent chiral selectivity and excellent reaction efficiency, the e.e value of the product can achieve more than 99%, the yield is excellent, the yield loss caused by the traditional resolution process is effectively avoided, and the method has characteristics of good compatibility with a variety of organic solvents, and can be used for industrial production. By adding the alkaline auxiliary agent, the reaction effect can be further improved, the process is stable, and the industrial application value is relatively high.

This invention provides a ketone reductase mutant and its application in the synthesis of a key chiral intermediate for ticoraxene. The mutant contains amino acid sequences such as SEQ ID NO: 4, 6, 8, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, or 42. This ketone reductase mutant exhibits higher carbonyl catalytic activity and chiral selectivity than the wild type, and is used in the preparation of the key intermediate R-5,7-difluorobenzodihydropyran-4-ol for ticoraxene.

The invention relates to the field of medicinal chemistry, in particular to a synthesis method of (2S, 3R)-3-(4-methoxyphenyl) serine. The invention relates to a synthesis method of (2S, 3R)-3-(4-methoxyphenyl) serine, which comprises the following steps: carrying out condensation reaction on p-methoxybenzaldehyde and glycine to obtain a compound 1; adding into water containing a polar solvent, adding an alkaline compound and acetic anhydride, reacting, drying, filtering and concentrating to obtain a compound 2; adding L-acetylase into the compound 2 to react, and treating a crude product to obtain a compound 3; in order to effectively improve the problems of low production efficiency, tedious intermediate purification steps and difficulty in industrial large-scale synthesis of the existing target product in a synthesis process, high chemical purity and high chiral selectivity of the product are achieved through cooperation of the steps; the reaction path is simple, the operation is simple and convenient, harsh reaction conditions or complex purification equipment is not needed, and industrial large-scale production requirements are met.

This invention discloses a method for preparing phenelzine, comprising the following steps: dissolving compounds of formula 1 and formula 2 in a solvent, adding piperidine and acetic acid, and performing carbon-carbon coupling to synthesize compound 3; dissolving compounds of formula 3 and formula 4 in a solvent, performing cyclization to synthesize compound 5; dissolving compound 5 in a solvent, adding triethyl orthoformate, and performing alkylation under acid catalysis to synthesize compound 6; dissolving compound 6 in a solvent, adding DDQ to synthesize compound 7; dissolving compound 7 in a solvent, and hydrolyzing it with NaOH to synthesize compound 8; dissolving compound 8 in a solvent, and performing amination under the action of CDI and hexamethyldisilazane to synthesize compound 9; dissolving compound 9 in a solvent, and performing reduction resolution under the action of catalysts A and B to synthesize phenelzine of formula 10. The method for preparing phenelzine of this invention has advantages such as high chiral selectivity, no need for column chromatography separation, high yield, and low cost.

 The invention discloses a threonine aldolase mutant, a coding gene of the threonine aldolase mutant, a recombinant vector constructed by the coding gene, a recombinant genetically engineered bacterium obtained by transforming the recombinant vector, and an immobilized enzyme prepared from the threonine aldolase mutant. The invention also discloses an application of the threonine aldolase mutant and the immobilized enzyme prepared from the threonine aldolase mutant in preparation of (2S, 3R)-p-methylsulfonylphenylserine. According to the invention, site-directed mutagenesis is carried out on threonine aldolase Ps LTA from Pseudomonas putida, so that the threonine aldolase mutant with good stability and high chiral selectivity of the product is screened out, efficient synthesis of (2S, 3R)-p-methylsulfonylphenylserine is realized, and meanwhile, the method accords with green chemical production requirements and shows excellent application prospects.

This invention discloses a method for detecting 99 achiral / chiral endocrine disruptors in urine based on a dual-column coupled analysis system, belonging to the field of pollutant monitoring and analysis technology. The method involves a single pretreatment of the urine sample, including formic acid-acetonitrile extraction and ethylenediamine-N-propyl silica gel purification. A dual-column coupled analysis mode is then used, with a C18 column simultaneously quantifying the total concentration of 93 achiral endocrine disruptors (EDCs) and 6 chiral pesticides. The chiral column yields the R / S enantiomer signal intensity ratio, and the content of each enantiomer is calculated using a "total-proportional conversion" model. This invention achieves, for the first time, a unified detection system for achiral and chiral substances, eliminating the need for a single enantiomer standard; accurate quantification can be achieved using only racemic mixtures, effectively avoiding the direct quantitative bias of chiral columns. The method has a limit of quantification as low as 0.25 μg / L, is simple to operate, low in cost, and has good reproducibility, providing an efficient and reliable analytical tool for population exposure monitoring and chiral selective metabolism research.

The invention discloses an asymmetric hydroboration method of an unsaturated carbonyl compound, which comprises the following steps: by taking N-heterocyclic carbene borane NHC-BH3 as a boron free radical precursor, a chiral oxazolidinone group as an asymmetric induction group and diphenyl disulfide as a catalyst, realizing the asymmetric hydroboration of alpha, beta-unsaturated carbonyl compound at room temperature in a nitrogen environment and in the presence of an organic solvent. According to the method, the alpha-boron substituted product with high chiral selectivity is obtained through hydroboration reaction of the alpha, beta-unsaturated carbonyl compound, and the alpha-boron substituted product has wide substrate adaptability, stereoselectivity control capability and excellent economical efficiency; the invention also discloses a product and a preparation method thereof.

The invention discloses a novel chiral covalent organic framework material as well as a preparation method and application thereof. The chiral covalent organic framework compound is prepared by the following steps: carrying out Mitsunobo or SN2 reaction, Ullmann coupling and reduction reaction on chiral diol and iodohydroxy ethyl nicotinate to obtain an axial chiral bipyridine aldehyde group monomer, and carrying out Schiff base reaction on the axial chiral bipyridine aldehyde group monomer and a polyamino substituted monomer under a solvothermal condition. The chiral covalent organic framework compound disclosed by the invention can be complexed with various metals such as palladium, copper, nickel and the like to form a heterogeneous catalyst for asymmetric reaction, shows good catalytic effect and chiral selectivity, and also has good chemical stability; after the reaction, separation and recovery of the catalyst can be realized through simple centrifugation or filtration, so that the environmental pollution is effectively reduced, the cost is reduced, and the application prospect is good.

This invention provides an amidase mutant and its application in the preparation of ( S The application of pyrimethanil belongs to the fields of genetic engineering and enzyme catalysis technology. Compared with the amidase shown in SEQ ID No. 1, the amidase mutant of this invention contains one or more mutations at the following sites: alanine at position 132 is mutated to leucine; serine at position 205 is mutated to glycine; alanine at position 211 is mutated to glycine. Compared with wild-type amidase, the enzyme activity and stereoselectivity of the amidase mutant of this invention are significantly improved; based on the mild and simple preparation method of this mutant, the obtained ( S )-Pyrimethanil possesses excellent chiral selectivity and product optical purity, which aligns with the development trend of green pesticide creation and has significant industrial application value.

The application discloses a synthesis method of lumerizine and intermediates thereof, and belongs to the technical field of medicine synthesis. The application takes 1-(4-fluorophenyl)-4-(4-piperidone-1-yl) butan-1-one with 2-(methylamino) phenylhydrazine as starting materials, and efficiently prepares medical-grade lumerizine p-toluenesulfonate through four core reactions of Fischer indole condensation, intramolecular double SN2 ring closure, normal-pressure metal-free asymmetric transfer hydrogenation and salt formation and refinement. Three kinds of key intermediates and preparation processes thereof are completely protected, a non-metal normal-pressure catalytic system is used throughout the process, and a noble metal high-pressure hydrogenation process is abandoned, so that metal residues are avoided, chiral selectivity is high, the process is simple, three-waste quantity is small, the problems of low yield, high cost, many impurities and difficulty in industrialization of the existing process are effectively solved, and the application has extremely high industrialization popularization value and patent protection value.

The application relates to a drug controlled release system with a chiral drug selective loading function, a preparation method and application thereof, and belongs to the technical field of biological medicines. The drug controlled release system with the chiral drug selective loading function is prepared into a supermolecular hydrogel selective loading system after a gel factor is self-assembled into a supermolecular hydrogel, and chiral drugs with the same optical rotation as the supermolecular hydrogel are loaded into a three-dimensional network structure of the supermolecular hydrogel. The drug controlled release system with the chiral drug selective loading function prepared by the application can realize selective loading of different configurations of naproxen, and can realize controlled release of S-naproxen under alkaline conditions. The chiral selective controlled release system is simple in preparation, high in feasibility, and can be widely applied to the field of biological medicines.

The present invention relates to the fields of pharmaceutical intermediate compounds and organic synthesis, and specifically relates to a key intermediate of lotilaner and a preparation method therefor. The preparation method comprises: (1) reacting an organic base, 2-cyanoethyl 5-acetyl-3-methylthiophene-2-carboxylate, and 2,2,2-trifluoro-1-(3,4,5-trichlorophenyl)ethanone in an organic solvent to obtain an intermediate 1; (2) dehydrating the intermediate 1 to form a double bond to obtain an intermediate 2; and (3) reacting the intermediate 2 with a ligand to obtain a key intermediate of lotilaner. The intermediate is used for synthesizing lotilaner. The preparation method of the present invention has extremely high chiral selectivity, mild conditions, and stable yield, can be suitable for scale-up production, and provides a new technique suitable for industrial production for the key intermediate of lotilaner.

The invention discloses an MIM configuration chiral absorption metasurface, a verification method and a regulation and control method, and belongs to the field of metasurs.The MIM configuration chiral absorption metasurface comprises a top chiral pattern layer, a dielectric layer and a gold substrate which are sequentially stacked from top to bottom, and an MIM configuration is formed; wherein the top chiral pattern layer is chiral units which are arranged in a periodic array mode, each chiral unit is composed of a rectangular metal strip, two quarter arcs which are symmetrically arranged relative to the center of the rectangular metal strip and a rectangular VO2 patch, the rectangular VO2 patches are driven by temperature to generate metal-insulator transformation, circular dichroism continuous tuning is achieved, and the circular dichroism continuous tuning effect is achieved. Meanwhile, the function integration of absorption type CD tuning and reflection type beam shaping is achieved. By adopting the MIM configuration chiral absorption metasurface, the verification method and the regulation and control method, on the basis of combination of VO2 phase change characteristics and the MIM configuration chiral metasurface, collaborative integration of high-contrast tunable chiral absorption and chiral selective beam regulation and control is realized in a terahertz frequency band.

The application discloses a carbonyl reductase mutant, a preparation method and application thereof, and belongs to the technical field of enzyme engineering. A series of advantageous mutants are obtained by the method of directional evolution in the field of enzyme engineering on the basis of the carbonyl reductase BcKRED from Bacillus cereus. The obtained carbonyl reductase advantageous mutant has high catalytic activity, thermal stability and reversed chiral selectivity compared with the wild-type carbonyl reductase. The application provides a green and efficient way for industrial production of chiral alcohol by using the carbonyl reductase as a biological catalyst, and has a wide application prospect.

The invention discloses application of lipase in catalytic synthesis of S-flurbiprofen and a method, and belongs to the technical field of biology. The invention aims to solve the technical problems that the existing technology for synthesizing S-flurbiprofen by an enzyme method still has some problems, such as poor enzyme stability, easy inactivation in a reaction process and the like, so that the catalytic efficiency of the enzyme is reduced. According to the technical scheme, the application of the lipase with the sequence shown in SEQ ID NO.1 in S-flurbiprofen catalytic synthesis is provided, the lipase with the sequence shown in SEQ ID NO.1 is used for catalyzing S-flurbiprofen synthesis, the chiral selectivity can reach 97% or above, the method is suitable for multiple production scenes, and the problem that existing S-flurbiprofen chiral resolution steps are complex is solved. And moreover, the method is mild in reaction condition, high in optical purity, simple to operate, green and environment-friendly, and more beneficial to industrial production.