428 results about "Enantio selectivity" patented technology

The invention relates to the technical field of biochemical engineering, in particular to a method for preparing chiral alpha-trifluoromethyl alcohol by using imine reductase AtRedAm, trifluoromethyl ketone is reduced into corresponding chiral trifluoromethyl alcohol at an excellent conversion rate by using the imine reductase AtRedAm, and enantioselectivity is high. The reaction depends on an NADPH (Nicotinamide Adenine Dinucleotide Phosphate) coenzyme circulation system, 10% dimethyl sulfoxide is used as a reaction cosolvent, the reaction is carried out in a 100mM (pH = 7.5) phosphate buffer solution for 16 hours, the highest molar conversion rate reaches 99%, and the highest optical purity reaches 95%.

The invention provides a novel chiral ferrocene bridged binaphthyl skeleton phosphine ligand and application thereof. The ligand has the advantages of low cost, simplicity in synthesis, air stability and the like. The ligands have good catalytic activity and enantioselectivity in the asymmetric hydrogenation reaction of ketone, and have certain industrial application prospects in the synthesis of pharmaceutical molecules.

The invention discloses a p-nitrophenyl ethyl esterase mutant with high enantioselectivity as well as a construction method and application of the p-nitrophenyl ethyl esterase mutant. The p-nitrophenyl ethyl esterase mutant is obtained by mutating an amino acid sequence of wild p-nitrophenyl ethyl esterase pnbA as shown in SEQ ID NO.1 according to one or a combination of more of the following modes: leucine at the 273rd site is mutated into aspartic acid, phenylalanine at the 314th site is mutated into histidine, and leucine at the 362nd site is mutated into arginine. The mutant pnbA-L273D / F314H / L362R provided by the invention shows optimal catalytic performance (E = 47.16) for racemization-acetic acid pinyl hydrate, the enantiomeric excess value of the mutant is 95.13%, the conversion rate of 1S, 5R-acetic acid pinyl hydrate is 90.42%, the enantioselectivity of the mutant is obviously higher than that of a wild type, and the mutant has great application potential in biological catalytic synthesis of monocyclic monoterpenoid chiral alcohols.

The invention relates to a method for preparing a nerofloxacin chiral piperidylamine intermediate, which comprises the following steps of: carrying out condensation reaction on 5-hydroxy nicotinic acid which is simple and easy to obtain and is used as a raw material and different alcohols, screening through a series of asymmetric catalytic hydrogenation conditions to obtain optimal reaction conditions, and under the conditions, carrying out reaction on various 3, 3 '-dihydroxy nicotinic acid and 3, 3'-dihydroxy nicotinic acid to obtain the nerofloxacin chiral piperidylamine intermediate. The 2, 5-disubstituted pyridine quaternary ammonium salt is reduced into a tetrahydropyridine product, and the C5 site enantioselectivity of the product is excellent. The preparation method comprises the following steps: selecting methyl (R)-1-benzyl-5-hydroxy-1, 4, 5, 6-tetrahydropyridine-3-carboxylic acid methyl ester as a substrate, completely hydrogenating by using platinum dioxide hydrogen, and then carrying out methyl ester reduction, dehydroxylation, Mitsunobu reaction and protecting group removal to obtain a key chiral intermediate for industrial synthesis of a quinolone antibacterial drug nemonofloxacin with high enantioselectivity and high yield.

The invention discloses a method for synthesizing alpha, alpha-disubstituted dihydroquinoline by dearomatization of quinoline salt under the catalysis of asymmetric rhodium. The method is realized through asymmetric dearomatization arylation and alkenylation of rhodium-catalyzed 2-substituted quinoline salt and a boric acid reagent, and proper adjustment of counter ions of the 2-substituted quinoline salt is the key of success of the strategy. The method has the advantages of excellent enantioselectivity, wide substrate application range, convenience in product conversion, simplicity and feasibility in operation, low energy consumption, high efficiency and the like.

The invention discloses a preparation method of a six-membered azaspiro dihydrobenzofuran compound. According to the method, a C2-alkyne benzofuran derivative is taken as a raw material, metal palladium is taken as a catalyst, and a corresponding product is generated through reaction in an organic solvent at the temperature of 40-120 DEG C under the combined action of a ligand and acetic anhydride. Under the action of palladium, a ligand, a solvent and acetic anhydride, alkyne triple bonds and indole double bonds are subjected to triple addition and bicyclic addition, and rapid construction of a six-membered azaspiro structure dihydrobenzofuran product is achieved. The reaction conditions are mild, the operation is simple and convenient, and the method has the advantages of easily available reaction raw materials, wide substrate applicability, excellent yield and enantioselectivity, easily separated target products and the like.

The invention belongs to the technical field of enzyme engineering, and particularly relates to an enantioselectivity-improved imine reductase mutant and application thereof in production of S-nicotine, and the enantioselectivity-improved imine reductase mutant is obtained by performing single-point or multi-point mutation on the 118th site, the 168th site, the 169th site, the 172th site, the 234th site and the 238th site of the imine reductase with the amino acid sequence as shown in SEQ ID NO.2. According to the present invention, the imine reductase derived from Pseudomonas sp. RC4D1, the accession number of which is WP213665450.1 in NCBI is subjected to mutation to obtain a series of mutants, such that the high enzyme activity of the wild type imine reductase is maintained while the enantioselectivity in the S-nicotine catalytic preparation reaction is improved; compared with the prior art, the method has the advantages of simple production process, mild reaction conditions, high selectivity of imine reductase, high optical purity of the product and better industrial application prospect.

Disclosed herein are deuterated compounds and transition metal catalyzed methods for making deuterated compounds. The disclosed methods are regioselective and enantioselective and may be utilized to prepare isomerically and / or enantiomerically pure or enriched deuterated compounds. The disclosed methods also may be modified in order to prepared fluorinated compounds.

The preparation method comprises the following steps: adding sodium hydroxide into a D / L-cysteine ethyl ester hydrochloride aqueous solution to obtain a mixture, carrying out ultrasonic treatment until the solution is clarified to obtain a mixed solution A, and preparing a copper chloride dihydrate aqueous solution for later use; dropwise adding the mixed solution A into a copper chloride dihydrate aqueous solution in a water bath kettle to obtain a mixed solution B, and continuously stirring for reaction; and after the reaction is finished, centrifugally collecting the precipitate, and washing with water and ethanol. A one-pot self-assembly strategy is adopted, self-assembly is driven based on coordination of D / L-Cys.Oet.HCl and Cu < 2 + >, spherical and spiral supramolecular chiral nano-catalysts are constructed, and compared with the spherical and spiral supramolecular chiral nano-catalysts, the spherical and spiral supramolecular chiral nano-catalysts have obvious spatial asymmetry morphology, and have good application prospects. Therefore, the compound has a higher enantioselective catalytic effect on a chiral substrate dopa, and can be used for selectively catalyzing dopa molecules with specific configurations.

The present application belongs to the technical field of the synthesis of chiral boron compounds, and in particular relates to an MOF-Cu(II) / CMC composite material, and a preparation method therefor and the use thereof. The preparation method for an MOF-Cu(II) / CMC composite material of the present application comprises: dropwise adding an aqueous solution of sodium carboxymethyl cellulose to an aqueous solution of a bivalent copper salt, performing solid-liquid separation, mixing obtained composite microspheres with an organic solution of trimesic acid, heating the resulting mixture, and subjecting same to solid-liquid separation, so as to obtain an MOF-Cu(II) / CMC composite material. The MOF-Cu(II) / CMC composite material is used in an asymmetric chiral boron addition reaction. The reaction is performed at room temperature, involves mild conditions, is applicable to a wide range of substrates and has a high yield and enantioselectivity. Moreover, the method can achieve the synthesis of a chiral organic boride in a solvent having simple components, providing an efficient new method for the preparation of drug molecules and active intermediates, and also broadening the range of substrates used for the preparation of chiral organic borides.

The invention discloses a chiral alpha-hydroxyamide derivative as well as a synthesis method and application thereof. The synthesis method comprises the following steps: in the presence of a chiral thiourea catalyst, aromatic amine and alpha-carbonyl acyl silane are subjected to a catalytic asymmetric nucleophilic addition reaction in a solvent under illumination, and the chiral alpha-hydroxyamide derivative is generated. The reaction takes illumination as driving force, so that green synthesis is realized; and secondly, due to the introduction of the chiral thiourea catalyst, the enantioselectivity is remarkably improved, the use of a metal catalyst is avoided, and the concept of green chemistry is met. In addition, the reaction substrates alpha-carbonyl acyl silane and aromatic amine are cheap and easily available chemicals, so that the synthesis cost is reduced, and the feasibility and practicability of the method are improved.

The invention discloses a compound containing a bicyclic hemiketal structure and a preparation method thereof, alkynyl allyl carbonate is used as a raw material, in the presence of a nucleophilic catalyst, alkynyl allyl carbonate reacts with a benzoylacetonitrile derivative, ABB'multi-component reaction is carried out through a continuous [5 + 1] / addition / cyclization reaction sequence, and the compound containing the bicyclic hemiketal structure is obtained. Bicyclic hemiketal derivatives commonly seen in natural product structures are obtained with good to excellent diastereoselectivity. The method has the advantages of good diastereoselectivity products, excellent chemical selectivity, greenness, mild reaction conditions, convenience in operation, few byproducts and the like, the synthesis steps are good in economy, and four chemical bonds and three continuous chiral centers are simultaneously constructed through one-step operation. Meanwhile, the compound with the bicyclic hemiketal structure has important application value in multiple fields of medicinal chemistry, natural product chemistry, traditional Chinese medicine chemistry and the like, and an efficient preparation means and a series of candidate compounds are provided for development of functionality or biological activity of related compounds with the bicyclic hemiketal / hemiacetal structure.

The invention disclosed herein relates to metal-catalyst free, green enantioselective synthesis of sulfoxide compounds of Formula-I. Particularly, the present invention relates to in situ process to obtain enantioselective sulfoxide compounds of Formula-I with high yield and purity and specific optical rotation. Further, the enantioselective sulfoxide compounds of Formula-I are useful in the treatment of neurological, neuropsychiatric, metabolic and neurodevelopmental disorder.

The invention discloses a chiral alpha-amino acid with a C3 symmetric structure and a preparation method and application thereof, the chiral alpha-amino acid with the C3 symmetric structure provided by the invention is used as an ion pair catalyst, and the structure of the chiral alpha-amino acid with the C3 symmetric structure is more stable than that of other ion pair catalysts due to the C3 symmetric structure; and meanwhile, the chiral phosphamide compound is successfully constructed with relatively high yield (70-80%) and enantioselectivity (80-95%), so that the chiral phosphamide compound has excellent catalytic performance, and the problem that the chiral phosphamide compound is difficult to construct by a traditional ion pair catalyst is solved.

The application belongs to the field of organic synthesis and particularly relates to a synthesis method of polysubstituted indole propionate derivatives. Aryl acetate compounds and sulfonyl indole compounds are used as raw materials, and the reaction is carried out through an isothiourea organic small molecule catalyst. The reaction raw materials are simple and easy to obtain, the reaction conditions are mild, the operation is simple, the reaction time is short, the reaction has good diastereoselectivity and high yield, the synthesis method of the polysubstituted indole propionate derivatives overcomes the defects and deficiencies of the existing synthesis method, and has the characteristics of high efficiency, simplicity and wide universality.

The present application relates to a kind of catalyst composition and its application in catalytic preparation optically active secondary alcohol, the catalyst composition includes chiral ionic bridged aryloxyalkane rare earth complex and additive, the additive is selected from one or more of pyrimidine, N,N-dicyclohexylmethylamine, 4,4'-dipyridyl.The above-mentioned catalyst composition can be used for synergistically catalyzing asymmetric borohydration of chalcone and its derivatives with pinacol borane, and show high catalytic activity and high enantioselectivity, product yield is as high as 99%, ee value can reach 84%, provide a reliable new way for the efficient, high selective synthesis of optically active secondary alcohol.

A quinazolinone catalyst with both N-N and C-C axis chirality and its synthesis method and application, its chemical structural formula is shown in Formula 4; Synthesis method: using indole-derived o-aminobenzamide and 1-naphthaldehyde derivative as raw materials, using molecular sieve as dehydrating agent, bromobenzene as reaction solvent, stirring for 4h under the catalysis of chiral phosphoric acid and 10°C, then adding ethyl acetate, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, stirring for 10h under room temperature, TLC tracking reaction to complete formula 3 compound; using formula 3 compound, phenylsilane, trifluoromethanesulfonic acid as raw materials, adding toluene, stirring reaction under 100°C, TLC tracking reaction to end to obtain formula 4 compound. The catalyst prepared by the present invention can be used as a chiral ligand in transition metal-catalyzed asymmetric allylation reaction, with excellent stereoselectivity control effect; the method has mild reaction conditions, low cost and high enantioselectivity.

Catalytic systems capable of catalyzing enantioselective C-H functionalization reactions are described, and methods of use thereof are described. These catalytic systems contain an iron complex as a host catalyst, and a diammonium guest template as a co-catalyst. The iron-based main catalyst contains a crown ether phthalocyanine ligand. The diammonium guest template is a bidentate compound with chirality. The iron-based host catalyst and the bidentate ammonium guest template can provide a complex spatial environment for stereotactic and site-selective C-H functionalization, such as C-H amination. For example, enantioselective C-H amination reactions carried out using the disclosed methods can achieve high enantiomer ratios (i.e., at least 2: 1) and optionally high yields (i.e., at least 30%).

The application belongs to the field of organic synthesis, and discloses a method for preparing chiral 2-(1,3-diarylallyl)malonate by using a Pd / phosphine oxygen bidentate phosphine phenol ligand catalysis, which comprises the following steps: under a protective atmosphere, mixing P, O-bidentate phosphine phenol ligand, a palladium catalyst, N, O-bis(trimethylsilyl)acetamide, a malonate nucleophilic reagent and an allyl acetate electrophilic reagent in dichloromethane, and reacting to obtain chiral 2-(1,3-diarylallyl)malonate product. The system has the advantages of high enantioselectivity, high catalytic efficiency, wide substrate application range and mild conditions.

The invention discloses a method for catalytically synthesizing alpha-disubstituted ester, amide, malonic acid monoester or monoamide from disubstituted Meldrum's acid. By developing a new strategy for promoting the ring-opening reaction of the disubstituted Meldrum's acid by alkali, the disubstituted malonic acid monoester or monoamide can be efficiently prepared, and compared with the previous method, the strategy can obtain the target product at the room temperature at the yield of 99%. The method successfully breaks through the limitation of the existing disubstituted malonic acid monoester synthesis method, and enriches the types of target compounds. Besides, a series of novel disubstituted malonic acid monoesters are obtained, and simple chemical conversion is applied to obtain a series of disubstituted malonic acid derivatives with quaternary carbon centers. Then, under the action of a chiral organic catalyst, chiral disubstituted malonic acid monoester is obtained with high yield and high enantioselectivity. And a solid foundation is laid for subsequent application of the compounds in subjects of materials, medicines and the like.

The invention discloses a flaky supramolecular chiral copper catalyst based on molecular self-assembly and application thereof, and belongs to the technical field of asymmetric catalysis, the flaky supramolecular chiral copper catalyst is prepared by the following preparation method: dissolving L-ThrC10-20 in a solvent, and stirring to obtain a methanol solution of the L-ThrC10-20; adding ultrapure water into the system, and stirring to obtain a sheet-shaped supramolecular assembly body L-ThrC10-20-NS; and adding Cu < 2 + >, and stirring to obtain the flaky supramolecular chiral copper catalyst L-ThrC16-NS-Cu (II). According to the invention, the flaky supramolecular chiral copper catalyst L-ThrC10-20-NS-Cu (II) assembled on the basis of L-ThrC10-20 and Cu < 2 + > is successfully constructed for the first time, and the catalyst shows obvious enantioselectivity in a Diels-Alder reaction and can be used for efficiently catalyzing to generate an S-endo configuration product.

The invention relates to the technical field of synthesis of ambrota ethers, and discloses a synthesis method of ambrota ethers, the reaction is mainly carried out through a synergistic way, and in the presence of fluorinated alcohol, the strong acidic site of an imino diphosphoryl imide ester catalyst promotes protonation of a distal double bond of (3E, 7E)-homofarnesyl alcohol to form a cationic intermediate. Meanwhile, the imino diphosphoryl imide ester catalyst promotes the (3E, 7E)-homofarnesyl alcohol to be combined in an all-trans conformation manner, and guides carbocations and olefin to be subjected to stereotactic addition, so that a polyene cyclization reaction with high diastereoselectivity and enantioselectivity is realized, and the ambrota ether is finally generated. The fluorinated alcohol stabilizes the cation intermediate through a hydrogen bond, so that the activity and selectivity of the reaction are further improved. The synthesis method of ambrota ether is low in cost and efficient.

The invention discloses a method for preparing a chiral benzhydrol compound through asymmetric hydrogenation of o-amido benzophenone under catalysis of rhodium. The chiral rhodium catalyst is generated in situ from a metal rhodium salt and a chiral phosphine-phosphoramidite ligand in various solvents. Compared with other methods for synthesizing chiral benzhydrol, the method has the characteristics of cheap catalyst, easiness in preparation of chiral ligand, mild reaction conditions, simplicity and convenience in operation, high yield, high enantioselectivity and the like, and can be applied to large-scale preparation of chiral benzhydrol compounds. The method is also suitable for efficient preparation of the rice plant growth regulation inhibitor (S)-Inabenide, the yield can reach 92%, the enantioselectivity can reach 96%, and the method has good industrial application prospects.

The invention discloses a method for olefin enantioselective carbon oxidation through photoelectric synergistic vanadium catalysis, and belongs to the technical field of photoelectric asymmetric catalysis. A bulk chemical organic solvent, an olefin substrate and an N-hydroxyimide substrate are used as raw materials, a vanadium catalyst, an electrolyte and a cathode hydrogen evolution reagent are added, and the enantiomerically enriched olefin carbon oxidation chiral product is prepared under the conditions of electrification and irradiation of an ultraviolet lamp. The method has the characteristics of simple and easily available raw materials, mild reaction conditions, simple and efficient reaction operation, simple and convenient reaction post-treatment, good functional group compatibility, large-scale preparation potential and the like.

The present invention discloses a chiral α -hydroxyamide derivative, and its synthesis method and application. The synthesis method includes: in the presence of a chiral thiourea catalyst, an aromatic amine and α -carbonyl acylsilane undergo a catalytic asymmetric nucleophilic addition reaction under light in a solvent to form a chiral α -hydroxyamide derivative. The reaction of the present invention uses light as the driving force to achieve green synthesis; secondly, the introduction of the chiral thiourea catalyst not only significantly improves the enantioselectivity but also avoids the use of metal catalysts, which conforms to the concept of green chemistry. In addition, the reaction substrates α -carbonyl acylsilane and aromatic amine are both inexpensive and easily accessible chemicals, thereby reducing the synthesis cost and improving the feasibility and practicality of the method.

The invention discloses a benzoxphosphine ligand and a complex and application thereof. The structure of the benzoxphosphine ligand is shown as a formula (I), in the formula (I), R1 is alkyl or aryl substituted oxazolidinyl or imidazoline, R2 is alkyl and / or aryl, and R3 is at least one of fluorine, carbazolyl and 2, 6-dimethoxyphenyl. According to the benzoxphosphine ligand disclosed by the invention, the metal iridium complex can be used as a catalyst to be applied to an asymmetric hydrogenation reaction of alpha-phenyl vinyl diethyl phosphate, and has excellent activity and relatively high enantioselectivity; moreover, the benzoxphosphine ligand disclosed by the invention can be directly synthesized from simple and easily available chiral aldehyde, and the preparation method is simple and easy to operate.

The invention discloses a biological catalytic synthesis method of chiral 2-amino-1-methylenepropanamide and an enzyme catalyst of the chiral 2-amino-1-methylenepropanamide. According to the present invention, one or more key amino acids in the amide hydrolase derived from Rhodococcus erythropolis AJ270 are subjected to mutation to obtain the mutant, the mutant has characteristics of high or reverse enantioselectivity when the hydrolysis reaction of the racemization 2-substituted-2-amino-1-methylene propanamide substrate is catalyzed, and the chiral compound is obtained with the high ee value; and an enantiomer of a wild type amide hydrolase catalytic product can be obtained. A method for preparing chiral 2-substituted-2-amino-1-methylene propanamide by using the mutant through biological catalysis has the characteristics of simplicity and convenience in operation, high reaction efficiency, mild reaction conditions, high enantioselectivity, easiness in product separation and high product purity, and has a very good application prospect.

This invention belongs to the field of organic synthesis technology and relates to a precursor of an obisec key intermediate and a method for preparing the key intermediate. The method involves a [4+2] cycloaddition reaction of 4-trifluoromethylaniline, propionaldehyde, and N-vinylformamide under the catalysis of chiral phosphoric acid, yielding the obisec key intermediate precursor with high enantioselectivity. N -((2) R 4 S )-2-ethyl-6-trifluoromethyl-1,2,3,4-tetrahydroquinoline-4-yl)formamide; subsequently, the key intermediate of obisetri can be obtained through a deprotection reaction under acidic conditions. The method provided by this invention uses a small amount of chiral catalyst and commercially available reagents to efficiently obtain the key intermediate of obisetri in just two steps. R 4 S )-2-ethyl-6-trifluoromethyl-1,2,3,4-tetrahydroquinoline-4-amine; under mild conditions without the need for chiral resolution, the utilization of starting materials is greatly improved, thereby significantly increasing the yield of the target product and the economic efficiency of the process.

The present invention relates to a method for the asymmetric deuterium functionalization of alkenes promoted by chiral thiols and deuterated water. Specifically, the present invention provides a method for synthesizing compounds with high deuteration rates and high optical activity through visible light-catalyzed deuterium functionalization of alkenes, using inexpensive deuterated water as a deuterium source and a peptide- or sugar-derived thiol as a chiral source. The method has the advantages of a short synthetic route, simple operation, readily available deuterium sources, no metal requirements, broad substrate applicability, high deuteration rates and overall yields, and high enantioselectivity.

The application belongs to the technical field of chiral catalysis and medicine, and particularly relates to a dendritic chiral phase transfer catalyst, a structural formula of which is shown as formula (I) or formula (II). A series of chiral phase transfer catalysts based on soluble dendritic macromolecules are synthesized by changing the number of repeated carbon chains on the core molecular structure, and it is found through catalyzing asymmetric alkylation of amino acid derivatives that the dendritic chiral phase transfer catalysts provided by the application have excellent yield and enantioselectivity in catalyzing preparation of chiral amino acid derivatives.