583 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 discloses ketene reductase and a method for preparing a brivaracetam intermediate by using the ketene reductase. The ketene reductase has at least a difference of an amino acid residue W117 or a homologous site thereof relative to an amino acid sequence as shown in SEQ ID NO: 1, SEQ ID NO: 3 or SEQ ID NO: 5 or an amino acid sequence having at least 95%, 96%, 97%, 98% or 99% identity with the amino acid sequence as shown in SEQ ID NO: 1, SEQ ID NO: 3 or SEQ ID NO: 5, and the position 117 refers to an amino acid residue number in SEQ ID NO: 1. Compared with a wild type, the single mutant or the combined mutant of ketene reductase from different sources has good enantioselectivity and relatively high conversion rate when the brivaracetam intermediate (R)-4-propyl-dihydrofuran-2-ketone is produced, and a good strategy is provided for industrial production of (R)-4-propyl-dihydrofuran-2-ketone.

The invention discloses a method for respectively realizing asymmetric hydroamination and migration hydroamination of olefin by using nickel and ligand combined catalysis, and belongs to the field of organic chemistry and medicinal chemistry. Under the action of a metal nickel source, a chiral ligand, a hydrogen source, an additive and the like, olefin and azide amination reagents protected by different carbonates are used as amine sources to react in an organic solvent, and a series of chiral amine and alkylamine compounds are obtained with excellent enantioselectivity and good yield. Cheap transition metal nickel is used as a catalyst, simple and easily available alkene and carbonic ester protected azide amination reagents are used as raw materials, conditions are mild and simple, functional group compatibility is good, and operation is easy and convenient.

The invention belongs to the technical field of chiral boron compound synthesis, and particularly relates to an MOF-Cu (II) / CMC composite material and a preparation method and application thereof. The preparation method of the MOF-Cu (II) / CMC composite material comprises the following steps: dropwise adding an aqueous solution of sodium carboxymethyl cellulose into an aqueous solution of bivalent copper salt, carrying out solid-liquid separation, mixing obtained composite microspheres and an organic solution of trimesic acid, heating, and carrying out solid-liquid separation to obtain the MOF-Cu (II) / CMC composite material. The composite material is applied to an asymmetric chiral boron addition reaction, the reaction is carried out at room temperature, the conditions are mild, the use range of a substrate is wide, and the yield and enantioselectivity are high. According to the method, the chiral organic boride can be synthesized in a simple component solvent, an efficient new method is provided for preparation of drug molecules and active intermediates, the substrate range of preparation of the chiral organic boride is widened, and the method has important theoretical and practical significance.

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 relates to a chiral pyridinium salt carbonyl catalyst as well as a preparation method and application thereof, the structural general formula of the catalyst is # imgabs0 #, in the formula, R1 is # imgabs1 #, X1-6 comprises N or C-R6-11; r2, R4 and R6-11 comprise hydrogen, alkyl of C1-24, alkyloxy, # imgabs2 # CO2Rd, halogen, nitryl, cyano or trifluoromethyl; r3 comprises substituted or unsubstituted C1-24 alkyl groups, substituent groups comprise halogen, C1-10 alkyl groups, C3-10 cycloalkyl or aryl groups, C1-8 carbonyl groups, C1-8 sulfonyl or phosphoryl groups, and C1-10 alkoxy or amido groups, and carbonyl groups comprise aldehyde groups, ketone carbonyl groups, ester carbonyl groups, carboxyl groups or amido groups; and R5 has the structural formula of # imgabs3 # X <-> which is an anion. Compared with the prior art, the catalyst disclosed by the invention is used for a bionic aldol reaction of amino acid derivatives to synthesize a series of beta-hydroxyl-alpha-amino acid compounds with extremely high enantioselectivity.

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.

The invention discloses a spiro pyrrolo-indolone derivative and a preparation method thereof, and belongs to the field of chemical synthesis, a cyclic imine ylide derivative and a 2-alkenyl indole derivative are used as raw materials, a catalyst, a solvent and alkali are added, a reaction is performed for 6-24 h, and the spiro pyrrolo-indolone derivative is obtained through one-step efficient synthesis. The preparation method has the advantages of simple operation, few reaction steps, easily available raw materials, high yield, no need of a transition metal catalyst, and environmental protection; a new path is provided for synthesizing the compounds; the enantioselectivity and diastereoselectivity of the product obtained by the preparation method disclosed by the invention are high; the preparation method has wide substrate universality and strong compatibility with substituent groups on substrates, and through one-pot one-step reaction, a tedious separation process and an intermediate compound purification process in a post-treatment process are avoided, so that time and resources are saved, and the yield is improved.

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 selective asymmetric hydrogenation method of 4-substituted-1, 2-dihydroquinoline and application of the selective asymmetric hydrogenation method, and relates to the technical field of pesticide chemistry. According to the present invention, in the presence of the chiral ligand and the rhodium catalyst, the 4-substituted-1, 2-dihydroquinoline is subjected to the selective asymmetric hydrogenation reaction, and the selective asymmetric hydrogenation method has advantages of simple steps, high conversion rate and high enantioselectivity.

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.

The invention belongs to the technical field of preparation of four-membered ring derivatives, and particularly relates to a four-membered ring derivative and a preparation method thereof. The preparation method of the four-membered ring derivative comprises the following steps: (1) adding two substrates, a photocatalyst and a solvent into a quartz tube, and stirring; (2) putting the quartz tube under ultraviolet light to carry out photocatalytic reaction; and (3) evaporating the reaction liquid to dryness, and separating through column chromatography to obtain the target compound. According to the invention, cis-olefin is used as an initial raw material to carry out cycloaddition reaction, so that the method has high regioselectivity and diastereoselectivity; the homodimerization reaction of olefin is effectively inhibited through reversible cis-trans isomerization reaction, so that the four-membered ring derivative is efficiently obtained. The four-membered ring derivative prepared by the invention plays a basic role in drug design, and provides a solid structural support for medical molecules.

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.