652results about "Asymmetric syntheses" patented technology

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 relates to a method for preparing S-citalopram based on an R-diol intermediate. The method comprises the following steps: (1) carrying out SN2 configuration inversion on a citalopram R-diol intermediate under the action of a large-steric-hindrance acid and a large-steric-hindrance ligand to obtain a mixture containing S-citalopram and R-citalopram; and (2) obtaining the S-citalopram from the mixture in the step (1) under the action of a resolving agent. In addition, the invention also discloses a preparation method of the S-citalopram. The optical purity of the S-citalopram prepared by the method is greater than 95%, and the optical purity is greater than 99% after the S-citalopram is purified. In addition, the total yield of S-citalopram is increased to 82% from 31% in the prior art.

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 present invention relates to amide derivatives of Formula (XIIIa) and pharmaceutical compositions thereof that modulate the activity of the PGI2 receptor.Compounds of the present invention and pharmaceutical compositions thereof are directed to methods useful in the treatment of: pulmonary arterial hypertension (PAH); idiopathic PAH; familial PAH; PAH associated with a collagen vascular disease, a congenital heart disease, portal hypertension, HIV infection, ingestion of a drug or toxin, hereditary hemorrhagic telangiectasia, splenectomy, pulmonary veno-occlusive disease (PVOD) or pulmonary capillary hemangiomatosis (PCH); PAH with significant venous or capillary involvement; platelet aggregation; coronary artery disease; myocardial infarction; transient ischemic attack; angina; stroke; ischemia-reperfusion injury; restenosis; atrial fibrillation; blood clot formation in an angioplasty or coronary bypass surgery individual or in an individual suffering from atrial fibrillation; atherosclerosis; atherothrombosis; asthma or a symptom thereof; a diabetic-related disorder such as diabetic peripheral neuropathy, diabetic nephropathy or diabetic retinopathy; glaucoma or other disease of the eye with abnormal intraocular pressure; hypertension; inflammation; psoriasis; psoriatic arthritis; rheumatoid arthritis; Crohn's disease; transplant rejection; multiple sclerosis; systemic lupus erythematosus (SLE); ulcerative colitis; ischemia-reperfusion injury; restenosis; atherosclerosis; acne; type 1 diabetes; type 2 diabetes; sepsis, and chronic obstructive pulmonary disorder (COPD).

A method for preparing bedaquiline using a low-temperature continuous flow, and a product prepared. The preparation method comprises the following steps: step S1, carrying out first continuous flow reaction on a feed liquid A and a feed liquid B by using a continuous flow to obtain a reaction liquid D; step S2, carrying out second continuous flow reaction on the reaction liquid D and a feed liquid C by using a continuous flow, wherein the reaction residence time of the first continuous flow reaction is 30-600 s, and the reaction residence time of the second continuous flow reaction is 30-200 s; and step S3, carrying out quenching. The preparation method achieves a good yield, and by using the method for preparation of bedaquiline, a crude product obtained requires only simple post-treatment to achieve a purity of pure bedaquiline of up to 99.8%.

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.

The invention provides a two-dimensional cyclodextrin polymer material as well as a preparation method and application thereof. The two-dimensional cyclodextrin polymer material is prepared by a method comprising the following steps: stirring a self-assembly agent and cyclodextrin molecules in a solvent, standing, and carrying out self-assembly to form a dispersion liquid with a sheet structure crystal; and mixing the dispersion liquid with a cross-linking agent, reacting, carrying out solid-liquid separation, washing and drying to obtain the product. The method is simple and convenient in preparation process, the two-dimensional cyclodextrin polymer with monomolecular layer thickness is obtained, and the method has considerable industrial application prospects. The invention also provides a two-dimensional cyclodextrin polymer material and application thereof.

The invention discloses an asymmetric synthesis method of an efinaconazole intermediate, which comprises the following steps: adding auxiliary materials and water into a reaction bottle, then adding hydrogen peroxide, controlling a certain temperature to dropwise add an organic solution of a substrate I and a catalyst II into the reaction bottle, controlling a certain temperature to carry out a heat preservation reaction, and carrying out post-treatment to obtain a product III. The target product is obtained through the proper chiral catalyst, and the method is mild in condition and high in chiral selectivity.

The invention belongs to the technical field of organic electroluminescent materials, and particularly discloses a paracyclophane-based purple light chiral host material and application thereof. Paracyclophane is used as a molecular structure center, two paracyclophane derivatives are constructed, and the novel purple light chiral main body material is synthesized by combining indole carbazole groups on the periphery. Because the periphery is combined with an indolocarbazole group, the excellent photophysical property of indolocarbazole can be fully utilized, and through separation of cycloarane, intermolecular conjugation is broken, a novel purple light material is constructed, emission of 372 nm is realized, relatively high S1 and T1 energy levels are obtained, a chiral signal is provided for participation of cycloarane, and the material has a wide application prospect. The important significance is provided for constructing a novel chiral main body material.

To provide a novel stereoselective method for producing a cyclic dinucleotide derivative that can be used for an antibody-immunostimulator conjugate, and a production intermediate thereof, and to provide methods for producing a cyclic dinucleotide-linker and antibody-immunostimulator conjugate using the production method.SOLUTION: The present invention relates to a method that makes it possible to produce, in large amounts and with high yield, a cyclic dinucleotide derivative having a desired steric configuration, by using an optically active phosphitylation agent twice, during coupling and cyclization.SELECTED DRAWING: None

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 chiral ferrocene framework tetradentate ligand and application thereof in asymmetric hydrogenation reaction. The ligand has the advantages of low cost, simplicity and convenience in synthesis, good stability 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 and the like into corresponding chiral alcohol, and has huge industrial application potential.

The invention relates to the technical field of synthesis of organic compounds, and discloses a preparation method of N-Boc-cis-4-hydroxy-L-proline methyl ester, which comprises the following steps: step 1, synthesis of (2S, 4R)-4-p-toluenesulfonyloxy-1, 2-pyrroline dicarboxylic acid-1-tert-butyl ester-2-methyl ester (2): (2S, 4R)-4-hydroxy-1, 2, 4-triazole-2-methyl ester (3) is prepared from (2S, 4R)-4-hydroxy-1, 2, 4-triazole-2-methyl ester and (2S, 4R)-4-p-toluenesulfonyloxy-1, 2-pyrroline dicarboxylic acid-1- The preparation method comprises the following steps: dissolving 1-tert-butyl-2-methyl 2-pyrroline dicarboxylic acid-1-tert-butyl ester-2-methyl ester in dichloromethane; according to the method, (2S, 4R)-4-hydroxy-1, 2-pyrroline dicarboxylic acid-1-tert-butyl-2-methyl ester which is cheap and easy to obtain in the market is adopted as a raw material, after p-benzoylation and acetylation are performed, hydroxyl of the raw material is converted from trans form to cis form, chiral conversion is performed, and finally the target product is synthesized. The used acetate replaces benzoate, the raw materials are cheaper, and the generated by-product acetic acid is more environment-friendly than benzoic acid, so that the method is suitable for large-scale production.

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 present disclosure relates to an asymmetric process for preparing nicotine without protection, in particular to a process for preparing optically pure nicotine by taking nicotinate as a starting material and carrying out four-step reaction. The process comprises the following steps: nicotinate and γ-butyrolactone are subjected to condensation reaction, asymmetric catalytic reduction reaction, activation, and reaction with methylamine to give optically pure nicotine. The asymmetric catalytic reduction for preparing the chiral alcohol intermediate compound with high optical activity is a key step of the method. The method of the present disclosure has the characteristics of high atom economy, very high reaction activity, capability of keeping excellent stereocontrol, capability of obtaining a chiral product with very high enantioselectivity, short reaction steps, low cost of raw materials, green and pollution-free, capability of greatly reducing the quantity of “three wastes”, and easiness in realizing industrial amplification production.

The present application provides a synthetic process for production of lipoxin B4 and analogues thereof, which is modular and scalable, thus permitting synthesis of large quantities of LXB4 and analogues thereof, including radiolabeled analogues. Also provided are intermediate compounds that are useful in the synthetic process for production of lipoxin B4 and analogues thereof.

The purpose of the present invention is to provide a method for more efficiently producing specific optically active compounds including optically active 1-acetyl-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline.　The present invention provides a method for producing an optically active compound represented by formula (3) (wherein R5 represents a hydrogen atom, etc., R6 and R7 each independently represent a hydrogen atom, etc., R8 represents a C1-C6 alkyl group, R9, R10, and R11 each independently represent a hydrogen atom, etc., and the asterisked carbon atom is an asymmetric carbon atom), the method comprising reacting a compound represented by formula (2) (wherein R5, R6, R7, R8, R9, R10, and R11 respectively have the same meanings as defined above) with hydrogen in the presence of an asymmetric cobalt complex.

Disclosed herein is a method for preparing tertiary alcohols from optionally substituted phenyl ketones or optionally substituted pyridinyl ketones, comprising the use of chiral ligands and boron trifluoride diethyl etherate. The tertiary alcohols can be used to prepare synthetic versions of natural products and / or pharmaceuticals.

The invention discloses a method for constructing an axially chiral 2-aryl indole derivative. According to the method, a chiral secondary amine catalyst is combined with a triethylamine additive, so that asymmetric Friedel-Crafts reaction of acrolein and indole binaphthol compounds is realized, and catalytic asymmetric synthesis of a series of axially chiral 2-aryl indole structures is realized in a dynamic kinetic resolution form.

The invention provides a 1-phosphorus-doped norbornene-dimethyl xanthene chiral ligand as well as a synthesis method and application of the 1-phosphorus-doped norbornene-dimethyl xanthene chiral ligand. The structural formula of the chiral ligand is shown as a formula III and a formula III ': # imgabs0 #, a group R is C1-6 alkyl, C1-6 alkoxy, C1-6 alkenyl, phenyl, halogenated phenyl, C1-6 alkyl substituted phenyl or C1-6 alkoxy substituted phenyl, and a group R1 is C1-6 alkyl. The chiral ligand serves as a chiral phosphine ligand with a novel structure, three completely bound P-C bonds are formed through introduction of a rigid framework, the scientific problem that a phosphorus chiral center is easy to racemize is successfully solved, the phosphorus chiral ligand can be widely applied to asymmetric reactions such as asymmetric cyclization catalyzed by metal, and the phosphorus chiral ligand has a wide application prospect. And the method has a wide commercial application prospect. The synthesis method of the chiral ligand comprises the steps that the 9, 9-dimethyl xanthene compound and the 1-phosphorus-doped norbornene amine compound serve as raw materials, the chiral ligand is generated through H [1, 5] migration and phosphorus-doped D-A reaction, and the synthesis method is simple, good in feasibility and high in yield.

This invention discloses a chiral [oxyindole-pyrrolidine-β-lactam] bispirocyclic compound containing trifluoromethyl groups, with the following structural formula: The preparation includes the following steps: 1. Sequentially adding a metal catalyst, a chiral ligand, a base, indigo-derived trifluoromethylimine ylide, and 3-methylene β-lactam, followed by the addition of an organic solvent to obtain a mixture. The mixture is stirred at a reaction temperature of 0℃ to 50℃. 2. After the reaction is complete, the chiral [oxyindole-pyrrolidine-β-lactam] bispirocyclic compound containing trifluoromethyl groups is obtained through post-processing. The chiral [oxyindole-pyrrolidine-β-lactam] bispirocyclic compound containing trifluoromethyl groups prepared in this application lays a material foundation for in-depth drug activity research based on new drug development.

The invention discloses a chiral 1, 4-diazabicyclo [3.1. 1] heptane derivative as well as a synthesis method and application of the chiral 1, 4-diazabicyclo [3.1. 1] heptane derivative. According to the invention, a 1-azabicyclo [1.1. 0] butane derivative is taken as a raw material, under the catalytic action of a chiral iridium complex, the 1-azabicyclo [1.1. 1] butane derivative and an N-allyl carbonate derivative are subjected to [3 + 2] cycloaddition reaction, a series of chiral 1, 4-diazabicyclo [3.1. 1] heptane skeletons with diversified structures are constructed with high stereoselectivity, and the obtained product has the potential of further derivatization. The method has the advantages of easily available raw materials, mild reaction conditions, simplicity and convenience in operation, good functional group compatibility and the like.

The invention provides an efficient method for asymmetric hydroarylation of internal olefin. The method provided by the invention has the advantages of high yield, simple operation, mild reaction conditions, strong chiral control ability and wide substrate applicability, and has high academic and application values.

The present invention relates to the preparation of amino acid derivatives VII, including the use of catalysts. The structure of the catalyst disclosed by the invention can be shown as a formula (VI), or the catalyst is loaded on a molecular sieve, and the structure of the catalyst is shown as a formula (I). The invention also discloses preparation of the catalyst and intermediates thereof. A plurality of molecules prepared by the method are all of brand new structures, and are of great significance.

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 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 application belongs to the technical field of chemical synthesis, and specifically provides a chiral hydroxyphosphonate, a preparation method and application thereof. The chiral hydroxyphosphonate has a structure as shown in formula II: each R is independently H, an alkyl group, an alkenyl group, an alkynyl group or a halogenated alkyl group; Ar is an aromatic ring or a heteroaromatic ring; X is a bond, -O-, -N(R 1 )- 2 q , -S(=O) m -; the chiral hydroxyphosphonate is obtained by reducing an alpha phosphonate substituted benzocycloalkanone compound through an asymmetric hydrogenation method, has two chiral centers, and has a yield of up to 99% and an enantiomeric selectivity of up to 99%. The chiral hydroxyphosphonate has wide application potential and value in skin tissue soothing, repairing, anti-aging and the like.​

The invention discloses a preparation method of an optically pure mepivacaine hydrochloride intermediate. According to the method, N-(2, 6-dimethylphenyl) pyridine carboxamide is used as a starting material, hydrogenation reduction is carried out in the presence of a ligand and a catalyst to obtain the mepivacaine hydrochloride intermediate ((S)-N-(2, 6-dimethylphenyl) piperidine-2-carboxamide), the ee value of the obtained mepivacaine hydrochloride intermediate can reach 93%, the yield can reach 95%, post-treatment is simple, and the method is suitable for industrial production. The method is very suitable for large-scale workshop production. The ligand used in the invention is cheap and easily available, and can be refined and recovered through column chromatography, and the catalytic effect of the recovered ligand is consistent with that of a newly purchased ligand.

The invention discloses a novel C2 symmetric chiral bisamide ligand and a preparation method and application thereof, the ligand has a structure as shown in # imgabs0 #, Ar is aryl, the relative positions of two sulfur in the general formula are different, * represents a chiral center, R is 4-methylbenzyl, 4-bromobenzyl, 2, 6-dimethylbenzyl, methyl or benzyl, and n represents 1 or 2. Dithiophenol and (2S, 3S)-2, 3-diphenylaziridine react to obtain an intermediate, and the intermediate and nitrogen-substituted chiral cyclic amino acid or 2-diphenylphosphinobenzoic acid are subjected to dehydration condensation to obtain various ligands with novel structures. A catalyst formed by complexing the ligand and an allyl palladium chloride dimer can be used as a chiral ligand for efficiently catalyzing an asymmetric allyl alkylation reaction.