239 results about "Racemization" patented technology

S-Beta-hydroxybutyric acid compositions for oral delivery are effective in rapidly raising blood ketone levels without causing acute acidosis or gastrointestinal (GI) distress when consumed in sufficiently dilute form and / or as a gel or suspension. By limiting added beta-hydroxybutyrate salts containing alkali or alkaline earth metal ions, beta-hydroxybutyric acid solutions, gels, or suspensions can deliver exogenous ketone bodies without significantly altering electrolyte balance. Although aqueous beta-hydroxybutyric acid solutions are moderately acidic with a pH of about 3.5 to 4, when diluted with sufficient water, the water acts as a pseudo buffering agent that offsets otherwise harsh acidic effects when consumed orally. Gels and suspensions can also ameliorate acidic effects by partially encapsulating the beta-hydroxybutyric acid. Beta-hydroxybutyric acid can be pure S-beta-hydroxybutyric acid or a non-racemic mixture enriched with S-beta-hydroxybutyric acid relative to R-beta-hydroxybutyric acid.

Provided in the present invention is a small molecule compound, which is characterized in that it is a compound or a stereoisomer, geometric isomer, tautomer, racemate, hydrate, solvate, metabolite, and pharmaceutically acceptable salt or prodrug of the compound as represented by the following structural formula: formula (I). The small molecule compound of the present invention is applicable as a highly efficient and specific JAK kinase inhibitor, specifically a Tyk2 inhibitor and / or a JAK1 inhibitor, and / or a JAK1 / Tyk2 dual inhibitor.

The invention relates to a pyrimidine derivative as well as a pharmaceutical composition and application thereof, and particularly provides a compound as shown in the following formula H, and a raceme, a stereoisomer, a tautomer, an isotope label, a solvate, a polymorphic substance, a metabolite, a pharmaceutically acceptable salt or a prodrug of the compound.

A specific topoisomerase inhibitor, a use as an antibody drug conjugate, and a preparation method therefor, which relate to the technical field of medicinal chemistry. The inhibitor is a compound A or a tautomer, a mesomer, a racemate, an optical antipode, a diastereoisomer, or a mixture form thereof, or a pharmaceutically acceptable salt thereof; the structure of the compound A is such that the compound may also be further prepared to obtain an antibody drug conjugate, the antibody drug conjugate has good solubility and pharmaceutical properties, and the conjugation process does not result in precipitation, the antibody drug conjugate exhibits obvious in-vivo anti-tumor activity, and shows markedly stronger anti-tumor activity when compared with a control sample.

The present application relates to the technical field of organic synthesis, and particularly relates to a method for preparing (+)-crispine A by means of biological enzyme resolution. First, 6,7-dimethoxy-3,4-dihydroisoquinoline-2-oxide is subjected to 1,3-dipolar cycloaddition with allyl alcohol to obtain a first compound; then the first compound is added into a sulfonylation reagent and zinc powder to obtain a racemate second compound through a three-step continuous series reaction of primary alcohol sulfonylation, nitrogen-oxygen bond cleavage and ring formation; then the second compound is mixed with vinyl acetate and biological enzyme, and chiral resolution is carried out under the action of the biological enzyme to obtain a third compound with right-handed optical rotation and a fourth compound with left-handed optical rotation; finally, the third compound is mixed with an alkaline reagent and a sulfonylation reagent, and then secondary alcohol sulfonylation is carried out to obtain a fifth compound with right-handed optical rotation; the fifth compound is mixed with a deoxidizing reagent to carry out deoxidation reaction, and (+)-crispine A is prepared. The method is simple, green and environmentally friendly, and can be produced in large quantities.

Provided herein are methods composition for treating lung cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of an imidazolate gold compound according to Formula I, or a pharmaceutically acceptable salt, racemate, or enantiomer thereof, wherein Formula I is a gold complex having a structure Au(L)(L′)n, wherein: n is an integer from 1 to 3; L is an imidazolyl-based N-heterocyclic carbene (NHC) ligand; and each L′ is independently selected from an imidazolyl-based NHC ligand, a triaryl phosphine, or a halide.

The invention discloses a fused ring compound, a pharmaceutical composition containing the fused ring compound and application. The compound has a structure as shown in a formula (I) or a tautomer, a meso-mer, a raceme, an enantiomer, a diastereoisomer or a mixture form, a metabolite, a metabolism precursor, an isotope substitution form, a pharmaceutically acceptable salt, a hydrate, a solvate, a polymorphic substance or an eutectic substance thereof, the compound can be used for treating one or more cancers caused by KRAS mutation.

The invention discloses a method for preparing an ester compound and a macrolide compound, and belongs to the technical field of organic chemistry, the preparation method of the ester compound is as follows: in an organic solvent, an alpha-carbonyl alkenyl ester compound reacts with alcohol or phenol under the catalytic condition of alkali to obtain the ester compound; the preparation method of the macrolide compound comprises the following step: in an organic solvent, carrying out intramolecular hydroxyl reaction on an alpha-carbonyl alkenyl ester compound under the catalysis condition of alkali or acid, thereby obtaining the macrolide compound. The method is wide in substrate range, high in practicability and high in yield, racemization of a carboxylic acid alpha-chiral center can be inhibited in intermolecular esterification reaction and macrocyclic lactonization reaction, and the method can be applied to total synthesis of a Brevicidine natural product containing a 13-membered cyclic ester peptide core structure; the method disclosed by the invention has the advantages of mild reaction conditions, simplicity, easiness in operation, wide substrate adaptability, no racemization of the product and the like.

The invention discloses a fused ring compound, a pharmaceutical composition containing the fused ring compound and application. The compound has a structure as shown in a formula (I) or a tautomer, a meso-mer, a raceme, an enantiomer, a diastereoisomer or a mixture form, a metabolite, a metabolism precursor, an isotope substitution form, a pharmaceutically acceptable salt, a hydrate, a solvate, a polymorphic substance or an eutectic substance thereof. The compound can be used for treating cancers caused by KRAS mutation, the cancers caused by KRAS mutation are selected from one or more of cancers caused by KRASG12C, KRASG12V, KRASG12A and G12D mutation, and particularly, the compound can be used as a G12D inhibitor and has relatively high inhibitory activity.

A sulfonamide compound and a pharmaceutical use thereof, specifically relating to a compound of general formula (II) or a racemate, stereoisomer, tautomer, pharmaceutically acceptable salt, and intermediate thereof, a preparation method therefor, and a use thereof in the preparation of drugs for treating solid tumors.

The invention discloses a pyridazinone compound as well as a pharmaceutical composition and application thereof. The structure of the compound is shown as a formula (I), and the compound comprises a racemate, a stereoisomer, a tautomer, a nitrogen oxide, a stable isotope compound, a metabolite, a solvate, a pharmaceutically acceptable salt or a mixture of the racemate, the stereoisomer, the tautomer, the nitrogen oxide, the stable isotope compound and the metabolite. The compound has a proper half-life period, can be decomposed in blood through injection or oral administration to generate a PARP7 inhibitor compound and dextroborneol, and the PARP7 inhibitor compound and dextroborneol can penetrate through a blood brain barrier, show a good synergistic interaction effect, are beneficial to medicine formation and have a clinical application prospect in prevention or / and treatment of cerebral apoplexy.

The present invention relates to a process for the preparation of (±)‑2‑exo‑(2‑methylbenzyloxy)‑1‑methyl‑4‑isopropyl‑7‑oxabicyclo[2.2.1]heptane of formula (I), any of its individual enantiomers or any non-racemic mixture thereof, comprising the steps of: (a) reacting (±)‑2‑exo‑hydroxy‑1‑methyl‑4‑isopropyl‑7‑oxabicyclo[2.2.1]heptane of formula (II), any of its individual enantiomers or any non-racemic mixture thereof, with a 2-methylbenzyl compound of formula (III), wherein X is a leaving group, in the presence of at least one base capable of forming water or a C1-C4 alkyl alcohol under the reaction conditions and at least one inert organic solvent, and (b) simultaneously removing water, C1-C4 alkyl alcohol or any mixture thereof from the reaction mixture.

The invention belongs to the field of preparation of polypeptide drugs, and discloses a synthesis method of tilpotide, which mainly comprises the following steps: 1) taking amino resin as initial resin, and coupling with protected amino acid and polypeptide fragments by adopting a solid-phase synthesis method to obtain peptide resin of tilpotide; wherein the Glu3-Gly4 adopts a Glu-Gly dipeptide fragment, the Thr5-Phe6 adopts a Thr-Phe dipeptide fragment, the Lys20 adopts a Lys [AEA-AEA-gamma-Glu-C20] fragment, and the Gly29-Gly30 adopts a Gly-Gly dipeptide fragment; 2) cracking the peptide resin to obtain crude peptide of the tilpotide; and (3) purifying the crude peptide by reversed-phase chromatography to obtain the fine peptide of the tilpotide. The invention provides a synthesis method of telpotide, which can effectively reduce the generation of [D-Glu] racemization impurities, [D-Thr] racemization impurities, [D-Phe] racemization impurities and [+ Gly] impurities, thereby enhancing the purity and yield of the telpotide, obviously lowering the difficulty of purifying crude peptide, greatly enhancing the total yield of the telpotide on the premise of ensuring the purity of the telpotide, and lowering the production cost of the telpotide. In addition, synthesis of a plurality of fragments can be performed simultaneously, so that the synthesis time is shortened. The purity of the crude tirpotide prepared by the method can reach 86.22% or above, and the yield of the crude tirpotide is 101.51% or above. Through simple purification steps, the impurities in the tilpotide are basically removed, the purity of refined peptide can reach 99.21% or above, the maximum single impurity is lower than 0.15%, the total yield can reach 63.02% or above, the synthesis cost is reduced, and industrial mass production is facilitated.

The present application provides a compound having a structure shown in Formula I, II or III or its enantiomer, diastereoisomer, racemate, stereoisomer, geometric isomer, nitroxide, metabolite or its pharmaceutically acceptable salt, ester, solvate, hydrate, isotopically labeled compound or prodrug. The non-fenofibrate 4-position ether derivative of the present application has an excellent xanthine oxidase activity inhibitory activity.

The invention discloses a chiral phenol calix [4] aryl porous organic molecular cage material as well as a preparation method and application thereof. A chiral calix [4] arene raceme and an acyl chloride chiral auxiliary agent are used as initial raw materials to react to prepare a pair of diastereoisomers, gram-grade separation is achieved through silica gel column chromatography, then the chiral auxiliary agent is removed respectively, and the single enantiomer chiral phenol calix [4] arene compound with the ee value being 99.9% or above can be obtained. The preparation method comprises the following steps of: synthesizing tetraaldehyde chiral phenol calix [4] arene by introducing an aldehyde group unit on the tetraaldehyde chiral phenol calix [4] arene through Duff reaction, and assembling the tetraaldehyde chiral phenol calix [4] arene serving as a construction element with a polyamino organic synthesizer to prepare the chiral phenol calix [4] arene porous organic cage with a larger cavity. The preparation method of the chiral porous organic cage does not need a catalyst, the preparation process is simple, operation is easy and convenient, expansibility is good, the yield is high, and the prepared chiral molecular cage is large in cavity, large in specific surface area and good in repeatability and can be used for chiral recognition and gas adsorption.

The present invention relates to an integrin ligand key intermediate and a preparation method therefor, and specifically provides a new process for synthesizing target compound (7). Compared with existing synthesis processes, the new synthesis process can avoid racemic intermediate compound resolution, improve yields and reduce costs, thereby strongly supporting cost reduction and large-scale production of an αvβ6 integrin ligand.

This invention relates to the application of cyclic quaternary ammonium bases in the preparation of racemic nicotine. The structure of the cyclic quaternary ammonium base is shown in Formula I or Formula II, where n is an integer from 1 to 7; t and m are independently integers from 1 to 4. When the cyclic quaternary ammonium base of this invention is used as a catalyst in the preparation of racemic nicotine, racemic nicotine can be synthesized in one step. This method uses S-nicotine as a raw material and has the advantages of readily available raw materials, fewer reaction steps, fewer reaction byproducts, less likelihood of introducing other impurities, no introduction of other carbon sources during preparation, and ease of large-scale preparation.

This invention discloses an α-indolylpyrrolo[1,2-a]indole derivative and its preparation method. The derivative is a levorotatory or dextrorotatory optically active form or racemate with the following structural formula: The preparation involves using α-indolylpropynyl alcohols and indole compounds as raw materials, and 3,5-bis(trifluoromethyl)phenylbinaphthylphosphonic acid as a catalyst, reacting in an organic solvent to obtain the α-indolylpyrrolo[1,2-a]indole derivative. This invention utilizes an organophosphate-catalyzed tandem reaction of two components to synthesize the α-indolylpyrrolo[1,2-a]indole derivative. The reaction conditions are mild, the process is simple, and the operation is convenient. The obtained product is the core skeleton of the indole bases of the natural products isoborreverine and dimethyl isoborreverine, which is of great significance for the synthesis of analogs of these natural products.

A method for resolving a phenylalanine derivative of formula (I), and an intermediate. The method comprises: a resolving step comprising using a resolving reagent to react with the phenylalanine derivative represented by formula (I) in a reaction solvent to obtain a resolved intermediate, wherein the resolving reagent is selected from N-acetyl-D-phenylalanine and / or (2R,3R)-(−)-dibenzoyl-L-tartaric acid, and the reaction solvent is selected from 90-99% aqueous ethanol, absolute ethyl alcohol, or acetone. The method uses a chiral reagent to perform salt formation and racemate resolution, and has the advantages of being easy to operate, requiring no special production devices, and being easy to scale up production.

The invention provides a compound or an enantiomer, a diastereoisomer, a racemate, a tautomer, a stereoisomer, a geometric isomer, nitrogen oxide, a metabolite or pharmaceutically acceptable salt, ester, solvate, hydrate, isotope labeled compound or prodrug thereof. The invention further provides a composition containing the compound and medical application. The compound has a good patent medicine prospect in the aspect of treating or preventing PTPN2-related diseases or symptoms.

Compositions and methods for the production of L-glufosinate are provided. The method involves converting racemic glufosinate to the L-glufosinate enantiomer or converting PPO to L-glufosinate in an efficient manner. In particular, the method involves the specific amination of PPO to L-glufosinate, using L-glutamate, racemic glutamate, or another amine source as an amine donor. PPO can be obtained by the oxidative deamination of D-glufosinate to PRO (2-oxo-4-(hydroxy (methyl) phosphinoyl) butyric acid) or generated via chemical synthesis. PPO is then converted to L-glufosinate using a transaminase in the presence of an amine donor. When the amine donor donates an amine to PPO. L-glufosinate and a reaction by product are formed. Because the PPO remaining represents a yield loss of L-glufosinate, it is desirable to minimize the amount of PPO remaining in the reaction mixture. Degradation, other chemical modification, extraction, sequestration, binding, or other methods to reduce the effective concentration of the by-product. i.e., the corresponding alpha ketoacid or ketone to the chosen amine donor will shift the reaction equilibrium toward L-glufosinate, thereby reducing the amount of PPO and increasing the yield of L-glufosinate. Therefore, the methods described herein involve the conversion or elimination of the alpha ketoacid or ketone by-product to another product to shift the equilibrium towards L-glufosinate.

The invention discloses a preparation method of (2R, 3S)-2-Boc amino-3-hydroxy-3-(pyridine-4-yl) alanine, and belongs to the technical field of medical intermediates. The preparation method comprises the following steps: by taking glycine ester hydrochloride as a raw material, carrying out benzophenone dimethyl ketal reaction to generate a glycine ester imine intermediate; then, the 2-amino-3-hydroxyl-3-(pyridine-4-yl) alanine and pyridine-4-formaldehyde are subjected to acidolysis, and 2-amino-3-hydroxyl-3-(pyridine-4-yl) alanine is generated; then, the 2-Boc amino-3-hydroxyl-3-(pyridine-4-yl) alanine is subjected to a reaction with Boc2O, and a 2-Boc amino-3-hydroxyl-3-(pyridine-4-yl) alanine racemate is generated; and finally, salifying and resolving by adopting a cyclohexanedibenzylamine resolving agent, and then dissociating to obtain a target product. The raw materials are available in the market, direct condensation reaction is performed between pyridine-4-formaldehyde and amino acid imine, effective resolution can be performed by adopting 0.5 eq of a resolution reagent, and the whole route is simple and convenient to operate and suitable for large-scale production.

The invention provides a preparation method of polypeptide, which comprises the following steps: dissolving a compound as shown in a formula I, a compound as shown in a formula II, pivaloic anhydride, an alkaline substance and N-methylimidazole in an organic solvent to obtain a reaction mixed solution, reacting at 15-80 DEG C for 3-10 hours, performing post-treatment on the obtained reaction solution to obtain a dipeptide compound as shown in a formula III, and performing ester hydrolysis on the dipeptide compound as shown in the formula III to obtain the polypeptide. The preparation method comprises the following steps: dissolving a compound as shown in a formula I in an organic solvent to obtain a dipeptide compound only containing an Fmoc protecting group, dissolving the dipeptide compound only containing the Fmoc protecting group, a compound as shown in a formula II, pivaloic anhydride, an alkaline substance and N-methylimidazole in the organic solvent, reacting at 15-80 DEG C for 4-10 hours, and post-treating the obtained mixed solution to obtain the polypeptide. According to the invention, pivaloic anhydride is used as a condensing agent, the structure is simple, the reaction is safe, cheap and non-toxic, only a catalytic amount of N-methylimidazole is needed in the reaction, a large amount of nitrogen-containing by-products are not generated, and purification is easy; various amino acid side chains can be tolerated, and racemization isomerization cannot occur in the reaction; environment-friendly solvents such as ethyl acetate are used, and the reaction conditions are mild.

The invention discloses imidazopyridine derivatives and application thereof, a pharmaceutical composition and a pharmaceutical preparation, and belongs to the technical field of medical chemistry. The technical problems to be solved are that the existing P2X3 receptor inhibitor is poor in safety, low in P2X3 or P2X2 / 3 selectivity, poor in metabolic stability and the like. According to the key points of the technical scheme, the imidazopyridine derivative is selected from a compound as shown in a formula I or a racemate, a stereoisomer, a geometric isomer, a tautomer, a nitrogen oxide, a hydrate, an isotope label, a solvate, a polymorphic substance, a metabolite, an ester, a pharmaceutically acceptable salt or a prodrug thereof.

Compounds of formula (I) or their pharmaceutically acceptable salts, hydrates, solvates, esters or their optical isomers, racemates, diastereoisomers, enantiomers, tautomers, or a mixture thereof; said compounds exhibits anti-plasmidal activities, in particular for the treatment of malaria diseases.

The invention belongs to the field of chemistry and chemical engineering, and particularly relates to a novel method for synthesizing quizalofop-p-ethyl. The quizalofop-p-ethyl racemate reacts with a configuration conversion reagent, so that the quizalofop-p-ethyl racemate is efficiently converted into R-configuration quizalofop-p-ethyl. According to the method, the quizalofop-p-ethyl racemate is converted into quizalofop-p-ethyl with high optical purity under the action of the configuration conversion agent, the use of a high-optical-purity intermediate for synthesizing quizalofop-p-ethyl is avoided, so that the raw material cost can be greatly reduced, and meanwhile, for a quizalofop-p-ethyl product with insufficient optical purity, the yield of the quizalofop-p-ethyl is greatly improved. The optical purity can be improved by the method.

The invention discloses a method for synthesizing a five-membered lactam skeleton bulk drug with high optical purity under the catalysis of rhodium, which is characterized in that racemic and cheap gamma-substituted alpha, beta-unsaturated gamma-lactam is used as a raw material, a dicyclooctene hydroxyl rhodium (I) dimer is used as a catalyst, a cheap chiral phosphine ligand is used as a ligand, and the raw material is synthesized by a one-step method. The high enantioselectivity arylation reaction with arylboronic acid is realized. According to the method, the optical purity limit of a traditional route is successfully broken through, the specific rotation of the obtained trans-beta, gamma-disubstituted gamma-lactams with three single configurations is remarkably higher than the highest value in the literature, and a high-enantioselectivity key synthesis building block is provided for synthesis of a protein kinase C regulator, a glutamate receptor antagonist and CGN-10100. The method provided by the invention is simple and easy to operate, mild in reaction condition, high in yield and strong in derivation ability, and provides a new method for efficient and high-enantioselectivity preparation of chiral bulk drugs.

The invention provides a method for efficiently preparing various substituted chiral phosphoramides, which comprises the following steps: in the presence of an organic solvent, alkali, a chiral ligand and a catalyst, reacting a nucleoside compound or alcohol with racemic amino phosphoryl dichloride or alkoxy phosphoryl dichloride to generate chiral phosphoryl chloride; and reacting the chiral phosphoryl chloride with a nucleophilic reagent to obtain the chiral phosphamide. The synthesis method provided by the invention is simple to operate, high in yield and good in diastereoselectivity or enantioselectivity, and the obtained target compound has the characteristics of good functional group compatibility and wide substrate universality. The obtained product is diversified in structure and good in controllability, and has good application potential in the field of medicine synthesis.

The application relates to an asymmetric catalytic synthesis method and application of chiral azido tertiary alcohol and azulenic compound. The method is characterized in that under an air atmosphere, a racemic azido tertiary alcohol compound ((+ / -) I) and tri (4-methylphenyl) phosphorus (II) are reacted in toluene by taking chiral tartaric acid derivative phosphoric acid C1, a spirochiral phosphoric acid C2 or octahydroazulene phosphoric acid C3 as a chiral catalyst, the reaction is carried out at 30 DEG C for 17-72 hours, and target chiral azido tertiary alcohol compound (I) and chiral azulenic compound (III) are obtained through separation and purification. S I) and chiral azulenic compound (III) can be used for synthesizing chiral ligand IV, and deuterium water can be added in the reaction system to be used for synthesizing chiral deuterated azulenic compound (D-III).

The invention relates to processes for producing racemic (4R,4S)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridin-3-carboxamide of formula (I) from the enantiomers (Ia) or (Ib); a process for producing (4S)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridin-3-carboxamide of formula (Ia); a process for producing racemic (4R,4S)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridin-3-carboxamide of formula (I) from the pyridine of formula (II). The subjects of the invention have in common the irradiation of the compound of formulas (Ia), (Ib) and / or (II) with light in a suitable solvent, or solvent mixture, in the presence of a base. The compounds of formulas (Ia), (Ib) and / or (II) are intermediate products, by-products or target compounds in the synthesis of finerenone (compound according to formula (Ia)).