46 results about "Carbonyl reduction" patented technology

The invention provides a carbonyl reductase mutant and an application of the carbonyl reductase mutant in synthesis of S-glassine. The mutant protein is a non-natural protein, and the mutant protein can significantly improve the activity of catalyzing the reduction of carbonyl in 1-C-(beta-D-xylopyranosyl)-acetone to generate S-configuration alcohol. When the activity-improved carbonyl reductase mutant strain is applied to the production process of S-configuration glassine, the carbonyl reduction capacity of the S-configuration glassine can be improved, 100-240 g / L of substrate can be completely converted, and the S-configuration glassine is generated.

The invention discloses a synthetic method of an alfasalone intermediate and a synthetic method of alfasalone, the synthetic method of the alfasalone intermediate comprises the following steps: carrying out hydrogenation reaction on a compound IN-2 to obtain a compound I, the hydrogenation condition is that a solvent ethanol or acetic acid and palladium on carbon are added, and the addition volume of the ethanol or acetic acid is 10-80 times of the weight of the IN-2; the synthesis method of the alfasalone comprises the following steps: carrying out elimination reaction on a compound SM to obtain an intermediate IN-1; performing ketal protection reaction on the intermediate IN-1 to obtain an intermediate IN-2; carrying out hydrogenation reaction on the intermediate IN-2 to obtain a compound I; carrying out ketal removal protection reaction on the compound I to obtain an intermediate IN-3; the intermediate IN-3 is subjected to carbonyl reduction through an enzyme method to obtain alfasalone; by exploring the reaction raw materials, the reaction solvent, the solvent addition amount, the reaction time and the like in the synthesis process of the alfasalone, the obtained product is high in yield and purity, and the industrial production of the alfasalone is realized.

The invention belongs to the technical field of detergents, and particularly relates to a preparation method of a composite fluorescent whitening agent. The method comprises an acylation reaction, a sulfonation reaction, a carbonyl reduction reaction, a dehydration reaction and a sulfonic acid salification reaction. Compared with a commercially available fluorescent whitening agent such as CBS, the composite fluorescent whitening agent synthesized by the preparation method disclosed by the invention has similar application effects, but the preparation process disclosed by the invention is simple, low in cost, environment-friendly in route and environment-friendly in working environment.

The application discloses a method for preparing 6-hydroxy-8-chlorooctanoic acid ethyl ester by hydrogenation reduction of 6-carbonyl-8-chlorooctanoic acid ethyl ester. The carbonyl group of 6-carbonyl-8-chlorooctanoic acid ethyl ester is reduced to a hydroxyl group through a catalytic hydrogenation reduction reaction under high pressure, so that 6-hydroxy-8-chlorooctanoic acid ethyl ester is obtained. In the reaction process, strong acid, strong base and toxic substances are not involved, the catalyst used can be repeatedly used, the required equipment is not high, the process is simple, the obtained product has high purity and yield, and the method is favorable for large-scale production of enterprises, and provides a new preparation method which is simple and easy to realize, safe and stable, green and environmental protection, low in production cost and high in efficiency, and is suitable for the prior art and actual production.

The invention relates to a preparation method of a mianserin hydrochloride intermediate and a derivative thereof, belongs to the field of drug intermediates, and particularly relates to a method for reducing carbonyl in a core intermediate into hydroxyl so as to thoroughly solve the quality problem caused by a large number of isomer impurities generated in an original process route for preparing mianserin hydrochloride. According to the preparation process of the intermediate, the obtained product is high in purity, does not need to be further purified and is high in yield; the reaction conditions are mild, the reaction can be completed only at 40 DEG C or below, and the method is more suitable for large-scale industrial production.

The invention belongs to the technical field of medicine synthesis, and particularly relates to a synthesis method of a suzertraline impurity, the process route is shown as the following reaction formula: S1, a compound I is subjected to double bond reduction to obtain a compound II; s2, carrying out carbonyl reduction on the compound II to obtain a compound III; s3, esterifying the compound III to obtain a compound IV; s4, performing nucleophilic substitution on the compound IV to obtain a compound V; s5, hydrolyzing the compound V to obtain a compound VI; and S6, carrying out condensation reaction on the compound VI and the compound VII to obtain an isomer impurity VIII. The invention discloses a synthesis route of the suzertraline isomer impurity VIII for the first time, solves the problem that the impurity lacks a standard reference substance in drug quality control, and provides a necessary material basis for quality research and analysis method development and verification of suzertraline bulk drugs and preparations.

The invention discloses a process method for synthesizing trans-3-hydroxy cyclobutane formic acid, which comprises the following steps: by taking 3-oxo-cyclobutane formate as a raw material, reducing carbonyl by adopting aluminum triisopropoxide under the catalysis of tri (pentafluorophenyl) borane to generate a cis-trans isomer with trans as a main component, and reacting with a solvent to obtain trans-3-hydroxy cyclobutane formic acid. The preparation method comprises the following steps: preparing a 3-hydroxycyclobutane formic acid cis-trans mixture, hydrolyzing in alkali to obtain the 3-hydroxycyclobutane formic acid cis-trans mixture, salifying and purifying the 3-hydroxycyclobutane formic acid cis-trans mixture and an alpha-methylbenzylamine compound to obtain trans-3-hydroxycyclobutane formic acid amine salt, and dissociating to obtain the trans-3-hydroxycyclobutane formic acid. According to the method, the selectivity of a trans-product during carbonyl reduction is improved, cis-trans isomers are separated in a salifying manner, single trans-3-hydroxycyclobutanecarboxylic acid is purified, the process conditions are mild, the operation is simple and convenient, and the method is suitable for process production.

The invention discloses a synthetic method of a high-grade intermediate of didrogesterone. The synthetic route of the invention is as shown in the specification, and more specifically, a compound 1 (9-hydroxyandrostenedione) is used as an initial raw material, a strategy of aromatization and dearomatization is adopted, and the synthetic route of bromination, A-ring aromatization, silicon-based protection of phenolic hydroxyl, carbonyl reduction, sulfonylation or halogenation of hydroxyl, deprotection of phenolic hydroxyl and dearomatization cyclization is adopted, so that the compound 1 (9-hydroxyandrostenedione) is obtained. According to the present invention, the non-natural steroid skeleton of the type of the didrogesterone can be obtained from the cheap 9-hydroxyandrostenedione, the high-grade intermediate (compound 8) of the didrogesterone can be efficiently and massively synthesized, and the sufficient raw material is provided for the further synthesis of the didrogesterone or the analogue thereof. # imgabs0 #

The invention discloses a dapagliflozin intermediate synthesis method and application, and the dapagliflozin intermediate synthesis method comprises the following steps: heating 2-chloro-5-bromobenzoic acid, 1, 2-dichloroethane, bis (trichloromethyl) carbonate and a catalyst for reflux reaction, and cooling to obtain a 2-chloro-5-bromobenzoyl chloride solution; the preparation method comprises the following steps: mixing phenetole, 1, 2-dichloroethane and aluminum trichloride, stirring, and dropwise adding a 2-chloro-5-bromobenzoyl chloride solution to obtain 2-chloro-5-bromo-4 '-ethoxybenzophenone; and synthesizing the 4-bromine-2-chloro-2-(4-ethoxybenzyl) benzene. According to the method, the cheap BTC is used as an acylating chlorination reagent, so that the reagent cost is greatly reduced, the dosage of NaBH4 and AlCl3 in carbonyl reduction is reduced, the reagent cost and the amount of three wastes in the industry are further reduced, a foundation is laid for industrial production of the dapagliflozin intermediate, the yield is relatively high after each step of reaction, and the production cost of an enterprise is reduced.

The invention provides atomoxetine hydrochloride and a preparation method thereof, and relates to the technical field of medicinal chemistry and organic synthesis. The method provided by the invention comprises the following steps: adopting acetophenone, methylamine hydrochloride and a formaldehyde aqueous solution as raw materials, carrying out Mannich reaction to construct a beta-amino carbonyl skeleton, reducing carbonyl into hydroxyl by adopting sodium borohydride, then reacting with di-tert-butyl dicarbonate to form an amino protecting group, adopting o-methylphenol as a raw material, and preparing the beta-amino carbonyl skeleton. The method comprises the following steps: adding p-toluenesulfonic acid monohydrate and a (2-hydroxybenzyl) phosphine oxide catalyst to construct an ether bond through a Mitsunobu reaction, then removing a t-butyloxycarboryl protecting group, and carrying out chiral resolution and salinization reaction by using S-mandelic acid to obtain atomoxetine hydrochloride. The method of dropwise adding the formaldehyde aqueous solution in batches and controlling the reaction temperature is adopted, so that the generation of impurities can be reduced, and the yield is effectively improved; the p-toluenesulfonic acid monohydrate and the (2-hydroxybenzyl) phosphine oxide catalyst capable of participating in catalytic circulation are used for catalyzing the Mitsunobu reaction, the economic principle is met, and the purity and the yield of the product are greatly improved.

The invention discloses a carbonyl reductase mutant and application of the carbonyl reductase mutant in synthesis of a posaconazole intermediate. The mutant protein is a non-natural protein, and the mutant protein can significantly improve the activity of catalyzing reduction of carbonyl in (S)-2-benzyloxy-3-pentanone to generate R-configuration alcohol. When the carbonyl reductase mutant strain with improved activity is applied to the production process of a posaconazole intermediate, 100-200 g / L of a substrate can be completely converted, and (2S, 3R)-2-benzyloxy-3-pentanol is generated.

This invention relates to the field of compound preparation technology and discloses a method for the asymmetric synthesis of R-6,8-dichlorooctanoate by hydrogenation catalyzed by a composite catalyst. The method includes the following steps: S1. Activation of the alumina support; S2. Preparation of the composite catalyst; S3. High-pressure hydrogenation; S4. Chlorination. The activated alumina support and ruthenium-palladium mixed catalyst of this invention exhibit high selectivity (over 99%) and optical purity (over 98%) in the hydrogenation reduction of 6-carbonyl-8-chlorooctanoate to R-6-hydroxy-8-chlorooctanoate under suitable temperature and pressure. The activated alumina support and ruthenium-palladium mixed catalyst also demonstrate high inhibition of dechlorination and ester reduction during carbonyl reduction under suitable temperature and pressure. The high-pressure hydrogenation process provides a novel process route for the carbonyl reduction of compounds. The use of the same solvent in both high-pressure hydrogenation and chlorination reduces the difficulty of subsequent post-processing and makes the method more suitable for industrial production.

The invention provides a preparation method of an intermediate for synthesizing dextromethorphan, which is characterized by: taking 2-(2-oxocyclohexyl)acetonitrile as a raw material, undergoing a Robinson annulation reaction to generate a compound 2; undergoing an aromatization reaction to generate a compound 3; undergoing a ketocarbonyl reduction reaction to generate a compound 4; and undergoing a cyano reduction to generate an intermediate 5; the reaction process is as follows: The invention discloses a new intermediate 5 and a new preparation method thereof for the first time, avoiding low yield caused by splitting the intermediate, and not only improving the yield but also improving the purity.

This invention provides a method for preparing pyrrolidine derivatives, belonging to the field of organic synthesis. The method comprises the following steps: Step 1, reacting compound 1 in the presence of an alkaline ester hydrolysis reagent to obtain compound 2; Step 2, adding compound 2 to an aqueous solution of hydrogen bromide, followed by the addition of sodium nitrite to react and obtain compound 3; Step 3, reacting compound 3 in the presence of a dehalogenating reducing agent to obtain compound 4; Step 4, reacting compound 4 in the presence of a carbonyl reducing agent to obtain compound 5. The preparation method provided by this invention enables the industrial production of compound 5 and its derivatives.

The invention relates to the technical field of biology, in particular to a bose synthesis system and application thereof.In the presence of coenzyme NAD < + >, glucose dehydrogenase catalyzes glucose to generate gluconic acid, and NAD < + > is reduced into coenzyme NADH; in the presence of a coenzyme NADH (Nicotinamide Adenine Dinucleotide), the carbonyl reductase mutant performs carbonyl reduction catalysis on beta-acetone xyloside to generate a bose, the NADH is oxidized into NAD < + >, and the carbonyl reductase mutant generates mutation which is favorable for improving the reducibility of carbonyl in the beta-acetone xyloside at at least one key site in an amino acid sequence shown as SEQ ID NO: 40. Excellent carbonyl reduction catalytic activity is shown, so that the circulating speed of coenzymes NADH and NAD < + > is increased, and the synthesis efficiency of the bose is improved.

The invention provides a novel method for preparing an epinastine intermediate N-[2-(phenyl methyl) phenyl]-2-chloroacetamide. The method mainly comprises the following steps: by taking 2-aminobenzophenone as an initial raw material, firstly reducing and then acylating, and carrying out reduction reaction on carbonyl of 2-aminobenzophenone to methylene under the catalysis of RaneyNi by taking water as a proton source. The method has the advantages that RaneyNi is recycled and reused, the organic solvent can be recycled and reused, hydrogen and a hydrogenation kettle are not needed, introduction of a high-boiling-point solvent and a toxic reagent is avoided, and the method is easy and convenient to operate, mild in reaction condition, short in reaction time, low in cost, small in pollution, high in product yield and purity and suitable for industrial large-scale production.

The application belongs to the technical field of medicine synthesis, and particularly relates to a synthesis method of a key intermediate N-methyl-3-hydroxyphenylamine, which comprises the following steps: using N-methyl-N-trifluoroacetyl phenylamine as a starting material, esterifying the starting material with a carboxylic acid under the action of an oxidizing agent system, and further hydrolyzing the ester and trifluoroacetyl under alkaline conditions to obtain N-methyl-3-hydroxyphenylamine. Compared with the prior art, the scheme has the characteristics of high product yield, high purity, avoidance of the step of using a reducing agent for carbonyl reduction, and easy separation and purification of the reaction product, and is suitable for industrial production.

This invention relates to the field of asymmetric catalytic hydrogenation, specifically to a method for preparing chiral chromone or chromane carboxylic acid compounds. The method involves preparing a chiral catalyst from a nickel compound and ligands. By controlling the combination of the nickel compound-ligand-solvent, enantioselective hydrogenation of the conjugated C=C bonds of the substrate chromone carboxylic acid compound is achieved, yielding the semi-reduced product chiral chromone carboxylic acid; or, further, the carbonyl group is reduced, and carbonyl reduction and dehydroxylation reactions are carried out at room temperature under trifluoroacetic acid and triethylsilane conditions to obtain the fully reduced product chiral chromane carboxylic acid. The catalytic system of this invention is simple to construct, and the selectivity can be controlled by the solvent system. It maintains high conversion and excellent enantioselectivity even under high S / C conditions, making it suitable for the efficient preparation of chiral chromone / chromane skeletal carboxylic acid compounds.

The invention belongs to the field of coordination polymers, and particularly relates to a novel metal quinoline covalent organic framework and preparation thereof, and application of the novel metal quinoline covalent organic framework in photocatalytic alkenyl carbonyl reductive cross-coupling. The invention provides various metal quinoline covalent organic frameworks. Raw materials of the metal quinoline covalent organic frameworks comprise an amino monomer, an aldehyde group-containing organic monomer, pyruvic acid and transition metal salt. The metal quinoline covalent organic framework obtained by the invention has ultralong-life excitons exceeding 8000 picoseconds, and shows excellent performance of photocatalytic alkenyl carbonyl reduction cross coupling; the method has remarkable conversion efficiency and separation yield in a wide substrate range, the highest conversion efficiency is 99%, and the catalyst has recoverability.

The present invention provides an estetrol synthesis process, and relates to the technical field of steroid compound synthesis processes, and the method comprises the following steps: taking estrone as an initial raw material, firstly carrying out 3-site hydroxyl protection, and then carrying out an oxidative dehydrogenation reaction in the presence of a metal catalyst and in an oxygen atmosphere to prepare a key intermediate ketene, then 17-site carbonyl reduction, 17-site hydroxyl protection, 15, 16-site double bond dihydroxylation, 3-site protecting group removal and hydrolysis reaction are sequentially carried out, and finally the target product estetrol is obtained. The method adopts metal catalysis to directly oxidize to construct cycloenone, effectively avoids the problem of poor stability of partial intermediates in the prior art, has the advantages of simple process, short reaction steps, greenness, environmental protection and the like, and is suitable for industrial production.

The invention relates to the technical field of biology, in particular to a carbonyl reductase mutant and application. According to the carbonyl reductase mutant and application provided by the embodiment of the invention, the carbonyl reductase mutant generates mutation which is generated at at least one key site in an amino acid sequence as shown in SEQ ID NO: 40 and is beneficial to improving the reducibility of carbonyl in beta-acetone xyloside; through the mode, the carbonyl reductase mutant shows excellent carbonyl reduction catalytic activity, beta-acetone xyloside can be efficiently converted into (S)-glassine, and the synthesis efficiency of the (S)-glassine is improved.

The invention relates to the technical field of pharmaceutical chemicals, in particular to a preparation method of cholesterol. The method comprises the following steps: 3-position carbonyl ketal protection reaction: uniformly mixing BA, ethylene glycol, p-toluene phosphoric acid and triethyl orthoformate, controlling the temperature to be 40-60 DEG C, reacting for 2-8 hours, cooling to-10-10 DEG C, controlling the temperature to be 1-5 hours, filtering, and drying at 40-70 DEG C to obtain a compound IM1; oxidation of 21-site hydroxyl into aldehyde; s3, carrying out Grignard reaction on the 21-site aldehyde group; carrying out a reaction of oxidizing 21-site hydroxyl into ketone; carrying out a reaction of reducing 21-site carbonyl into methylene; carrying out 3-position carbonyl ester forming reaction; the method disclosed by the invention has the characteristics of good selectivity, low cost and small pollution, and the method is stable and easy to realize industrial production.

The invention relates to the technical field of synthesis of drug intermediates, in particular to a preparation method of a posaconazole starting material SM3. CeCl3. 7H2O and sodium borohydride are added into a compound POS-1 for an asymmetric reduction reaction to obtain a compound POS-2, the compound POS-2 reacts with 3, 5-bis (trifluoromethyl) benzene sulfonyl chloride to obtain a compound POS-3, hydrazine hydrate attacks from the back side of the compound POS-3 with large steric hindrance, an SN2 reaction is carried out to obtain a compound POS-4 with specific stereoselectivity, the compound POS-4 reacts with ethyl formate, and the compound POS-4 reacts with ethyl formate to obtain a compound POS-3 with specific stereoselectivity. And salifying with oxalic acid to obtain the initial raw material SM3 of the product posaconazole. According to the method, the chiral resolution step is effectively avoided in the modes of asymmetric carbonyl reduction and selective nucleophilic substitution, so that the content of isomer impurities is reduced, the prepared product is high in ee value, the yield is also remarkably improved, and the production cost is greatly reduced.

The invention provides a water-soluble ruthenium catalyst as well as a preparation method and application thereof. The water-soluble ruthenium catalyst disclosed by the invention has the advantages of good water solubility, high catalytic efficiency, high chemical stability and no toxicity; the water-soluble ruthenium catalyst can be used for reduction of carbonyl compounds and catalysis of reduction reaction of carbonyl in bufalin precursor molecules in water to generate bufalin molecules; the polymer ruthenium catalyst is synthesized through a reversible addition-fragmentation transfer polymerization method, and the synthesis method is simple and short in synthesis step.

A method for preparing a squalamine key intermediate of formula (I), wherein R is as defined in the description. In the method, 5α-chenodeoxycholic acid is used as a raw material, and is reacted with a Weinreb reagent to obtain a Weinreb amide; then, the Weinreb amide is sequentially subjected to an oxidation reaction, a ketalization reaction with ethylene glycol, and a nucleophilic reaction with an organometallic reagent, and is finally subjected to a reductase-catalyzed asymmetric carbonyl reduction reaction to obtain the compound of formula I. The method has the advantages of simple steps, high overall yield, high product purity, etc., and is suitable for industrial production.

The present application relates to the field of medicine preparation, in particular to a synthesis method of atipamezole hydrochloride. The method comprises the following steps: 4-cyanomethyl imidazole is subjected to acylation reaction, and a secondary amine group at position 1 of 4-cyanomethyl imidazole is subjected to acetyl protection to generate compound II; the compound II is subjected to two alkylations in sequence, and the cyanogen of the reaction product after the alkylation is hydrolyzed into a carboxyl group to generate compound III; under the catalysis of a Lewis acid, the compound III is subjected to intramolecular Friedel-Crafts acylation to generate compound IV; the carbonyl group of the compound IV is reduced into a methylene group to obtain a target product compound V; the method has the advantages of short synthesis route, mild reaction condition, low equipment requirement, convenient operation, high yield of reaction product, high yield of product obtained without complex purification method, and the like, and is easy to realize large-scale industrial production.

The invention belongs to the technical field of pharmaceutical chemicals, and relates to a synthesis method of a clomastine intermediate. Comprising the following steps: taking N-methyl pyrrolidone and vinyl acetate as raw materials, and obtaining N-methyl-2-(2-ethoxyl) pyrrolidine according to the following reaction route; wherein the intermediate 1, sodium borohydride and boron trifluoride diethyl etherate are subjected to heating reflux in a solvent, and a reduction reaction is performed to obtain an intermediate 2. According to the synthesis method provided by the invention, the yield and the purity of carbonyl reduction products of amide can be improved at the same time, the dosage of a reducing agent can be reduced, and the cost of the clomastine intermediate can be reduced.

The application discloses a synthetic method of plant-derived deoxycholic acid, which comprises the following steps: taking plant-derived 9-OH-BA as raw material, and synthesizing the deoxycholic acid through side chain oxidation reaction, Wittig or Wittig-Horner reaction, dehydration reaction, hydrogenation reduction reaction, esterification reaction, C ring oxidation reaction, carbonyl reduction reaction and hydrolysis reaction. In view of the safety problem existing in the preparation of traditional animal-derived deoxycholic acid, the deoxycholic acid is synthesized by using plant-derived 9-OH-BA, so that the risk of pathogenic bacteria and virus infection is avoided, the safety of clinical use is improved, the synthetic yield is high, the environment is friendly, and the method is suitable for industrialized production and application.

To provide a simple method for synthesizing a tetrabenzochrysene derivative without using a cross-coupling method using heavy metals, and to provide a novel tetrabenzochrysene derivative.SOLUTION: There is provided a method for synthesizing a tetrabenzochrysene derivative, including the steps of: (a) dimerizing a benzofluorenone derivative to produce a spiroketone derivative; (b) reducing the carbonyl group of the obtained spiroketone derivative to produce a spiroalcohol derivative having a hydroxyl group; and (c) dehydrating the obtained spiroalcohol derivative to obtain the tetrabenzochrysene derivative.SELECTED DRAWING: None

The invention relates to the technical field of biology, in particular to an isopropanol system for synthesis of glassine and application thereof.In the presence of coenzyme NAD < + >, isopropanol dehydrogenase catalyzes isopropanol to generate acetone, and NAD < + > is reduced into coenzyme NADH; in the presence of a coenzyme NADH (Nicotinamide Adenine Dinucleotide), the carbonyl reductase mutant performs carbonyl reduction catalysis on beta-acetone xyloside to generate a bose, the NADH is oxidized into NAD < + >, and the carbonyl reductase mutant generates mutation which is favorable for improving the reducibility of carbonyl in the beta-acetone xyloside at at least one key site in an amino acid sequence shown as SEQ ID NO: 40. Excellent carbonyl reduction catalytic activity is shown, so that the circulating speed of coenzymes NADH and NAD < + > is increased, and the synthesis efficiency of (S)-glassine is improved.