23 results about "Carbonyl reduction" patented technology

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 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 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.

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 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 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.

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 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.

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.

The invention discloses an organic photocatalyst based on an isothiatruxene skeleton as well as a preparation method and application of the organic photocatalyst. The preparation method of the organic photocatalyst comprises the following steps: by taking substituted or unsubstituted benzothiophene as a raw material, adding dichloro dicyanobenzoquinone, dropwise adding trifluoromethanesulfonic acid, and stirring at room temperature for 3-12 hours, or by taking substituted or unsubstituted benzothiophene and ninhydrin as raw materials, adding acetic acid and concentrated sulfuric acid, and reacting at 90 DEG C for 3-12 hours, thereby obtaining the photocatalyst based on the isothiatruxene skeleton. And adding hydrogen peroxide or m-chloroperoxybenzoic acid into the catalyst, and reacting at room temperature for 6-48 hours to obtain the photocatalyst based on the sulfoxide impurity or sulfone impurity isotruxene skeleton. The organic photocatalyst can catalyze a plurality of photooxidation reduction reactions under visible light, including carbonyl reductive coupling, alkyne oxidation, decarboxylation fluorination, toluene oxidation, amino heteroarylation of non-activated olefin, arone reductive deoxidation, styrene hydroformylation, styrene alkoxy acylation and aryl halide dehalogenation hydrogenation.

This application discloses a method for synthesizing 2,6-difluorostyrene, belonging to the field of organic chemical synthesis technology, including the following steps: (1) 2,6-dichlorobenzonitrile undergoes a halogen exchange fluorination reaction with a fluorinating agent in a polar aprotic solvent to obtain 2,6-difluorobenzonitrile; (2) the obtained 2,6-difluorobenzonitrile undergoes an addition reaction with methyl magnesium halide in an inert solvent, followed by hydrolysis to obtain 2,6-difluoroacetophenone; (3) the obtained 2,6-difluoroacetophenone undergoes a carbonyl reduction reaction in a solvent to obtain 1-(2,6-difluorophenyl)ethanol; (4) the obtained 1-(2,6-difluorophenyl)ethanol undergoes a dehydration reaction in an alkane solvent under protic acid catalysis to obtain 2,6-difluorostyrene. This synthesis method has the advantages of inexpensive and readily available raw materials, good atom economy, simple reaction operation, high synthesis yield, and good product purity, making it suitable for industrial application.

The invention belongs to the technical field of organic chemical synthesis, and particularly relates to an N-N axial chiral monophosphine ligand as well as a preparation method and application thereof. The structure of the N-N axial chiral monophosphine ligand is shown as a formula I and a formula II, wherein in the formula I and the formula II, Ar is aryl, substituted aryl or heteroaryl; r < 1 >-R < 3 > are respectively and independently selected from hydrogen, aryl, substituted aryl, heteroaryl, alkyl, alkylene and halogen. The N-N axial chiral monophosphine ligand is constructed by taking a phosphine-containing indole derivative and acrylate as raw materials under the action of an iridium catalyst and a chiral ligand. The ligand can be used for carbonyl reduction reaction catalyzed by rhodium and coupling reaction catalyzed by palladium, and shows excellent enantioselectivity; the conjugated structure of indole and pyrrole is combined with the electronic characteristics of phosphine groups, so that the compound is expected to be applied to the development of organic photoelectric materials and bioactive molecules. The method provides a wide space for developing a novel efficient chiral catalyst, and has a very good application prospect.

This invention relates to the field of artificial bear bile powder preparation technology, specifically to a novel 7α-hydroxysteroid dehydrogenase gene R-α-1 and its application in the production and conversion of bear bile powder. This method isolates a novel gene catalyzing asymmetric carbonyl reduction reactions from the feces of Sichuan brown bears. This gene encodes a 7α-hydroxysteroid dehydrogenase, which catalyzes the formation of the intermediate tauroursodeoxycholic acid from tauroursodeoxycholic acid, which is further catalyzed by a 7β-hydroxysteroid dehydrogenase to produce tauroursodeoxycholic acid, the main component of bear bile powder. The nucleotide sequence of this gene is shown in SEQ ID NO.1, and its encoded amino acid sequence is shown in SEQ ID NO.2. This technical solution can solve the technical problem that existing types of 7α-hydroxysteroid dehydrogenases cannot meet the needs of large-scale production due to unsatisfactory enzyme activity and thermostability, and has ideal prospects for widespread application.

The invention provides a synthesis method of evocamide, and belongs to the technical field of medicines. The preparation method comprises the following steps: S1, carrying out dehydration condensation on D-malic acid, and then carrying out amidation and dehydration cyclization on D-malic acid and aryl p-aminophenylacetate to obtain an intermediate 1; s2, carrying out carbonyl reduction on an amido bond of the intermediate 1 to obtain an intermediate 2; s3, removing acetyl from the intermediate 2 to obtain an intermediate 3; s4, reacting the intermediate 3 with p-nitrobenzenesulfonyl chloride or o-nitrobenzenesulfonyl chloride to obtain an intermediate 4, substituting the intermediate 4 with (R)-1-(1-naphthyl) ethylamine, and salifying with hydrogen chloride to obtain an intermediate 5; and S5, hydrolyzing the intermediate 5 to obtain the ivacalcet. The starting material is low in price, so that the production cost is greatly reduced; the route is simple, and the synthesis method which is simpler and more convenient and higher in yield is provided; the preparation of the intermediate 5 does not need the participation of a palladium catalyst, so that the target product has no heavy metal residue, and the safety of the medicine is improved.

According to the chlorine-containing fluorescein synthesis method, 2-chloro-1, 3-benzenediol serves as a starting raw material, a fluorescein key intermediate compound III is obtained through Friedel-Crafts acylation and carbonyl reduction, the synthesis step is shortened to two steps from original five steps, the starting raw material is lower in price, use of a noble metal catalyst is saved, high-temperature reaction is avoided, and the method is suitable for industrial production. The method is safer and easier to amplify.

The invention belongs to the technical field of medicine synthesis, and discloses a chemical-enzyme method for synthesizing 7alpha, 24R-dihydroxy-5alpha-cholestane-3-ketone, which comprises the following steps: (1) activating 5alpha-chenodeoxycholic acid by a carboxylic acid activator under an alkaline condition, and reacting with potassium monomethyl malonate in the presence of anhydrous magnesium chloride to obtain beta-ketoester A1; (2) enabling the A1 to react with methyl iodide under an alkaline condition, so as to obtain 3alpha, 7alpha-dyhydroxyl-5alpha-cholestane-24-ketone A2; (3) adding an oxidizing agent into the A2, and oxidizing to obtain 7 alpha-hydroxy-5alpha-cholestane-3, 24-diketone A3; and (4) on the basis of an NADPH regeneration reduction system, catalyzing A3 by adopting ketoreductase to carry out selective asymmetric carbonyl reduction reaction, so as to obtain 7alpha, 24R-dihydroxy-5alpha-cholestane-3-ketone A4. The method is simple in process, mild in reaction condition, low in production cost and suitable for large-scale production.

The invention provides an asymmetric synthesis method of (R)-glabridin, which comprises the following steps: synthesizing 5-hydroxy-6-hydroxymethyl-2, 2-dimethylchroman-4-ketone by using 2, 6-dihydroxyacetophenone as a raw material, then carrying out nuclear substitution reaction, Wittig reaction, asymmetric hydrogenation reaction, protecting group removal and carbonyl reduction reaction, and finally dehydrating under an acidic condition to obtain the (R)-glabridin. The chiral center is constructed by a method of catalyzing asymmetric hydrogenation through a chiral metal catalyst, the addition amount is as low as 0.5 mol%, the reaction selectivity is good (eegt, 98%), the conversion rate is high (the yield gt, 89%), and the problem of low construction efficiency of the chiral center in asymmetric synthesis of glabridin is solved. The asymmetric synthesis route of (R)-glabridin provided by the invention is novel and efficient, the reaction conditions are mild, and technical support is provided for industrial large-scale production.

The invention discloses a silicon-supported solid catalyst and a method for preparing a bose by using the silicon-supported solid catalyst, and the silicon-supported solid catalyst is prepared by the following steps: adding dialkyldialkoxysilane, (S, S)-N-(p-toluenesulfonyl)-1, 2-diphenylethane diamine (p-isopropyl benzene) ruthenium chloride (II) and a proper amount of reaction solvent into a reaction container, stirring and dissolving, adding a catalyst, stirring, and reacting for 2-3 hours at the temperature of 50-60 DEG C to obtain the silicon-supported solid catalyst. And adding calcium hydroxide, carrying out nitrogen displacement, heating to 60-120 DEG C, carrying out a reaction for 2-5 h, carrying out reduced pressure distillation to dryness and low boiling to obtain a catalyst solid, and finely grinding the catalyst solid to obtain silicon-loaded solid catalyst powder. The silicon-loaded solid catalyst provided by the invention can be used for synthesizing the glassine, and the catalyst can be used as a catalyst for a condensation step and also can be used as a catalyst for a carbonyl reduction step, so that the high-purity (S)-glassine is finally obtained.