CN103626821B - The synthetic method of 25-HYDROXY CHOLESTEROL - Google Patents

The synthetic method of 25-HYDROXY CHOLESTEROL Download PDF

Info

Publication number
CN103626821B
CN103626821B CN201310548840.7A CN201310548840A CN103626821B CN 103626821 B CN103626821 B CN 103626821B CN 201310548840 A CN201310548840 A CN 201310548840A CN 103626821 B CN103626821 B CN 103626821B
Authority
CN
China
Prior art keywords
reaction
desmesterol
epoxidation
hydroxy cholesterol
product
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN201310548840.7A
Other languages
Chinese (zh)
Other versions
CN103626821A (en
Inventor
陈新志
赵倩
计立
钱国平
刘建刚
王子强
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
ZHEJIANG GARDEN BIOCHEMICAL HIGH-TECH CO LTD
Zhejiang University ZJU
Original Assignee
ZHEJIANG GARDEN BIOCHEMICAL HIGH-TECH CO LTD
Zhejiang University ZJU
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by ZHEJIANG GARDEN BIOCHEMICAL HIGH-TECH CO LTD, Zhejiang University ZJU filed Critical ZHEJIANG GARDEN BIOCHEMICAL HIGH-TECH CO LTD
Priority to CN201310548840.7A priority Critical patent/CN103626821B/en
Publication of CN103626821A publication Critical patent/CN103626821A/en
Application granted granted Critical
Publication of CN103626821B publication Critical patent/CN103626821B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Landscapes

  • Steroid Compounds (AREA)

Abstract

The invention discloses a kind of synthetic method of 25-HYDROXY CHOLESTEROL, comprise the steps: 1), the 3-hydroxyl of desmesterol is protected; Obtain acidylate desmesterol; 2) double bond, by step 1) obtained on product 24 carries out epoxidation reaction: in solvent II, under the katalysis of manganese salt, and acidylate desmesterol and epoxidation reagent carry out epoxidation reaction, obtain epoxidation product; 3) by step 2) obtained product carries out reductive ring open: in solvent III, step 2) epoxidation product of gained with go back original reagent and carry out reduction ring-opening reaction, obtain 25-HYDROXY CHOLESTEROL.The synthetic method of 25-HYDROXY CHOLESTEROL of the present invention, uses nontoxic and cheap Peracetic Acid, metachloroperbenzoic acid as epoxidation reagent, environmental friendliness; Reaction is carried out at low temperatures, and adopt manganese salt as catalyzer, selectivity is high.

Description

The synthetic method of 25-HYDROXY CHOLESTEROL
Technical field
The present invention relates to a kind of method of being synthesized 25-HYDROXY CHOLESTEROL by desmesterol, particularly a kind of method of synthesizing 25-HYDROXY CHOLESTEROL based on epoxidation and reduction ring-opening reaction.
Background technology
Vitamins D 3referring to the sterols material of a class to Ca,P metabolism and children's bone growth important, is the key agents for the treatment of rickets, richets and hypothyroidism clinically.At present, people pass through various vitamins D 3the research of meta-bolites, not only further illustrates vitamins D 3binding mode, also enriched vitamins D 3the intension of chemistry.As vitamins D 3one of meta-bolites, 1,25-(OH) 2d 3biological activity intensity be vitamins D 310000 times.But due to vitamins D 3various meta-bolitess content extremely pettiness in vivo, separation and purification is very difficult, therefore, in order to study their physiological action, these vitamins Ds of chemosynthesis of having to 3meta-bolites.Wherein, as vitamins D 3the 25-HYDROXY CHOLESTEROL of meta-bolites precursor, its synthesis seems particularly important.
The structural formula of 25-HYDROXY CHOLESTEROL is as shown in following formula I:
In the synthetic method of current bibliographical information, comprise following 2 classes:
1), hydroxyl mercury method synthesis 25-HYDROXY CHOLESTEROL (C.R.Chimie, 6,79-82,2003.).The method, using desmesterol as raw material, adopts mercuric acetate and water to carry out oxymercuration reaction, and the temperature of reaction of oxymercuration reaction is room temperature, and yield is 85%, and hydroxyl mercury method relates to heavy metal Hg, there is toxicity, pollutes large.
2), the method for epoxidation open loop is again adopted to react.The method using desmesterol as starting raw material, metachloroperbenzoic acid as epoxidation reagent, chloroform as the condition of solvent under carry out epoxidation reaction.Lithium Aluminium Hydride is utilized to carry out open loop (Chem.Pharm.Bull.21 (2), 457-458,1973.) after epoxidation reaction terminates.Epoxidation reaction temperature is about 0 DEG C, and ultimate yield is 50%, and epoxidation step yield is 60%.The major defect of the method is: selectivity is poor, and yield is relatively low.
So, need a rational alternative route at present badly to carry out the production of 25-HYDROXY CHOLESTEROL.
Summary of the invention
The technical problem to be solved in the present invention is to provide that a kind of reaction conditions is gentleer, and selectivity is higher, simple to operate, the synthetic method of eco-friendly 25-HYDROXY CHOLESTEROL.
In order to solve the problems of the technologies described above, the invention provides a kind of synthetic method of 25-HYDROXY CHOLESTEROL, comprising the steps:
1) hydroxyl of compound 3-shown in formula II is protected:
In solvent I and acid binding agent, under the katalysis of DMAP (DMAP), desmesterol and carboxylic acid anhydride or acyl chlorides at the 10 DEG C ~ temperature that refluxes (being such as 10 ~ 40 DEG C) react 10 ~ 24h; The mol ratio of described desmesterol and carboxylic acid anhydride or acyl chlorides is 1:1.2 ~ 2; DMAP (DMAP) is 0.005 ~ 0.05:1 with the mass ratio of desmesterol consumption; The mol ratio of the consumption of acid binding agent and desmesterol is 1.8 ~ 10:1;
The reaction solution of gained, through aftertreatment, obtains acidylate desmesterol;
The structural formula of described desmesterol is as shown in following formula II:
Formula II
2), double bond step 1) obtained on product 24 carries out epoxidation reaction:
In solvent II, under the katalysis of manganese salt, acidylate desmesterol and epoxidation reagent carry out epoxidation reaction, and temperature of reaction is-20 ~-1 DEG C, and the reaction times is 1 ~ 3h; The mol ratio of described acidylate desmesterol and epoxidation reagent is that 1:1 ~ 4(is preferably 1:1 ~ 3), described manganese salt is that 0.01 ~ 0.1(of acidylate desmesterol molar weight is preferably 0.05 ~ 0.1);
The reaction solution of gained successively after filtration, dilution, extraction, dry after the extraction liquid washing of gained, then the rotary evaporation that reduces pressure (object is to remove extraction agents useful for same), obtain oily matter; Described oily matter carries out pillar layer separation, obtains epoxidation product;
3) by step 2) obtained product carries out reductive ring open:
In solvent III, step 2) gained epoxidation product with go back original reagent and carry out reduction ring-opening reaction, temperature of reaction is 20 ~ 70 DEG C, and the reaction times is 3 ~ 8h; Described mol ratio of going back original reagent and epoxidation product is 2 ~ 6:1;
Utilize shrend to go out after the reaction solution of gained is cooled to room temperature and excessively in reaction solution go back original reagent, then successively through pickling and extraction; Dry after the extraction liquid washing of gained, then the rotary evaporation that reduces pressure (object is to remove extraction agents useful for same), obtain 25-HYDROXY CHOLESTEROL crude product, described 25-HYDROXY CHOLESTEROL crude product, through recrystallization, obtains 25-HYDROXY CHOLESTEROL;
The structural formula of described 25-HYDROXY CHOLESTEROL is as shown in following formula I:
Formula I
Improvement as the synthetic method of 25-HYDROXY CHOLESTEROL of the present invention: in step 1):
Acid binding agent is triethylamine, diethylamine, quadrol, ammonia, pyridine or piperidines;
Carboxylic acid anhydride is diacetyl oxide (aceticanhydride), propionic anhydride, butyryl oxide, valeric anhydride, benzoyl oxide, Succinic anhydried or Tetra hydro Phthalic anhydride;
Acyl chlorides is Acetyl Chloride 98Min., propionyl chloride, butyryl chloride or Benzoyl chloride.
Further improvement as the synthetic method of 25-HYDROXY CHOLESTEROL of the present invention: step 2) in: epoxidation reagent to be mass concentration be 6% ~ 40% Peracetic Acid or mass concentration be the metachloroperbenzoic acid of 56%-80%.
Further improvement as the synthetic method of 25-HYDROXY CHOLESTEROL of the present invention: step 2) in: manganese salt is manganous sulfate, Manganous chloride tetrahydrate, manganous nitrate, manganese acetate or manganous carbonate.
Further improvement as the synthetic method of 25-HYDROXY CHOLESTEROL of the present invention: in step 3): going back original reagent is Lithium Aluminium Hydride.
Further improvement as the synthetic method of 25-HYDROXY CHOLESTEROL of the present invention: step 2) in: the manganese acetate of acidylate desmesterol adapted 0.05mmol, the metachloroperbenzoic acid 1.1mmol of mass concentration 80% of every 1mmol; Temperature of reaction is-10 DEG C, and the reaction times is 1h ~ 1.5h.
In the present invention,
In step 1), solvent I can select pyridine, methylene dichloride, tetrahydrofuran (THF), toluene etc.; Generally, the solvent I of the desmesterol adapted 100 ~ 200ml of every 0.052mol.
When selecting pyridine, tetrahydrofuran (THF) as solvent I; aftertreatment is: by the reaction solution of gained successively through washing, pickling (dilute hydrochloric acid of 5%) extracts afterwards, and described extraction liquid alkali cleaning (utilizing saturated sodium bicarbonate solution to wash) is to neutral; drying, obtains acidylate desmesterol.
When selecting methylene dichloride, toluene as solvent I; aftertreatment is: by the reaction solution of gained successively after pickling (dilute hydrochloric acid of 5%), alkali cleaning (saturated sodium bicarbonate solution), salt wash (saturated nacl aqueous solution); drying, obtains acetylize desmesterol.
Step 2) in solvent II used can select methylene dichloride, trichloromethane, benzene, acetone, dioxan etc.; Generally, the solvent II of the acidylate desmesterol adapted 10 ~ 50ml of every 1mmol.
Solvent III used in step 1) can select tetrahydrofuran (THF), anhydrous diethyl ether, diethylene glycol dimethyl ether etc.; Generally, the solvent III of the epoxidation product adapted 10 ~ 50ml of every 1mmol.
Room temperature refers generally to 10 ~ 25 DEG C.
In the present invention:
Step 1) is: utilize carboxylic acid anhydride or acyl chlorides to protect the hydroxyl on desmesterol 3.
Step 2) be: by obtained for step 1), product---the double bond on 24 of acidylate desmesterol carries out epoxidation reaction under manganese salt is as the condition of catalyzer to utilize epoxidation reagent.
The synthetic method of 25-HYDROXY CHOLESTEROL of the present invention, uses nontoxic and cheap Peracetic Acid, metachloroperbenzoic acid as epoxidation reagent, environmental friendliness; Reaction is carried out at low temperatures, and adopt manganese salt as catalyzer, selectivity is high.Adopt the inventive method to prepare 25-HYDROXY CHOLESTEROL, there is simple, the eco-friendly feature of technique.
The synthetic method of 25-HYDROXY CHOLESTEROL of the present invention, the method 2 relative to informing in background technology) for, select manganese salt as catalyzer, reduced temperature of reaction, improve the selectivity of this step reaction, thus further increase the yield of the finished product.
Embodiment
The synthetic method of embodiment 1, a kind of 25-HYDROXY CHOLESTEROL, carry out following steps successively:
1) using 120mL pyridine as solvent, using 30mL pyridine (about 0.372mol)), as acid binding agent, add the desmesterol (about 0.052mol) of 20g, the DMAP of 0.2g, drip 10g(under room temperature and be about 0.097mmol) aceticanhydride (dripping off for about 30 minutes).Reaction process utilizes TLC to monitor, and drip after terminating under room temperature, continue reaction 10h, reaction terminates.
Reaction solution washing (consumption of water is 50ml × 2); pickling (utilize volumetric concentration be 5% dilute hydrochloric acid solution; consumption is 50ml × 2) after; methylene dichloride (consumption is 30ml × 3) is utilized to extract; extraction liquid utilizes saturated sodium bicarbonate solution to be washed till neutrality, de-dry solvent (that is, methylene dichloride) after anhydrous sodium sulphate (about 5g) is dry; obtain acetylize desmesterol 19.1g, yield is 90.0%.
Yield=actual theoretical amount obtaining quality product/product.
2) with 30mL methylene dichloride for solvent, add 0.4226g(and be about 1mmol) acetylize desmesterol and 6.2mg(0.05mmol) Manganous chloride tetrahydrate; 38%(mass concentration) Peracetic Acid 0.4g(2mmol) be dissolved in 10mL methylene dichloride after, be slowly added dropwise in reaction flask at-10 DEG C, the time length is 30min, and reaction process utilizes TLC to monitor, react 2h at-10 DEG C after, terminate reaction.
Remarks illustrate: Peracetic Acid being dissolved in methylene dichloride is dilution in order to carry out to a certain degree, prevents a large amount of heat releases caused in reaction process from temperature of reaction is ascended to heaven, and ensure the carrying out that reaction is milder.
The reacting liquid filtering of gained, filtrate is diluted with 50mL water, add methylene dichloride (30ml × 3) extraction, gained extraction liquid uses saturated sodium bisulfite solution (30ml × 2), saturated sodium bicarbonate solution (30ml × 2), saturated nacl aqueous solution (30ml) to wash rear anhydrous sodium sulphate (5g) drying successively, and decompression (0.1MPa) rotary evaporation is except desolventizing (that is, methylene dichloride), obtain oily matter, this oily matter carries out pillar layer separation, obtains 0.24g epoxidation product, yield 54%.
The particular content of pillar layer separation is: adopt internal diameter to be the glass column of 2cm, 200-300 object silica gel wet method dress post, dry method loading, adopt n-hexane/ethyl acetate=8:1(volume ratio) eluent carry out wash-out, elutriant adopts TLC to detect, and now collects for during epoxidation solid pure product in elutriant when detecting, through decompression (0.1MPa) rotary evaporation, desolventizing is removed to the effluent liquid collected, epoxidation solid (that is, epoxidation product) 0.24g can be obtained, yield 54%.
3) with 30mL tetrahydrofuran (THF) for solvent, add 0.44g(and be about 1mmol) epoxidation product, slowly add 0.15g(4mmol under room temperature) after Lithium Aluminium Hydride (within about 10 minutes, adding) be warming up to 70 DEG C, reaction process utilizes TLC to monitor, stopped reaction after 70 DEG C of reaction 4h.
Reaction solution utilizes water (about 100ml) cancellation excessive Lithium Aluminium Hydride after being cooled to room temperature, reaction solution pickling (utilize concentration be 5% dilute hydrochloric acid solution, consumption is 50ml × 2), methylene dichloride (30ml × 3) extracts, extraction liquid utilizes saturated sodium bicarbonate solution (30ml × 2) successively, saturated nacl aqueous solution (30ml) the rear anhydrous sodium sulphate of washing (about 5g) is dry, (namely decompression (0.1MPa) rotary evaporation removes desolventizing, methylene dichloride), obtain 25-HYDROXY CHOLESTEROL crude product 0.39g, crude product utilizes toluene (10ml) recrystallization, obtain the finished product 25-HYDROXY CHOLESTEROL 0.33g, yield 88%.
The synthetic method of embodiment 2, a kind of 25-HYDROXY CHOLESTEROL,
In this embodiment 2, step 1), 2) different from embodiment 1, difference is:
1), using 100mL methylene dichloride as solvent, the desmesterol (about 0.052mol), 0.2gDMAP, the 10.1g(that add 20g are about 0.1mmol) triethylamine, drip 10g(under room temperature and be about 0.097mmol) aceticanhydride.Reaction process utilizes TLC to monitor, and drip under continuing at room temperature after terminating and react 10h, reaction terminates.
Reaction solution uses dilute hydrochloric acid successively, and (volumetric concentration is 5%; consumption 50ml × 2), saturated sodium bicarbonate solution (30ml × 2), saturated nacl aqueous solution (30ml) washing rear anhydrous sodium sulphate (about 5g) drying; decompression (0.1MPa) rotary evaporation is except desolventizing (i.e. methylene dichloride); obtain acetylize desmesterol 19.0g, yield is 90.0%.
2), 6% Peracetic Acid 3.8g(3mmol is utilized) as " the 38%(mass concentration) Peracetic Acid 0.4g(2mmol) " in epoxidation reagent alternate embodiment 1, temperature of reaction makes-1 DEG C into by-10 DEG C.
All the other are equal to the step 2 of embodiment 1).Obtain 0.15g epoxidation product, yield: 32.8%.
The synthetic method of embodiment 3, a kind of 25-HYDROXY CHOLESTEROL,
In this embodiment 3, step 1), 2) different from embodiment 1, difference is:
1) using 100mL methylene dichloride as solvent, add the desmesterol (about 0.052mol) of 20g, the DMAP of 0.2g, 10.1g(is about 0.1mmol) triethylamine, drip 14.1g(under room temperature and be about 0.1mol) Benzoyl chloride, be warming up to backflow after dropping terminates, after reaction 24h, terminate reaction.
All the other are equal to the step 1) of embodiment 2 substantially, obtain benzoylated desmesterol 23.2g, and yield is 95.0%.
2) 40% Peracetic Acid 0.4g(2mmol is utilized) as " the 38%(mass concentration) Peracetic Acid 0.4g(2mmol) " in epoxidation reagent alternate embodiment 1, temperature of reaction makes-20 DEG C into by-10 DEG C.
All the other are equal to the step 2 of embodiment 1 substantially); Obtain 0.27g epoxidation product, yield: 62%.
The synthetic method of embodiment 4, a kind of 25-HYDROXY CHOLESTEROL,
In this embodiment 4, step 2) different from embodiment 1, difference is:
2) with 30mL methylene dichloride for solvent; add 0.4226g(and be about 1mmol) acetylize desmesterol; 8.65mg(0.05mmol) manganese acetate; 80%(is mass concentration) metachloroperbenzoic acid 0.24g(1.1mmol) be dissolved in 10mL methylene dichloride; slowly be added dropwise in reaction flask at-10 DEG C, the time length is 30min, and reaction process utilizes TLC to monitor; after reacting 1h at-10 DEG C, terminate reaction.
All the other are equal to the step 2 of embodiment 1 substantially); Obtain 0.33g epoxidation product, yield 75%.
Comparative example 1-1, to make the following changes relative to embodiment 4:
In step 2) in, temperature of reaction is risen to 20 DEG C by-10 DEG C, and all the other are equal to the step 2 of embodiment 4); Can obtain epoxidation solid 0.13g, yield is only 30%.
Comparative example 1-2, to make the following changes relative to embodiment 4:
In step 2) in, by the amount of metachloroperbenzoic acid (80% mass concentration) from 0.24g(1.1mmol) become 0.32g(1.5mmol), all the other are equal to the step 2 of embodiment 4); Can obtain epoxidation solid 0.17g, yield is only 39%.
Comparative example 2-1, to make the following changes relative to embodiment 4:
In step 2) in, cancel and use manganese acetate as catalyzer (namely not adopting any catalyzer), all the other are equal to the step 2 of embodiment 4); Can obtain epoxidation solid 0.26g, yield is 59.1%.
Comparative example 2-2, to make the following changes relative to embodiment 4:
In step 2) in, adopt the hydrogen peroxide 1.1g(10.0mmol of 30% mass concentration) as " the 80%(mass concentration) metachloroperbenzoic acid 0.24g(1.1mmol) " in epoxidation reagent alternate embodiment 4, all the other are equal to the step 2 of embodiment 4); Can obtain epoxidation solid 0.1g, yield is 23.2%.
Finally, it is also to be noted that what enumerate above is only several specific embodiments of the present invention.Obviously, the invention is not restricted to above embodiment, many distortion can also be had.All distortion that those of ordinary skill in the art can directly derive from content disclosed by the invention or associate, all should think protection scope of the present invention.

Claims (4)

  1. The synthetic method of 1.25-hydroxycholesterol, is characterized in that comprising the steps:
    1) hydroxyl of compound 3-shown in formula II is protected:
    In solvent I and acid binding agent, under the katalysis of DMAP, desmesterol and carboxylic acid anhydride or acyl chlorides react 10 ~ 24h at the 10 DEG C ~ temperature that refluxes; The mol ratio of described desmesterol and carboxylic acid anhydride or acyl chlorides is 1:1.2 ~ 2; The mass ratio of DMAP and desmesterol consumption is 0.005 ~ 0.05:1; The mol ratio of the consumption of acid binding agent and desmesterol is 1.8 ~ 10:1;
    The reaction solution of gained, through aftertreatment, obtains acidylate desmesterol;
    The structural formula of described desmesterol is as shown in following formula II:
    Acid binding agent is triethylamine, diethylamine, quadrol, ammonia, pyridine or piperidines;
    Carboxylic acid anhydride is diacetyl oxide, propionic anhydride, butyryl oxide, valeric anhydride, benzoyl oxide, Succinic anhydried or Tetra hydro Phthalic anhydride;
    Acyl chlorides is Acetyl Chloride 98Min., propionyl chloride, butyryl chloride or Benzoyl chloride;
    2), by step 1) double bond on obtained product 24 carries out epoxidation reaction:
    In solvent II, under the katalysis of manganese salt, acidylate desmesterol and epoxidation reagent carry out epoxidation reaction, and temperature of reaction is-20 ~-1 DEG C, and the reaction times is 1 ~ 3h; The mol ratio of described acidylate desmesterol and epoxidation reagent is 1:1 ~ 4, and described manganese salt is 0.01 ~ 0.1 of acidylate desmesterol molar weight; Epoxidation reagent to be mass concentration be 6% ~ 40% Peracetic Acid or mass concentration be the metachloroperbenzoic acid of 56%-80%;
    The reaction solution of gained successively after filtration, dilution, extraction, dry after the extraction liquid washing of gained, then the rotary evaporation that reduces pressure, obtain oily matter; Described oily matter carries out pillar layer separation, obtains epoxidation product;
    3) by step 2) obtained product carries out reductive ring open:
    In solvent III, step 2) gained epoxidation product with go back original reagent and carry out reduction ring-opening reaction, temperature of reaction is 20 ~ 70 DEG C, and the reaction times is 3 ~ 8h; Described mol ratio of going back original reagent and epoxidation product is 2 ~ 6:1;
    Utilize shrend to go out after the reaction solution of gained is cooled to room temperature and excessively in reaction solution go back original reagent, then successively through pickling and extraction; Dry after the extraction liquid washing of gained, then the rotary evaporation that reduces pressure, obtain 25-HYDROXY CHOLESTEROL crude product, described 25-HYDROXY CHOLESTEROL crude product, through recrystallization, obtains 25-HYDROXY CHOLESTEROL;
    The structural formula of described 25-HYDROXY CHOLESTEROL is as shown in following formula I:
  2. 2. the synthetic method of 25-HYDROXY CHOLESTEROL according to claim 1, is characterized in that described step 2) in: manganese salt is manganous sulfate, Manganous chloride tetrahydrate, manganous nitrate, manganese acetate or manganous carbonate.
  3. 3. the synthetic method of 25-HYDROXY CHOLESTEROL according to claim 2, is characterized in that described step 3) in: going back original reagent is Lithium Aluminium Hydride.
  4. 4. the synthetic method of 25-HYDROXY CHOLESTEROL according to claim 3, is characterized in that:
    Described step 2) in: the manganese acetate of acidylate desmesterol adapted 0.05mmol, the metachloroperbenzoic acid 1.1mmol of mass concentration 80% of every 1mmol; Temperature of reaction is-10 DEG C, and the reaction times is 1h ~ 1.5h.
CN201310548840.7A 2013-11-07 2013-11-07 The synthetic method of 25-HYDROXY CHOLESTEROL Active CN103626821B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201310548840.7A CN103626821B (en) 2013-11-07 2013-11-07 The synthetic method of 25-HYDROXY CHOLESTEROL

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201310548840.7A CN103626821B (en) 2013-11-07 2013-11-07 The synthetic method of 25-HYDROXY CHOLESTEROL

Publications (2)

Publication Number Publication Date
CN103626821A CN103626821A (en) 2014-03-12
CN103626821B true CN103626821B (en) 2015-09-23

Family

ID=50208299

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201310548840.7A Active CN103626821B (en) 2013-11-07 2013-11-07 The synthetic method of 25-HYDROXY CHOLESTEROL

Country Status (1)

Country Link
CN (1) CN103626821B (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104130306B (en) * 2014-07-30 2016-05-18 浙江工业大学 A kind of synthetic method of 25-HYDROXY CHOLESTEROL
CN113004367A (en) * 2019-12-19 2021-06-22 帝斯曼知识产权资产管理有限公司 Diels-alder adducts and derivatives
CN113185565B (en) * 2021-03-25 2022-04-05 江西天新药业股份有限公司 Method for synthesizing and purifying 25-hydroxycholesterol

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3846455A (en) * 1972-05-22 1974-11-05 Eisai Co Ltd Process for the preparation of 25-hydroxy-cholesterol and esters thereof
CN1176082C (en) * 2003-03-17 2004-11-17 中国科学院广州化学研究所 Epoxidizing method of alpha-pinene
CN102060902A (en) * 2011-01-21 2011-05-18 郑州大学 Chenodeoxycholic acid synthesis method

Also Published As

Publication number Publication date
CN103626821A (en) 2014-03-12

Similar Documents

Publication Publication Date Title
CN103626821B (en) The synthetic method of 25-HYDROXY CHOLESTEROL
CN103086964B (en) Preparation method of 6-bromine-2-pyridine methyl formate
CN111004303A (en) Method for synthesizing 24-epibrassinolide
CN103073536B (en) Preparation method of ilaprazole
CN102010308B (en) Preparation method of 8-hydroxyl caprylaldehyde of intermediate for synchronizing royaljelly acid
CN103626822B (en) Synthetic method of 25-hydroxycholesterol
CN102911087A (en) Preparation method of trifluoro methanesulfonic acid
CN103421075B (en) The preparation method of the acetal of pregnane derivatives 16,17 (ketone)
CN103254265B (en) Abiraterone acetate trifluoroacetate and its preparation method and application
CN106831576B (en) Preparation method of 2-methyl-1-oxo-1, 2-dihydroisoquinoline-6-formic acid
CN101759740B (en) Method for synthesizing 3-alpha-acetoxy-deoxidized androstane-5-17-ketone
CN104892418A (en) Synthesis method of citric acid tributyl citrate
CN104530019A (en) Method for synthesizing VE nicotinate
CN102675267B (en) Preparation method of dronedarone hydrochloride and intermediate of dronedarone hydrochloride
CN109651474A (en) A kind of new preparation method of 16a- hydroxy prednisonlone
CN104356043A (en) Method for preparing 5-(2-fluorophenyl)-1H-pyrryl-3-formaldehyde
CN112125942B (en) Synthetic method of abiraterone acetate and intermediate thereof
CN105566376B (en) A kind of new intermediate for being used to prepare prostaglandin and preparation method and application
CN107955029A (en) A kind of preparation method of the western Nader of thunder
CN102690211B (en) The preparation method of tolvaptan intermediate
CN106749138B (en) A kind of preparation method of sulfuric acid Walla pa sand intermediate aldehydes
CN102070644A (en) Method for preparing camptothecin derivatives and intermediates thereof
CN111925333A (en) Preparation method, product and application of 2-amino-5-methylpyrazine
CN101220073B (en) Synthesis of polyhydroxy ocean steroid (25R)-5 alpha-cholesteric-2 beta,3 alpha,26-triol
CN104557965A (en) Preparation technology for beta-artemether

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant