A kind of synthetic method of 25-hydroxycholesterol

A technology of hydroxycholesterol and its synthesis method, which is applied in the fields of steroids and organic chemistry, and can solve problems such as difficult industrialization, Hg residue, and difficult operation, and achieve convenient operation and post-processing, mild reaction conditions, and post-processing simple effect

Active Publication Date: 2016-05-18
ZHEJIANG UNIV OF TECH +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Method (a) uses 24-dehydrocholesterol derivatives as raw materials and uses highly toxic Hg reagents. The operation is unsafe, and there are great safety and environmental risks. Post-processing is troublesome, and it is easy to cause Hg residues in the product. Difficult, unable to meet medicinal standards, industrialization is difficult
[0008] Method (b) is prepared by oxidizing 5,6-dibromocholesterol derivatives at the 25th position with oxytrifluoroacetone, but trifluoroacetones are extremely toxic and may have special toxicity, that is, teratogenicity , carcinogenic, mutagenic, high equipment requirements, difficult operation, troublesome post-processing, and great safety and environmental protection risks
[0009] Method (c) uses 5,6-dichlorocholesterol derivatives as raw materials, oxidizes them with chromium trioxide, acetic anhydride or trifluoroacetic anhydride, and then reduces them with zinc powder. This method also uses heavy metal Cr reagents. Disposal is troublesome, environmental hazards are great, and industrialization cannot be realized

Method used

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  • A kind of synthetic method of 25-hydroxycholesterol
  • A kind of synthetic method of 25-hydroxycholesterol
  • A kind of synthetic method of 25-hydroxycholesterol

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] At room temperature (20-25°C), dissolve 4.27g (10mmol) 24-dehydrocholesterol acetate in 20mL toluene, add 6.01g (100mmol) acetic acid, 49.2mg (0.1mmol) scandium trifluoromethanesulfonate (Sc(OTf) 3 ), heat up to 50°C, stir for 5 hours, after TLC traces the reaction is complete, add 10mL of water layer to remove the water phase, add sodium hydroxide aqueous solution to the organic phase, keep the system pH ≥ 12, heat up to 50°C, and stir for 1 hour . After the reaction was detected by TLC, the aqueous phase was removed by liquid separation, and the organic phase was washed with 10 mL of water to separate the layers. The organic phase was dried with anhydrous sodium sulfate, filtered, and concentrated to obtain a light yellow crude product, which was washed with 20 mL ethyl acetate / petroleum ether (v / v=2:3) recrystallized to obtain 3.45g of 25-hydroxycholesterol, yield 85.6%, melting point 179.4~180.8℃, 1 HNMR (CDCl 3 ,400MHz):δ5.34(m,1H,6-CH),3.51(m,1H,3-CH),2.27(m,2...

Embodiment 2

[0031] At room temperature (20-25°C), dissolve 3.84g (10mmol) of 24-dehydrocholesterol in 20mL of chloroform, add 6.01g (100mmol) of acetic acid, 0.14g (1mmol) of aluminum trichloride, and 0.1g of concentrated hydrochloric acid, Raise the temperature to 60°C, stir and react for 8 hours, after the completion of the reaction by TLC, add 10 mL of water layer to remove the aqueous phase, add aqueous sodium hydroxide solution to the organic phase, keep the system pH ≥ 12, raise the temperature to 50°C, and stir for 1 hour. After the reaction was detected by TLC, the aqueous phase was removed by liquid separation, and the organic phase was washed with 10 mL of water to separate the layers. The organic phase was dried with anhydrous sodium sulfate, filtered, and concentrated to obtain a light yellow crude product, which was washed with 20 mL ethyl acetate / petroleum ether (v / v=2:3) recrystallized to obtain 3.24g of 25-hydroxycholesterol with a yield of 80.5% and a melting point of 179...

Embodiment 3

[0033]At room temperature (20-25°C), dissolve 4.88g (10mmol) of 24-dehydrocholesteryl benzoate in 30mL of xylene, add 12.20g (100mmol) of benzoic acid, 34.6mg (0.1mmol) of trifluoroform Gold sulfonate (AuOTf), heat up to 80°C, stir and react for 8 hours, after the reaction is complete by TLC, add 10mL of water layer to remove the water phase, add sodium hydroxide aqueous solution to the organic phase, keep the system pH ≥ 13, heat up to 80°C , and stirred for 1 hour. After the reaction was detected by TLC, the aqueous phase was removed by liquid separation, and the organic phase was washed with 10 mL of water to separate the layers. The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated to obtain a light yellow crude product, which was washed with 20 mL of ethyl acetate / petroleum ether (v / v=2:3) Recrystallized to obtain 2.95g of 25-hydroxycholesterol with a yield of 73.4% and a melting point of 179.1~180.9℃.

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Abstract

The present invention discloses a method for synthesizing 25-hydroxy cholesterol. The method is as below: subjecting 24-dehydrocholesterol derivative as a raw material, which undergoes an addition reaction with a hydroxyl containing reagent in an organic solvent under catalysis, and then hydrolyzing the reaction product and separating to obtain 25-hydroxy cholesterol. The present invention adopts hydroxyl containing reagents such as water, formic acid, acetic acid, propionic acid, butyric acid, benzoic acid, p-methyl benzoic acid to replace the commonly used extremely toxic reagents such as Cr reagent, Hg reagent and polyfluorinated acetone in the prior art. The raw materials of the present invention are easily available, and have low effect on environment. The operation and post treatment are convenient. Moreover, the method has the advantages of mild reaction conditions, simple operation, good selectivity, high efficiency, high yield, simple post treatment, easy product separation, less three wastes and easy industrialization.

Description

technical field [0001] The invention belongs to the technical field of intermediate synthesis, and in particular relates to a synthesis method of 25-hydroxycholesterol. Background technique [0002] 25-hydroxycholesterol for the synthesis of 25-hydroxyvitamin D 3 An important raw material, 25-hydroxyvitamin D 3 Also known as calcifediol, vitamin D 3 The active metabolite has stronger physiological activity and does not need to be metabolized by the liver. It Has More Than Regular Vitamin D 3 All functions also have the following unique functions: ①Some human or animals cannot synthesize vitamin D due to liver dysfunction 3 Direct conversion to 25-hydroxyvitamin D 3 , even with more vitamin D intake 3 Nor can it be absorbed. Therefore 25-hydroxyvitamin D 3 As an active substance, it bypasses liver transformation and is directly absorbed by humans or animals; ② 25-hydroxyvitamin D 3 Used in animals, it can promote the bone development of poultry animals, promote the m...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07J9/00
CPCC07J9/00
Inventor 金灿苏为科王子强刘建刚孙彬许文灏
Owner ZHEJIANG UNIV OF TECH
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