A kind of preparation method of dexamethasone intermediate

A technology for dexamethasone and intermediates, which is applied in the field of biological fermentation and synthesis of dexamethasone intermediate 8DM, can solve the problems of cumbersome operation, mutual inhibition of strains, difficulty in regulating the fermentation process, and large investment in equipment, so as to achieve process stability and reduce The risk of system contamination and the effect of simple operation

Active Publication Date: 2021-01-29
ZHEJIANG XIANJU PHARMA
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Problems solved by technology

Although this result is better than the 8DM obtained by the first method, there are problems such as mutual inhibition of strains in the mixed strains, difficulty in regulating the fermentation process, material degradation, and reduced yield; in addition, since the two strains need to be cultured separately and then mixed , the equipment investment is large, the operation is cumbersome, and the risk of system contamination is increased, so it is not suitable for industrial production

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  • A kind of preparation method of dexamethasone intermediate
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  • A kind of preparation method of dexamethasone intermediate

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Effect test

Embodiment 1

[0053] A kind of preparation method of dexamethasone intermediate, described dexamethasone intermediate refers to 8-DM, operates according to the following steps:

[0054] (1) Strain cultivation: prepare the primary medium according to the ratio, glucose 2.0%, corn steep liquor 3.2%, yeast extract 1.5%, potassium dihydrogen phosphate 0.3%, foam enemy 0.04%, use 30% sodium hydroxide Adjust the pH to 7.5, sterilize at 121°C for 30 minutes, cool to room temperature, inoculate the slant of Arthrobacter simplex CPCC 140451 cultured in 100mL eggplant-shaped flasks with 50mL sterile water, and inoculate 20% to 100mL of medium Medium (500mL volume of the culture shaker flask), the primary culture was carried out on a shaker, the culture temperature was 30°C, the speed of the shaker was 180rpm, the culture was 19h, and the second inoculation was carried out;

[0055] (2) Fermentation conversion: carry out fermentation medium preparation according to proportioning, glucose 2.0%, corn st...

Embodiment 2

[0063] A kind of preparation method of dexamethasone intermediate, described dexamethasone intermediate refers to 8-DM, operates according to the following steps:

[0064] (1) Strain cultivation: prepare the primary medium according to the ratio, glucose 2.0%, corn steep liquor 3.2%, yeast extract 1.5%, potassium dihydrogen phosphate 0.3%, foam enemy 0.04%, use 30% sodium hydroxide Adjust the pH to 7.2, 121°C, sterilize for 30 minutes, cool to room temperature, inoculate the slant of Arthrobacter simplex CPCC140451 cultivated in 100mL eggplant-shaped flasks with 50mL sterile water, and inoculate 20% to 100mL of medium (The volume of the culture shaker flask is 500mL), the shaker is used for primary cultivation, the cultivation temperature is 30°C, the rotation speed of the shaker is 180rpm, cultivated for 18h, and then the secondary transplantation is carried out;

[0065] (2) Fermentation conversion: carry out fermentation medium preparation according to proportioning, glucos...

Embodiment 3

[0068] A kind of preparation method of dexamethasone intermediate, described dexamethasone intermediate refers to 8-DM, operates according to the following steps:

[0069](1) Strain cultivation: prepare the primary medium according to the ratio, glucose 2.0%, corn steep liquor 3.2%, yeast extract 1.5%, potassium dihydrogen phosphate 0.3%, foam enemy 0.04%, use 30% sodium hydroxide Adjust the pH to 7.5, sterilize at 121°C for 30 minutes, cool to room temperature, inoculate the slant of Arthrobacter simplex CPCC 140451 cultured in 100mL eggplant-shaped flasks with 50mL sterile water, and inoculate 20% to 100mL of medium Medium (500mL volume of the culture shaker flask), the primary culture was carried out on a shaker, the culture temperature was 30°C, the speed of the shaker was 180rpm, the culture was 19h, and the second inoculation was carried out;

[0070] (2) Fermentation conversion: carry out fermentation medium preparation according to proportioning, glucose 2.0%, corn ste...

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Abstract

The invention discloses a method for preparing a dexamethasone epoxy hydrolysate 8DM from arthrobacter simple CPCC140451 through one-step fermentation. The method is simple in operation manner, stablein process and suitable for industrial mass production.

Description

technical field [0001] The invention belongs to the field of steroid biotechnology, in particular to a method for synthesizing dexamethasone intermediate 8DM by biological fermentation. Background technique [0002] Dexamethasone is widely used in the treatment of various diseases clinically, such as active rheumatism, rheumatoid arthritis, severe bronchial asthma, severe dermatitis, acute leukemia, etc., and its clinical dosage is increasing year by year. 8DM, also known as dexamethasone epoxy hydrolyzate, is one of the important intermediates in steroid medicinal chemistry, its CAS#: 24916-90-3, and its structural formula is as follows: [0003] [0004] 8-DM is mainly used to synthesize glucocorticoids such as dexamethasone, clocotorone pitava, and mometasone furoate. [0005] Initially, the process of dexamethasone was prepared with diene derivatives as starting materials, and 8DM was one of the key intermediates. Diene derivatives are derived from diosgenin extract...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12P33/20C12N1/20C12R1/06
CPCC12N1/20C12P33/20
Inventor 刘建蒋随新王小飞张小强
Owner ZHEJIANG XIANJU PHARMA
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