Method for preparing delta 1-11 alpha,17 alpha-dihydroxyprogesterone with one-pot continuous fermentation process

A technology of dihydroxy and progesterone, which is applied in the field of one-pot continuous fermentation to prepare Δ1-11α, can solve problems such as yield loss, complicated preparation process, and environmental pollution, and achieve convenient operation, simplified process, and reduced environmental pressure Effect

Inactive Publication Date: 2015-06-17
JIANGXI JUNYE BIOLOGICAL PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The present invention proposes a one-pot method for continuous fermentation to prepare Δ 1 The method of -11α, 17α-dihydroxyprogesterone solves the problems of complex preparation process, serious environmental pollution and yield loss of the key intermediate of prednisolone acetate in the prior art

Method used

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  • Method for preparing delta 1-11 alpha,17 alpha-dihydroxyprogesterone with one-pot continuous fermentation process
  • Method for preparing delta 1-11 alpha,17 alpha-dihydroxyprogesterone with one-pot continuous fermentation process

Examples

Experimental program
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Effect test

Embodiment 1

[0023] 200ml of the first substratum is housed in the 500 milliliter shake flask, and the first substratum comprises 1% (weight percentage) glucose, 1% (weight percentage) corn steep liquor, 0.3% (weight percentage) peptone, 0.15% (weight percentage) K H 2 PO 4 ; Sterilize the culture medium in an autoclave at 120°C for 30 minutes; cool it to 30±1°C, then inoculate the slant culture of Arthrobacter simplex in the culture medium; place the culture medium inoculated with the strain in a shaker Incubate at 165 rpm at 30±1°C for 24 hours. Add 12g of 17α-hydroxyprogesterone through jet milling, and transform for 48 hours.

[0024] Then add 800ml of sterilized second substratum with 10% inoculum size, the second substratum comprises 2% (weight percent) glucose, 1% (weight percent) corn steep liquor, 1% (weight percent) peptone, 0.2% (weight percent) ammonium sulfate; then the slant culture of Ochraus ochrax was inoculated in the culture medium; the culture medium inoculated with ...

Embodiment 2

[0027] 200ml of the first substratum is housed in the 500 milliliter shake flask, and the first substratum comprises 1% (weight percentage) glucose, 1% (weight percentage) corn steep liquor, 0.3% (weight percentage) peptone, 0.15% (weight percentage) K H 2 PO 4 ; Sterilize the culture medium in an autoclave at 120°C for 30 minutes; cool it to 30±1°C, then inoculate the slant culture of Arthrobacter simplex in the culture medium; place the culture medium inoculated with the strain in a shaker Incubate at 165 rpm at 30±1°C for 24 hours. Add 12g of 17α-hydroxyprogesterone through jet milling, and transform for 48 hours.

[0028] Then add 800ml of sterilized second substratum with 5% inoculum size, the second substratum comprises 2% (weight percent) glucose, 1% (weight percent) corn steep liquor, 1% (weight percent) peptone, 0.2% (weight percent) ammonium sulfate; then the slant culture of Ochraus ochrax was inoculated in the culture medium; the culture medium inoculated with t...

Embodiment 3

[0031] 200ml of the first substratum is housed in the 500 milliliter shake flask, and the first substratum comprises 1% (weight percentage) glucose, 1% (weight percentage) corn steep liquor, 0.3% (weight percentage) peptone, 0.15% (weight percentage) K H 2 PO 4 ; Sterilize the culture medium in an autoclave at 120°C for 30 minutes; cool it to 30±1°C, then inoculate the slant culture of Arthrobacter simplex in the culture medium; place the culture medium inoculated with the strain in a shaker Incubate at 165 rpm at 30±1°C for 24 hours. Add 12g of 17α-hydroxyprogesterone through jet milling, and transform for 48 hours.

[0032] Then add 800ml of sterilized second substratum with 10% inoculum size, the second substratum comprises 2% (weight percent) glucose, 1% (weight percent) corn steep liquor, 1% (weight percent) peptone, 0.2% (weight percent) ammonium sulfate; then the slant culture of Ochraus ochrax was inoculated in the culture medium; the culture medium inoculated with ...

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Abstract

The invention discloses a method for preparing delta 1-11 alpha,17 alpha-dihydroxyprogesterone with a one-pot continuous fermentation process, and belongs to the technical field of intermediate preparation. The method comprises the following specific steps: (1) inoculating slant culture of arthrobacter simplex into a first culture medium, performing culture for 20-30 hours, adding ground 17 alpha-hydroxyprogesterone, and performing transformation; (2) inoculating fermentation liquor after finishing the step (1) into a second culture medium, inoculating slant culture of aspergillus ochraceus into the second culture medium, performing culture, and performing post-treatment to obtain delta 1-11 alpha,17 alpha-dihydroxyprogesterone. Delta 1-11 alpha,17 alpha-dihydroxyprogesterone is prepared with the one-pot continuous fermentation process, so that a step of filtering, extracting, refining and drying a dehydrogenation material is reduced, discharge of 50% pollutants is reduced, environmental pressure is reduced, the time is saved, the yield is increased, the efficiency is improved, the process is simplified, the whole reaction operation is convenient, and the method is suitable for industrialized popularization and application.

Description

technical field [0001] The invention relates to the technical field of preparation of intermediates, in particular to a method for preparing Δ1-11α, 17α-dihydroxyprogesterone by one-pot continuous fermentation. Background technique [0002] The traditional production process of prednisolone acetate uses dienes as raw materials, and undergoes epoxy, Woshi oxidation, fermentation hydroxylation, oxidation, debromination, iodination, replacement, fermentation dehydrogenation, protection, reduction, hydrolysis, and esterification. 13 step reaction generation. [0003] Concrete reaction formula is as follows: [0004] [0005] [0006] A very important intermediate in the above preparation process Δ 1 -11α, 17α-dihydroxyprogesterone is separated by two-step fermentation, and each step of the reaction must go through steps such as fermentation, filtration, extraction, refining, drying, and packaging. The treatment in the process has yield loss and increases Sewage discharg...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P33/10C12R1/06
Inventor 张峥斌
Owner JIANGXI JUNYE BIOLOGICAL PHARM CO LTD
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