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Method for raising conversion rate of 15 alpha, 17 alpha-epoxyprogesterone

A technology of ketone conversion rate and corpus luteum, which is applied in the field of microbial fermentation, can solve the problems of shortening the conversion time and increasing the contact area, and achieve the effect of shortening the conversion time, increasing the contact area and improving the conversion rate

Inactive Publication Date: 2013-08-21
TIANJIN UNIVERSITY OF SCIENCE AND TECHNOLOGY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] Aiming at the defects of existing microbial fermentation production of 11α-hydroxyl-16α, 17α-epoxy progesterone process, the technical problem solved by the present invention is to utilize toluene-tolerant aspergillus ochraceus bacterial strains, in a two-phase catalytic system, Realize the selective 11α biocatalysis of steroidal substrate 16α, 17α-epoxyprogesterone with multiple chiral carbons at the 11-position chiral carbon, and obtain the product 11α-hydroxyl-16α, 17α-epoxyprogesterone, two-liquid phase The fermentation method can effectively solve the dissolution problem of substrates and products, increase the contact area with cells, shorten the conversion time, and effectively improve the solubility and conversion rate of 16α, 17α-epoxy progesterone

Method used

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  • Method for raising conversion rate of 15 alpha, 17 alpha-epoxyprogesterone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] (1) Bevel preparation

[0058] Inoculate the strain of Ochraus ochrax in the potato slant medium, culture at 28°C for 4 days to produce yellow spores, cover the slant, the color is grayish yellow, red pigment can be observed on the back of the potato slant, and then transfer to the yeast paste slant culture On the basal slant, cultivate it at 28°C for 7 days to produce golden yellow spores to obtain the slant for production, and store it in the refrigerator at a constant temperature of 4°C for 2 months for later use. After this time limit, follow the above steps to re-cultivate and save.

[0059] (2) Preparation of spore suspension

[0060] Add sterile water containing 2‰ (w / v) Tween 80 to the production slope preserved in step (1), wash the spores, count on a hemocytometer, prepare and adjust the concentration of the spore suspension to 4×10 6 individual / mL.

[0061] (3) Resting cell preparation

[0062] Insert the spore suspension in step (2) into the liquid cultu...

Embodiment 2

[0076] (1) Bevel preparation

[0077] Inoculate the strain of Ochraus ochrax in the potato slant medium, culture at 26°C for 5 days to produce yellow spores, cover the slant, the color is grayish yellow, red pigment can be observed on the back of the potato slant, and then transfer to yeast paste slant culture On the basal slant, culture at 26°C for 8 days, golden spores can be produced, and the slant for production can be obtained, and stored in the refrigerator at a constant temperature of 4°C for 2 months for later use. After this time limit, follow the above steps to re-cultivate and save.

[0078] (2) Preparation of spore suspension

[0079] Add sterile water containing 2‰ (w / v) Tween 80 to the production slant preserved in step (1), wash the spores, count on a hemocytometer, prepare and adjust the concentration of the spore suspension to 6×10 6 individual / mL.

[0080] (3) Resting cell preparation

[0081] Insert the spore suspension in the step (2) into the liquid cu...

Embodiment 3

[0095] (1) Bevel preparation

[0096] Inoculate the strain of Ochraus ochrax in the potato slant medium, culture at 25°C for 7 days to produce yellow spores, cover the slant, the color is grayish yellow, red pigment can be observed on the back of the potato slant, and then transfer to yeast paste slant culture On the basal slant, cultivate at 25°C for 10 days to produce golden yellow spores to obtain the slant for production, and store it in the refrigerator at a constant temperature of 4°C for 2 months for later use. After this time limit, follow the above steps to re-cultivate and save.

[0097] (2) Preparation of spore suspension

[0098] Add sterile water containing 2‰ (w / v) Tween 80 to the production slope preserved in step (1), wash the spores, count on a hemocytometer, prepare and adjust the concentration of the spore suspension to 8×10 6 individual / mL.

[0099] (3) Resting cell preparation

[0100] Insert the spore suspension in step (2) into the liquid culture med...

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Abstract

The invention provides a method for catalyst production of 11alpha-hydroxy-16alpha, 17alpha-epoxyprogesterone in a binary system by the use of aspergillus ochraceus. By the addition of an organic solvent dibutyl phthalate, dissolving problem of a substrate and a product is effectively solved, contact area with cells is increased, separation process is simplified, conversion time is shortened, conversion rate of the substrate is greatly raised, and conversion rate of 16 alpha, 17 alpha-epoxyprogesterone can reach more than 84%. The method provided by the invention lays a solid practical production foundation for production of high-yield and high-purity 11 alpha-hydroxy-16 alpha, 17 alpha-epoxyprogesterone. Production costs are reduced, and economic benefits of enterprises are raised.

Description

Technical field: [0001] The invention belongs to the technical field of microbial fermentation, and specifically refers to a method for improving the conversion rate of 16α, 17α-epoxyprogesterone in the preparation method of 11α-hydroxyl-16α, 17α-epoxyprogesterone. technical background: [0002] 11α-hydroxyl-16α, 17α-epoxy progesterone (referred to as mold), is an important hormone drug intermediate, widely used in the synthesis of hormone drugs, is hydrocortisone, cortisone, prednisone An important raw material of steroid hormone drugs such as Hefuacinolone. [0003] 16α, 17α-epoxyprogesterone (16α, 17α-Epoxyprogesterone, EP) full name 16,17a-epoxy-4-pregnene-3,20-dione, also known as Woshi oxide, is a non-toxic Odor, white crystalline powder, low solubility in methanol, ethanol, benzene. [0004] [0005] Conversion of 16α, 17α-epoxyprogesterone to 11α-hydroxy-16α, 17α-epoxyprogesterone molecular structure [0006] In 1952, Murray and Peterson of Upjohn Company first...

Claims

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Application Information

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IPC IPC(8): C12P33/20C12P33/10C12R1/66
Inventor 别松涛王家明路福平
Owner TIANJIN UNIVERSITY OF SCIENCE AND TECHNOLOGY
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