Preparation method of hydrocortisone acetate or analogue thereof

A technology for hydrocortisone acetate and its analogues, which is applied in the field of preparation of pine or its analogues, can solve the problems of unfavorable environmental protection, high price, etc., and achieve the effect of stable and high yield

Active Publication Date: 2012-07-25
HUNAN NORCHEM PHARMACEUTICAL CO LTD
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Document ZL92110286.0 reported a chemical synthesis route for the preparation of hydrocortisone, starting with 9a-bromo-11β-hydroxy-androst-4-ene-3,17-dione, debrominated, protected

Method used

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  • Preparation method of hydrocortisone acetate or analogue thereof
  • Preparation method of hydrocortisone acetate or analogue thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Oxidation reaction: 4-ene-pregna-3,11,17-trione;

[0022] At room temperature, under the protection of nitrogen, add 180ml of glacial acetic acid and 50ml of manganese acetate aqueous solution with a mass concentration of 50% to a clean and dry 500ml four-necked round-bottomed flask equipped with a thermometer, a reflux condenser, and mechanical stirring, and add 100.0g of it under stirring. For compound I, the temperature of the system was lowered to 0 to 10°C, and 50ml of chromium trioxide aqueous solution with a mass concentration of 50% was added dropwise at a temperature of 0 to 10°C. After the dropwise addition, the temperature was raised to 30°C-35°C to react for 2 hours. TLC followed the reaction until no raw material remained. The system was cooled to room temperature. The reaction system was added dropwise to 2L of purified water, a large amount of solids were precipitated, and the stirring was continued for 2 hours. The system was suction-filtered, the fil...

Embodiment 2

[0036] Oxidation reaction: 4-ene-pregna-3,11,17-trione;

[0037] At room temperature, under the protection of nitrogen, add 200 ml of acetone and 50 ml of periodic acid solution with a mass concentration of 40% to a clean and dry 500 ml four-necked round-bottomed flask equipped with a thermometer, a reflux condenser, and mechanical stirring, and stir. 100.0 g of compound I was added, the temperature of the system was lowered to 0 to 10°C, and 50ml of chromium trioxide aqueous solution with a mass concentration of 60% was added dropwise at a temperature of 0 to 10°C. After the dropwise addition, the temperature was raised to 35°C-37°C to react for 3 hours. TLC followed the reaction until no raw material remained. The system was cooled to room temperature. The reaction system was added dropwise to 3 L of purified water, a large amount of solids were precipitated, and the stirring was continued for 2.5 hours. The system was suction-filtered, the filter cake was washed with wat...

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PUM

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Abstract

The invention relates to a preparation method of hydrocortisone acetate or an analogue thereof. Hydrocortisone acetate or the analogue thereof has a structural formula represented as a formula VIII. According to the invention, a compound I is subject to an oxidation reaction, a carbonyl protection reaction, a reduction and hydrolysis reaction, a cyano substitution reaction, a silicon alkyloxy protection reaction, an intramolecular nucleophilic substitution reaction, and a substitution reaction, such that hydrocortisone acetate or the analogue thereof is prepared. The initial raw materials areeasy to obtain, and the yield is high and stable. The compound I is represented by a formula I, wherein R is H or alkyl.

Description

technical field [0001] The invention relates to a preparation method of hydrocortisone acetate or its analogs. Background technique [0002] Hydrocortisone, as the most produced variety of steroidal corticosteroids, is widely used in the treatment of adrenal insufficiency and autoimmune diseases. my country's steroid drug and its intermediate industry has reached a certain scale, and it has become the largest exporter of hydrocortisone and prednisolone in the world. Currently, hydrocortisone is mainly synthesized by biological fermentation and chemical synthesis, which have the problems of low yield and high cost. [0003] The difficulty in the synthesis of hydrocortisone lies in the introduction of 11β-hydroxyl. Because there is no active functional group around the C-11 position, conventional chemical methods are difficult to oxidize inactive carbon-hydrogen bonds, but biocatalytic methods can oxidize it stereoselectively. The effective strains are Rhizopus niger and Ab...

Claims

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Application Information

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IPC IPC(8): C07J5/00
Inventor 刘喜荣蒋青锋曾春玲胡冬晴
Owner HUNAN NORCHEM PHARMACEUTICAL CO LTD
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