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Method for preparing R-isomer by using S-isomer of budesonide

A technology of isomers and systems, applied in the field of preparation of highly active R isomers, can solve problems affecting product yield and achieve good recovery and high conversion

Active Publication Date: 2014-04-02
CHENGDU YILUKANG MEDICAL TECH & SERVICE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The purpose of the present invention is to overcome the problem that a large amount of S isomers are produced when preparing dexbudesonide in the prior art, which affects the yield of the product, and to provide a method for preparing high-activity R isomers using budesonide S isomers. body method

Method used

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  • Method for preparing R-isomer by using S-isomer of budesonide

Examples

Experimental program
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Effect test

Embodiment 1

[0018] Put 50g of recovered budesonide (R / S=20 / 80) into the reaction kettle, add 200ml of dichloromethane, stir and dissolve completely. Then the temperature was lowered to 0°C, and 15 ml of acetic anhydride was added dropwise. After dropping, keep warm for 30 minutes. Then it was washed with aqueous sodium bicarbonate solution, and the layers were separated. The dichloromethane layer was concentrated to dryness under reduced pressure to obtain budesonide acetate, formula II, yield.

Embodiment 2

[0020] Put 57g of budesonide acetate obtained in Example 1 into the reaction kettle, add 900ml of methanol, 10ml of formic acid, and heat to dissolve completely. Then the temperature was lowered to 10°C, 220ml of 10% potassium permanganate aqueous solution was added dropwise, and the reaction was incubated for 1.5 hours after the drop was completed. After the reaction was complete, it was filtered, and the filtrate was concentrated to dryness under reduced pressure to obtain 16-α-hydroxyprednisolone acetate, formula III, with a yield of 85%.

[0021] At the same time, potassium dichromate and chromium trioxide were used instead of potassium permanganate, and the oxidation ring-opening reaction was carried out under the same conditions, and the yields were 76% and 81%, respectively.

Embodiment 3

[0023] Put 600ml of perchloric acid into the reaction kettle, ventilate with nitrogen, and stir. Cool down to -20°C and add 23ml of n-butyraldehyde, then add 48.7g of the budesonide intermediate obtained in Example 2 while maintaining the temperature. The reaction was incubated for 3 hours. After the reaction was complete, the reaction solution was poured into 5 L of water, filtered, and the filter cake was recrystallized with ethanol to obtain 32.4 g of dexbudesonide acetate with a yield of 64.8%.

[0024] R isomer: 99.2%

[0025] S isomer: 0.8%

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Abstract

The invention discloses a method for preparing an R-isomer by using an S-isomer of budesonide. The method comprises the steps: enabling budesonide and acetic anhydride to be subjected to esterification reaction to obtain budesonide acetate; then, carrying out oxidative ring cleavage under the action of a strong oxidant to obtain 16-alpha hydroxyprednisonlone acetate; and condensing butyraldehyde and the 16-alpha hydroxyprednisonlone acetate to obtain budesonide acetate, and hydrolyzing to obtain R-budesonide. The method disclosed by the invention is high in conversion rate, high in yield and capable of effectively converting the S-isomer of the budesonide into the R-isomer.

Description

technical field [0001] The invention relates to a method for preparing a highly active R isomer by utilizing budesonide S isomer. Background technique [0002] Budesonide is a glucocorticoid with highly effective local anti-inflammatory effect developed by AB Bofors in Sweden. Budesonide is a racemate composed of two isomers 22R and 22S at the C-22 position in a ratio of approximately 1:1. It is clinically used topically to treat skin or respiratory symptoms caused by inflammation and allergies (such as skin diseases, asthma and rhinitis), etc. [0003] Dexbudesonide (R isomer) belongs to adrenal corticosteroid drugs, and is a single isomer at the C-22 position of budesonide prepared by chemical synthesis. Its local anti-inflammatory activity (rat auricle swelling method) is 1.4 to 1.7 times that of budesonide, 1.6 to 2 times that of levobudesonide (S isomer), and 13 times that of dexamethasone; the local glucocorticoid effect (human vasoconstriction test) is It is 1.5 ti...

Claims

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Application Information

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IPC IPC(8): C07J71/00
Inventor 骆均勇陶长戈
Owner CHENGDU YILUKANG MEDICAL TECH & SERVICE
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