Method for producing 6 alpha-methylprednisolone and its derivatives

A technology for producing methylprednisolone and its production method, which is applied in the direction of chemical instruments and methods, preparation of steroids, steroids, etc., can solve the problems of low yield, complex production process, cumbersome steps, etc., and achieve high yield , good reaction specificity and less by-products

Inactive Publication Date: 2007-06-13
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Because the current production process is complex and the steps are cumbersome, the yield is low, and dangerous reagents such as Grignard reagent, dichromic acid, liquid bromine, selenium dioxide or DDQ need to be used at the same time, so a high-yield, high-reaction The process method with mild conditions and avoiding the use of various dangerous reagents is of great significance to the development of steroid drugs

Method used

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  • Method for producing 6 alpha-methylprednisolone and its derivatives
  • Method for producing 6 alpha-methylprednisolone and its derivatives
  • Method for producing 6 alpha-methylprednisolone and its derivatives

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1-1

[0060] (1) Add 4 g of cortisone acetate shown in formula II to 40 ml of tetrahydrofuran, add 2 g of triethyl orthoformate, 3 ml of absolute ethanol, and 0.04 g of p-toluenesulfonic acid after dissolving, and react at a temperature of 25° C. for 1 hour. The compound represented by formula III can be obtained.

[0061] (2) Add 1ml of N-methylaniline and 1ml of formaldehyde to the above product, react at 20°C for 1 hour, add 400ml of water, react at 20°C for 1 hour, cool to 8°C and keep it for 2 hours, filter and dry to obtain Compound shown in formula VI. The compound shown in formula VI is dissolved with 20ml of dimethyl sulfoxide, and 0.4g of 7.5%Pd / CaCO is added 3 , 4ml of cyclohexene, reacted at 20°C for 2 hours, then concentrated under reduced pressure at a temperature of 0°C and vacuum ≥ 0.085atm to remove the solvent, cooled to 40°C, and added dropwise 12ml of 37% hydrochloric acid under stirring , keep warm for 0.5 hour, slowly adjust the pH to 6, add 10 times of water...

Embodiment 1-2

[0066] (1) Add 4 g of cortisone acetate shown in formula II in 48 ml of ether, add 3.2 g of triethyl orthoformate, 3 ml of absolute ethanol, 0.08 g of sulfuric acid after dissolving, and react at a temperature of 30° C. for 1 hour. The compound represented by formula III can be obtained.

[0067] (2) Add 1.2ml of N-methylaniline and 1.2ml of acetaldehyde to the above product, react at 35°C for 1.5 hours, add 60ml of water, react at 30°C for 1 hour, cool to 9°C for 2 hours, filter and dry , to obtain the compound shown in formula VI. The compound shown in formula VI is dissolved with 28ml of dimethyl sulfoxide, and 0.6g7.5%Pd / CaCO is added 3 , 4ml of cyclohexene, reacted at 100°C for 3 hours, then concentrated under reduced pressure at a temperature of 60°C and vacuum ≥ 0.085atm to remove the solvent, cooled to 45°C, and added dropwise 16ml of 37% hydrochloric acid with stirring , keep warm for 0.75 hours, slowly adjust the pH to 7, add 15 times of water and stir for 2 hours,...

Embodiment 1-3

[0072] (1) Add 4g of cortisone acetate shown in formula II to 60ml of ethyl propyl ether, add 4g of triethyl orthoformate, 3ml of absolute ethanol, 0.12g of perchloric acid after dissolving, and react at a temperature of 40°C for 1 hour . The compound represented by formula III can be obtained.

[0073] (2) Add 1.6ml of N-1-methylaniline and 1.6ml of propionaldehyde to the above product, react at 46°C for 2 hours, add 80ml of water, react at 35°C for 1 hour, cool to 10°C for 2 hours, filter, drying to obtain the compound shown in formula VI. The compound shown in formula VI is dissolved with 40ml of dimethyl sulfoxide, and 0.8g7.5%Pd / CaCO is added 3 , 4ml of cyclohexene, reacted at 180°C for 4 hours, then concentrated under reduced pressure at a temperature of 120°C and vacuum ≥ 0.085atm to remove the solvent, cooled to 50°C, and added dropwise 20ml of 37% hydrochloric acid under stirring , keep warm for 1 hour, slowly adjust the pH to 8, add 20 times of water and stir for ...

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PUM

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Abstract

This invention discloses a 6alpha-methylprednisolone and production method of its derivate. This invention uses cortisone acetate and its derivate as raw material to produce 6alpha-methylprednisolone and its derivate. Its production method includes steps such as: lead-in methenyl at sixth position, methenyl is transformed to alpha-methyl, 1,2 position is dehydrogenated to 6alpha-methyl prednisoni acetasby by method of arthrobacterium biotransformation, then selectively hydrogenise 11-ketone to 11 beta-hydroxy group. Using this invention can obtain higher 6alpha-methylprednisolone and yield and quality of its derivate. This invention has characteristics such as: position specificity is high, yield is high. It has important significance for preparing steroid medicine.

Description

technical field [0001] The invention belongs to the fields of biological pharmacy and medical engineering. The invention specifically relates to a production process of 6α-methylprednisolone and its derivatives. Background technique [0002] The structural formula of 6α-methylprednisolone and its derivatives is shown in formula I, wherein R is any one of methyl, ethyl, 1-propyl or 2-propyl, and R1 and R2 are hydrogen, acetyl Any one of propionyl, propionyl, butyryl or succinyl, R 3 is hydrogen; when R is methyl, R 1 is acetyl, R 2 for hydrogen, R 3 When it is hydrogen, structural formula I represents 6α-methylprednisolone, also known as 6α-methylprednisolone, and its chemical name is 11β, 17α, 21-trihydroxy-6α-methylpregna-1,4 - Diene-3,20-dione. 6α-methylprednisolone and its derivatives are a class of highly effective anti-immune stress response adrenal corticosteroids, and are widely used in clinical anti-immune stress response. It is mainly used for organ transplan...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07J5/00C07J75/00
Inventor 王海清关怡新姚善泾
Owner ZHEJIANG UNIV
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