Preparation of fluorine-containing steroid hormone

A technology of fluoclon and its compounds, which is applied in the field of preparation of fluoclon and its esters, and can solve the problems of low production efficiency, low yield, unfavorable industrialized production, etc.

Inactive Publication Date: 2010-12-29
TIANJIN JINYAO GRP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Although the route for preparing fluocoron in the above-mentioned patent is feasible, the microbial fermentation method used to introduce β-hydroxyl at the 11-position and dehydrogenate at the 1 and 2 positions respectively has a feed rate of only 0.025%, low production efficiency,

Method used

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  • Preparation of fluorine-containing steroid hormone
  • Preparation of fluorine-containing steroid hormone
  • Preparation of fluorine-containing steroid hormone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0071] Preparation of embodiment 1 Fluocoron and Fluocoron 21-pivalate

[0072] Starting from 6α-fluoro-9,11-epoxy-17,21-dihydroxy-pregna-1,4-diene-3,20-dione-17,21-diacetate (I) , followed by 9, 11-epoxy ring opening, 9-position debromination reduction, 17-position deesterification to generate 16, 17-position double bonds, Grignard reaction 16-position methyl, get fluocorone 21-acetate, after hydrolysis Fluorocolon is obtained, and Fluorocorone is esterified to obtain the 21-position pivalate of Fluorocorone.

[0073] The reaction scheme is as follows:

[0074]

[0075] (1.1) 6α-fluoro-9α-bromo-11,17,21-trihydroxy-pregna-1,4-diene-3,20-dione-17,21-diacetate (1-II) preparation

[0076] 10g (I) and 40ml of acetic acid are dropped into the reaction flask under stirring, cooled to 10°C, then 10ml of hydrobromic acid is added dropwise in the reaction flask, monitored by thin-layer chromatography until no raw material is reacted, and the reaction time is 0.5 hour. The reacti...

Embodiment 2

[0087] The preparation of embodiment 2 fluoclon and fluoclon 21-butyrate

[0088] The reaction starts with 6α-fluoro-9,11-epoxy-17,21-dihydroxy-pregna-1,4-diene-3,20-dione-17,21-diacetate (I) 17-position deesterification to generate 16, 17-position double bond, 9, 11-epoxy ring opening, 9-position debromination reduction, 16, 17-position double bond through Grignard reaction, 16-position methyl, 21- Acetate is hydrolyzed to obtain fluoclon, and then esterified to obtain fluoclon 21-butyrate.

[0089]

[0090] (2.1) Preparation of 6α-fluoro-9,11-epoxy-21-hydroxy-pregna-1,4,16-triene-3,20-dione-21-acetate (2-II)

[0091] Put 10g of compound (I), 70ml of dimethylformamide, and 7g of potassium acetate into the reaction flask in turn, feed nitrogen gas, stir, and react at 125°C. Monitor with thin-layer chromatography until the reaction is complete. The reaction time is 1 hour, and then cooled When the temperature was below 40°C, the reaction solution was poured into 50 times i...

Embodiment 3

[0102] The preparation of embodiment 3 fluoclon and fluoclon 21-propionate

[0103] Starting from 6α-fluoro-9,11-epoxy-17,21-dihydroxy-pregna-1,4-diene-3,20-dione-17,21-diacetate (I) , followed by 9, 11-epoxy ring opening, 17-position deesterification to generate 16, 17-position double bond, 9-position debromination reduction, Grignard reaction 16-position methyl, get fluocorone 21-acetate, after hydrolysis Fluoroclon is obtained, and then esterified to obtain Fluoroclon 21-propionate.

[0104] The reaction scheme is as follows:

[0105]

[0106]

[0107] (3.1) 6α-fluoro-9α-bromo-11,17,21-trihydroxy-pregna-1,4-diene-3,20-dione-17,21-diacetate (3-II) preparation

[0108] Put 10g of compound (I) and 40ml of acetic acid into the reaction flask under stirring, the temperature is controlled at 25°C, then 12ml of hydrobromic acid is added dropwise into the reaction flask, and the reaction is completed by thin-layer chromatography monitoring until there is no raw material. T...

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Abstract

The invention provides application of compounds(I) of 6 alpha-fluorine-9,11-epoxy-17,21-dihydroxyl-pregnan-1,4-diene-3,20-dione-17,21-diacetate in preparing fluocortolone and 21-bit esters(Z) thereof. By reduction of bromine hydroxides at the 17th and 21st bits, degreasing and grignard reaction at the 16th and 17th bits, modification of methyl at the 16th bit and hydrolysis of acetate and esterification at the 21st bit, the compounds(I) are converted into the fluocortolone and the 21-bit esters(Z) thereof.

Description

technical field [0001] The present invention relates to the preparation method of steroid compound, especially relates to the preparation of fluocorolone and its ester. Background technique [0002] Fluocorolone and its esters are fluorine-containing corticosteroid drugs for topical application, which have anti-inflammatory activity and are often used in the form of ointments or creams for a variety of dermatological problems. For example: the product Ultralan is a combination of Fluocorolone and The compound preparation of fluocorone butyrate is used to treat various skin problems such as contact dermatosis, eczema, occupational eczema, ichthyosis, neurodermatitis, anal eczema, and dyshidrosis eczema. Schering AG has launched a product named Ultraproct, which is a combination of fluocoron pivalate and anesthetic lidocaine, which can effectively reduce the pain caused by hemorrhoids and the redness and swelling around the anus. [0003] Fluoroclon was first developed by Sch...

Claims

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Application Information

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IPC IPC(8): C07J5/00
Inventor 李桢李金禄
Owner TIANJIN JINYAO GRP
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