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Synthetic method of 16-ene-20-hydroxy steroid compound

A technology of steroidal compounds and hydroxysteroids, applied in the direction of steroidal compounds, chemical instruments and methods, organic chemistry, etc., can solve the problems of no industrial production value, low selectivity, complicated reaction operation, etc., and reach the price of reagents Inexpensive, short reaction time, high chemoselectivity effect

Inactive Publication Date: 2016-09-14
SHANGHAI INST OF ORGANIC CHEM CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] For method one, its conversion rate is low, and only 18% of 16-ene-20-hydroxyl steroid compounds have been generated in two hours, the ratio of main product and by-product is 10:1, and the selectivity is not very high
And for method two, this reaction operation complexity, catalyst Cp 2 Hf(O-i-Pr) 2 It needs to be prepared, and the conversion rate is low. Only 20% of 16-ene-20-hydroxy steroid compounds are produced at 80°C in 98 hours, and there is no good industrial production value

Method used

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  • Synthetic method of 16-ene-20-hydroxy steroid compound
  • Synthetic method of 16-ene-20-hydroxy steroid compound
  • Synthetic method of 16-ene-20-hydroxy steroid compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 120

[0028] Example 120 Synthesis of α-hydroxy-pregna-4,16(17)-dien-3-one (II-1)

[0029]

[0030] In 3.12 grams (0.01 moles) of steroidal compound pregna-4,16(17)-diene-3,20-dione (English name 16-dehydro-Δ 4 -progestene-3,20-diones) (I-1), add 40 mL of glacial acetic acid, 20 mL of dichloromethane and 0.4 mL of water, stir at 0 ° C, then add 6.54 g (0.1 mole) of zinc powder, thin-layer chromatography The reaction was monitored by TLC until complete (about 3 hours). Post-treatment: filter out the zinc powder, spin off the dichloromethane, slowly pour the system into 400mL of water, stir for 30 minutes, filter, and dry in the air. Recrystallized with ethyl acetate to obtain 2.1 g of white solid, the filtrate was spin-dried and then column chromatographed to obtain 0.755 g of white solid, and finally 2.855 g of white solid 20α-hydroxy-pregna-4,16(17)-di En-3-one (English name is 16-dehydro-20α-hydroxy-Δ 4 -progesten-3-one) (II-1), the isolated yield is 90.8%.

[0031] Compoun...

Embodiment 220

[0032] Example 220 Synthesis of α-hydroxy-pregna-4,16(17)-dien-3-one (II-1)

[0033]

[0034] In 0.312 grams (0.001 moles) of steroidal compound pregnane-4,16(17)-diene-3,20-dione (English name is 16-dehydro-Δ 4 -progestene-3,20-diones) (I-1) was added 4 mL of acetic acid, stirred at 25°C, and then 0.654 g (0.01 mol) of zinc powder was added, and the reaction was monitored by thin layer chromatography (TLC) until it was complete. Post-treatment: filter out zinc powder, slowly add saturated sodium carbonate solution to the filtrate until no gas is produced. Separate the liquid, extract the aqueous phase twice with 15 mL ethyl acetate each time, combine the organic phases, then wash with water, wash with saturated brine, dry over anhydrous sodium sulfate, spin the filtrate and perform column chromatography to obtain 0.280 g of white solid 20α-hydroxyl -Pregnant-4,16(17)-diene-3-one (English name is 16-dehydro-20α-hydroxy-Δ 4 -progesten-3-one) (II-1), the isolated yield was ...

Embodiment 320

[0035] Example 320 Synthesis of α-hydroxy-pregna-4,16(17)-dien-3-one (II-1)

[0036]

[0037] In 0.312 grams (0.001 moles) of steroidal compound pregnane-4,16(17)-diene-3,20-dione (English name is 16-dehydro-Δ 4 -progestene-3,20-diones) (I-1) was added propionic acid 4mL, stirred at 25°C, then 0.654g (0.01mol) zinc powder was added, and the reaction was monitored by thin layer chromatography (TLC) until complete. Post-treatment: filter out zinc powder, slowly add saturated sodium carbonate solution to the filtrate until no gas is generated. Separate the liquid, extract the aqueous phase twice with 15 mL ethyl acetate each time, combine the organic phases, then wash with water, wash with saturated saline, dry over anhydrous sodium sulfate, spin the filtrate and perform column chromatography to obtain 0.265 g of white solid 20α-hydroxyl -Pregnant-4,16(17)-diene-3-one (English name is 16-dehydro-20α-hydroxy-Δ 4 -progesten-3-one) (II-I), the isolated yield was 84.3%.

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Abstract

The invention provides a synthetic method for 16-alkene-20-hydroxy steroid, which can be applied to synthesis of intermediates of steroid drugs. The 16-alkene-20-hydroxy steroid has a structural formula as shown in the specification, and 16-alkene-20-ketone steroid hasa structural formula a shown in the specification. According to the method, in the presence or absence of an organic solvent or water, zinc powder is used as a reductant, acetic acid is used as an additive, and the 16-alkene-20-ketone steroid is reduced to obtain the 16-alkene-20-hydroxy steroid. The reaction has high chemoselectivity, regioselectivity and stereoselectivity. The reaction condition is mild, the reagent is cheap, the operation is simple, and industrial scale production is easy.

Description

technical field [0001] The invention relates to a synthesis method of 16-en-20 hydroxy steroid compound, which can be highly selectively reduced under the simultaneous presence of 4-en-3-one and 16-en-20-one to obtain 16-en-20 Hydroxysteroids. Background technique [0002] Steroidal drugs refer to hormonal drugs containing cyclopentane polyhydrophenanthrene core structure in their molecular structure. Typical varieties include dexamethasone, prednisone, betamethasone, and hydrocortisone. The synthesis and application of steroidal drugs and antibiotics are called the two most striking achievements of the pharmaceutical industry in the 20th century. They have significant clinical effects in the preparation of health products, treatment of respiratory diseases, endocrine disorders, tumors and other diseases. [0003] Steroidal corticosteroids have been using dienes obtained from the degradation of diosgenin as starting materials for many years, but the production process of di...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07J7/00C07J9/00C07J75/00
CPCC07J7/0005C07J9/00C07J75/00
Inventor 丁凯曹伟
Owner SHANGHAI INST OF ORGANIC CHEM CHINESE ACAD OF SCI