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Method for catalytically synthesizing atazanavir intermediate

A technology of atazanavir and intermediates, applied in the direction of fixing on or in inorganic carriers, chemical industry, sustainable manufacturing/processing, etc., to achieve the effects of improving regeneration efficiency, reducing dosage, and reducing production costs

Active Publication Date: 2015-09-16
NANJING UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In existing reports, there is no co-immobilization of carbonyl reductase and coenzyme for the preparation of atazanavir intermediate (3S)-3-(tert-butoxycarbonyl)amino-1-chloro-4-benzene Report on the group-(2R)-butanol

Method used

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  • Method for catalytically synthesizing atazanavir intermediate
  • Method for catalytically synthesizing atazanavir intermediate
  • Method for catalytically synthesizing atazanavir intermediate

Examples

Experimental program
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Effect test

Embodiment 1

[0029] Example 1 This example illustrates the method for obtaining the modified magnetic mesoporous material

[0030] Weigh 1 g SBA-15 and add it to the content of 1.75 g (NH 4 ) 2 Fe(SO 4 ) 2 .6H 2 O, 4.29 g NH 4 Fe(SO 4 ) 2 .12H 2 In the aqueous solution of O, adjust the pH to 11~12 with 5 M ammonia water, stir at 65°C for 30 min, and magnetically adsorb to obtain the mesoporous material SBA-15 / Fe containing magnetism. 3 O 4 . Weigh 1 g SBA-15 / Fe 3 O 4 Add to 500 ml of ethanol aqueous solution (V / V=1:1), stir under the protection of argon, add glacial acetic acid to pH 4.0, add 50 ml of 3-aminopropyl triethoxy group dropwise to the system Silane, stirred at 60°C for 24 hours, magnetically adsorbed, and washed with ethanol three times to obtain the modified magnetic mesoporous material SBA-15 / Fe 3 O 4 -NH 2 .

Embodiment 2

[0031] Example 2 This example illustrates the method of obtaining a co-immobilized enzyme

[0032] Weigh 50 mg of coenzyme NAD and add it to 10 ml of phosphate buffer (pH 7.0) containing 50 mg / ml carbonyl reductase, and let stand at 4°C for 1 h; add 1.5 g of SBA prepared in Example 1 to the above solution -15 / Fe 3 O 4 -NH 2 , 25℃, 100-150 rpm, incubate for 8 h, obtain the suspension, remove the supernatant by magnetic adsorption, wash the precipitate with physiological saline, repeat three times, the obtained solid is the co-immobilized enzyme of carbonyl reductase and coenzyme, freeze-dried Store at 4°C for later use.

Embodiment 3

[0033] Example 3 This example illustrates another method of co-immobilizing enzymes

[0034] Weigh 50 mg of coenzyme NADP and add it to 10 ml of phosphate buffer (pH 7.0) containing 50 mg / ml ketoreductase, and let stand at 4°C for 1 h; add 1.5 g of SBA prepared in Example 1 to the above solution -15 / Fe 3 O 4 -NH 2 , 25℃, 100-150 rpm, warm bath for 8 hours, obtain the suspension, remove the supernatant by magnetic adsorption, wash the precipitate with physiological saline, repeat three times, the obtained solid is the co-immobilized enzyme of carbonyl reductase and coenzyme, freeze-dried Store at 4°C for later use.

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PUM

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Abstract

The invention discloses a method for catalytically synthesizing an atazanavir intermediate, which comprises the following steps: preparing a magnetic modified mesoporous material, co-immobilizing a carbonyl reduction enzyme and a coenzyme in the magnetic mesoporous material, and catalyzing (3S)-3-(tert-butyloxycarbonyl)amino-1-chloro-4-phenyl-(2R)-butanone by using the immobilized enzyme to generate the (3S)-3-(tert-butyloxycarbonyl)amino-1-chloro-4-phenyl-(2R)-butanol intermediate. The method has the advantages of high recovery rate of the carbonyl reduction enzyme and coenzyme, high regeneration efficiency of the coenzyme, low cost, wide market prospects and the like.

Description

Technical field [0001] The invention relates to a carbonyl reductase and coenzyme co-immobilization system to catalyze the synthesis of atazanavir intermediate (3S)-3-(tert-butoxycarbonyl)amino-1-chloro-4-phenyl-(2R)-butan The alcohol method belongs to the fields of biotechnology and biopharmaceuticals. Background technique [0002] At present, there are three main types of AIDS treatment drugs. Among them, protease inhibitors (Pls) have a strong anti-HIV effect and are currently frequently used drugs (about 26%). Atazanavir, an anti-HIV protease inhibitor, is currently the world's main anti-AIDS drug. In 1998, Bristol-Myers Squibb developed a commercial drug of atazanavir-atazanavir sulfate, which was approved by the US FDA in June 2003. This is the world's first once-daily drug A protease inhibitor, which is mainly used in combination with other antiretroviral drugs to treat the HIV virus. China also approved its listing in April 2007, under the trade name Rui Aito ? . [0003...

Claims

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Application Information

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IPC IPC(8): C12P13/02C12N11/14
CPCY02P20/50
Inventor 黄和唐苏苏江凌徐晴徐娴
Owner NANJING UNIV OF TECH
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