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Method for preparing optically active (S)-bufuralol by enzyme catalysis

A technology for catalytic preparation and optical activity, applied in the field of chiral compound synthesis, can solve the problems of low yield and optical purity, and achieve the effects of high optical purity of products, easy availability of raw materials and high yields

Inactive Publication Date: 2012-08-29
NANJING UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] The purpose of the present invention is to solve the problem of low yield and optical purity in the existing alcohol nitrilase catalyzed preparation of (S)-butyfuralol, and to provide a highly efficient enzyme-catalyzed preparation of optically active (S)-butyfurol The method of Er, this method is simple, economical, efficient, suitable for industrialized production, the product obtained has high optical purity

Method used

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  • Method for preparing optically active (S)-bufuralol by enzyme catalysis
  • Method for preparing optically active (S)-bufuralol by enzyme catalysis
  • Method for preparing optically active (S)-bufuralol by enzyme catalysis

Examples

Experimental program
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Effect test

Embodiment 1

[0033] The preparation of (S)-bufurolol catalyzed by the cross-linking enzyme polymer of almond nitrilase comprises the following steps:

[0034] (1) Preparation of almond nitrilase cross-linked enzyme polymer

[0035] Soak peach kernels with 0.1% (v / v) sodium hypochlorite aqueous solution for 3 hours, rinse with deionized water, dry, add 3% polyvinylpyrrolidone and potassium phosphate buffer (10mM, pH6.0, 100mL / 100mg) and homogenize Homogenize, filter, centrifuge the filtrate, and collect the supernatant. The supernatant is precipitated with ammonium sulfate at 0-30%, 30-80%, and the 30-80% precipitate is centrifuged, and the above-mentioned potassium phosphate buffer solution is used to dissolve the precipitate, dialyzed overnight, centrifuged, and the supernatant is collected. The above enzyme purification processes were all carried out at 4°C. Add 80% (v / v) ethylene glycol dimethyl ether to the supernatant at 0°C to precipitate the enzyme protein. Add 0.5% (v / v) glutara...

Embodiment 2

[0055] The preparation of (S)-bufurolol catalyzed by the cross-linking enzyme polymer of almond nitrilase comprises the following steps:

[0056] (1) Preparation of almond nitrilase cross-linked enzyme polymer

[0057] The preparation method is described in step (1) in Example 1.

[0058] (2) synthesis of formula 2 compound

[0059]

[0060] Take 13mmol, 600mg of almond alcohol nitrilase cross-linking enzyme polymer, add 0.75mL of citric acid buffer (pH value is 5.0, 0.15mol / L) and 15mL of methyl tert-butyl ether, 8mmol of acetonitrile alcohol, 30 ℃ constant temperature conditions After reacting for 48 hours, the reaction liquid was filtered and concentrated under reduced pressure to obtain product 2.

[0061] (3) synthesis of formula 3 compounds

[0062]

[0063] Add 5 mL of CH to 2 2 Cl 2 Dissolve, acetyl chloride 6mmol, 0.06mmol PPY, react at room temperature for 1.5 hours, add 25mL CH 2 Cl 2 and 25 mL saturated NaHCO 3 solution, the aqueous phase was then CH ...

Embodiment 3

[0077] Lilinol nitrilase cross-linking enzyme polymer catalyzes the preparation of (S)-bufurolol, and the specific steps include:

[0078] (1) Preparation of linalonitrile enzyme cross-linked enzyme polymer

[0079] The preparation method is as described in step (1) in Example 1.

[0080] (2) synthesis of formula 2 compound

[0081]

[0082] Take 13mmol, 1000mg of linaloyl nitrilase cross-linking enzyme polymer, add 1.5mL of citric acid buffer (pH value is 5.5, 0.2mol / L) and 15mL of diisopropyl ether, HCN12mmol, and react for 24 hours under constant temperature at 40°C Afterwards, the reaction solution was filtered and concentrated under reduced pressure to obtain product 2.

[0083] (3) synthesis of formula 3 compounds

[0084]

[0085] Add 5 mL of CH to 2 2 Cl 2 Dissolve, 9mmol acetic acid, 0.3mmol DMAP, react at room temperature for 1 hour, add 25mL CH to the reaction solution 2 Cl 2 and 25 mL saturated NaHCO 3 solution, the aqueous phase was then CH 2 Cl 2 ...

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Abstract

The invention provides a method for preparing optically active (S)-bufuralol by enzyme catalysis. By taking 7-ethylbenzofuran-2-formaldehyde as a raw material, the (S)-bufuralol is obtained through the catalysis asymmetric cyanation of cross-linked enzyme aggregates (CLEA for short) of (R)-hydroxynitrile lyase [(R)-Oxynitrilase], hydroxyl protection, Ritter reaction and amide reduction reaction. The preparation method for the (S)-bufuralol has the advantages that the reaction steps are simple, the reaction condition is mild, the yield is high and the optical purity of the obtained (S)-bufuralol is high.

Description

technical field [0001] The invention relates to the technical field of chiral compound synthesis, in particular to a preparation method of (S)-bufurolol. Background technique [0002] (S)-Bufuralol English name is (S)-bufuralol, chemical name is (S)-1-(7-ethylbenzofuran-2-yl)-2-tert-butylamino-1-ethanol , is widely used as a substrate for the study of cytochrome P450 (CYP) enzymes, has non-selective blocking effect on β-adrenergic receptors, and can be used to treat mild and moderate hypertension, (S)-bufurolol The blocking performance of β-receptor is 100 times stronger than that of (R)-bufurolol. [0003] So far, the preparation method of the optically active butfuralol of literature report mainly contains: (1) racemic 1-(7-ethylbenzofuran-2-yl)-2-substituent-1-ethanol is The substrate is subjected to a hydroxyl esterification resolution reaction; (2) a carbonyl asymmetric hydrogenation reduction reaction is carried out with 1-(7-ethylbenzofuran-2-yl)-2-substituent-1-ace...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P17/04
Inventor 韩世清褚朝森周双利
Owner NANJING UNIV OF TECH
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