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Preparation method of D-pantoic acid inner ester

A pantothenolactone and pantothenic acid technology, applied in the field of biosynthesis, can solve the problems of high VOC emissions, difficult wastewater treatment, raw material toxicity, etc., and achieve the effects of low cost, easy conversion process, and good product quality

Active Publication Date: 2018-08-28
JING JING PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Aiming at the problems of high raw material toxicity, high cost, difficult wastewater treatment, and high VOC emissions in the existing preparation process, the present invention provides a preparation method of D-pantolactone

Method used

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preparation example Construction

[0012] The embodiment of the present invention provides a preparation method of D-pantolactone, the preparation method at least includes the following steps:

[0013] (1) Under the action of catalase and α-ketoisovalerate reductase, valine is subjected to enzymatic conversion to obtain α-ketoisovalerate;

[0014] (2) reacting the α-ketoisovaleric acid and tetrahydrofolate under the action of hydroxymethyltransferase and magnesium chloride to prepare ketopantoic acid;

[0015] (3) performing enzymatic conversion of the ketopantoate under the action of α-ketoisovalerate reductase to obtain pantoate;

[0016] (4) preparing the pantoate to obtain the pantoate lactone.

[0017] Compared with the prior art, in the preparation method of D-pantolactone provided by the present invention, cheap and easy-to-obtain valine is catalyzed and converted by a biological enzymatic method to prepare pantoic acid. The invention has simple operation process, mild conversion conditions, high produ...

Embodiment 1

[0036] This implementation provides a kind of preparation method of D-pantolactone, and described preparation method comprises the following steps:

[0037] (1) Put 58.8g of valine into 850mL of water, control the temperature within the range of 25-40°C, use dilute sulfuric acid and sodium hydroxide to dissolve and adjust the pH value to 4.0-9.0, and simultaneously put 2.5g of valine into the feed liquid Catalase and 3g of α-ketoisovalerate reductase, carry out enzymatic conversion reaction, the pH value is 4.0-9.0 during the reaction, transform 2 hours and take samples to detect the generation amount of α-ketoisovalerate and the content of valine Residual amount, when the remaining valine is less than 3%, the reaction is considered to be complete, the reaction is terminated, and the α-ketoisovaleric acid feed liquid is obtained by filtration;

[0038] (2) The α-ketoisovaleric acid feed solution obtained in step (1) is warmed up to 60-75° C., and after being incubated for 30 m...

Embodiment 2

[0042] This implementation provides a kind of preparation method of D-pantolactone, and described preparation method comprises the following steps:

[0043](1) Ketopantoic acid can also be prepared by a chemical method, which is prepared by reacting isobutyraldehyde, formaldehyde and diethyl oxalate: in sodium methoxide solution, add diethyl oxalate and isobutyraldehyde under stirring at room temperature Butyraldehyde, after stirring and reacting for 2 hours, heat up to 25-35°C, add sodium hydroxide or triethylamine solution dropwise, continue to react for 4-5 hours, then control the temperature at 30-40°C, add dropwise an equimolar amount of sodium methoxide 37wt% formaldehyde solution, stirred and reacted for 6-15 hours, cooled to 10°C, acidified with sulfuric acid, kept at temperature above 30°C for no less than 2 hours, removed methanol and generated salt, adjusted pH with ammonia water or sodium hydroxide , the residue is extracted with ethyl acetate, the ethyl acetate is...

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Abstract

The invention relates to the technical field of biosynthesis, and concretely discloses a preparation method of D-pantoic acid inner ester. The preparation method at least comprises the following stepsthat 1, valine is subjected to enzymatic conversion under the effects of catalase and alpha-ketoisovaleric acid reductase to obtain alpha-ketoisovaleric acid; 2, the alpha-ketoisovaleric acid and tetrahydrofolic acid react under the effects of hydroxylmethyl transferase and magnesium chloride to prepare ketopantoic acid; 3, ketopantoic acid is subjected to enzymatic conversion under the effects of alpha-ketoisovaleric acid reductase to obtain pantoic acid; 4, pantoic acid is prepared into the pantoic acid inner ester. The operation process is simple; the conversion condition is mild; the production efficiency is high; the product quality is high; the enzyme used in the process can be cyclically used; the preparation method belongs to an energy-saving, environment-friendly, green and efficient production technology; the industrial production is convenient.

Description

technical field [0001] The invention relates to the technical field of biosynthesis, in particular to a preparation method of D-pantolactone. Background technique [0002] D-pantothenate lactone is an important API intermediate, mainly used for calcium D-pantothenate (D-(+)-N-(2,4-dihydroxy-3,3-dimethylbutyryl )-β-alanine calcium) and D-panthenol synthesis. In the prior art, some use isobutyraldehyde, formaldehyde and sodium cyanide as raw materials to obtain DL-pantolactone through chemical synthesis, and DL-pantolactone is then generated into D-pantolactone under the action of Fusarium moniliforme Deacidification, D-pantoate lactone is obtained through lactonization, but this method uses sodium cyanide with high toxicity, which has a large safety risk in actual production operations, and the waste water is not easy to treat. Using DL-pantoate lactone The process of preparing D-pantolactone from ester is cumbersome and inefficient. In the prior art, Fusarium oxysporum is...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P17/04
CPCC12P17/04
Inventor 何连顺李斌水米造吉马腾
Owner JING JING PHARMA
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