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Chemical and biological synthesis method for large-scale preparation of nicotinamide adenine dinucleotide

A technology for synthesizing nicotinamide adenine and nicotinamide adenine, which is applied in fermentation and other directions, can solve problems such as hindering the development of biocatalysis technology, difficulty in extraction, and low yield, and achieve the goals of promoting development, increasing yield, and reducing costs Effect

Active Publication Date: 2013-08-07
ZHEJIANG JIAHUA CHEM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] At present, NAD is mostly extracted from animals and plants, which has the disadvantages of low yield, high cost, and difficult extraction, which greatly hinders the development of modern biocatalytic technology.
At present, there is no large-scale production of NAD by chemical and biological methods. If NAD can be produced on a large scale by chemical and biological synthesis methods, it will have great social significance and economic benefits.

Method used

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  • Chemical and biological synthesis method for large-scale preparation of nicotinamide adenine dinucleotide

Examples

Experimental program
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Effect test

Embodiment 1

[0024] Add 20 kg of tetraacetylribose to No. 1 reactor, dissolve it with 200 kg of tetrahydrofuran, then add 10 kg of ethyl nicotinate, and directly add 5 kg of methyl trifluoromethanesulfonate. The temperature was raised to produce reflux, and timing was started after reflux, and the reaction was carried out for 3 hours. After the reaction, the solvent was recovered under reduced pressure, and after recovery, 150 kg of ethanol was added for dissolution.

[0025] Pump 150 kg of ethanol into the No. 2 reaction kettle, turn on the freezer and cool down to -5°C. Open the decompression valve of the liquefied ammonia steel cylinder, start to pass through the ammonia, measure it, and after feeding 10 kilograms of ammonia, finish the flow through the ammonia. Freeze and cool down to below -10°C to obtain low-temperature ammonia ethanol. Drop the low-temperature ammonia ethanol into the No. 1 reaction kettle. After the dropwise addition, start timing, accurately control the reaction...

Embodiment 2

[0028] Add 100 kg of tetraacetylribose to No. 3 reactor, dissolve it with 1000 kg of dioxane, then add 50 kg of ethyl nicotinate, and directly add 25 kg of methyl trifluoromethanesulfonate. The temperature was raised to produce reflux, and timing was started after reflux, and the reaction was carried out for 3 hours. After the reaction was completed, the solvent was recovered under reduced pressure, and after the recovery was completed, 750 kg of ethanol was added for dissolution.

[0029] Pump 750 kg of ethanol into the No. 4 reactor, turn on the freezer and cool down to -5°C. Open the decompression valve of the liquefied ammonia steel cylinder, start to pass through the ammonia, measure, after feeding 50 kilograms of ammonia, end the flow through the ammonia. Freeze and cool down to below -10°C to obtain low-temperature ammonia ethanol. Drop the low-temperature ammonia ethanol into the No. 3 reaction kettle. After the dropwise addition, start timing, accurately control the...

Embodiment 3

[0032] Add 200 kg of tetraacetylribose to No. 5 reactor, dissolve it with 2000 kg of tetrahydrofuran, then add 100 kg of ethyl nicotinate, and directly add 50 kg of methyl trifluoromethanesulfonate. The temperature was raised to produce reflux, and timing was started after reflux, and the reaction was carried out for 3 hours. After the reaction, the solvent was recovered under reduced pressure, and after recovery, 1500 kg of ethanol was added for dissolution.

[0033] Pump 1500 kg of ethanol into the No. 6 reactor, turn on the freezer and cool down to -5°C. Open the decompression valve of the liquefied ammonia steel cylinder, start to pass through the ammonia, measure it, and after feeding 100 kilograms of ammonia, finish the flow through the ammonia. Freeze and cool down to below -10°C to obtain low-temperature ammonia ethanol. Drop the low-temperature ammonia ethanol into the No. 5 reaction kettle. After the dropwise addition, start timing, accurately control the reaction ...

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Abstract

The invention relates to a chemical and biological synthesis method for large-scale preparation of nicotinamide adenine dinucleotide (NAD). According to the invention, ribofuranose tetraacetate and ethyl nicotinate are adopted as initial raw materials, and the following steps are carried out that: (1) a refluxing reaction is carried out; (2) ammonia ethanol is dropped under a low temperature, such that a reaction is carried out; (3) phosphorus trichloride is dropped under a low temperature, such that a reaction is carried out; and (4) extraction, separation, and purification are carried out, and the material is added into cell fluid and is biologically converted into nicotinamide adenine dinucleotide; and a pure product is obtained by purification and drying.

Description

technical field [0001] The invention relates to a method for large-scale preparation of nicotinamide adenine dinucleotide by chemical biosynthesis. Background technique [0002] Nicotinamide adenine dinucleotide (NAD for short) is the coenzyme of dehydrogenase, also known as coenzyme I, which plays an irreplaceable role in glycolysis, gluconeogenesis, tricarboxylic acid cycle and respiratory chain. The product will pass the hydrogen off to NAD, making it NADH. NADH will act as a carrier of hydrogen to synthesize ATP through chemiosmotic coupling in the respiratory chain. [0003] NAD is one of the essential coenzymes in modern biocatalytic reactions. Leucine dehydrogenase, ammonia formate dehydrogenase, and glucose dehydrogenase all need the help of NAD to complete the entire reaction. [0004] Because NAD is a coenzyme for a large number of oxidoreductases in humans and animals, it can also be used as a direct template for drug design, or to design enzyme inhibitors or st...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P19/36
Inventor 施自恩周少华林军许康林
Owner ZHEJIANG JIAHUA CHEM
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