CN113173900A

CN113173900A - Synthetic method of vitreous chromogen

Info

Publication number: CN113173900A
Application number: CN202110384696.2A
Authority: CN
Inventors: 韩津; 蓝艳
Original assignee: Hainan Quark Technology Co ltd
Current assignee: Hainan Quark Technology Co ltd
Priority date: 2021-04-09
Filing date: 2021-04-09
Publication date: 2021-07-27

Abstract

The invention discloses a synthetic method of a vitreous chromogen, which comprises the following steps: taking xylose and acetoacetic ester as raw materials, carrying out condensation reaction under the action of an alkaline compound as a catalyst, and hydrolyzing and decarboxylating to obtain an intermediate; then reducing the obtained intermediate to obtain the product vitronectin. The invention adopts the conventional alkaline compound as the catalyst to carry out the condensation reaction, has high yield and is suitable for industrial production.

Description

Synthetic method of vitreous chromogen

Technical Field

The invention relates to the field of organic synthesis, in particular to a synthetic method of a vitronectin.

Background

Boseine, known under the scientific name hydroxypropyl tetrahydropyrane triol, is a bioactive ingredient developed by Eriya in 2006 for use in cosmetics. The gel can promote the generation and the construction of protein polysaccharide in extracellular matrix, absorb water, enable the matrix to be in a gel shape, and increase the compactness of cells and skin; it also can stimulate aging cells, promote regeneration of damaged tissue, help maintain elasticity of dermis, and prevent skin aging. Researches show that the vitreous color is easy to biodegrade, cannot be accumulated in organisms and has no toxicity, and the application heat of the vitreous color in the fields of biology, medicines, cosmetics and the like is further increased due to the characteristic.

For the synthesis method of the vitronectin, only some chemical synthesis documents are reported at home at present, but a plurality of steps of reactions are often needed, the process is complex, and the cost is higher.

CN110467591A discloses a method for synthesizing vitronectin by a one-pot method promoted by a rare earth metal complex, which uses the rare earth metal complex as a catalyst to catalyze the glycosylation of xylose and ethyl acetoacetate and simultaneously catalyze the hydrolysis decarboxylation and carbonyl reduction of an ester group, and the yield is more than 80%. The catalyst used in the method has a complex structure and is difficult to prepare, and the production cost of the integral synthesis process is high.

CN111876452 discloses a method for preparing vitreous chromogen by using a biological enzyme one-pot method, which takes xylose and isopropanol as substrates and generates the vitreous chromogen under the catalysis of isopropanol dehydrogenase, vitreous chromogen synthetase, carbonyl reductase and coenzyme nicotinamide adenine dinucleotide. Although the method is green and environment-friendly, the used biological enzyme preparation is not easy to prepare, the filtration requirement of post-treatment is higher, corresponding special treatment instruments are required, and the method is not suitable for industrial production.

Disclosure of Invention

Aiming at the problem that the catalyst in the prior art is difficult to prepare, the invention provides a method for preparing a vitronectin intermediate by using xylose and acetoacetic ester substances as raw materials, adopting a conventional alkaline compound as a catalyst to perform condensation reaction, simultaneously performing hydrolysis and decarboxylation, and then reducing carbonyl in the intermediate product to obtain the vitronectin intermediate. The method of the invention only adopts the conventional alkaline compound as the catalyst to carry out the condensation reaction, has high yield and is suitable for industrial production.

In order to achieve the purpose, the technical scheme of the invention is as follows:

a method for synthesizing a vitronectin, comprising the following steps:

(1) taking xylose and acetoacetic ester as raw materials, carrying out condensation reaction under the action of an alkaline compound as a catalyst, and hydrolyzing and decarboxylating to obtain an intermediate I;

(2) and (3) reducing the intermediate I obtained in the step (1) to obtain a product boscalid.

The acetoacetic ester substance in the step (1) of the invention is one selected from the group consisting of ethyl acetoacetate, propyl acetoacetate, isopropyl acetoacetate, butyl acetoacetate, isobutyl acetoacetate and tert-butyl acetoacetate.

In the step (1), the alkaline compound is preferably sodium bicarbonate, potassium bicarbonate, sodium carbonate, potassium carbonate, lithium carbonate, sodium hydroxide, potassium hydroxide or lithium hydroxide, wherein the amount of the alkaline compound is 1-10% of the amount of the xylose substance, and preferably 1-5%.

The mass ratio of the acetoacetic ester substance to the xylose substance is (1-5): 1, preferably (1-1.5): 1.

in the condensation reaction process in the step (1), the reaction temperature is 25-150 ℃, and preferably 50-90 ℃. The reaction time is 0.5-36 h, preferably 2-10 h.

Further, in the step (2), the intermediate I obtained in the step (1) is subjected to a reduction reaction with hydrogen under the condition of a catalyst to obtain the vitronectin.

The catalyst is a Raney type catalyst and/or a transition metal supported catalyst; the Raney type catalyst is preferably one or the combination of more of Raney nickel, Raney cobalt, Raney palladium and Raney copper; the transition metal supported catalyst is preferably one or more of palladium/carbon, platinum/carbon, ruthenium/carbon, nickel/alumina, platinum/alumina, palladium/ferroferric oxide, nickel-copper/alumina, rhodium/silica and platinum-rhodium/alumina.

The using amount of the catalyst is 1-5% of the mass of the intermediate obtained in the step (1).

The pressure of the hydrogen is 1-8 MPa, and the reaction temperature is preferably 50-150 ℃ and preferably 50-80 ℃.

The solvent is preferably one or more of water, methanol, ethanol, isopropanol and tetrahydrofuran.

Compared with the prior art, the method has the beneficial effects that the conventional alkaline compound is used as the catalyst for condensation reaction, so that the reaction yield is high; in addition, the catalyst can also be hydrolyzed and decarboxylated without adding other alkaline substances, so that the side reaction is less; in addition, the catalyst is common and easy to obtain, does not need preparation, has low price and low production cost, and is suitable for industrial production.

Detailed Description

The invention is further illustrated by the following specific examples.

Example 1

500g of ethanol, 30g (0.2mol) of xylose, 0.17g (2mmol) of sodium bicarbonate and 26g (0.2mol) of ethyl acetoacetate were sequentially added to a 1000mL reaction flask and stirred uniformly. After the reaction was carried out for 10 hours while heating to 50 ℃, the reaction solution was checked by TLC until xylose was substantially disappeared (GF254 silica gel plate, developing solvent dichloromethane: methanol 4:1, 20% ethanol sulfate solution was developed), and the reaction was completed. Cooling, adjusting pH to neutral with 2mol/L hydrochloric acid, concentrating, evaporating to remove solvent and low boiling point substance, dissolving in 500ml ethanol, filtering, and distilling the filtrate under reduced pressure to obtain brown oily substance.

Transferring the brown oily substance obtained in the previous step into a 500mL high-pressure kettle, adding 1.9g of Raney nickel catalyst and 300mL of isopropanol, sealing the high-pressure kettle, introducing nitrogen, replacing air in the kettle for three times, introducing hydrogen, adding to the required pressure, checking to ensure that the reaction kettle is airtight, then introducing hydrogen to evacuate, repeating for three times, stirring and heating to 80 ℃, maintaining the hydrogen pressure at 5MPa, reacting for 6h, stopping the reaction, cooling, evacuating the hydrogen, extracting the reaction liquid in the kettle, filtering to remove the catalyst, and carrying out reduced pressure distillation and concentration to obtain a light yellow oily substance, namely, the vitreous chromone, wherein the yield is 80.8%.

¹H NMR(DMSO)δ＝4.25(brs,4H),3.77(m,1H),3.67(m,1H),3.24(m,1H),3.14(m,1H),2.95(m,2H),2.82(m,1H),1.72(m,1H),1.46(m,1H),1.04(d,3H).

Example 2

500g of isopropanol, 30g (0.2mol) of xylose, 0.4g (0.01mol) of sodium hydroxide and 43.2g (0.3mol) of isopropyl acetoacetate were sequentially added to a 1000mL reaction flask and stirred uniformly. After the reaction was carried out for 2 hours while heating to 90 ℃, the reaction solution was checked by TLC until xylose was substantially disappeared (GF254 silica gel plate, developing solvent dichloromethane: methanol 4:1, 20% ethanol sulfate solution was developed), and the reaction was completed. Cooling, adjusting pH to neutral with 2mol/L hydrochloric acid, concentrating, evaporating to remove solvent and low boiling point substance, dissolving in 500ml ethanol, filtering, and distilling the filtrate under reduced pressure to obtain brown oily substance.

Transferring the brown oily substance obtained in the previous step into a 500mL high-pressure kettle, adding 1.1g of ruthenium/carbon catalyst and 300mL of ethanol, sealing the high-pressure kettle, introducing nitrogen to replace air in the kettle for three times, repeating the steps for three times, introducing hydrogen, adding the hydrogen to the required pressure, testing to ensure that the reaction kettle is airtight, stirring, heating to 70 ℃, maintaining the hydrogen pressure at 8MPa, reacting for 8 hours, stopping the reaction, cooling, slowly discharging the exhausted hydrogen, stopping stirring, pumping out the reaction liquid in the kettle, filtering to remove the catalyst, and carrying out reduced pressure distillation and concentration to obtain a light yellow oily substance, namely, the vitreous color factor, wherein the yield is 86.6%.

Example 3

A1000 mL reaction flask was charged with 500g of methanol, 30g (0.2mol) of xylose, 0.34g (6mmol) of potassium hydroxide, and 38g (0.24mol) of isobutyl acetoacetate in this order, and the mixture was stirred uniformly. After the reaction was carried out for 6 hours while heating to 80 ℃, the reaction solution was checked by TLC until xylose was substantially disappeared (GF254 silica gel plate, developing solvent dichloromethane: methanol 4:1, 20% ethanol sulfate solution was developed), and the reaction was completed. Cooling, adjusting pH to neutral with 2mol/L hydrochloric acid, concentrating, evaporating to remove solvent and low boiling point substance, dissolving in 500ml ethanol, filtering, and distilling the filtrate under reduced pressure to obtain brown oily substance.

Transferring the brown oily substance obtained in the previous step into a 500mL high-pressure kettle, adding 0.4g of palladium/carbon catalyst and 300mL of methanol, sealing the high-pressure kettle, introducing nitrogen to replace air in the kettle for three times, repeating the steps for three times, introducing hydrogen, adding the hydrogen to the required pressure, testing to ensure that the reaction kettle is airtight, stirring, heating to 50 ℃, maintaining the hydrogen pressure at 1MPa, reacting for 12 hours, stopping the reaction, cooling, slowly discharging the exhausted hydrogen, stopping stirring, pumping out the reaction liquid in the kettle, filtering to remove the catalyst, and carrying out reduced pressure distillation and concentration to obtain a light yellow oily substance, namely, vitreous chromone, wherein the yield is 89.6%.

The foregoing description of specific embodiments of the present invention has been presented. It is to be understood that the invention is not limited to the embodiments described above, which are described in the specification only to illustrate the principles of the invention. The invention also includes various insubstantial changes and modifications within the spirit of the invention, as claimed by those skilled in the art.

Claims

1. A method for synthesizing a vitronectin, comprising the following steps:

2. The method according to claim 1, wherein the acetoacetate is selected from one of ethyl acetoacetate, propyl acetoacetate, isopropyl acetoacetate, butyl acetoacetate, isobutyl acetoacetate, and tert-butyl acetoacetate.

3. The process according to claim 1 or 2, characterized in that the basic compound is sodium bicarbonate, potassium bicarbonate, sodium carbonate, potassium carbonate, lithium carbonate, sodium hydroxide, potassium hydroxide or lithium hydroxide.

4. A method according to any one of claims 1 to 3, characterized in that the amount of said basic compound is 1 to 10%, preferably 1 to 5% of the amount of monosaccharide substance; the mass ratio of the acetoacetic ester substance to the monosaccharide is (1-5): 1, preferably (1-1.5): 1.

5. a process according to any one of claims 1 to 3, characterized in that the reaction temperature during the condensation reaction in step (1) is from 25 to 150 ℃, preferably from 50 to 90 ℃.

6. The method according to claim 1, wherein the step (2) is to perform a reduction reaction of the intermediate I obtained in the step (1) with hydrogen under the condition of a catalyst to obtain the vitreous chromogen.

7. The process according to claim 6, characterized in that the catalyst is a Raney-type catalyst and/or a transition metal supported catalyst.

8. The process according to claim 7, characterized in that the Raney-type catalyst is preferably one or a combination of more of Raney nickel, Raney cobalt, Raney palladium, Raney copper; the transition metal supported catalyst is preferably one or more of palladium/carbon, platinum/carbon, ruthenium/carbon, nickel/alumina, platinum/alumina, palladium/ferroferric oxide, nickel-copper/alumina, rhodium/silica and platinum-rhodium/alumina.

9. The process according to claim 6, characterized in that the amount of catalyst used is 1-5% by mass of the intermediate obtained in step (1).

10. The method according to claim 6, wherein the pressure of the hydrogen is 1 to 8MPa, and the reaction temperature is 50 to 150 ℃, preferably 50 to 80 ℃; the solvent is preferably one or more of water, methanol, ethanol, isopropanol and tetrahydrofuran.