CN111138332B - Seleno-glycyrrhetinic acid, preparation method and application thereof - Google Patents
Seleno-glycyrrhetinic acid, preparation method and application thereof Download PDFInfo
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- CN111138332B CN111138332B CN202010045508.9A CN202010045508A CN111138332B CN 111138332 B CN111138332 B CN 111138332B CN 202010045508 A CN202010045508 A CN 202010045508A CN 111138332 B CN111138332 B CN 111138332B
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Abstract
The invention provides seleno-glycyrrhetinic acid, which has a structural formula as follows:
the invention also provides a preparation method and application of the seleno-glycyrrhetinic acid; in the preparation method, glycyrrhetinic acid and selenious acid chloride are subjected to acylation reaction in a DMF solvent to obtain seleno-glycyrrhetinic acid; the seleno-glycyrrhetinic acid has the effects of resisting oxidation and enhancing the immunity of the organism, has better effect than inorganic selenium, and can be developed into a feed additive for livestock. The seleno-glycyrrhetinic acid prepared by the invention has the purity of 95 percent and the yield of 30.1-68.6 percent, and when the seleno-glycyrrhetinic acid prepared by the invention is applied to the feed of newborn rabbits, the seleno-glycyrrhetinic acid is added into basic daily ration, the addition amount is 0.3 mg/kg, the average daily gain is 26.03 +/-1.00 g, the material weight ratio is 3.28 +/-0.12 g, and the content of the kidney selenium is 1.23 +/-0.06 mg/kg.
Description
Technical Field
The invention relates to a preparation method of seleno-glycyrrhetinic acid, belonging to the technical field of chemical synthesis.
Background
Licorice (Glycyrrhiza uralensis) belongs to leguminous plants, is distributed in western China, Russia and other countries, is loaded in Shennong herbal Jing, and is listed as the top grade. It is sweet and mild in nature and taste. It is mainly used for treating weakness of spleen and stomach, deficiency of middle-warmer energy, cough, asthma, and food poisoning. The main pharmacologically active substances of glycyrrhiza uralensis are Glycyrrhizic acid (GR), aglycon Glycyrrhetic Acid (GA), and licoflavone, among which Glycyrrhizic acid has the strongest pharmacological activity, and the research on this aspect is relatively extensive.
Glycyrrhetinic acid is pentacyclic triterpenoid compound extracted from Glycyrrhrizae radix rhizome, and its structure has different optical isomers such as 18 α -type and 18 β -type, and 18 β -type structure is shown below.
Modern researches show that 18 beta-glycyrrhetinic acid has the effects of resisting inflammation, detoxifying, resisting ulcer, resisting virus and the like. The compound has been applied to animal feed additives at present, and achieves better effects of preventing diseases, promoting growth and the like.
Selenium is an essential nutrient for animals and has important significance for the growth, immunity and reproduction of animals. Nutritional muscular atrophy (also called white muscle disease) often occurs when animals are short of selenium, and the disease is mostly seen in young animals, most commonly in lambs. The selenium deficiency of chicks is manifested by exudative disease, the selenium deficiency of pigs is manifested by nutritional hepatic necrosis, purple heart disease and the like, and the problems of fertilization rate reduction, stillbirth or weak birth and the like can occur in various animals. About two thirds of areas in China belong to selenium-deficient areas, and the content of selenium in the compound feed prepared by processing crops produced in the selenium-deficient areas is low, so that the normal physiological requirements of animals cannot be met.
At present, selenium-containing compounds are usually added into the feed to solve the problem of selenium deficiency of animals, and the selenium is mainly supplemented into the animal feed in the form of inorganic selenium (sodium selenite and sodium selenate) or organic selenium (yeast selenium and selenomethionine). Inorganic selenium has been gradually limited in its application in animal feed due to its high toxicity, low utilization rate, environmental pollution, etc. The yeast selenium is an organic selenium source developed by utilizing yeast, is produced by enriching selenium in a cell protein structure of growing yeast, but the yeast is fermented to obtain single-configuration L-selenomethionine, the content of the organic selenium in the obtained selenium yeast is about 0.03 percent, a large amount of fermentation liquor needs to be separated and concentrated in the working procedure, the yield is low, the energy consumption is high, and the environment is not protected.
With the research of selenium additives, organically synthesized selenium is also explored, but at present, the industrialization and the application of organic selenium are relatively deficient, the action effect of the organic selenium is related to various factors, the action mechanism is not clear, and further exploration is needed.
The method for synthesizing selenomethionine in the prior art generally adopts a selenium simple substance or selenium powder as a raw material, and synthesizes selenomethionine through multiple steps, for example, CN110078649A is purified to synthesize dimethyl diselenide and dimethyl diselenide, the dimethyl diselenide, hydrazine hydrate and ferric chloride are reacted to synthesize sodium methylselenolate, the sodium methylselenolate is refluxed and reacted with alpha-amino-gamma-butyrolactone hydrobromide for a period of time, water is added for hydrolysis to obtain a crude product of sodium selenomethionine salt, and the selenomethionine is obtained through purification.
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides a preparation method of seleno-glycyrrhetinic acid, which realizes the following purposes:
the yield and the purity are improved;
the synthesis process is simplified;
when the selenium-enriched animal feed is applied to animal feed, the feed-weight ratio is reduced, and the content of the kidney selenium is increased.
In order to solve the technical problems, the invention provides the following technical scheme:
a method for preparing seleno-glycyrrhetinic acid comprises the following steps: in DMF solvent, glycyrrhetinic acid and selenious acid chloride are subjected to acylation reaction to obtain seleno glycyrrhetinic acid.
The reaction temperature of the glycyrrhetinic acid and the selenious acid chloride is 10-30 ℃.
Preferably, the optimum reaction temperature is 25 deg.C
The reaction time of the glycyrrhetinic acid and the selenious acid chloride is 2-10 hours.
Preferably, the optimal reaction time is 6 h.
The molar ratio of the glycyrrhetinic acid to the selenious acyl chloride is 1.0-1.4.
Preferably, the optimum reaction molar ratio is 1.2.
The acylation reaction needs to be added with K2CO3, and the molar ratio of the K2CO3 to the glycyrrhetinic acid is as follows: 1.4-1.6: 1;
the acylation reaction is carried out, wherein the stirring speed is 500-700 r/min;
and (3) after the acylation reaction is finished, standing overnight, adding a saturated sodium chloride solution to quench the reaction, extracting for 2 times by using DCM, washing an organic phase by using a large amount of saturated sodium chloride solution, drying, removing the solvent by rotary evaporation to obtain a crude product, and separating by column chromatography to obtain a pure product.
The chemical reaction equation of the invention is as follows:
in DMF solvent, glycyrrhetinic acid and selenious acid chloride are subjected to acylation reaction to obtain seleno glycyrrhetinic acid.
The applicant establishes a research team to carry out the synthesis research of the selenium glycyrrhetate, and successfully synthesizes the seleno-glycyrrhetinic acid compound through the work accumulation for years, so that the selenium glycyrrhetinic acid compound is safe to use, has high bioavailability, effective biological functions and the like, and can become an advantageous selenium supplement.
Compared with the prior art, the invention has the following beneficial effects:
(1) the seleno-glycyrrhetinic acid prepared by the method has the purity of 95 percent and the yield of 30.1 to 68.6 percent, and the preferred technical scheme has the purity of 95 percent and the yield of 61.2 to 68.6 percent;
(2) when the seleno-glycyrrhetinic acid prepared by the invention is applied to the feed of newborn rabbits, the seleno-glycyrrhetinic acid is added into basic daily ration, the addition amount is 0.3 mg/kg based on the amount of selenium, the average daily gain is 26.03 +/-1.00 g, and the material weight ratio is 3.28 +/-0.12 g; the content of the kidney selenium is 1.23 plus or minus 0.06 mg/kg;
(3) the preparation method of the seleno-glycyrrhetinic acid has simple synthesis process.
Description of the drawings:
FIG. 1 is a thin layer chromatography of a crude seleno-glycyrrhetinic acid prepared by the present invention;
FIG. 2 is a diagram of the UV-VIS absorption spectrum of seleno-glycyrrhetinic acid prepared in accordance with the present invention;
FIG. 3 is an infrared absorption spectrum of seleno-glycyrrhetinic acid prepared by the present invention;
FIG. 4 is a nuclear magnetic resonance hydrogen spectrum of seleno-glycyrrhetinic acid prepared by the present invention;
FIG. 5 is the nuclear magnetic resonance carbon spectrum of seleno-glycyrrhetinic acid prepared by the present invention.
Detailed Description
The preferred embodiments of the present invention will be described in conjunction with the accompanying drawings, and it will be understood that they are described herein for the purpose of illustration and explanation and not limitation.
Example 1A method for preparing seleno-glycyrrhetinic acid
Adding glycyrrhetinic acid (0.47g,1mmol), selenious acid chloride (0.0816mL,1.2mmol) and DMF (5mL) into a 50mL round-bottom flask, controlling the temperature to be 30 ℃, stirring to dissolve, adding K2CO3(0.21g,1.5 mmol), stirring at the reaction temperature of 25 ℃ for 6h (the stirring speed is 600 revolutions per minute), standing overnight after the reaction is finished, adding saturated sodium chloride solution (40mL) to quench the reaction, extracting with DCM (50mLx2), adding 50mLDCM each time, washing an organic phase with a large amount of saturated sodium chloride solution, drying, removing a column chromatography solvent by rotary evaporation to obtain a crude product, and separating to obtain a pure product (purity of 95% and yield of 68.6%).
The glycyrrhetinic acid adopted by the invention is as follows: 99% of the total content, purchased from Gansu pan-planted pharmaceuticals, Inc.;
the selenious acyl chloride adopted by the invention is as follows: the content is 98.0 percent, the reagent is purchased from Henan navigation chemical product development limited company, and the other reagents are chemical pure reagents.
Example 2 thin layer chromatography identification
Preparing 2mg/ml glycyrrhetinic acid (the content is more than or equal to 98 percent) and chloroform solution as standard solution, and marking 1; chloroform solution, 2mg/ml seleno-glycyrrhetinic acid solution (prepared from the crude seleno-glycyrrhetinic acid prepared in example 1 without column separation) as sample solution, and labeled 2 in sequence. Different developer systems were investigated, using petroleum ether: benzene: ethyl acetate: glacial acetic acid = 5: 10: 3.5: 0.3 (V: V) was developed and adsorbed using a silica gel GF254 plate; drying after unfolding, and inspecting under 365 nm ultraviolet lamp to obtain the result shown in figure 1.
As can be seen from the attached figure 1, the glycyrrhetinic acid standard solution is one point, and the seleno-glycyrrhetinic acid solution prepared by the method has two points without column separation, which indicates that unreacted glycyrrhetinic acid exists.
Example 3 UV-Vis absorption Spectroscopy
The purified product (pure product from example 1, column separated) 0.5 mg was dissolved in 100 mL 80% ethanol, and the mixture was subjected to spectral scanning in a TU-1810 UV-Vis spectrophotometer using 80% ethanol as a blank, the results are shown in FIG. 2.
As can be seen from the attached figure 2, the synthesized product seleno-glycyrrhetinic acid has a characteristic absorption peak, the peak of a parabola is a strong absorption band, the absorption wavelength is 249 nm, and the maximum absorption wavelength is within the range of 220-250 nm, which shows that the structure contains a conjugated large pi bond formed by two double bonds; the absorption wavelength is 300nm, and a weak absorption band exists in the range of 250-350 nm, which indicates that the molecular structure contains a plurality of carbonyl groups.
Example 4 Infrared absorption Spectroscopy
The purified product (pure product from example 1, column separated) was dried in an oven, 1.5 mg taken, and about 200 mg of 200 mesh dried KBr powder (spectrally pure) was placed in an agate mortar, ground and mixed well with a pestle, pressed into a transparent sample piece of KBr with a diameter of about 13 mm and a thickness of about 1mm, and scanned with an infrared spectrophotometer, as shown in fig. 3.
As can be seen from FIG. 3, v as (-OH) is 3450 cm-1; the v as (-CH 3) is 2900 cm-1, 1400cm-1, 1380 cm-1, and the v as (-COOSe) is 1700 cm-1, which is characteristic peak of ester; ν as (O = C) is 1660 cm-1; va (-C = C) is 1610 cm-1, indicating the presence of a carbon-carbon double bond; the v as (-C-O-C-) is 1220 cm-1 and 1160 cm-1, is the second characteristic peak of the ester, and the synthetic product is determined to be seleno-glycyrrhetinic acid by analyzing the structural coincidence of the characteristic absorption peaks and the seleno-glycyrrhetinic acid.
Example 5 nuclear magnetic resonance Spectroscopy
The nuclear magnetic resonance spectrum has important function in the aspect of determining the structure of the compound, and has wide application and reliable determination result. The research adopts nuclear magnetic resonance spectrum detection, and the detection results of the synthesized products are shown in the attached figures 4 and 5.
As shown in FIG. 4, 1HNMR (300 MHz, CDCl3) delta ppm: 5.60(s, 1H,12-H) is the signal for the 12-position olefinic hydrogen on the steroid parent nucleus, 3.70(m, 2H, 31-H), 3.28(m,1H,3-H) is the signal for the hydrogen on the hydroxyl group, 2.40(s, 1H,8-H) is the signal for the 8-position hydrogen on the steroid parent nucleus, 1.40(s, 3H, 29-H), 1.38(s, 3H, 26-H), 1.36 (s, 3H, 27-H), 1.22 (s, 3H, 25-H), 1.15 (s, 3H, 28-H), 1.00(t, J =7.2Hz,3H,31-H), 0.80 (s, 6H,23-24-H) are the steroid parent nucleus and the signal for the hydrogen on the alcohol.
As shown in FIG. 5, 13C NMR (75 MHz, CDCl3) delta ppm: the carbon spectrum data gave 30 signals as follows: 200.00 and 177.11 are steroid parent nucleus C11 and C30 carbonyl carbon signals, 170.00 and 129.00 are steroid parent nucleus C13 and C12 olefinic carbon signals, 79.00 is a steroid parent nucleus 3-position hydroxyl carbon signal, 62.00 is a hydroxyl carbon signal, 55.00, 52.00, 41.00, 39.20, 38.00, 33.00, 32.00, 31.00, 28.20, 28.11, 28.00, 27.31, 26.22, 23.41, 18.22, 17.39, 16.32, 15.60, 25.48, 22.41, 21.39, 17.70, 16.50, 15.38 and 14.56 are saturated carbon signals in the steroid parent nucleus and methanol groups.
Since seleno-glycyrrhetinic acid and glycyrrhetinic acid have been separated by column separation, the compound was determined to be seleno-glycyrrhetinic acid by IR, 1H NMR, 13C NMR spectral analysis.
Example 6 optimization of Synthesis Process of Seleno-Glycyrrhetinic acid
(1) Influence of raw material ratio
On the basis of example 1, the amount of glycyrrhetinic acid was fixed, the reaction temperature was 25 ℃, and the reaction time was 6 hours. The influence of the glycyrrhetinic acid/selenious acid chloride molar ratio on the yield is examined, and the results are shown in table 1.
TABLE 1 influence of raw material formulation on yield
As can be seen from Table 1, the molar ratio of glycyrrhetinic acid/selenious acid chloride can be controlled to 1:1.0-1.4, and the optimal molar ratio is 1: 1.2.
(2) Effect of reaction time on yield
The amount of glycyrrhetinic acid is fixed, the reaction temperature is 25 ℃, and the molar ratio of glycyrrhetinic acid to selenious acid chloride is 1: 1.2. The effect of reaction time on yield was examined and the results are shown in Table 1.
TABLE 2 Effect of reaction time on yield
As is clear from Table 2, the reaction time has a certain influence on the yield, and from 2h to 8h, the product yield increases with the increase in the reaction time, but the increase is not significant. The reaction time can be controlled within 2-10h, and the optimal reaction time is determined to be 6h from the aspects of cost and yield.
(3) Effect of reaction temperature on yield
Fixing the amount of glycyrrhetinic acid, reacting for 6 hours, wherein the molar ratio of glycyrrhetinic acid to selenious acid chloride is 1: 1.2. The effect of reaction temperature on yield was examined and the results are shown in Table 3.
TABLE 3 influence of reaction temperature on yield
As is clear from Table 3, the reaction temperature has a certain influence on the yield. The reaction temperature is preferably 10 to 30 ℃ and more preferably 25 ℃.
Through the optimization of the process, the temperature for carrying out acylation reaction on glycyrrhetinic acid and selenious acid chloride is 10-30 ℃, and the optimal temperature is 25 ℃; the reaction time is 2-10h, and the optimal reaction time is 6 h; the molar ratio of glycyrrhetinic acid to selenious acyl chloride is 1.0-1.4, and the optimal reaction molar ratio is 1: 1.2.
Example 7 Effect of seleno-glycyrrhetinic acid on the growth of baby rabbits
Seleno-glycyrrhetinic acid is an organic selenium compound synthesized by artificial chemistry, and can be decomposed into selenium element and glycyrrhetinic acid which can be absorbed in a donor through metabolism in an animal body. Selenium is a trace element essential for breeding and growth of rabbits, cannot be synthesized in animals, and must be taken in through food. The selenium deficiency can seriously affect the reproduction of the rabbits, hinder the growth and development of the young rabbits and even cause death. Inorganic selenium (such as sodium selenite) or organic selenium (such as yeast selenium) is added into the feed, so that the growth and development of the house immunity can be effectively promoted, and the immunity of the house immunity can be improved. However, inorganic selenium has the disadvantages of high toxicity, low absorption rate and difficult control of dosage, and organic selenium has low toxicity and high bioavailability. At present, the use of organic selenium is vigorously advocated in many countries in Europe and America, and the organic selenium is required to be used in feeds as required in Sweden; the use of inorganic selenium in feed has been regulated in japan. The Glycyrrhrizae radix is root and rhizome of Leguminosae plant Glycyrrhrizae radix, radix Glycyrrhizae Inflatae or Glycyrrhiza glabra, and has effects of invigorating spleen and qi, eliminating phlegm and relieving cough, clearing heat and detoxicating, relieving spasm and pain, and harmonizing drug property. Modern pharmacological studies show that Glycyrrhetinic Acid (GA) is one of the effective components of liquorice, and has the effects of resisting inflammation, ulcer, allergy, virus, liver protection, immunoregulation and the like. The molecular structure of the compound is similar to that of hydrocortisone, and the compound can slow down the conversion of the hydrocortisone and improve the action strength by inhibiting the activity of 11 beta-hydroxysteroid denitrase-2 in an animal body, so the compound is often used as a substitute of the hydrocortisone clinically. Recent studies have shown that glucocorticoids have a promoting effect on the growth of new-born animals. For example, dexamethasone is used in birth, the growth performance of animals is enhanced, hydrocortisone can promote the small intestine development of new animals and the synthesis function of endogenous arginine of small intestine epithelial cells, and since the milk arginine of female animals cannot meet the requirements of the small animals, the endogenous arginine synthesized by the animals has important physiological significance, the increase of the nutrition of the animal arginine is an effective means for promoting the growth performance of the animals.
1 materials and methods
1.1 materials
1.1.1 Experimental animals
60 common-grade New Zealand weaned young rabbits are 35 days old and half female and male, and are provided by a Weifang rabbit farm.
1.1.2 test drugs
Seleno-glycyrrhetinic acid: 95% (product prepared in example 1), developed by Shandong ark biotechnology Co., Ltd, sodium selenite: content 98%, Anhui Youti bioengineering Co., Ltd.
1.1.3 Experimental reagents
A kit for measuring the activity of serum glutathione peroxidase (GSH-Px), the activity of superoxide dismutase (SOD), the activity of Catalase (CAT) and the content of Malondialdehyde (MDA) is provided by Nanjing's institute of established biology.
1.1.4 Experimental instruments
A full-automatic biochemical Analyzer and a matched kit (IDEXX Catalyst Dx Analyzer, USA), and a full-wavelength enzyme standard Analyzer (Multiskan GO, Thermo Fisher, USA).
1.2 Experimental methods
1.2.1 Experimental grouping and feeding management and Glycyrrhetinic acid dosage screening test
The experimental design and management of 60 common-grade New Zealand weaned young rabbits with 30-day age and half female and male are provided by the research institute of laboratory animals of traditional Chinese medicine institute in Chongqing.
The control group is fed with basic ration (selenium content is 0.02 mg/kg), the inorganic group is fed with basic ration added with 0.3 mg/kg selenium (sodium selenite), and the organic group is fed with basic ration added with 0.3 mg/kg selenium (seleno-glycyrrhetinic acid).
1.2.2 growth Performance index detection
The initial weight of each rabbit was weighed before the start of the experiment, and the weight of each group of rabbits was weighed on days 5, 10, 15, 20, 25, and 30 of the experiment. The amount of the feed left in the previous day is weighed before the feed is fed every day, and the consumption of each group of feed is accurately recorded. Average daily gain = total gain during trial/number of days of trial; feed weight ratio = total feed consumption/total gain weight. On the 30 th day of the experiment, the rabbits were euthanized, and the liver, spleen, and kidney were weighed, respectively, and the organ index (mg/g) = organ weight/live rabbit weight.
1.2.3 determination of serum antioxidant index and biochemical index
On the 30 th day of the experiment, blood is collected from the marginal veins of the rabbits at 3000r/min, the centrifugation is carried out for 10min, serum is separated, the content detection of glutathione peroxidase (GSH-Px) activity, superoxide dismutase (SOD) activity, Catalase (CAT) activity and Malonaldehyde (MDA) is carried out according to the instruction, and the ratio of blood sugar (GLU), Uric Acid (UA), Total Protein (TP), Albumin (ALB), Globulin (GLOB) and albumin/globulin is determined by a full-automatic biochemical analyzer.
1.2.4 tissue selenium content detection
On day 30 of the experiment, 8 rabbits were randomly selected from each of the three groups of experimental rabbits, and the selenium content of the tissues was measured.
2 results
Growth performance of three groups of laboratory rabbits
As can be seen from Table 1, the body weight growth of the young rabbits in the control group and the inorganic group was almost the same during the experiment, but the growth rate of the organic selenium group was significantly higher than that of the other two groups.
TABLE 1 average daily gain and feed/weight ratio of rabbits in each group
| Group of | Number of | Average daily gain (g) | Average daily consumptive material (g) | Material to weight ratio |
| Seleno- |
20 | 26.03 ±1.00 | 85.33 ±0.70 | 3.28 ±0.12 |
| |
20 | 24.82± 0.87 | 84.04± 1.26 | 3.39± 0.07 |
| |
20 | 24.54± 0.60 | 86.35± 1.32 | 3.52± 0.06 |
2.3 Biochemical function of serum of three groups of experimental newborn rabbits
The results of the serum biochemical indicators GLU, TP, ALB, GLOB, ALB/GLOB and UA detection of the three groups of experimental newborn rabbits are shown in Table 2. Compared with a control group, the biochemical indexes of the blood of the organic selenium group and the inorganic selenium group have no obvious difference.
TABLE 2 serum Biochemical indices GLU, TP, ALB, GLOB, ALB/GLOB and UA of rabbits
| Group of | GLU（mg/dL） | TP（g/dL） | ALB（g/dL） | GLOB（g/dL） | ALB/GLOB | UA（mg/dL） |
| Seleno-glycyrrhetinic acid | 135.1±1.76 | 5.59±0.12 | 3.12± 0.14 | 2.43± 0.06 | 1.28±0.08 | ‹0.1 |
| Sodium selenite group | 132.1±1.71 | 5.49±0.10 | 3.18± 0.08 | 2.27± 0.04 | 1.33±0.08 | ‹0.1 |
| Control group | 132.1±5.00 | 5.75±0.16 | 3.27± 0.13 | 2.44± 0.05 | 1.28±0.04 | ‹0.1 |
2.4 conditions of selenium content in Rabbit kidneys of three groups of experiments
The detection results of the kidney selenium content of the control group, the organic selenium group and the inorganic selenium group are respectively (0.97 +/-0.05) mg/kg, (1.23 +/-0.06) mg/kg and (1.09 +/-0.05) mg/kg. Compared with the control group, the kidney selenium content of the organic selenium group and the kidney selenium content of the inorganic selenium group are increased, and the kidney selenium content of the organic selenium group is higher than that of the inorganic selenium group (after selenium is added into the feed, rabbits grow better, and through determination, the kidney selenium is found to be higher, which indicates that the selenium is beneficial to animal growth, and the effect of the organic group is better than that of the inorganic group).
3. Small knot
Selenium is one of the essential trace elements of animals, most of the selenium in different forms is absorbed and converted in duodenum, mainly distributed in systemic histiocyte in the form of seleno-amino acid, selenium-containing protein and selenoprotein, and finally discharged out of body in the form of feces, urine or breath. The main biological effects of selenium in vivo comprise biological functions of resisting oxidation, promoting growth, enhancing organism immunity, improving animal reproductive performance and the like, the rabbit selenium deficiency can cause sparse hair or no hair, anorexia, adult rabbit weight reduction, growth and development retardation of young rabbits, lassitude, obvious response retardation to external stimulation, and the selenium excess can cause adverse consequences such as acute poisoning and the like. Selenium required by the rabbits comes from feed, and the selenium added in the feed at present is inorganic selenium sodium selenate. The test proves that the effect of the organic selenium is superior to that of the inorganic selenium. Glycyrrhetinic acid is the main pharmacological component of traditional Chinese medicine Glycyrrhrizae radix, has main effects of resisting inflammation, resisting ulcer, removing toxic substance etc. because its structure is similar to adrenocortical hormone, so has adrenocortical hormone-like effect, not only can promote selenium absorption, but also has growth promoting effect.
Claims (9)
1. Seleno-glycyrrhetinic acid is characterized in that: the seleno-glycyrrhetinic acid has a structural formula as follows:
2. a preparation method of seleno-glycyrrhetinic acid is characterized by comprising the following steps: according to the preparation method, glycyrrhetinic acid and selenious acid chloride are subjected to acylation reaction in a DMF solvent to obtain seleno-glycyrrhetinic acid.
3. The method of claim 2, wherein: the temperature of the acylation reaction is 10-30 ℃.
4. The method of claim 2, wherein: the time of the acylation reaction is 2-10 h.
5. The method of claim 2, wherein: the molar ratio of the glycyrrhetinic acid to the selenious acyl chloride is 1.0-1.4.
6. The method of claim 2, wherein: the acylation reaction is carried out by adding glycyrrhetinic acid,
Dissolving selenious acyl chloride at 29-31 deg.C, and adding K2CO3Stirring for reaction; said K2CO3The molar ratio of the glycyrrhetinic acid to the glycyrrhetinic acid is as follows: 1.4-1.6:1.
7. The method of claim 6, wherein: the stirring speed is 500-700 r/min.
8. The method of claim 2, wherein: and (3) after the acylation reaction is finished, standing overnight, adding a saturated sodium chloride solution to quench the reaction, extracting for 2 times by using DCM, washing an organic phase by using the saturated sodium chloride solution, drying, removing the solvent by rotary evaporation to obtain a crude product, and separating by using column chromatography to obtain a pure product.
9. The application of seleno-glycyrrhetinic acid in preparing the feed for resisting oxygen and/or enhancing the immunity of the organism is characterized in that: the seleno-glycyrrhetinic acid has a structural formula of
The addition amount of the selenium-enriched feed additive is 0.28-0.32mg/kg in terms of selenium.
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