Vitamin C derivative, preparation method and application thereof

Abstract

The present invention belongs to the field of organic synthesis technology and specifically relates to a vitamin C derivative, a preparation method thereof, and applications thereof. The preparation method of the vitamin C derivative provided by the present invention is simple and easy to implement, and the prepared vitamin C derivative has good stability, biosafety, and whitening efficacy.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis, and in particular relates to a vitamin C derivative and a preparation method and application thereof. Background Art

[0002] Vitamin C, also known as sodium ascorbate, is a naturally occurring antioxidant and free radical scavenger, and a recognized whitening agent in cosmetics. However, sodium ascorbate is readily soluble in water, poorly absorbed by the skin, and easily oxidized, causing discoloration. This reduces its efficiency and application in daily chemical applications. Therefore, providing a stable, safe, and effective vitamin C derivative with whitening effects is a pressing technical challenge for those skilled in the art. Summary of the Invention

[0003] The purpose of the present invention is to provide a vitamin C derivative and a preparation method and application thereof. The vitamin C derivative provided by the present invention is not only stable and safe, but also has a good whitening effect.

[0004] In order to achieve the above object, the present invention provides the following technical solutions:

[0005] The present invention provides a vitamin C derivative having a structure shown in Formula I:

[0006]

[0007] The present invention also provides a method for preparing the vitamin C derivative described in the above technical solution, comprising the following steps:

[0008] mixing sodium ascorbate, bromide and a polar organic solvent, and performing a substitution reaction to obtain the vitamin C derivative;

[0009] The bromide has a structure shown in Formula II:

[0010]

[0011] Preferably, the molar ratio of sodium ascorbate to bromide is 1:1 to 10:1.

[0012] Preferably, the polar organic solvent includes one or more of DMSO, DMF and 1,4-dioxane.

[0013] Preferably, the substitution reaction is carried out under microwave conditions; the temperature of the substitution reaction is 60-140° C., and the time is 10-50 min.

[0014] Preferably, after the substitution reaction is completed, the obtained reaction system is further subjected to salting out; the salting out process is: pouring the reaction system into saturated saline water under stirring.

[0015] Preferably, after the salting out, the obtained system is filtered, dried and purified in sequence.

[0016] Preferably, the purification comprises dissolving, filtering and concentrating in sequence; the solvent used for the dissolution comprises one or more of methanol, ethanol, isopropanol and deionized water.

[0017] The present invention also provides the use of the vitamin C derivative described in the above technical solution or the vitamin C derivative prepared by the preparation method described in the above technical solution in cosmetics.

[0018] The present invention provides a vitamin C derivative having a structure shown in Formula I:

[0019]

[0020] The vitamin C derivative provided by the present invention has good stability, biosafety and whitening effect. The results of the embodiment show that the m / z of the vitamin C derivative prepared by the present invention is: 633.2670 [M+Na] + The vitamin C derivatives prepared by the present invention greatly overcome the shortcomings of vitamin C's instability to light, heat, high and low temperatures and acidic environments. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 This is a mass spectrometry characterization of the vitamin C derivative prepared in Example 1;

[0022] Figure 2 This is the ultraviolet absorption spectrum of the vitamin C derivative prepared in Example 1;

[0023] Figure 3 This is the UV absorption spectrum of the stability test of ordinary vitamin C;

[0024] Figure 4 This is a diagram showing the whitening effect of the vitamin C derivative prepared in Example 1 on zebrafish;

[0025] Figure 5 This is a bar graph showing the inhibition of melanin production by the vitamin C derivative prepared in Example 1 at the zebrafish level;

[0026] Figure 6 This is a bar graph showing the inhibition of tyrosinase activity by the vitamin C derivatives prepared in Example 1 at the zebrafish level. DETAILED DESCRIPTION

[0027] The present invention provides a vitamin C derivative having a structure shown in Formula I:

[0028]

[0029] The present invention also provides a method for preparing the vitamin C derivative described in the above technical solution, comprising the following steps:

[0030] mixing sodium ascorbate, bromide and a polar organic solvent, and performing a substitution reaction to obtain the vitamin C derivative;

[0031] The bromide has a structure shown in Formula II:

[0032]

[0033] In the present invention, unless otherwise specified, all preparation raw materials are commercially available products well known to those skilled in the art.

[0034] In the present invention, the molar ratio of sodium ascorbate to bromide is preferably 1:1 to 10:1, more preferably 1.5:1.

[0035] In the present invention, the polar organic solvent preferably includes one or more of DMSO, DMF, and 1,4-dioxane, more preferably DMSO. In the present invention, the ratio of the polar organic solvent to sodium ascorbate is preferably 15 mL:1-1.5 mol, more preferably 15 mL:1.5 mol. The present invention has no particular requirements for the mixing method; methods familiar to those skilled in the art can be used.

[0036] In the present invention, the substitution reaction is preferably carried out under microwave conditions; the temperature of the substitution reaction is preferably 60 to 140° C., more preferably 80 to 120° C., and more preferably 90° C. In the present invention, the substitution reaction time is preferably 10 to 50 minutes, more preferably 20 to 40 minutes, and more preferably 30 minutes.

[0037] After the substitution reaction is completed, the present invention further preferably includes subjecting the resulting reaction system to salting out; the salting out process is preferably performed by pouring the reaction system into saturated saline solution under stirring. The present invention does not particularly limit the stirring process, and any method well known to those skilled in the art can be used; after the stirring is completed, the present invention further preferably includes allowing the reaction system to stand overnight.

[0038] After the salting out, the present invention preferably further comprises filtering, drying, and purifying the resulting reaction system in sequence. In the present invention, the filtration method is preferably suction filtration. The present invention does not specifically limit the suction filtration process; a method well known to those skilled in the art may be employed. In the present invention, the drying method is preferably oven drying; the oven drying temperature is preferably 55°C. The present invention does not specifically limit the oven drying process; a method well known to those skilled in the art may be employed.

[0039] In the present invention, the purification preferably includes dissolution, filtration, and concentration in sequence; the solvent used for the dissolution preferably includes one or more of methanol, ethanol, isopropanol, and deionized water, more preferably ethanol. In the present invention, the filtration method is preferably suction filtration, and the present invention does not specifically limit the suction filtration process, and can be used by those skilled in the art. In the present invention, the concentration method is preferably vacuum distillation, and the present invention does not specifically limit the vacuum distillation process, and can be used by those skilled in the art.

[0040] The present invention also provides the use of the vitamin C derivative described in the above technical solution or the vitamin C derivative prepared by the preparation method described in the above technical solution in cosmetics.

[0041] To further illustrate the present invention, the vitamin C derivatives provided by the present invention, their preparation methods and applications are described in detail below with reference to the accompanying drawings and examples, but they should not be construed as limiting the scope of protection of the present invention.

[0042] Example 1

[0043] 1.5 mol of sodium ascorbate, 1 mol of bromide (as shown in Formula II) and 15 mL of DMSO were added to a reaction container, stirred and mixed uniformly, and then heated under microwave radiation at 90° C. for 30 min.

[0044]

[0045] After the reaction, the reaction solution was poured into 100 mL of saturated brine under stirring, stirred evenly, and allowed to stand overnight. The resulting salting-out solution was filtered, and the solid was collected and dried at 55° C. to obtain a crude product.

[0046] The crude product was dissolved with ethanol, and the insoluble matter was discarded. The filtrate was distilled under reduced pressure, concentrated and dried to obtain the vitamin C derivative with a yield of 96.5%.

[0047] Example 2

[0048] 1 mol of sodium ascorbate, 1 mol of bromide (as shown in Formula II) and 15 mL of DMSO were added to a reaction container, stirred and mixed uniformly, and then heated under microwave radiation at 90° C. for 30 min.

[0049] After the reaction, the treatment method was the same as in Example 1, and the yield was 45.5%.

[0050] Example 3

[0051] 1.5 mol of sodium ascorbate, 1 mol of bromide (as shown in Formula II) and 15 mL of DMSO were added to a reaction container, stirred and mixed uniformly, and then heated under microwave radiation at 90° C. for 20 min.

[0052] After the reaction, the treatment method was the same as in Example 1, and the yield was 83.6%.

[0053] Example 4

[0054] 1.5 mol of sodium ascorbate, 1 mol of bromide (as shown in Formula II) and 15 mL of DMSO were added to a reaction container, stirred and mixed uniformly, and then heated under microwave radiation at 60° C. for 30 min.

[0055] After the reaction, the treatment method was the same as in Example 1, and the yield was 63.2%.

[0056] Performance Testing

[0057] 1. Mass spectrometry was performed on the vitamin C derivative prepared in Example 1. The results were as follows: Figure 1 As shown. Figure 1 It can be seen that the m / z of the vitamin C derivative prepared in Example 1 is: 633.2670 [M+Na] + .

[0058] 2. The vitamin C derivative prepared in Example 1 was subjected to stability testing under light, different temperatures and different pH values. The testing method was as follows:

[0059] The vitamin C derivative prepared in Example 1 was weighed, prepared into a 1 mg / mL solution using ethanol, and divided into 7 portions of equal volume for later use.

[0060] Similarly, vitamin C was weighed and prepared into a 1 mg / mL solution with water as a control.

[0061] (1) Light

[0062] Take one portion of the vitamin C derivative solution and one portion of the vitamin C solution, place them under sunlight for 2 hours.

[0063] (2) Temperature

[0064] Take one portion of the vitamin C derivative solution and one portion of the vitamin C solution, place them at 4°C and 60°C respectively, and store them at constant temperature for 2 hours.

[0065] (3) pH value

[0066] Take one portion of the vitamin C derivative solution and one portion of the vitamin C solution, and add 1 mol / L hydrochloric acid, distilled water, and 1 mol / L sodium hydroxide, respectively.

[0067] After two hours, the UV absorption spectrum was measured using a UV spectrophotometer. Figures 2-3 , as shown in Table 1.

[0068] Table 1 Stability test results of vitamin C derivatives and vitamin C

[0069] Vitamin C derivatives Vitamin C Maximum absorption wavelength 249nm 265nm No treatment 1.886 1.338 illumination 1.930 1.263 4℃ 1.970 1.305 60℃ 1.870 1.193 hydrochloric acid 1.775 0.799 (245nm) distilled water 1.594 1.038 Sodium hydroxide 1.530(263nm) 0.247

[0070] From Table 1 and Figures 2-3 The results show that under the conditions of light and high and low temperatures, the absorbance value of the vitamin C derivative does not change much. Since the derivative is soluble in ethanol, a small amount of ethanol may evaporate during the experiment, causing the concentration to increase and the absorbance value to increase accordingly. However, from the overall results, the derivative does not change much under these conditions, proving that the derivative has good stability under light and high and low temperatures.

[0071] In addition, after adding solutions of different pH values, the concentration decreased, and the absorbance value also decreased accordingly. This shows that under acidic conditions, the derivative is relatively stable. Since the derivative is insoluble in water, after adding distilled water, the sample precipitates in water and the content decreases. Under alkaline conditions, the sample precipitates more, and the maximum absorption wavelength red-shifts. This shows that the derivative is unstable under alkaline conditions and has low solubility in water, but its stability remains unchanged. Under the same conditions, vitamin C is relatively stable under low temperature conditions, but is unstable under light, high temperature, and acid-base conditions. This shows that the vitamin C derivative provided by the present invention greatly overcomes the shortcomings of vitamin C's instability to light, heat, and acidic environments.

[0072] 3. The vitamin C derivative prepared in Example 1 was subjected to safety testing using the following method:

[0073] The vitamin C derivative prepared in Example 1 was prepared into a 10 mmol / L stock solution using DMSO.

[0074] The sample was diluted with standard dilution water to a series of concentrations (100, 75, 50, 25, 12.5, 6.25, and 3.125 μmol / L). Ten juveniles were tested at each concentration (24-well cell culture plates, 1.0 mL of sample solution). Survival of juveniles at 24 hpf, 48 hpf, and 72 hpf was observed and recorded under a stereomicroscope (2x-3x objective). Cumulative mortality and deformity rates were calculated. The approximate range of sample dilution concentrations corresponding to cumulative mortality and deformity rates of 0% to 100% was estimated.

[0075] The test results show that the maximum safe concentration of vitamin C derivatives is 75μmol / L. Under the same conditions, the maximum safe concentration of vitamin C is 12.5μmol / L. In comparison, the safety of vitamin C derivatives is greatly improved.

[0076] 4. The vitamin C derivative prepared in Example 1 was tested for its ability to inhibit melanin production. The test method was as follows:

[0077] Healthy AB zebrafish embryos at 9 hpf were randomly placed in a 6-well cell culture plate, 30 per well. 5 mL of 12.5 μmol / L solution was added to each well. Three replicates were set up for each group. The cells were incubated in a biochemical incubator with a controlled flow cytometer.

[0078] After 72 hours of incubation, add the lysis buffer solution and sonicate to create a homogenate. Centrifuge, remove the precipitate, and vibrate to fully dissolve the melanin in the centrifuge tube. Place 100 μL of the solution in a 96-well plate and measure the absorbance at 405 nm using a microplate reader. Calculate the inhibition rate of melanin synthesis using the following formula:

[0079]

[0080] All experimental data are expressed as mean ± SEM.

[0081] The test results are as follows Figure 5 As shown by Figure 5 It can be seen that after the zebrafish was treated with 0.125mM vitamin C derivatives to 72hpf, the melanin production inhibition rate was 9.77±0.75%, which was 9.77% higher than that of the blank control group. After the zebrafish was treated with 0.125mM VC to 72hpf, the melanin production inhibition rate was 14.55±0.12%, which was 14.55% higher than that of the blank control group. This shows that the modified vitamin C derivatives and VC both have the effect of inhibiting melanin production.

[0082] 5. The vitamin C derivative prepared in Example 1 was tested for its inhibition on tyrosinase activity. The test method was as follows:

[0083] Healthy AB zebrafish embryos at 9 hpf were randomly placed in a 6-well cell culture plate, 30 per well, and 5 mL of solution (75, 50, or 12.5 μmol / L) was added to each well. Three replicates were set up for each group and incubated in a curve-controlled biochemical incubator.

[0084] After 72 hours of incubation, the lysate solution was added and ultrasonically prepared into a homogenate. Centrifugation was performed, and the supernatant was placed in a 96-well plate. L-DOPA solution was added and incubated for 1 hour. The absorbance value (OD475nm value) of each experimental group was measured using a microplate reader. The tyrosinase activity inhibition rate was calculated according to the following formula:

[0085]

[0086] All experimental data are expressed as mean ± SEM.

[0087] The test results are as follows Figure 6 As shown by Figure 6 It can be seen that after the zebrafish was treated with 0.125mM vitamin C derivatives to 72hpf, the tyrosinase activity inhibition rate was 14.14±2.51%, which was 14.14% higher than that of the blank control group; after the zebrafish was treated with 0.125mM VC (control) to 72hpf, the tyrosinase activity inhibition rate was 17.41±1.95%, which was 17.41% higher than that of the blank control group, indicating that the modified vitamin C derivatives and VC both have a very significant effect in inhibiting tyrosinase activity.

[0088] In summary, after the modification and transformation of the ordinary vitamin C structure in the present invention, the whitening activity of the vitamin C derivative obtained is not significantly improved compared with the parent vitamin C, but it still maintains whitening activity. In addition, compared with the parent structure vitamin C, its stability and safety are greatly improved. It is expected to be used as a safe and stable whitening raw material in cosmetic raw materials, and it also plays a certain guiding role in the modification of the vitamin C structure.

[0089] Although the above embodiment provides a detailed description of the present invention, it is only a part of the embodiments of the present invention, not all of the embodiments. Other embodiments can be obtained based on this embodiment without creativity, and these embodiments all fall within the scope of protection of the present invention.

Claims

1. A vitamin C derivative, characterized in that Having the structure shown in formula I:

2. The method for preparing the vitamin C derivative according to claim 1, characterized in that: The following steps are involved: mixing sodium ascorbate, bromide and a polar organic solvent, and performing a substitution reaction to obtain the vitamin C derivative; The bromide has a structure shown in Formula II:

3. The preparation method according to claim 2, characterized in that The molar ratio of the sodium ascorbate to the bromide is 1:1 to 10:

1.

4. The preparation method according to claim 2, characterized in that The polar organic solvent includes one or more of DMSO, DMF and 1,4-dioxane.

5. The preparation method according to claim 2, characterized in that The substitution reaction is carried out under microwave conditions; the temperature of the substitution reaction is 60-140° C., and the time is 10-50 minutes.

6. The preparation method according to claim 2 or 5, characterized in that After the substitution reaction is completed, the obtained reaction system is subjected to salting out. The salting out process is as follows: pouring the reaction system into saturated saline solution under stirring.

7. The preparation method according to claim 6, characterized in that After the salting out, the obtained reaction system is filtered, dried and purified in sequence.

8. The preparation method according to claim 7, characterized in that The purification includes dissolving, filtering and concentrating in sequence; the solvent used for the dissolution includes one or more of methanol, ethanol, isopropanol and deionized water.

9. Use of the vitamin C derivative according to claim 1 or the vitamin C derivative prepared by the preparation method according to any one of claims 2 to 8 in cosmetics.

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