CN111533776B

CN111533776B - 11-O-mogrol oxime ester derivative and preparation method thereof

Info

Publication number: CN111533776B
Application number: CN202010482684.9A
Authority: CN
Inventors: 李伟; 黄华学
Original assignee: Hunan Huacheng Biotech Inc
Current assignee: Hunan Huacheng Biotech Inc
Priority date: 2020-06-01
Filing date: 2020-06-01
Publication date: 2021-03-19
Anticipated expiration: 2040-06-01
Also published as: CN111533776A

Abstract

The invention provides11-O-mogrol oxime ester derivatives and a preparation method thereof. The structural formula of the 11-O-mogrol oxime ester derivative is shown as a formula (I). The derivative is subjected to ketooximation and esterification of 11-O-mogrol to obtain the product 11-O-mogrol oxime ester derivative. The 11-O-mogrol oxime ester derivative provided by the invention has the advantages of simple preparation method, high purity and high yield. Compared with 11-O-mogrol, the obtained 11-O-mogrol oxime ester derivative has obviously enhanced antioxidant activity, and the ester water distribution ratio is suitable for serving as an antioxidant component in cosmetics, so that the aging condition of skin can be obviously improved.

Description

11-O-mogrol oxime ester derivative and preparation method thereof

Technical Field

The invention relates to a derivative of a natural product, in particular to an 11-O-mogrol oxime ester derivative and a preparation method thereof.

Background

The momordica grosvenori is a unique medicinal and edible plant in China, and is rich in various nutrient elements and bioactive substances such as flavone, polysaccharide, polyphenol and the like. Mogroside, especially mogroside V, is the most popular sweetener at present to replace sucrose, and is very popular in the European and American markets due to the characteristics of high sweetness and low calorie. The biological activity, particularly the antioxidation, of the mogroside is researched in the literature, and the mogroside V is found to have certain antioxidation capability and certain scavenging effect on hydroxyl and superoxide anion free radicals. Generally, mogroside is considered to have antioxidant activity because hydrogen atoms on aglycone have certain activity and can be combined with hydroxyl free radicals, and carbon atoms on saponin parent nucleus can form carbon free radicals and further be oxidized to form peroxy radicals. Aglycone and hydroxyl of tetracyclic triterpenoid saponin are key groups with antioxidant activity. However, the antioxidant mechanism of mogroside compounds has not been studied deeply and needs to be further researched.

Mogrol (Mogrol) is aglycone of mogroside IA 1, IE 1, IE, III, IV, IEE, V and siamenoside I; 11-O-Mogrol (11-O-Mogrol) is the aglycone of 11-O-mogroside V.

With aging, the antioxidant active components in vivo are reduced, the protective function is reduced, and the cumulative damage of free radicals is increased, so that the organism is aged. The antioxidant skin care product sold at present generally contains irritant chemical components, has poor antioxidant effect and cannot meet the requirements of people. Reactive Oxygen Species (ROS) include oxygen ions, radicals, peroxides, and the like, and have strong reactivity due to the presence of unpaired electrons. ROS, which are mainly present in the environment, include oxidative radicals, hydroxyl radicals, superoxide, singlet oxygen. Since human skin is often exposed to the environment, it is vulnerable to various free radicals, causing damage. The antioxidant can protect human skin. However, more antioxidant in the skin is not required for oxidation resistance than food grade antioxidants. Because the antioxidant has strong oxidizability, the antioxidant can react with ROS preferentially to further achieve the purpose of protecting the skin, but if the antioxidant for the skin care product has too strong oxidizability, the antioxidant effect can be lost quickly after the antioxidant is applied to the skin, and the skin cannot be protected for a long time. In addition, since skin care products are often oily creams, antioxidants are also required to have a certain ratio of hydrophilic to lipophilic. Therefore, the antioxidant in the skin care product is required to have certain stability and ester water distribution ratio besides certain antioxidant performance.

Due to the unique structural characteristics of oxime ester compounds, oxime ester compounds have been widely applied in the fields of biology, medicine, chemical industry, modern agriculture and the like, such as hormones, insecticides, anti-inflammatory agents, photoinitiators and the like. With the continuous and deep scientific research, the oxime ester compound has wider development prospect. Thus, the present patent discloses a 11-O-mogrol derivative-11-oxime ester-mogrol-and a process for its preparation.

At present, no 11-O-mogrol oxime ester derivatives are reported. The patent researches and determines a synthetic method of the 11-O-mogrol oxime ester derivative.

Disclosure of Invention

The technical scheme adopted by the invention for solving the technical problems is as follows:

an 11-O-mogrol oxime ester derivative has a structural formula shown in a formula (I):

wherein, R is H, alkyl, alkoxy, alkenyl, alkynyl, aryl or heteroaryl.

The alkyl, alkoxy, alkenyl, alkynyl groups have 1 to 20 carbon atoms, preferably 1 to 6 carbon atoms; said aryl, heteroaryl groups having 4 to 20 carbon atoms, preferably 5 to 12 carbon atoms, and said heteroaryl groups further having 1 to 3 heteroatoms selected from O, S, N, P.

Preferably, the alkyl group is selected from C1-6 alkyl groups such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl; the alkenyl is selected from ethenyl, propenyl, butenyl; the alkynyl is selected from ethynyl, propynyl and butynyl; the aryl is selected from phenyl and naphthyl; the heteroaryl is selected from furyl, piperidyl furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, oxazolyl, 1, 3, 4-oxadiazolyl, thiazolyl, benzimidazole, benzothiophene and benzofuran.

More preferably, the present invention provides the following specific compounds:

the second purpose of the invention is to provide a preparation method of the 11-O-momordica grosvenori oxime ester derivative, which comprises the following steps:

(1) oximation and post-treatment: dissolving 11-O-mogrol in alcohol, adding hydroxylamine salt and an acid-binding agent, carrying out reflux reaction, concentrating under reduced pressure after the reaction is finished, cooling the concentrated solution, stirring for crystallization, filtering, and drying to obtain 11-oxime-mogrol;

(2) esterification and post-treatment: dissolving 11-oxime-mogrol in dichloromethane or chloroform, adding an acid-binding agent, dropwise adding acid anhydride or acyl halide (solution) at low temperature, and stirring at low temperature for reaction; pouring the reaction solution into ice water after the reaction is finished, separating the solution, collecting an organic layer, washing the organic layer to be neutral by using water, concentrating the organic layer under reduced pressure, adding column chromatography silica gel into the concentrated solution, stirring uniformly, and drying to constant weight to obtain sample-mixing silica gel;

(3) silica gel column chromatography separation: adding the sample-mixed silica gel slowly and uniformly above a silica gel column filled with silica gel in advance, paving and compacting, eluting the silica gel column by using an eluent, collecting the eluent, concentrating and drying to obtain 11-oxime ester-mogrol.

The synthesis route is as follows:

preferably, in the step (1), the 11-O-mogrol is obtained by hydrolyzing a natural component 11-O-mogroside V to obtain aglycone, or is semi-synthesized or fully synthesized by mogrol.

Preferably, in the step (1), the alcohol is absolute methanol or absolute ethanol, and the amount of the alcohol is 4-20 times (ml/g) of the weight of the 11-O-mogrol.

Preferably, in the step (1), the hydroxylamine salt is hydroxylamine hydrochloride, hydroxylamine sulfate or hydroxylamine phosphate, wherein the molar ratio of hydroxylamine groups (not hydroxylamine salt) to 11-O-mogrol is (1.0-1.5): 1.

preferably, in the step (1), the acid-binding agent is an organic base, specifically, one or more of pyridine, piperidine, imidazole, methylimidazole, dimethylamine, diethylamine, trimethylamine, triethylamine, ethylenediamine, propylenediamine, cyclohexylamine, and dicyclohexylamine, and the molar ratio of the acid-binding agent to 11-O-mogrol is (0.5-5): 1. the acid-binding agent is added in order to combine with the acid generated during the reaction and allow the reaction to proceed to the right, thereby accelerating and completing the reaction. If the dosage of the acid binding agent is too small, the purpose can not be fully achieved; if the dosage of the acid binding agent is too much, the energy and the materials are wasted.

Preferably, in the step (1), the reaction temperature is 65-85 ℃, and the reaction time is 2-10 hours.

Preferably, in the step (1), the content of solid in the concentrated solution is 20% -30%, the cooling temperature is 5-10 ℃, the stirring speed is 10-20 r/min, and the crystallization time is 12-24 hours.

Preferably, in the step (2), the amount of the dichloromethane or chloroform is 5 to 10 times (ml/g) of the weight of the 11-oxime-mogrol.

Preferably, in the step (2), the acid-binding agent is the same as that in the step (1), and the molar ratio of the acid-binding agent to 11-oxime-mogrol is (0.5-5): 1.

preferably, in the step (2), the acid anhydride is acetic anhydride, propionic anhydride, succinic anhydride, maleic anhydride, benzoic anhydride, or phthalic anhydride, and the molar ratio of the acid anhydride to 11-oxime-mogrol is (1-2): 1.

preferably, in the step (2), the acyl halide is acyl fluoride, acyl chloride, acyl bromide, acyl iodide, and the molar ratio of the acyl halide to 11-oxime-mogrol is (1-2): 1.

preferably, in the step (2), the low-temperature reaction temperature is-15 to 25 ℃, and the reaction time is 2 to 24 hours.

Preferably, in the step (2), the solid content in the concentrated solution is 20-50%.

In the present invention, after the reaction in step (2) is completed, the reaction solution is poured into ice water to remove excess acid anhydride or acid halide.

The step (2) of the invention is to wash the organic layer with water to neutrality, and is to remove the acid-binding agent in the acylation reaction solution. If not washing, direct concentration of adverse consequences: the organic acid-binding agent generally has a very high boiling point and is difficult to volatilize, the residual acid-binding agent in the sample-mixing silica gel influences the subsequent elution effect, and the acid-binding agent is mixed into the eluent and finally exists in the 11-oxime ester-mogrol finished product, so that the content of the 11-oxime ester-mogrol finished product is low.

Preferably, in the step (2), the amount of the silica gel is 0.5-3 times of the weight of the 11-oxime-mogrol. The purpose of using silica gel to mix and dry is that the adsorption capacity of silica gel is very strong, various components in the concentrated solution can be uniformly adsorbed, and through the drying process, various components in the concentrated solution are firmly adsorbed in the silica gel, so that the process of 'column loading-adsorption' in the traditional silica gel column chromatographic separation can be efficiently replaced.

Preferably, in the step (3), the amount of the silica gel is 5-20 times of the weight of the 11-oxime-mogrol, and the height-diameter ratio of the silica gel column is 3-6: 1. adding the sample-mixed silica gel above a silica gel column filled with silica gel in advance, and aiming at providing a separation carrier of a target component (11-oxime ester-mogrol) and impurities in the elution process. If the consumption of the silica gel is too small or the height-diameter ratio of the silica gel column is too small, target components and impurities cannot be completely separated; if the consumption of silica gel is too much or the height-diameter ratio of the silica gel column is too large, energy and materials are wasted.

Preferably, in the step (3), the eluent is a mixed solvent of ethyl acetate and any one of petroleum ether, cyclohexane, n-hexane, 6# solvent oil and 120# solvent oil, and the ratio of the mixed solvent is 4-20: 1(V/V), the dosage of the eluent is 2-5 BV, and the flow rate of the elution is 0.5-2 BV/h. Eluting silica gel column filled with sample-mixed silica gel with eluent, wherein various components in the sample-mixed silica gel are eluted, and separating target component (11-oxime ester-mogrol) from impurities is realized by utilizing different retention time of various components in the silica gel column under the same elution condition.

In the method, 1BV is equal to 1 silica gel chromatographic column volume.

The third purpose of the invention is to provide the application of the 11-O-mogrol oxime ester derivative as an antioxidant in cosmetics and skin care products.

Compared with 11-O-mogrol, the 11-O-mogrol oxime ester derivative provided by the invention has remarkably enhanced antioxidant performance, and the ester water distribution ratio is very suitable for serving as an antioxidant component in cosmetics.

The invention also provides a skin care product, wherein the antioxidant active ingredient comprises the 11-O-momordica grosvenori oxime alcohol ester derivative.

The beneficial effects obtained by the invention are as follows:

firstly, oxime esterification is carried out on 11-O-mogrol for the first time, and the obtained oxime ester derivative has obviously enhanced oxidation resistance, so that the application range of the mogroside extract is widened, and a new idea is provided for the total utilization of the mogrosides.

The obtained 11-O-mogrol oxime ester derivative is suitable for being used as an antioxidant in skin care products and cosmetics, can effectively protect the skin and relieve the aging condition of the skin, and is proved by experiments to have long-lasting and effective antioxidant effect on the skin. Is a novel antioxidant suitable for skin care products.

Detailed Description

The present invention will be further described with reference to the following examples.

The 11-O-mogrol used in the embodiment of the invention is purchased from Huacheng biological resource GmbH of Hunan, and is aglycone obtained by hydrolyzing natural component of fructus Siraitiae Grosvenorii, 11-O-mogroside V, with hydrochloric acid, and the purity is 97.5% by High Performance Liquid Chromatography (HPLC) area normalization method, and the 11-O-mogrol sample is determined to have weight loss on drying and ash content less than 0.5%; the adjuvants or chemicals used in the examples of the present invention are commercially available in the usual manner unless otherwise specified.

Example 1

(1) Oximation and post-treatment: dissolving 23.8g of 11-O-mogrol in 120ml of absolute ethyl alcohol, adding 4.17g of hydroxylamine hydrochloride (containing 0.06mol of hydroxylamine) and 7.9g of pyridine, carrying out reflux reaction at 82 ℃ for 4 hours, carrying out silica gel TLC (thin layer chromatography) inspection reaction, concentrating under reduced pressure until the solid content of the concentrated solution is 20%, cooling the concentrated solution to the temperature of 5 ℃, stirring at the speed of 10r/min, crystallizing for 16 hours, carrying out suction filtration, and drying to obtain 21.6g of 11-oxime-mogrol.

(2) Esterification and post-treatment: dissolving 20.2g of 11-oxime-mogrol in 120ml of dichloromethane, adding 6.3g of pyridine, dropwise adding 8.2g of acetic anhydride at-5 ℃, and stirring at 10 ℃ for reaction for 5 hours; and after the silica gel TLC detection reaction is finished, pouring the reaction solution into ice water, separating the liquid, collecting an organic layer, washing the organic layer to be neutral by using water, concentrating the organic layer under reduced pressure until the solid content is 30%, adding 40g of column chromatography silica gel into the concentrated solution, uniformly stirring, and drying to constant weight to obtain the sample-mixing silica gel.

(3) Silica gel column chromatography separation: adding the sample-mixed silica gel slowly and uniformly above a silica gel column filled with the silica gel in advance (the dosage of the silica gel in the silica gel column is 220g, the height-diameter ratio of the silica gel column is 6: 1), paving and compacting, eluting the silica gel column by using a 4BV eluent (6# solvent oil: ethyl acetate: 10: 1) at the elution flow rate of 1 BV/h, collecting eluent, concentrating and drying to obtain 18.1g of 11-oxiranyl-mogrol, the purity of which is 99.2 percent and the yield of which is 66.4 percent.

¹H NMR(CDCl₃)：1.09(d,3H)，1.13-1.21(m,15H),1.24-1.26(m,11H),1.29(q,2H)，1,43-1.47(m,5H),1.65(t，1H)，1.92(d,2H)1.97(t,1H),2.27(q,2H)，3.23(t，1H)，3.28(t,1H),,5.37(s,1H)。Anal.Calcd.for C₃₃H₅₅NO₅:C.72.62,H.10.17,N.2.57,O.14.65。m/z:545.41,Found:545.79。

Example 2

(1) Oximation and post-treatment: dissolving 23.8g of 11-O-mogrol in 150ml of anhydrous methanol, adding 4.5g of hydroxylamine sulfate (containing 0.055mol of hydroxylamine) and 20.2g of triethylamine, carrying out reflux reaction at 70 ℃ for 4 hours, after the silica gel TLC test reaction is finished, concentrating under reduced pressure until the solid content of the concentrated solution is 25%, cooling the concentrated solution to 10 ℃, stirring at the speed of 20r/min, crystallizing for 20 hours, carrying out suction filtration, and drying to obtain 21.1g of 11-oxime-mogrol.

(2) Esterification and post-treatment: dissolving 20.2g of 11-oxime-mogrol in 120ml of chloroform, adding 6.1g of triethylamine, dropwise adding 8.3g of cyclopropane carbonyl chloride at 0 ℃, and stirring at 20 ℃ for reacting for 3 hours; and after the silica gel TLC detection reaction is finished, pouring the reaction solution into ice water, separating the liquid, collecting an organic layer, washing the organic layer to be neutral by using water, concentrating the organic layer under reduced pressure until the solid content is 25%, adding 50g of column chromatography silica gel into the concentrated solution, uniformly stirring, and drying to constant weight to obtain the sample-mixing silica gel.

(3) Silica gel column chromatography separation: adding the sample-mixed silica gel slowly and uniformly above a silica gel column filled with silica gel in advance (the dosage of the silica gel in the silica gel column is 280g, and the height-diameter ratio of the silica gel column is 4: 1), paving and compacting, eluting the silica gel column by using a 5BV eluent (cyclohexane: ethyl acetate: 12: 1) at the elution flow rate of 1.5 BV/h, collecting eluent, concentrating and drying to obtain 17.9g of 11-oxime cyclopropyl methyl ester-mogrol, wherein the purity is 99.4 percent, and the yield is 64.3 percent.

¹H NMR(CDCl₃)：0.45-0.47(m,4H),1.05(dd,1H)，1.12-1.20(m,15H),1.24-1.27(m,11H),1.29(q,2H)，1,42-1.47(m,5H),1.65(t，1H)，1.92(d,2H)1.97(t,1H),3.23(t，1H)，3.28(t,1H),,5.37(s,1H)。Anal.Calcd.for C₃₄H₅₅NO₅:C.73.21,H.9.94,N.2.51,O.14.34。m/z:557.46,Found:557.70。

Example 3

(1) Oximation and post-treatment: dissolving 23.8g of 11-O-mogrol in 150ml of absolute ethyl alcohol, adding 3.94g of hydroxylamine phosphate (containing 0.06mol of hydroxylamine) and 11g of diethylamine, carrying out reflux reaction at 85 ℃ for 6 hours, carrying out silica gel TLC (thin layer chromatography) inspection reaction, concentrating under reduced pressure until the solid content of the concentrated solution is 30%, cooling the concentrated solution to 8 ℃, stirring at the speed of 10r/min, crystallizing for 20 hours, carrying out suction filtration, and drying to obtain 22.6g of 11-oxime-mogrol.

(2) Esterification and post-treatment: dissolving 20.2g of 11-oxime-mogrol in 150ml of dichloromethane, adding 8.8g of diethylamine, dropwise adding 8.4g of benzoyl chloride at-10 ℃, and stirring at 0 ℃ for reacting for 6 hours; and after the silica gel TLC detection reaction is finished, pouring the reaction solution into ice water, separating the liquid, collecting an organic layer, washing the organic layer to be neutral by using water, concentrating the organic layer under reduced pressure until the solid content is 20%, adding 50g of column chromatography silica gel into the concentrated solution, uniformly stirring, and drying to constant weight to obtain the sample-mixing silica gel.

(3) Silica gel column chromatography separation: adding the sample-mixed silica gel slowly and uniformly above a silica gel column filled with silica gel in advance (the dosage of the silica gel in the silica gel column is 320g, the height-diameter ratio of the silica gel column is 5: 1), paving and compacting, eluting the silica gel column by using 4BV eluent (petroleum ether: ethyl acetate: 11: 1) at the eluting flow rate of 1 BV/h, collecting eluent, concentrating and drying to obtain 18.17g of 11-oxime benzyl ester-mogrol, the purity of which is 98.6 percent and the yield of which is 61.2 percent.

¹H NMR(CDCl₃)：1.13-1.21(m,15H),1.24-1.26(m,11H),1.29(q,2H)，1,43-1.47(m,5H),1.65(t，1H)，1.92(d,2H)1.97(t,1H)3.23(t，1H)，3.28(t,1H),,5.37(s,1H)，7.47(dd,2H),.7.60(t,1H),8.13(d,2H)。Anal.Calcd.for C₃₇H₅₅NO₅:C.74.82,H.9.34,N.2.36,O.13.48。m/z:593.52,Found:593.76。

Effect example 1

The formula of the skin cream is as follows:

composition (I)	Content (wt%)
		Active ingredient of antioxidant	0.7
Glycerol	4
		Butanediol	3
Propylene glycol	2
		Oleate ester	1
Polysorbate ester	0.5
		Anhydrous ethanol	8.5
Polydimethylsiloxane	1.5
		Squalane	1
Trehalose	1
		Glycyrrhizic acid dipotassium salt	0.1
Hyaluronic acid sodium salt	0.05
		Water (W)	Balance of

Weighing the components according to the formula, and uniformly stirring the antioxidant active component, glycerol, butanediol, propylene glycol, oleate, polysorbate, absolute ethyl alcohol, polydimethylsiloxane and squalane at 50-60 ℃ to obtain an oil phase mixture; adding trehalose, dipotassium glycyrrhizinate and sodium hyaluronate into water, and uniformly stirring to obtain a water phase mixture; adding the oil phase mixture into the water phase mixture, stirring at 50-60 deg.C, emulsifying, and homogenizing to obtain ointment-like substance. The compounds (I-1), (I-2) and (I-3) obtained in examples 1 to 3 were prepared into skin creams as antioxidant active ingredients, respectively, which were named skin cream 1 (antioxidant active ingredient was compound I-1), skin cream 2 (antioxidant active ingredient was compound I-2) and skin cream 3 (antioxidant active ingredient was compound I-3). The skin cream 4 is prepared by using a commercial antioxidant 2, 6-di-tert-butyl-p-cresol (BHT) commonly used in cosmetics as an antioxidant active ingredient according to the formula. The 11-O-mogrol is used as an additive and is prepared into the skin cream 5 according to the formula.

The antioxidant performance of the skin cream is tested according to the following method, and the sample solution is prepared by taking the obtained skin cream 1 to 5, adding 95% ethanol solution to constant volume and preparing 10mg/mL test solutions respectively.

1.Radical DPPH scavenging assay.The antioxidant capacity of the 11-O-mogrol oxime ester derivative is quantitatively measured by adopting a DPPH method. The principle is that the DPPH free radical has a single electron, and has a strong absorption at 520nm, and the alcoholic solution is purple. The antioxidant enables the pairing of single electrons,thereby reducing the a520nm value and fading the solution. Since this change is quantitatively related to the number of electrons accepted, it can be measured by colorimetric methods such as a spectrophotometer. The method comprises the following steps:

(1) preparation of DPPH reagent: 0.00990g of DPPH (1, 1-diphenyl-2-piperidinylhydrazyl) powder (molecular weight is 394) is precisely weighed and placed in a 250mL volumetric flask, and dissolved by using a proper amount of 95% ethanol until the volume is up to 250mL, so that the DPPH reagent with the concentration of 0.10mmol/L is obtained.

(2) Preparing a test sample: respectively taking the test solutions containing 10mg/mL of the skin cream;

(3) and (3) testing:

a. sequentially adding 4.0ml DPPH solution and 1.0ml 95% ethanol into 10ml test tube, mixing, shaking, reacting in dark for 30min, stabilizing, measuring absorbance at 520nm with 95% ethanol as reference to obtain blank tube absorbance, and recording as A₀。

b. Sequentially adding 4.0ml DPPH solution and 1.0ml sample solution to be detected into 10ml test tube, mixing, shaking, reacting in dark for 30min, stabilizing, measuring absorbance at 520nm with 95% ethanol as reference to obtain sample tube absorbance, and recording as A₁。

c. Sequentially adding 4.0ml of 95% ethanol solution and 1.0ml of sample solution to be detected into a 10ml test tube, mixing, shaking, reacting in dark for 30min, stabilizing, measuring light absorption value at 520nm with 95% ethanol as reference to obtain background tube light absorption value, and recording as A₂。

d. Calculating the formula: clearance of sample on DPPH radicals SA (%):

2. ₂scavenging test for superoxide anion radical (O-): pyrogallol autoxidation method.

Adopting a pyrogallol autooxidation method, taking 4mL of 0.1mol/L Tris-HCl buffer solution with pH8.2 and 2mL of distilled water, uniformly mixing, preserving heat in a water bath at 25 ℃ for 20min, then adding 2mL of sample solution, taking out, immediately adding 0.5mL of 5mmol/L pyrogallol preheated at 25 ℃ (prepared by 10mmol/L HCL, a blank tube uses 10mmol/L HCL to replace HCL solution of the pyrogallol), shaking uniformly, pouring into a cuvette, measuring absorbance at 325nm every 30s, continuously measuring for 4min, and calculating the increase of the absorbance per minute in a linear range. The volume of distilled water was reduced while a volume of sample solution was added.

Inhibition ratio (%) (. DELTA.A 0-. DELTA.A)/. DELTA.A 0X 100

In the formula: delta A0 is the autoxidation rate of pyrogallol; delta A is the autoxidation rate of pyrogallol after the addition of the sample solution.

3.Scavenging test for hydroxyl radical scavenging rate: fenton method.

Taking 2 colorimetric tubes (sample tube, blank tube) of 25ml, adding 1mmol/L ferrous sulfate solution of 5ml and 3mmol/L H2O of 5ml respectively₂Adding 1ml of sample solution into a sample tube, adding 1ml of distilled water into a blank tube, uniformly mixing, fixing the volume to the scale by using a 3mmol/L salicylic acid solution, reacting in constant-temperature water at 37 ℃ (0.1 +/-DEG C) for 15min, and measuring the absorbance of each tube at the wavelength of 510nm by using a spectrophotometer. Zero adjustment was carried out with 3mmol/L salicylic acid solution.

The removal rate SA (%) of OH radicals can be calculated according to the following formula:

in the formula: a0 — absorbance without sample addition; a1-absorbance of the added sample

The antioxidant capacity of each skin cream, tested according to the above method, is shown in table 1 below:

TABLE 1

After the sample solution was exposed to air and sunlight for 4 hours, the oxidation resistance was retested according to the same method steps as described above, with the results shown in table 2:

TABLE 2

As can be seen from the data in tables 1 and 2, the 11-O-mogrol oxime ester derivative provided by the invention has remarkable oxidation resistance, and is suitable for being used as an antioxidant active ingredient of creams and cream products such as cosmetics and skin care products. Compared with commercial cosmetic antioxidants, the antioxidant has slightly weak antioxidant capacity but obviously enhanced durable antioxidant capacity, and can maintain the effect of protecting the skin for a longer time as an antioxidant active ingredient in a skin care product.

Effect example 2

Female subjects, age 35-40 years, were selected, inclusion criteria: the skin is aged, dry, fine-grained, rough, yellow, and has reduced elasticity. The conditions of no damage, acne scar and erosion of the mila are eliminated, the subjects with high skin sensitivity, the subjects who use chemical preparations for a long time or have recently performed freckle removing treatment are eliminated. Finally, 20 subjects per group were selected for the trial.

The test method comprises cleaning face in the morning and evening of each day, smearing skin cream, and smearing cream matrix (containing no antioxidant active ingredient) identical to that of observation group.

After each group of subjects is smeared with the skin cream for one month, the skin cream is scored, wherein the scoring standard is 5 options of roughness, dryness, fine lines, pigment change, facial color and skin elasticity, each option is divided into 1 (mild degree), 2 (moderate degree), 3 (severe degree) and 15 parts at most according to the severity, the higher the score is, the heavier the skin aging degree is, and the worse the skin is. The results are shown in table 3 below:

TABLE 3

Group of	Before smearing	After being smeared for 2 months
			Observation group-skin cream 1	12.57±0.79	8.83±0.49
Observation group-skin cream 2	12.73±0.81	9.12±0.53
			Observation group-skin cream 3	12.28±0.75	9.33±0.56
Observation group-skin cream 4	12.42±0.76	10.25±0.62
			Observation group-skin cream 5	12.67±0.74	11.68±0.68
Control group	12.62±0.78	12.31±0.73

As can be seen from the data in Table 3, the skin cream containing the 11-O-mogrol oxime ester derivative as an antioxidant active ingredient has excellent effects of relieving skin aging and improving skin color and elasticity when being applied. Observations 1-3 were significantly more effective than observation 4, which used BHT as an antioxidant. And the skin cream 5 added with the 11-O-mogrol is basically not different from the observation group 5 and the control group, which shows that the 11-O-mogrol has no skin protection and skin aging alleviation effects in the skin care product.

Finally, it should be noted that: the above embodiments are only used to illustrate the technical solution of the present invention, and not to limit the same; while the invention has been described in detail and with reference to the foregoing embodiments, it will be understood by those skilled in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some or all of the technical features may be equivalently replaced; and the modifications or the substitutions do not make the essence of the corresponding technical solutions depart from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. An 11-oxime ester-mogrol derivative has a structural formula shown in formula (I):

(I)

wherein R is alkyl, aryl or cyclopropyl;

the alkyl group has 1 to 6 carbon atoms; the aryl group has 6 to 12 carbon atoms.

2. The 11-oxime ester-mogrol derivative of claim 1 wherein the alkyl group is selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl; the aryl is selected from phenyl and naphthyl.

3. The 11-oxime ester-mogrol derivative of claim 1 having the chemical structure:

(I-1) (I-2)

(I-3)。

4. a process for preparing 11-oxime ester-mogrol derivatives as claimed in any one of claims 1 to 3, wherein the synthesis scheme is as follows:

。

5. a process for the preparation of 11-oxime ester-mogrol derivatives as claimed in any one of claims 1 to 3, which comprises the steps of:

(2) esterification and post-treatment: dissolving 11-oxime-mogrol in dichloromethane or chloroform, adding an acid-binding agent, dropwise adding an anhydride or acyl halide solution at low temperature, and stirring at low temperature for reaction; pouring the reaction solution into ice water after the reaction is finished, separating the solution, collecting an organic layer, washing the organic layer to be neutral by using water, concentrating the organic layer under reduced pressure, adding column chromatography silica gel into the concentrated solution, stirring uniformly, and drying to constant weight to obtain sample-mixing silica gel;

6. The method for preparing 11-oxime ester-mogrol derivative as claimed in claim 5, wherein in the step (1), the alcohol is absolute methanol or absolute ethanol, and the volume usage amount of the alcohol is 4-20 times of the weight of 11-O-mogrol; and/or the hydroxylamine salt is hydroxylamine hydrochloride, hydroxylamine sulfate and hydroxylamine phosphate, wherein the molar ratio of the hydroxylamine group to the 11-O-mogrol is (1.0-1.5): 1; and/or the acid-binding agent is an organic base, and the molar ratio of the acid-binding agent to 11-O-mogrol is (0.5-5): 1.

7. the method of claim 6, wherein the acid-binding agent is selected from one or more of pyridine, piperidine, imidazole, methylimidazole, dimethylamine, diethylamine, trimethylamine, triethylamine, ethylenediamine, propylenediamine, cyclohexylamine, and dicyclohexylamine.

8. The method for preparing 11-oxime ester-mogrol derivative as claimed in claim 5, wherein in step (2), the acid anhydride is acetic anhydride, propionic anhydride, benzoic anhydride, and the molar ratio of the acid anhydride to 11-oxime-mogrol is (1-2): 1; or the acyl halide is acyl fluoride, acyl chloride, acyl bromide and acyl iodide, and the molar ratio of the acyl halide to the 11-oxime-mogrol is (1-2): 1.

9. use of 11-oxime ester-mogrol derivatives as claimed in any one of claims 1 to 3 as antioxidants in skin care products.

10. A skin care product comprising the 11-oxime ester-mogrol derivative as defined in any one of claims 1 to 3, as an antioxidant active ingredient.