Anti-photoaging skin care product, anti-oxidation anti-aging compound and application

Abstract

The invention discloses an anti-photoaging skin care product, an anti-oxidation anti-aging compound and application, and can solve the anti-aging problem of the skin. Wherein the anti-oxidation and anti-aging compound has a structure as shown in a formula (1): # imgabs0 #, and R is a C1-C18 alkyl chain.

Description

Technical Field

[0001] The present invention relates to the technical field of skin care compounds, and more particularly to anti-photoaging skin care products, oxidation-resistant anti-aging compounds and uses thereof. Background Art

[0002] Retinol is an anti-aging ingredient commonly used in skin care products, but it has the disadvantage of easily causing skin irritation and allergies.

[0003] Bakuchiol also has good anti-aging effects and is a potential active ingredient for beauty and skin care. Moreover, compared with retinol, bakuchiol has fewer side effects and less irritation to the skin, so it can be used as a substitute for retinol to play an anti-aging role.

[0004] However, the storage conditions of bakuchiol are relatively harsh and its stability is poor, which makes it difficult for cosmetics containing bakuchiol to preserve their anti-aging effects.

[0005] Therefore, how to effectively provide anti-aging ingredients while overcoming the aforementioned defects is a technical difficulty in this field. Summary of the invention

[0006] An object of embodiments of the present invention is to solve the above-mentioned problems and provide advantages which will be described later.

[0007] Another purpose of the embodiments of the present invention is to provide an anti-photoaging skin care product, an oxidation-resistant anti-aging compound and its use, which can solve the anti-aging problem of the skin.

[0008] The present application examples found that bakuchiol is easily oxidized in the air due to the exposed phenolic hydroxyl groups in its structure, thereby losing its efficacy, and therefore has poor oxidation resistance stability. Therefore, by modifying bakuchiol with a reasonable structure, a derivative with similar functions and high stability is formed to replace bakuchiol, which is a feasible improvement measure. Based on the above conception, the present application examples provide the following technical solutions.

[0009] In a first aspect, the present invention provides a photo-oxidative anti-aging compound having a structure shown in formula (I):

[0010]

[0011] Wherein, R is a C1-C18 alkyl chain.

[0012] In some technical embodiments, R is a C3-C18 alkyl chain.

[0013] In some technical embodiments, R is a C1-C18 saturated or unsaturated linear alkyl chain.

[0014] In some technical embodiments, R is a C1-C18 saturated or unsaturated branched alkyl chain.

[0015] In some embodiments, the R group contains 1-2 alkenyl groups.

[0016] In some technical solutions, the oxidation-resistant and anti-aging compound is selected from any one of compounds 1a-9a:

[0017]

[0018]

[0019] In a second aspect, the embodiments of the present application provide a use of an oxidation-resistant anti-aging compound for protecting HaCaT cells against UVB photoaging.

[0020] In a third aspect, an embodiment of the present application provides a use of the oxidation-resistant anti-aging compound according to the first aspect for preparing an anti-photoaging skin care product or medicine.

[0021] In a fourth aspect, an embodiment of the present application provides an anti-photoaging skin care product, comprising: the photo-oxidation-resistant anti-aging compound described in the first aspect.

[0022] In yet another aspect, the embodiments of the present application also provide a use of a compound having a structure shown in formula (1) as an oxidation-resistant and anti-aging compound.

[0023] The beneficial effects that can be achieved by the embodiments of the present application include:

[0024] The oxidation-resistant anti-aging compound shown in formula (1) provided in the embodiment of the present application has a pharmacological activity similar to that of bakuchiol, can play a very good anti-aging effect, and has oxidation-resistant stability, which can overcome the defects of bakuchiol. Therefore, the oxidation-resistant anti-aging compound shown in formula (1) is used in the field of skin care as an anti-aging active ingredient, which can improve or improve the skin condition.

[0025] Other advantages, objectives and features of the present invention will be embodied in part through the following description, and in part will be understood by those skilled in the art through study and practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 A schematic diagram of cell survival rate in an embodiment of the present application;

[0027] Figure 2 This is another schematic diagram of cell survival rate according to an embodiment of the present application. DETAILED DESCRIPTION

[0028] The present invention is further described in detail below in conjunction with the accompanying drawings so that those skilled in the art can implement the invention with reference to the description.

[0029] The term "comprising" and any variations thereof in the embodiments of the present application are intended to cover non-exclusive inclusions. For example, a process, method, system, product, or device that includes a series of steps or units is not limited to the listed steps or units, but may optionally include steps or units that are not listed, or may optionally include other steps or units that are inherent to these processes, methods, products, or devices.

[0030] In addition to the above, it is still necessary to emphasize that the reference to "embodiment" in this article means that the specific features, structures or characteristics described in conjunction with the embodiment may be included in at least one embodiment of the present application. The appearance of this phrase in various places in the specification does not necessarily refer to the same embodiment, nor is it an independent or alternative embodiment that is mutually exclusive with other embodiments. It is explicitly and implicitly understood by those skilled in the art that the embodiments described herein can be combined with other embodiments.

[0031] As mentioned above, the present application examples found that bakuchiol has poor oxidation resistance. Therefore, by modifying bakuchiol with a reasonable structure, a derivative with similar function and high stability is formed to replace bakuchiol, which is a feasible improvement measure. However, how to reasonably modify bakuchiol is still a technical difficulty, because the product obtained after the modification of bakuchiol may not be able to obtain good fat solubility, and if the fat solubility is low, it will affect the bakuchiol modified product to enter the cell level, and it is difficult to play a good drug effect.

[0032] Therefore, the ideal bakuchiol-modified product pursued by the embodiments of the present application should not only have good oxidative stability, but also have a fat solubility no less than that of bakuchiol, and good anti-photoaging effect.

[0033] Based on the above concept, the embodiments of the present application provide the following technical solutions.

[0034] <Oxidative-resistant anti-aging compounds>

[0035] In the first aspect, the present invention provides a photo-oxidative anti-aging compound having a structure shown in formula (1):

[0036]

[0037] Wherein, the R group is a C1-C18 alkyl chain.

[0038] The photo-oxidative anti-aging compound shown in formula (1) provided in the embodiment of the present application is a bakuchiol ester derivative, which has similar pharmacological activity to bakuchiol, can play a very good anti-aging effect, and has oxidative stability, which can overcome the defects of bakuchiol. It is used as an anti-aging active ingredient in skin care products or other drugs, and can improve or improve skin condition.

[0039] Specifically, on one hand, due to the introduction of a specific R group, the exposed phenolic hydroxyl group of bakuchiol is eliminated. Therefore, compared with bakuchiol, the bakuchiol ester derivative shown in formula (1) has better stability, can reduce and lower the occurrence of oxidation, and is easy to preserve.

[0040] On the other hand, since the R group contains an alkyl group, the bakuchiol ester derivative shown in formula (1) has very good lipid solubility, is easy to enter cells, and is hydrolyzed under the action of ester hydrolases to release bakuchiol, thereby better exerting anti-aging effects.

[0041] It should be noted that in the embodiments of the present application, an alkyl chain refers to a carbon chain containing an alkyl group. C1-C18 refers to the number of carbon atoms in the alkyl chain. For example, a C1-C18 alkyl chain refers to an alkyl chain having 1-18 carbon atoms.

[0042] In some embodiments, the R group is a C1-C18 saturated or unsaturated linear alkyl chain. In other embodiments, the R group is a C1-C18 saturated or unsaturated branched alkyl chain.

[0043] In some embodiments, the R group is a C1-C18 saturated straight alkyl chain. Since unsaturated chains, such as alkyl chains containing alkenyl groups, reduce fat solubility to a certain extent, in this embodiment, the fat solubility of the photo-oxidative anti-aging compound can be improved.

[0044] In some embodiments, the R group is a C3-C18 saturated linear alkyl chain. The lipid solubility of the bakuchiol ester derivatives can be further improved.

[0045] In some embodiments, the R group contains 1-2 alkenyl groups. Unsaturated bakuchiol ester derivatives have better physiological activity than saturated bakuchiol ester derivatives. The addition of unsaturated fatty acid chains may improve the activity of the product.

[0046] In some embodiments, the oxidative stress-resistant anti-aging compound is selected from any one of compounds 1a-9a in Table 1:

[0047] Table 1

[0048]

[0049]

[0050] <Use of oxidative-resistant anti-aging compounds for HaCaT cells against UVB photoaging>

[0051] In yet another aspect, the embodiments of the present application provide uses of the oxidative-resistant and anti-aging compounds described in the embodiments of the first aspect, specifically, uses for resisting UVB photoaging of HaCaT cells.

[0052] Photoaging caused by UVB irradiation is a common form of cell aging. After treating HaCaT cells treated with UVB irradiation with the oxidative-resistant anti-aging compounds described in the examples of the present application, the cell survival rate can be significantly improved. Therefore, the oxidative-resistant anti-aging compounds provided in the examples of the present application can play a very good role in resisting UVB photoaging on HaCaT cells.

[0053] <Use of photo-oxidative anti-aging compounds for preparing anti-photoaging skin care products>

[0054] In yet another aspect, the embodiments of the present application also provide a use of the oxidation-resistant anti-aging compound according to the embodiment of the first aspect for preparing anti-photoaging skin care products or medicines.

[0055] Skin care products are often exposed to the air during use. Therefore, compared with the bakuchiol in the prior art, the anti-aging skin care products prepared by using the oxidation-resistant anti-aging compounds of the embodiments of the present application as anti-aging ingredients have better oxidation resistance and stability and are easier to store.

[0056] In addition, the photo-oxidation-resistant anti-aging compounds provided in the embodiments of the present application can also enhance the anti-aging effect on the skin after being applied to anti-photoaging skin care products. For example, when skin care products are applied on the skin, they are easily affected by the air. Therefore, if the skin care products are applied with bakuchiol as an anti-aging ingredient, the bakuchiol in them is easily oxidized and loses or reduces its effect. The photo-oxidation-resistant anti-aging compounds in the embodiments of the present application can overcome the aforementioned defects.

[0057] In yet another aspect, the embodiments of the present application also provide a use of the oxidation-resistant and anti-aging compound described in the embodiment of the first aspect for preparing a drug.

[0058] In yet another aspect, the embodiments of the present application also provide a use of a compound having a structure shown in formula (1) as an oxidation-resistant and anti-aging compound.

[0059] <Anti-photoaging skin care products>

[0060] In yet another aspect, the embodiments of the present application further provide an anti-photoaging skin care product, comprising: the photo-oxidation-resistant anti-aging compound described in the embodiment of the first aspect.

[0061] Compared with the prior art, the anti-photoaging skin care product provided in the embodiments of the present application has better oxidation stability and anti-aging effect.

[0062] <Method for preparing oxidation-resistant anti-aging compounds>

[0063] There are many methods for preparing oxidation-resistant and anti-aging compounds, which can be formed by modifying the structure of bakuchiol through derivatization methods such as esterification and etherification.

[0064] About esterification synthesis method:

[0065] The bakuchiol ester derivative of the structure of formula (1) can be generated by subjecting the raw material bakuchiol to an esterification reaction with the corresponding acid, acid anhydride or acid chloride.

[0066] The synthetic route of the bakuchiol ester derivatives of formula (1) using an acid, anhydride or acyl chloride for esterification reaction can be as follows:

[0067]

[0068] Unless otherwise stated, in the examples of the present application, base refers to a base, which may be an organic base, and further, may be triethylamine.

[0069] EDCI refers to carbodiimide.

[0070] RCOOH refers to carboxylic acid. Exemplarily, the acid used to prepare the antioxidant anti-aging compound can be selected from any one of acetic acid, propionic acid, butyric acid, oleic acid, octadecanoic acid, linoleic acid, palmitic acid and arachidonic acid.

[0071] RCOOOCR refers to anhydride.

[0072] RCOCl refers to acyl chloride.

[0073] Solvent refers to solvent.

[0074] The method adopted in the embodiment of the present invention has a very simple process route, low cost, high product yield, and can meet the needs of industrialization and expanded production.

[0075] Preparation example of oxidation-resistant anti-aging compound

[0076] Example 1

[0077] Preparation of compound 1a

[0078]

[0079] Synthesis method 1: Weigh bakuchiol (380 mg) in a 50 mL flask, stir and dissolve with 10 mL of THF (tetrahydrofuran), add 122 mg of acetic acid, 460 mg of EDCI and 20 mg of DMAP (4-dimethylaminopyridine), and finally add 550 μL of TEA (triethanolamine). The reaction was stirred at room temperature for 12 hours. The reaction solvent THF was removed under a rotary evaporator, and the resulting reaction mixture was purified by silica gel column chromatography (silica gel type is 200-300 mesh, mobile phase is petroleum ether (PE) and ethyl acetate (EA), volume ratio is PE: EA = 30: 1) to obtain compound 1a, with a mass of 470 mg.

[0080] Synthesis method 2: Weigh bakuchiol (190 mg) in a 30 mL flask, add 10 mL of THF (tetrahydrofuran) and stir to dissolve, and finally add 250 μL of TEA (triethanolamine). The resulting reaction system was placed in an ice bath, and 135 μL of acetic anhydride was added dropwise. The reaction was stirred at room temperature for 2 hours. The reaction solvent THF was removed under a rotary evaporator, and the resulting reaction mixture was purified by silica gel column chromatography (silica gel type is 200-300 mesh, mobile phase is petroleum ether (PE) and ethyl acetate (EA), volume ratio is PE: EA = 30: 1) to obtain compound 1a, mass 230 mg.

[0081] The NMR data of compound 1a are as follows:

[0082] 1 H NMR (400MHz, CDCl3) δ7.40–7.32(m,2H),7.07–6.98(m,2H),6.30(d,J=16.3Hz,1H),6.16(d,J=16.2Hz,1H),5.88(dd,J=17.5, 10.7Hz,1H),5.15–4.97(m,3H),2.29(s,3H),1.95(q,J=7.5Hz,2H),1.67(s,3H),1.58(s,3H),1.54–1.46(m,2H),1.20(s,3H).

[0083] 13 C NMR (101MHz, CDCl3) δ169.44,149.50,145.58,138.13,135.65,131.26,126.91,1 26.22,124.64,121.48,112.07,42.58,41.15,25.63,23.23,23.16,21.03,17.58.

[0084] Example 2

[0085] Preparation of compound 2a

[0086]

[0087] Experimental steps: Weigh 380 mg of bakuchiol into a 50 mL flask, stir and dissolve with 10 mL of THF (tetrahydrofuran), add 132 mg of propionic acid, 460 mg of EDCI and 20 mg of DMAP (4-dimethylaminopyridine), and finally add 550 μL of TEA (triethanolamine). The resulting reaction system was stirred at room temperature for 12 hours. The reaction solvent THF was removed under a rotary evaporator, and the resulting reaction mixture was purified by silica gel column chromatography (silica gel type is 200-300 mesh, mobile phase is petroleum ether (PE) and ethyl acetate (EA), volume ratio is PE: EA = 30: 1) to obtain compound 2a, with a mass of 400 mg.

[0088] The NMR data of compound 2a are as follows:

[0089] 1 H NMR (400MHz, CDCl3) δ7.38(d,J=8.6Hz,2H),7.05(d,J=8.5Hz,2H),6.34(d,J=16.3Hz,1H),6.19(d,J=16.2Hz,1H),5.91(dd,J=17.4,10.7Hz,1H), 5.22–4.99(m,3H),2.59(q,J=7.5Hz,2H),1.99(q,J=7.4Hz,2H),1.71(s, 3H),1.62(s,3H),1.57–1.51(m,2H),1.28(t,J=7.6Hz,3H),1.24(s,3H).

[0090] 13 C NMR (101MHz, CDCl3) δ172.79,149.60,145.54,137.97,135.46,131.18,126.84,126. 24,124.64,121.44,112.03,42.54,41.13,27.61,25.60,23.20,23.14,17.54,8.96.

[0091] Example 3

[0092] Preparation of compound 3a

[0093]

[0094] Preparation steps: 128 mg of bakuchiol was weighed into a 50 ml flask, and then 51 mg of TEA (triethanolamine) and 3 mL of dichloromethane (DCM) were added, and then 72 mg of valeryl chloride was slowly added dropwise at 0°C, and then stirred at room temperature (25°C) for 12 hours to fully react. After the reaction, the reaction solvent DCM was removed under a rotary evaporator, and the resulting reaction mixture was purified by silica gel column chromatography (silica gel type is 200-300 mesh, mobile phase is petroleum ether (PE) and ethyl acetate (EA), volume ratio is PE: EA = 30: 1), and the final product, that is, compound 3a, the mass of compound 3a is 141 mg.

[0095] The NMR data of compound 3a are as follows:

[0096] 1 H NMR (400MHz, CDCl3) δ7.36(d,J=8.6Hz,2H),7.01(d,J=8.6Hz,2H),6.31(d,J=16 .3Hz,1H),6.16(d,J=16.3Hz,1H),5.88(dd,J=17.5,10.7Hz,1H),5.15–4.97(m, 3H),2.55(t,J=7.5Hz,2H),1.95(dd,J=10.5,6.3Hz,2H),1.74(p,J=7.5Hz,2H), 1.68(s,3H),1.58(s,3H),1.54–1.42(m,4H),1.21(s,3H),0.97(t,J=7.4Hz,3H).

[0097] 13 C NMR (101MHz, CDCl3) δ172.33,149.63,145.64,138.08,135.56,131.34,126.91,126.29,124 .67,121.53,112.08,42.61,41.19,34.10,26.98,25.66,23.26,23.19,22.22,17.61,13.70.

[0098] Example 4

[0099] Preparation of compound 4a

[0100]

[0101] Experimental steps: 128 mg of bakuchiol was weighed into a 50 mL flask, 51 mg of TEA (triethanolamine) and 3 mL of DCM (dichloromethane) were added, 97 mg of octanoyl chloride was slowly added dropwise at 0°C, and the reaction was stirred at room temperature for 12 hours. The reaction solvent DCM was removed under a rotary evaporator, and the resulting reaction mixture was purified by silica gel column chromatography (silica gel type was 200-300 mesh, mobile phase was petroleum ether (PE) and ethyl acetate (EA), volume ratio was PE: EA = 30: 1) to obtain compound 4a, with a mass of 134 mg.

[0102] The NMR data of compound 4a are as follows:

[0103] 1 H NMR(400MHz, CDCl3)δ7.36(d,J=8.6Hz,2H),7.00(s,2H),6.31(d,J=16.3Hz,1H) ,6.16(d,J=16.2Hz,1H),5.88(dd,J=17.5,10.7Hz,1H),5.15–4.96(m,3H),2.54 (t,J=7.5Hz,2H),1.96(q,J=7.4Hz,2H),1.75(p,J=7.5Hz,2H),1.68(s,3H),1.5 9(s,3H),1.55–1.47(m,2H),1.46–1.30(m,8H),1.21(s,3H),0.94–0.86(m,3H).

[0104] 13 C NMR (101MHz, DMSO) δ172.33,149.63,145.64,138.07,135.55,131.33,126.91,126.29,124.68,121.53 ,112.08,42.61,41.19,34.38,31.63,29.04,28.89,25.66,24.92,23.26,23.19,22.57,17.61,14.03.

[0105] Example 5

[0106] Preparation of compound 5a

[0107]

[0108] Experimental steps: Weigh 128 mg of bakuchiol into a 50 mL flask, add 51 mg of TEA (triethanolamine), 3 mL of DCM (dichloromethane), and slowly add 131 mg of dodecanoyl chloride at 0°C. The reaction was stirred at room temperature for 12 hours. The reaction solvent DCM was removed under a rotary evaporator, and the resulting reaction mixture was purified by silica gel column chromatography (silica gel type is 200-300 mesh, mobile phase is petroleum ether (PE) and ethyl acetate (EA), volume ratio is PE: EA = 30: 1) to obtain compound 5a, with a mass of 180 mg.

[0109] The NMR data of compound 5a are as follows:

[0110] 1 H NMR (400MHz, CDCl3) δ7.36(d,J=8.6Hz,2H),7.01(d,J=8.6Hz,2H),6.31(d,J=16.2Hz,1H),6 .16(d,J=16.2Hz,1H),5.88(dd,J=17.4,10.7Hz,1H),5.11(tdd,J=6.9,2.9,1.5Hz,1H),5.08 –4.97(m,2H),2.54(t,J=7.5Hz,2H),1.96(q,J=7.4Hz,2H),1.75(p,J=7.5Hz,2H),1.68(d,J= 1.4Hz,3H),1.59(d,J=1.3Hz,3H),1.54–1.47(m,2H),1.45–1.27(m,16H),1.21(s,3H),0.93–

[0111] 0.85(m,3H).

[0112] 13 C NMR (101MHz, DMSO) δ172.34,149.63,145.64,138.07,135.55,131.33,126.91,126.29,124.68,121.53,112.08,4 2.61,41.19,34.39,31.89,29.57,29.43,29.31,29.23,29.09,25.66,24.93,23.26,23.19,22.66,17.61,14.09.

[0113] Example 6

[0114] Preparation of compound 6a

[0115]

[0116] Experimental steps: Weigh 512 mg of bakuchiol into a 50 mL flask, add 615 mg of hexadecanoic acid, 460 mg of EDCI and 20 mg of DMAP (4-dimethylaminopyridine), stir and dissolve with 10 mL of THF (tetrahydrofuran), and finally add 550 μL of TEA (triethanolamine). The reaction was stirred at room temperature for 12 hours. The reaction solvent was removed under a rotary evaporator, and the resulting reaction mixture was purified by silica gel column chromatography (silica gel type is 200-300 mesh, mobile phase is petroleum ether (PE) and ethyl acetate (EA), volume ratio is PE: EA = 30: 1) to obtain compound 6a, with a mass of 922 mg.

[0117] The NMR data of compound 6a are as follows:

[0118] 1 H NMR (400MHz, CDCl3) δ7.28(d,J=8.7Hz,2H),6.93(d,J=8.7Hz,2H),6.23(d,J=16.3 Hz,1H),6.08(d,J=16.3Hz,1H),5.80(dd,J=17.5,10.8Hz,1H),5.07–4.89(m,3H), 2.46(t,J=7.5Hz,2H),1.88(q,J=7.5Hz,2H),1.67(p,J=7.4Hz,2H),1.60(s,3H),1 .50(s,3H),1.46–1.39(m,2H),1.35-1.19(m,24H),1.13(s,3H),0.85–0.77(m,3H).

[0119] 13 C NMR (101MHz, CDCl3) δ172.34,149.64,145.64,138.08,135.56,131.80,126.92,126.30,124.68,121.54,112.09,42.62,41. 20,34.40,31.91,29.68,29.66,29.64,29.58,29.44,29.35,29.24,29.10,25.67,24.93,23.27,23.20,22.68,17.62,14.10.

[0120] Example 7

[0121] Preparation of compound 7a

[0122]

[0123] Experimental steps: Weigh 128 mg of bakuchiol into a 50 mL flask, add 170 mg of n-octadecanoic acid, 115 mg of EDCI and 5 mg of DMAP (4-dimethylaminopyridine), stir and dissolve with 10 mL of THF (tetrahydrofuran), and finally add 550 μL of TEA (triethanolamine). The reaction was stirred at room temperature for 12 hours. The reaction solvent THF was removed under a rotary evaporator, and the resulting reaction mixture was purified by silica gel column chromatography (silica gel type is 200-300 mesh, mobile phase is petroleum ether (PE) and ethyl acetate (EA), volume ratio is PE: EA = 30: 1) to obtain compound 7a, with a mass of 143 mg.

[0124] The NMR data of compound 7a are as follows:

[0125] 1 H NMR (400MHz, CDCl3) δ7.36 (d, J=8.6Hz, 2H), 7.01 (d, J=8.6Hz, 2H), 6.31 (d, J= 16.3Hz,1H),6.16(d,J=16.3Hz,1H),5.88(dd,J=17.5,10.7Hz,1H),5.18–4.9 4(m,3H),2.54(t,J=7.5Hz,2H),1.75(p,J=7.5Hz,2H),1.68(s,3H),1.59(s,3 H),1.54–1.48(m,2H),1.44–1.26(m,28H),1.21(s,3H),0.89(t,J=6.7Hz,3H).

[0126] 13 C NMR (101MHz, CDCl3) δ172.34,149.64,145.64,138.08,135.56,131.33,126.91,126.30,124.68,121.53,112.09,42.62,41.20, 34.40,31.91,29.68,29.66,29.64,29.63,29.58,29.44,29.35,29.24,29.10,25.67,24.93,23.27,23.20,22.68,17.61,14.10.

[0127] Example 8

[0128] Preparation of compound 8a

[0129]

[0130] Experimental steps: Weigh 380 mg of bakuchiol into a 50 mL flask, add 565 mg of oleic acid, 460 mg of EDCI and 20 mg of DMAP (4-dimethylaminopyridine), stir and dissolve with 10 mL of THF (tetrahydrofuran), and finally add 550 μL of TEA (triethanolamine). The reaction was stirred at room temperature for 12 hours. The reaction solvent THF was removed under a rotary evaporator, and the resulting reaction mixture was purified by silica gel column chromatography (silica gel type is 200-300 mesh, mobile phase is petroleum ether (PE) and ethyl acetate (EA), volume ratio is PE: EA = 30: 1) to obtain compound 8a, with a mass of 600 mg.

[0131] The NMR data of compound 8a are as follows:

[0132] 1 H NMR (400MHz, CDCl3) δ7.37(d,J=8.7Hz,2H),7.02(d,J=8.7Hz,2H),6.32(d,J=16.3Hz,1H),6.17(d ,J=16.2Hz,1H),5.90(dd,J=17.4,10.7Hz,1H),5.47–5.29(m,4H),5.17–4.98(m,3H),2.80(t,J=6 .4Hz,2H),2.55(t,J=7.5Hz,2H),2.14–2.02(m,4H),1.97(q,J=7.4Hz,2H),1.77(p,J=7.4Hz,2H), 1.69(s,3H),1.60(s,3H),1.56–1.48(m,2H),1.48–1.26(m,16H),1.22(s,3H),0.96–0.86(m,3H).

[0133] 13 C NMR (101MHz, CDCl3) δ172.22,149.61,145.60,138.05,135.53,131.27,130.16,129.96,128.04,127.86,126.89,126.28,124.67,121.50,112.0 7,42.59,41.18,34.34,31.49,29.55,29.31,29.29,29.12,29.06,29.04 ,27.17,27.15,25.65,25.60,24.89,23.25,23.18,22.54,17.59,14.04.

[0134] Example 9

[0135] Preparation of compound 9a

[0136]

[0137] Experimental steps: Weigh 512 mg of bakuchiol into a 50 mL flask, add 673 mg of linoleic acid, 460 mg of EDCI and 20 mg of DMAP (4-dimethylaminopyridine), stir and dissolve with 10 mL of THF (tetrahydrofuran), and finally add 550 μL of TEA (triethanolamine). The reaction was stirred at room temperature for 12 hours. The reaction solvent THF was removed under a rotary evaporator, and the resulting reaction mixture was purified by silica gel column chromatography (silica gel type is 200-300 mesh, mobile phase is petroleum ether (PE) and ethyl acetate (EA), volume ratio is PE: EA = 30: 1) to obtain compound 9a, with a mass of 600 mg.

[0138] The NMR data of compound 9a are as follows:

[0139] 1 H NMR (400MHz, CDCl3) δ7.37(d,J=8.6Hz,2H),7.02(d,J=8.6Hz,2H),6.32(d,J=16.2Hz, 1H),6.17(d,J=16.2Hz,1H),5.89(dd,J=17.5,10.7Hz,1H),5.45–5.32(m,2H),5.17–4. 98(m,3H),2.55(t,J=7.5Hz,2H),2.12–1.91(m,6H),1.76(p,J=7.5Hz,2H),1.69(s,3H ),1.60(s,3H),1.55–1.49(m,2H),1.46–1.29(m,18H),1.22(s,3H),0.94–0.85(m,3H).

[0140] 13 C NMR (101MHz, CDCl3) δ172.22,149.61,145.60,138.05,135.53,131.27,130.16,129.96,128.04,127.86,126.89,126.28,124.67,121.50,112.0 7,42.59,41.18,34.34,31.49,29.55,29.31,29.29,29.12,29.06,29.04 ,27.17,27.15,25.65,25.60,24.89,23.25,23.18,22.54,17.59,14.04.

[0141] In the embodiments of the present application, unless otherwise stated, the term "°C" refers to degrees Celsius and indicates temperature.

[0142] NMR spectral data were obtained in CDCl3 or d6 In DMSO, (unless otherwise specified) use a 400 MHz instrument to 1 H and 13 The chemical shift δ is recorded with TMS as the reference and is expressed in ppm, and the coupling constant J is expressed in Hz.

[0143] NMR data acquisition instrument: Bruker 400 MHz superconducting NMR spectrometer (Bruker AVANCE III 400 MHz Superconducting Fourier), model: AVANCE III HD 400.

[0144] Determination of lipid solubility of compounds

[0145] Lipophilicity refers to the distribution tendency of a compound between a non-polar lipid medium and an aqueous medium, and is an important factor in determining the properties of a compound. LogP and LogD are both parameters that reflect the lipophilicity of a molecule. LogP is suitable for characterizing the lipophilicity of neutral molecules, while LogD is suitable for molecules with different charge states due to pH.

[0146] Based on the structural characteristics of the compounds in the examples of the present application, LogP is suitable for characterizing the lipophilicity of the compounds described in the examples of the present application. The logP value refers to the logarithmic value of the ratio of the partition coefficients of a substance in n-octanol (oil) and water. It reflects the distribution of the substance in the oil-water phase. The smaller the logP value, the more hydrophilic it is, and the larger the logP value, the more lipophilic the substance is and the better the fat solubility is.

[0147] Therefore, in the examples of the present application, the logP value is used as an indicator to determine the fat solubility of compounds 1a-9a and bakuchiol to determine the anti-aging effects of these compounds.

[0148] Lipid solubility assay

[0149] Tested compounds: Compounds 1a-9a and bakuchiol.

[0150] Experimental reagents: n-octanol, DMF (N,N-dimethylformamide) and anhydrous sodium sulfate were purchased from Bidex Pharmaceuticals.

[0151] Experimental method: n-octanol-water was used for the dispersion system, shake-flask method was used for the determination method, and UV-visible spectrophotometry was used to determine compounds 1-9 and bakuchiol. LogP was calculated by the concentration ratio of the oil phase (n-octanol) and the water phase after the compound distribution equilibrium.

[0152] The experimental steps are as follows: 0.5 mg of the corresponding test compound is weighed in a volumetric flask, dissolved in 100 microliters of DMF, and diluted to 25 ml of solution with n-octanol. Take 5 ml from the solution and dilute to 10 ml with n-octanol. The absorbance of the test compound in the n-octanol solution is measured by UV-visible spectroscopy. Subsequently, 4 ml of each n-octanol solution and 8 ml of water are shaken on a mechanical oscillator for 30 minutes. After the n-octanol layer and the water layer are separated, the n-octanol layer is dried over anhydrous sodium sulfate, and the absorbance of the layer is measured. The concentration of each compound before and after the mechanical oscillator treatment is recorded. The logP value of each compound is calculated using the equation logP=log(y / xy), where x represents the concentration of the compound in the n-octanol phase before oscillation, and y represents the concentration of the compound in the n-octanol phase after oscillation.

[0153] As shown in Table 2, the LogP data of each compound are as follows:

[0154] Table 2

[0155]

[0156]

[0157] According to the results in Table 2, it can be seen that the compounds 1a-9a provided in the examples of the present application have good lipid solubility, which is higher than the bakuchiol in the prior art. This indicates that the compounds 1-9a provided in the examples of the present application are more likely to enter cells and exert their effects.

[0158] In addition, the lipid solubility of compounds 3a-9a is above 6, which is much higher than that of compounds 1a-2a, indicating that when the number of C atoms in the C chain of the compound is greater than or equal to 3, the lipid solubility can be greatly improved.

[0159] Cytotoxicity assay

[0160] Experimental reagents: MTT (thiazolyl blue), purchased from Solarbio (M8180-1000); trypsin, double antibody, DMEM medium, MEM medium and PBS buffer, all purchased from Gibco; fetal bovine serum, purchased from Biological Industries. DMEM medium is a complete medium, which is composed of 90% MEM basal medium, 9% fetal bovine serum and 1% double antibody by mass fraction.

[0161] Experimental equipment: SpectraMax microplate reader (MeiGu Molecular, SpectraMax i3x), optical microscope, digital display UV cross-linking instrument: Talboys.

[0162] Experimental methods:

[0163] A blank control group, a positive control group and 9 experimental groups were set up. The cell survival rate of each group was calculated. The experimental results are shown in Figure 1 .

[0164] The steps for experimental groups 1-9 are as follows:

[0165] 1) All experimental groups used HaCaT cells for the experiment. The cells were taken out of liquid nitrogen for recovery. After two to three generations of subculture and amplification, when the cell viability was good, the cell suspension was obtained after trypsin digestion and inoculated into a 96-well plate at a density of 50,000 cells / ml, with 100ul of cell suspension added to each well.

[0166] 2) After 24 hours, the cells adhered to the wall, the old culture medium was discarded, and each experimental group was replaced with a new serum-free MEM culture medium containing the same concentration of compound 1a-9a.

[0167] 3) After 24 hours, add 100 μl MTT (to dilute the MEM medium in step 2) to 0.5 mg / ml) to each well of the 96-well plate of each experimental group, wrap it with tin foil and place it in the incubator for 4 hours, discard the old solution, add 100 μl DMSO to each well, shake on a shaker for 10 minutes, measure the absorbance value of each experimental group at 570 nm on an ELISA reader, and calculate the cell survival rate of experimental groups 1-9 respectively. The experimental results are shown in Figure 1 .

[0168] The blank control group and the positive control group can be set up according to the steps of the experimental group. The main differences between the blank control group, the positive control group and the experimental group are:

[0169] Experimental groups 1-9 contained HaCaT cells and were administered with serum-free MEM medium containing compounds 1a-9a at a concentration of 2 uM, respectively;

[0170] The blank control group consisted of HaCaT cells, which were cultured with complete medium throughout the experiment. The absorbance was measured, the complete medium was discarded, and MTT was added;

[0171] The positive control group had HaCaT cells and was administered with MEM serum-free medium containing the same concentration of bakuchiol as experimental groups 1-9.

[0172] Cytotoxicity test results:

[0173] according to Figure 1 It can be seen that compared with the blank control group, the cell survival rates of the positive control group and the experimental groups 1-9 are roughly the same, indicating that the compounds 1a-9a provided in the examples of the present application have no cytotoxicity to HaCat cells.

[0174] Cell UV aging experiment

[0175] Experimental reagents: MTT (thiazolyl blue), purchased from Solarbio (M8180-1000); trypsin, double antibody, DMEM medium, MEM medium and PBS buffer, all purchased from Gibco; serum, purchased from Biological Industries; β-galactosidase cell senescence kit, purchased from Beyotime. DMEM medium is a complete medium, which is composed of 90% MEM basal medium, 9% fetal bovine serum and 1% double antibody by mass.

[0176] Experimental equipment: SpectraMax microplate reader (MeiGu Molecular, SpectraMax i3x), optical microscope, digital display UV cross-linking instrument: Talboys.

[0177] Experimental methods and steps:

[0178] 1. Determination of the optimal dose of UV:

[0179] 1) HaCat cells were used for the experiment. The cells were taken out from liquid nitrogen for recovery. After two to three generations of subculture, when the cell viability was good, they were inoculated in a 96-well plate at a density of 50,000 cells / ml, and 100ul of cell suspension was added to each well.

[0180] 2) After 24 hours, the cells adhered to the wall, the old culture medium was discarded, and then new serum-free culture medium containing the aforementioned compounds was added.

[0181] 3) After adding new PBS, irradiate with UVB at 100mJ / cm 2 、200mJ / cm 2 、300mJ / cm 2 、400mJ / cm 2 、500mJ / cm 2 、600mJ / cm 2 、700mJ / cm 2 、800mJ / cm 2 、900mJ / cm 2 , and then replace with new serum-free culture medium.

[0182] 4) After 24 hours, add 100 μl MTT (0.5 mg / ml, diluted in MEM medium) to each well of the 96-well plate, wrap it with tin foil and place it in the incubator for 4 hours, discard the old solution, add 100 μl DMSO to each well, shake on a shaker for 10 minutes, measure the absorbance at 570 nm on a microplate reader, and calculate the cell survival rate.

[0183] 5) The optimal UV dose for modeling was determined to be 700 mJ / cm by MTT method. 2 , at this dose, the cell survival rate was approximately 60%.

[0184] 2. UV aging experiment:

[0185] A blank control group, a positive control group and 9 experimental groups were set up, and the 9 experimental groups were experimental groups 1 to 9. The blank control group did not add HaCaT cells, and was used for the calibration well of absorbance; the blank group, the positive control group and the 9 experimental groups were all treated with HaCaT cells, among which the blank group was not treated with UVB light, and the other groups were treated with UVB light. After treatment, the cell survival rates of the blank group, the positive control group and the 9 experimental groups were calculated, and the experimental results are shown in Figure 2 .

[0186] The steps for experimental groups 1-9 are as follows:

[0187] 1) All experimental groups used HaCaT cells for the experiment. The cells were taken out from liquid nitrogen for recovery. After two to three generations of subculture and amplification, when the cell viability was good, HaCat cells were inoculated in a 96-well plate at a density of 50,000 cells / ml, and 100uL of HaCat cell suspension was added to each well.

[0188] 2) After 24 hours, the cells adhered to the wall, the old culture medium was discarded, and new PBS buffer was added to each experimental group.

[0189] 3) After adding new PBS buffer to each experimental group, irradiate with UVB at 700mJ / cm 2 , and then replaced with new serum-free medium (ie, MEM medium) containing compounds 1a-9a at a concentration of 2 μM. It should be noted that each experimental group added a serum-free medium containing the corresponding compound. For example, experimental group 1 added a serum-free medium containing 2 μM compound 1a, and so on, experimental group 9 added a serum-free medium containing 2 μM compound 9a.

[0190] 4) After 24 hours, add 100 μl of MTT (to dilute the serum-free medium in step 3) to a concentration of 0.5 mg / ml) to each well of the 96-well plate of each experimental group, wrap it with tin foil and place it in an incubator for 4 hours, then discard the old solution, add 100 μl of DMSO (dimethyl sulfoxide) to each well, shake it on a shaker for 10 minutes, measure the absorbance of each experimental group at 570 nm on a microplate reader, and calculate the cell survival rate of experimental groups 1-9.

[0191] The blank group, blank control group, positive control group and model group can be set up according to the steps of the experimental group. The main differences from the experimental group are:

[0192] Experimental groups 1-9 contained HaCaT cells and were administered with serum-free MEM medium containing different compounds 1a-9a at a concentration of 2 uM;

[0193] The blank control group was a control group without HaCaT cells. PBS buffer was added during the experiment. When measuring the absorbance, PBS was discarded, and then DMSO was added for the absorbance correction well;

[0194] The blank group consisted of HaCaT cells, which were cultured with complete medium throughout the whole process, and the absorbance was measured, discarded, and MTT was added after the completion of the culture;

[0195] The positive control group had HaCaT cells and was administered with MEM serum-free medium containing the same concentration of bakuchiol as the experimental group;

[0196] The model group is a non-medicated group that has HaCaT cells and is irradiated with UVB together with each of the drug-treated groups.

[0197] Experimental results: From Figure 2 It can be seen from the results that the compounds 1a-9a provided in the examples of the present application have higher cell survival rates than the model group, and the cell survival rates of most of the compounds are comparable to those of the positive control group. However, the compounds provided in the examples of the present application also have better oxidative stability. Therefore, from the overall effect point of view, the compounds provided in the examples of the present application are better than the positive compounds, that is, due to the anti-aging compounds provided by the prior art.

[0198] Although the embodiments of the present invention have been disclosed as above, they are not limited to the applications listed in the specification and the implementation modes, and they can be fully applied to various fields suitable for the present invention. For those familiar with the art, additional modifications can be easily implemented. Therefore, without departing from the general concept defined by the claims and the scope of equivalents, the present invention is not limited to the specific details and the illustrations shown and described herein.

Claims

1. An oxidation-resistant and anti-aging compound, characterized in that: It has the structure shown in formula (1): Wherein, R is a C1-C18 alkyl chain.

2. The oxidation-resistant and anti-aging compound according to claim 1, characterized in that: R is a C3-C18 alkyl chain.

3. The oxidation-resistant and anti-aging compound according to claim 1, characterized in that: R is a C3-C18 saturated or unsaturated linear alkyl chain.

4. The oxidation-resistant and anti-aging compound according to claim 1, characterized in that: R is a C3-C18 saturated or unsaturated branched alkyl chain.

5. The oxidation-resistant and anti-aging compound according to claim 1, characterized in that: The R group contains 1-2 alkenyl groups.

6. The oxidation-resistant and anti-aging compound according to claim 1, characterized in that: The oxidation-resistant and anti-aging compound is selected from any one of compounds 1a-9a:

7. Use of the oxidation-resistant anti-aging compound according to any one of claims 1 to 6 for resisting UVB photoaging of HaCaT cells.

8. Use of the oxidation-resistant anti-aging compound according to any one of claims 1 to 6 for preparing anti-photoaging skin care products or medicines.

9. An anti-photoaging skin care product, characterized in that: include: The oxidation-resistant and anti-aging compound according to any one of claims 1 to 6.

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