Hydroxycinnamic acid alkoxyl alcohol ester derivatives and their use in cosmetics

Abstract

The application discloses a hydroxyl cinnamic acid alkoxyl alcohol ester derivative and application thereof in cosmetics. Specifically, the application provides a hydroxyl cinnamic acid alkoxyl alcohol ester derivative which is a compound as shown in formula I. The compound provided by the application has good oil phase solubility, high stability in a system, and one or more effects such as antioxidation, whitening and ultraviolet absorption.

Description

TECHNICAL FIELD

[0001] The present application relates to a hydroxycinnamic acid alkoxyl alcohol ester derivative and its application in cosmetics. BACKGROUND

[0002] Hydroxycinnamic acid compounds such as hydroxycinnamic acid, caffeic acid, and ferulic acid have significant antioxidant, whitening, and antibacterial effects in the field of cosmetics. They can effectively resist the damage of free radicals to the skin, delay skin aging, inhibit melanin production, brighten skin color, and maintain a healthy skin environment. However, the application of such compounds is limited by their structural characteristics, poor solubility, and stability. In cosmetic formulations, due to the low solubility of cinnamic acid compounds in both aqueous and oil phases, they cannot be fully mixed with other ingredients in the formulation, affecting the uniformity and stability of the product. This not only limits their application range in cosmetics, but also may cause problems such as layering and precipitation during product use, affecting the user experience of consumers. In addition, such compounds are easily degraded under light conditions and in aqueous solutions with a pH greater than 5, causing discoloration and odor changes, affecting the application stability of the formulation and the shelf life of the product. Therefore, despite the many potential advantages of cinnamic acid compounds, these problems need to be addressed in practical applications to fully utilize their efficacy in cosmetics. SUMMARY

[0003] The technical problem to be solved by the present application is to overcome the defects of hydroxycinnamic acid compounds in the prior art, such as poor solubility and poor formulation stability. The present application provides a hydroxycinnamic acid alkoxyl alcohol ester derivative. The hydroxycinnamic acid alkoxyl alcohol ester derivative of the present application has good oil phase solubility, high stability in the system, and one or more effects such as antioxidant, whitening, and ultraviolet absorption.

[0004] The present application solves the above technical problems by the following technical solutions:

[0005] The present application provides a hydroxycinnamic acid alkoxyl alcohol ester derivative, which is a compound as shown in formula I,

[0006] ;

[0007] wherein the wavy line directly connected to the double bond indicates that the double bond is in E or Z configuration;

[0008] X is a polymer residue having 1, 2, 3, 4, 5, or 6 repeating units, the monomers of the polymer residue being one or more of ethylene glycol, 1,2-propanediol, 1,3-propanediol, and glycerol; each monomer of the polymer residue is connected by an ether bond; both ends of the polymer residue are -O-;

[0009] R1 is -H or C2-20 alkyl;

[0010] R1is C when the polymeric residue monomer is ethylene glycol or the polymeric residue is a polymeric residue having 1 repeating unit. 2-20 alkyl.

[0011] In some embodiments, in the compound of Formula I, the definition of certain groups can be as described below, and the definition of other groups can be as described in any of the aspects of the application (hereinafter in some embodiments), the polymeric residue has a carbon number of no more than 12.

[0012] In some embodiments, the double bond is in the E configuration.

[0013] In some embodiments, the monomer of the polymeric residue is ethylene glycol, 1,2- propanediol, 1,3-propanediol, or glycerol.

[0014] In some embodiments, X is a polymeric residue having 1, 2, or 3 repeating units.

[0015] In some embodiments, X is , , , , , , , or ; the terminal group is attached to R1.

[0016] In some embodiments, R1is H, ethyl, , , , , , or .

[0017] In some embodiments, the structural unit -X-R1is , , , , , , , , , , , , , or .

[0018] In some embodiments, the hydroxycinnamic acid alkoxyl ester derivative is: , , , , , , , , , , , , , or .

[0019] In some embodiments, the hydroxycinnamic acid alkoxyl alcohol ester derivative is: , , , , , , , , , , , , , or .

[0020] The present application also provides a method for preparing the aforementioned hydroxycinnamic acid alkoxyl alcohol ester derivative, comprising the following steps:

[0021] ;

[0022] condensing a compound as shown in Formula II and R1-X-H to generate a compound as shown in Formula I; wherein R1 and X are as defined in any of the schemes of the present application.

[0023] A conventional catalyst for such a reaction in the present application can be used in the condensation reaction; such as sulfuric acid, p-toluenesulfonic acid or trifluoroacetic acid.

[0024] A conventional solvent for such a reaction in the present application can be used in the condensation reaction; or no solvent can be used; the solvent can include one or more of an aromatic heterocyclic solvent, an aromatic hydrocarbon solvent, an amide solvent, a halogenated hydrocarbon solvent, an ether solvent, an aliphatic hydrocarbon solvent and a sulfoxide solvent; the aromatic heterocyclic solvent can be pyridine; the aromatic hydrocarbon solvent can be toluene; the amide solvent can be N,N-dimethylformamide; the halogenated hydrocarbon solvent can be dichloromethane or chloroform; the ether solvent can be tetrahydrofuran; the aliphatic hydrocarbon solvent can be cyclohexane or n-hexane; the sulfoxide solvent can be dimethyl sulfoxide; for example, the solvent for the condensation reaction is toluene.

[0025] The molar ratio of the compound of Formula II to R1-X-H in the condensation reaction can be a conventional molar ratio for such reactions in the art; such as 1 : (1-20); for example 1:1.5, 1:3, 1:5, 1:6, or 1:15.

[0026] The molar ratio of the compound of Formula II to the catalyst in the condensation reaction can be a conventional molar ratio for such reactions in the art; such as 1 : (0.01-2); for example 1:1 or 1:0.1.

[0027] The reaction temperature of the condensation reaction can be a conventional temperature for such reactions in the art; such as 20-100°C, for example 85°C.

[0028] The progress of the condensation reaction can be monitored using conventional detection methods in the art (e.g., HPLC, TLC, or NMR), and the reaction time can be 12-72 hours; for example 16 hours or 24 hours, generally until the compound of Formula II disappears or no longer converts.

[0029] The present application also provides a cosmetic product comprising the hydroxycinnamic acid alkoxy alcohol ester derivative according to any one of the aspects of the present application.

[0030] In some embodiments, the cosmetic product has one or more of the following effects: (1) antioxidant effect, (2) whitening effect, and (3) ultraviolet absorption effect.

[0031] The present application also provides the use of the hydroxycinnamic acid alkoxy alcohol ester derivative according to any one of the preceding aspects in a cosmetic product.

[0032] The positive progress effects of the present application are that the hydroxycinnamic acid alkoxy alcohol ester derivative provided by the present application has one or more of the following positive progress effects:

[0033] 1. greatly increases the solubility of hydroxycinnamic acid in the oil phase commonly used in formulations.

[0034] 2. greatly improves the stability of hydroxycinnamic acid in the formulation system.

[0035] 3. has good antioxidant, whitening, and ultraviolet absorption effects. BRIEF DESCRIPTION OF DRAWINGS

[0036] Figure 1 Figure showing the results of ultraviolet absorption testing of the compound. DETAILED DESCRIPTION

[0037] The present application is further illustrated by the following examples, but the present application is not limited to the examples.

[0038] Example 1:

[0039] The compounds shown in Table 1 were synthesized.

[0040] Table 1: Compound List

[0041]

[0042]

[0043] Alkoxyl alcohol ester derivatives of hydroxycinnamic acid and their synthesis method:

[0044] The hydroxycinnamic acid, short-chain polyether and fatty alcohol required as raw materials can be easily obtained from commercial channels.

[0045] Compound and synthesis method:

[0046] The compound can be prepared by using a conventional esterification reaction. The catalysts that can be used in the esterification reaction include sulfuric acid, p-toluenesulfonic acid, trifluoroacetic acid and the like; the solvents that can be used include toluene, N,N-dimethylformamide, dichloromethane, chloroform, tetrahydrofuran, cyclohexane, n-hexane, dimethyl sulfoxide and the like, which are good solvents for the reaction substances or combinations thereof; the reaction temperature can be 20-100°C depending on the nature of R1, and the reaction time can be 12-72 hours.

[0047] The purity and molecular weight of the sample were detected by LCMS.

[0048] The specific synthesis method of each compound is as follows:

[0049] Compound 1:

[0050] The reaction starting material was ferulic acid and ethylene glycol monoethyl ether (CAS No. 110-80-5). Ferulic acid (250 mg, 1.29 mmol, 1 eq) and ethylene glycol monoethyl ether (175.73 mg, 1.95 mmol, 1.5 eq) were dissolved in 12.5 mL of toluene, and sulfuric acid (12.63 mg, 128.74 μmol, 6.86 μL, 0.1 eq) was added dropwise, heated to 85°C and reacted for 16 hours. After the reaction was completed, the solvent was removed under reduced pressure, and HPLC purification and separation (HPLC (column: Waters Xbridge BEH C18 250 × 50mm × 10 um; mobile phase: [H2O (10mM NH4HCO3)-ACN]; gradient: 20%-50% B over 10.0 min)) was performed to obtain 155 mg of the target product, with a yield of 45%, a purity of 98.4%, and a white powder. Molecular formula C 14 H 18O5, 266.3 g / mol. MS (ESI) m / z 267.1 [M+H] + .

[0051] 1 H NMR (400 MHz, DMSO-d6) δ= 7.54 (d, 1H), 7.32 (d, 1H), 7.08 (br d,1H), 6.78 (d, 1H), 6.31 (d, 1H), 4.25 - 4.15 (m, 2H), 3.83 (s, 3H), 3.65 -3.61 (m, 2H), 3.53 - 3.47 (m, 2H), 1.09 (t, 3H).

[0052] Compound 2:

[0053] The reaction starting material was ferulic acid and ethylene glycol monobutyl ether (CAS No. 111-76-2). The reaction conditions were as before, ferulic acid (250 mg, 1.29 mmol, 1 eq) and ethylene glycol monobutyl ether (237.52 mg, 2.01 mmol, 1.5 eq) were dissolved in 12.5 mL of toluene, sulfuric acid (12.63 mg, 128.74 μmol, 6.86 μL, 0.1 eq) was added dropwise, heated to 85°C for 16 hours. HPLC purification gave 140 mg of the target product, yield 36%, purity 99.7%, colorless oil. Molecular formula C 16 H 22 O5, 294.4 g / mol. MS (ESI) m / z 295.1 [M+H] + .

[0054] 1 H NMR (400 MHz, DMSO-d6) δ= 7.52 (d, 1H), 7.32 (d, 1H), 7.03 (br d,1H), 6.73 (d, 1H), 6.30 (d, 1H), 4.27 - 4.17 (m, 2H), 3.83 (s, 3H), 3.63 -3.60 (m, 2H), 3.34 - 3.30 (m, 2H), 1.50 -1.40 (m, 4H), 0.92 (t, 3H).

[0055] Compound 3:

[0056] The reaction was started with ferulic acid and ethylene glycol mono-iso-octyl ether (CAS No. 1559-35-9). The reaction conditions were the same as before, ferulic acid (250 mg, 1.29 mmol, 1 eq) and ethylene glycol mono-iso-octyl ether (348.56 mg, 2.00 mmol, 1.5 eq) were dissolved in 12.5 mL of toluene, sulfuric acid (12.63 mg, 128.74 μmol, 6.86 μL, 0.1 eq) was added dropwise, heated to 85°C for 16 hours. HPLC purification to obtain 150 mg of the target product, yield 33%, purity 96.5%, light yellow oil. Molecular formula C 20 H 30 O5, molecular weight 350.5. MS (ESI) m / z 351.2 [M+H] + .

[0057] 1 H NMR (400 MHz, DMSO-d6) δ= 7.50 (d, 1H), 7.21 (d, 1H), 7.05 (br d,1H), 6.78 (d, 1H), 6.33 (d, 1H), 4.27 - 4.19 (m, 2H), 3.82 (s, 3H), 3.63 -3.40 (m, 3H), 1.50 -1.45 (m, 3H), 1.33 -1.21 (m, 6H), 0.99 (t, 3H), 0.82 (t,3H).

[0058] Compound 4:

[0059] The reaction was started with ferulic acid and diethylene glycol monoethyl ether (CAS No. 111-90-0), the reaction conditions were the same as before. Ferulic acid (250 mg, 1.29 mmol, 1 eq) and diethylene glycol monoethyl ether (259.11 mg, 1.93 mmol, 1.5 eq) were dissolved in 12.5 mL of toluene, sulfuric acid (12.63 mg, 128.74 μmol, 6.86 μL, 0.1 eq) was added dropwise, heated to 85°C for 16 hours. After the reaction was completed, the solvent was removed under reduced pressure, HPLC purification and separation to obtain 136 mg of the target product, yield 34%, purity 98.2%, colorless oil. Molecular formula C 16 H 22 O6, molecular weight 310.3. MS (ESI) m / z 311.1 [M+H] + .

[0060] 1H NMR (400 MHz, DMSO-d6) δ= 7.55 (d, 1H), 7.33 (d, 1H), 7.10 (br d, 1H), 6.78 (d, 1H), 6.50 (d, 1H), 4.29 - 4.18 (m, 2H), 3.81 (s, 3H), 3.69 -3.62 (m, 2H), 3.58 - 3.52 (m, 2H), 3.51 - 3.46 (m, 2H), 3.43 (q, 2H), 1.09(t, 3H)。

[0061] Compound 5:

[0062] The starting material was changed to diethylene glycol monobutyl ether (CAS No. 112-34-5) and the reaction conditions were the same as before. Ferulic acid (250 mg, 1.29 mmol, 1 eq) and diethylene glycol monobutyl ether (308.24 mg, 1.90 mmol, 1.5 eq) were dissolved in 12.5 mL of toluene, and sulfuric acid (12.63 mg, 128.74 μmol, 6.86 μL, 0.1 eq) was added dropwise, heated to 85°C for 16 hours. After the reaction was completed, the solvent was removed under reduced pressure, and HPLC purification and separation were performed to obtain 180 mg of the target product, with a yield of 42%, a purity of 99.7%, and colorless oil. Molecular formula C 18 H 26 O6, molecular weight 338.4, MS (ESI) m / z 339.1 [M+H] + .

[0063] 1 H NMR (400 MHz, DMSO-d6) δ= 7.53 (d, 1H), 7.29 (d, 1H), 7.06 (br d, 1H), 6.75 (d, 1H), 6.52 (d, 1H), 4.27 - 4.20 (m, 2H), 3.81 (s, 3H), 3.65 -3.55 (m, 6H), 3.32-3.26 (m, 2H), 1.55-1.43 (m, 4H), 0.96 (t, 3H)。

[0064] Compound 6:

[0065] Starting material was changed to ethylhexylglycerol (CAS No. 70445-33-9). Ferulic acid (300 mg, 1.54 mmol, 1 eq) and ethylhexylglycerol (1.58 g, 7.72 mmol, 5 eq) were dissolved in 10 mL of toluene, p-toluenesulfonic acid monohydrate (293.87 mg, 1.54 mmol, 1 eq) was added, heated to 85 °C for 16 hours. After the reaction was completed, the solvent was removed under reduced pressure, HPLC purification separation (HPLC (column: WePure Biotech XP tC18 150x40x7um; mobile phase: [H2O (10 mM NH4HCO3) - ACN]; gradient: 50%-80% B over 8.0 min) ) to obtain 100 mg of the target product, yield 17%, purity 99.6%, light yellow oil. Molecular formula C 21 H 32 O6, molecular weight 380.5. MS (ESI) m / z 381.2 [M+H] + .

[0066] 1 H NMR (400 MHz, DMSO-d6) δ= 9.59 (s, 1H), 7.56 (d, 1H), 7.31 (d, 1H),7.11 (dd, 1H), 6.79 (d, 1H), 6.47 (d, 1H), 5.02 (d, 1H), 4.17 - 4.10 (m, 1H),4.07 - 3.98 (m, 1H), 3.89 - 3.83 (m, 1H), 3.82 (s, 3H), 3.41 - 3.34 (m, 2H),3.29 (dd, 2H), 1.49 - 1.39 (m, 1H), 1.35 - 1.17 (m, 8H), 0.88 - 0.76 (m, 6H)。

[0067] Compound 7:

[0068] Starting material was replaced with chrysin (CAS No. 520-05-2), reaction conditions were same as before. Ferulic acid (400 mg, 2.06 mmol, 1 eq) and chrysin (2.0 g, 6.18 mmol, 3 eq) were dissolved in 10 mL of toluene, sulfuric acid (20.2 mg, 205.99 μmol, 10.98 μL, 0.1 eq) was added dropwise. The mixture was heated to 85 °C, reacted for 24 hours, after completion, the solvent was removed under reduced pressure, HPLC purification (HPLC (column: WePure Biotech XP tC18 150 × 40 × 7 um; mobile phase: [H2O (0.2% TFA) - ACN:THF = 1:1]; gradient: 70%-100% B over 15.0 min) ) was isolated to obtain 185 mg of the target product. Yield, purity 98.9%, white solid. Molecular formula C 29 H 48 O6, molecular weight, MS (ESI) m / z 521.3 [M+H] + .

[0069] 1 H NMR (400 MHz, DMSO-d 6) δ = 7.56 (d, 1H), 7.31 (d, 1H), 7.12 (dd, 1H), 6.80 (d, 1H), 6.42 (d, 1H), 5.05 (br d, 1H), 4.15 - 3.90 (m, 2H), 3.86 - 3.79 (m, 4H), 3.45 - 3.37 (m, 4H), 1.58 - 1.48 (m, 2H), 1.24 (br d, 26H), 0.92 - 0.80 (m, 3H).

[0070] Compound 8:

[0071] Starting material was replaced with tetracosanol (CAS No. 661-66-7) and the reaction conditions were the same as before. Ferulic acid (400 mg, 2.06 mmol, 1 eq) and tetracosanol (2.1 g, 6.18 mmol, 3 eq) were dissolved in 10 mL of toluene, and sulfuric acid (20.2 mg, 205.99 μmol, 10.98 μL, 0.1 eq) was added dropwise. The mixture was heated to 85°C and reacted for 24 hours. After completion, the solvent was removed under reduced pressure, and HPLC purification (HPLC (column: WePure Biotech XP tC18 150 × 40 × 7 um; mobile phase: [H2O (0.2% TFA) - ACN:THF = 1:1]; gradient: 70%-100% B over 15.0 min) was performed to isolate the target product 230 mg. Yield 22%, purity 97.3%, white solid. Molecular formula C 31 H 52 O6, molecular weight 520.8. MS (ESI) m / z 521.3 [M+H] + .

[0072] 1 H NMR (400 MHz, DMSO-d 6) δ= 9.59 (br s, 1H), 7.56 (d, 1H), 7.31 (d,1H), 7.10 (dd, 1H), 6.79 (d, 1H), 6.47 (d, 1H), 5.03 (br d, 1H), 4.20 - 3.95(m, 2H), 3.87 - 3.77 (m, 4H), 3.41 - 3.34 (m, 4H), 1.54 - 1.43 (m, 2H), 1.22(br d, 30H), 0.89 - 0.80 (m, 3H).

[0073] Compound 9:

[0074] Starting material was changed to isostearyl glyceryl ether (CAS No 78145-84-3) and reaction condition was same as compound 8. Ferulic acid (400 mg, 2.06 mmol, 1 eq) and isostearyl glyceryl ether (2.1 g, 6.18 mmol, 3 eq) were dissolved in 10 mL of toluene, sulfuric acid (20.2 mg, 205.99 pmol, 10.98 pL, 0.1 eq) was added dropwise. The mixture was heated to 85 °C and reacted for 24 hours. After completion, the solvent was removed under reduced pressure and HPLC purification (HPLC (column: WePure Biotech XPt C18 150 × 40 × 7 um; mobile phase: [H2O (0.2% TFA) - ACN:THF = 1:1]; gradient: 70%-100% B over 15.0 min) was performed to isolate the target product 320 mg. Yield 30%, purity 98.6%, white solid. Molecular formula C 31 H 52 O6, molecular weight 520.8. MS (ESI) m / z 521.3 [M+H] + .

[0075] Compound 10:

[0076] Starting material was changed to dipropylene glycol, which was commercially available as a mixture of three isomers and was used directly without separation. Ferulic acid (200 mg, 1.03 mmol, 1 eq) was dissolved in 2 mL of dipropylene glycol, p-toluenesulfonic acid monohydrate (195.91 mg, 1.03 mmol, 1 eq) was added, and the mixture was heated to 85 °C and reacted for 16 hours. After completion, the solvent was removed under reduced pressure and HPLC purification (HPLC (column: Waters Xbridge BEH C18 100 × 25 mm × 10 um; mobile phase: [H2O (10 mM NH4HCO3) - ACN]; gradient: 20%-50% B over 8.0 min) was performed to isolate the product 86 mg, yield 28%, purity 97.0%, yellow oil. Molecular formula C 16 H 22 O6, molecular weight 310.3. MS (ESI) m / z 311.1 [M+H] + .

[0077] 1H NMR (400 MHz, DMSO-d6) δ=9.58 (br s, 1H), 7.54 (dd, 1H), 7.33 (s,1H), 7.11 (ddd, 1H), 6.79 (dd, 1H), 6.54 - 6.42 (m, 1H), 5.15 - 4.90 (m, 1H),4.51 (br d, 1H), 4.15 - 3.98 (m, 1H), 3.82 (d, 3H), 3.74 - 3.64 (m, 1H), 3.56- 3.48 (m, 1H), 3.46 - 3.35 (m, 1H), 3.28 - 3.20 (m, 1H), 1.22 - 1.10 (m,3H), 1.07 - 0.99 (m, 3H)。

[0078] Compound 11:

[0079] The starting material was changed to polyglyceryl-2 lauryl ether, which can be purchased from the market or prepared by a conventional method using a fatty alcohol and epichlorohydrin as starting materials. The preparation method can refer to the paper: Xu XM, Cheng TL, Hao JH, et al. Synthesis and performance of dodecyl polyglyceryl ether nonionic surfactant [J]. Printing and dyeing auxiliaries, 2016, 33(11): 23-26. Ferulic acid (200 mg, 1.03 mmol, 1 eq) and polyglyceryl-2 lauryl ether (2 mL) were dissolved in 10 mL of toluene, and p-toluenesulfonic acid monohydrate (195.91 mg, 1.03 mmol, 1 eq) was added. The mixture was heated to 85°C and reacted for 16 hours. After the reaction was completed, the solvent was removed under reduced pressure, and HPLC purification (HPLC (column: WePure Biotech XP tC18 150 × 40 × 7um; mobile phase: [H2O (0.2% TFA)-ACN:THF = 1:1]; gradient: 50%-100% B over 20.0 min)) was performed to isolate 100 mg of the target product. Light yellow oil.

[0080] Compound 12:

[0081] The starting material was changed to polyglyceryl-3 lauryl ether, and the preparation method was the same as that of compound 11. Ferulic acid (200 mg, 1.03 mmol, 1 eq) and polyglyceryl-3 lauryl ether (2 mL) were dissolved in 10 mL of toluene, and p-toluenesulfonic acid monohydrate (195.91 mg, 1.03 mmol, 1 eq) was added, and heated to 85°C for 16 hours. After the reaction was completed, the solvent was removed under reduced pressure, and HPLC purification (HPLC (column: WePure Biotech XP tC18 150 × 40 × 7 um; mobile phase: [H2O (0.2% TFA) - ACN:THF = 1:1]; gradient: 50%-100% B over 20.0 min) was performed to isolate 120 mg of the target product. Light yellow oil.

[0082] Comparative Example 1:

[0083] Comparative compounds and their synthesis methods:

[0084] The comparative compounds are shown in Table 2.

[0085] Table 2: List of comparative compounds

[0086]

[0087] 2-4 ethyl ferulate (CAS No. 4046-02-0) and 2-5 ethylhexyl ferulate (CAS No. 391900-25-7) in the comparative compounds are commercially available raw materials. Other compounds can be synthesized by esterification reaction similar to the aforementioned compounds, and the reaction starting materials in the order of the table are ethylene glycol, diethylene glycol, glycerol, and palmityl alcohol, respectively.

[0088] Example 2:

[0089] Solubility of hydroxycinnamic acid alkoxyl alcohol ester derivatives in oil phase

[0090] The solubility of alkoxyl alcohol ester derivatives was detected using oils commonly used in cosmetics. Detection method: 1 mg of the sample to be tested was weighed into an EP tube, and 10 μL, 10 μL, 20 μL, 50 μL, 100 μL of oil (corresponding to 10%, 5%, 3%, 2%, 1%, 0.5% solubility) was added in turn, and the solubility was observed after ultrasonic treatment at room temperature for 3 min. When the solution was completely clear and transparent and was a homogeneous phase, it was considered to be completely dissolved, and the amount of the solution corresponding to complete dissolution was recorded. Solubility below 0.5% was not soluble. The results are shown in Table 3:

[0091] Table 3: Solubility of hydroxycinnamic acid alkoxyl alcohol ester derivatives in oil phase

[0092]

[0093] The results show that the oil solubility of the cinnamic acid alkoxyl alcohol ester derivatives is significantly improved compared to cinnamic acid. Compared with compounds 2-1~2-3, the terminal alkyl chain can increase the oil solubility of the cinnamic acid alkoxyl alcohol ester derivatives. The length and branching degree of the alkyl chain also affect the oil solubility of the cinnamic acid alkoxyl alcohol ester derivatives.

[0094] Example 3:

[0095] Stability of hydroxyl cinnamic acid alkoxyl alcohol ester derivatives in cosmetic formulations

[0096] In aqueous solution systems, the stability of hydroxyl cinnamic acid decreases. Therefore, this experiment uses a simple emulsion system to monitor the stability of the oil solution of cinnamic acid alkoxyl alcohol ester derivatives in the formulation. 10 mg of the corresponding sample was weighed in a 25 mL bottle, 200 μL of isopentyl laurate was added, and it was ultrasonically dissolved until it was completely dissolved. 50 μL of PEG-40 hydrogenated castor oil was added as an emulsifier, heated to 70°C until the solution was clear and transparent, 750 μL of deionized water was added, and the solution was stirred at 1000 rpm for 20 min. After sealing, it was placed in a 48±2°C oven for 4 weeks, the sample purity change was checked by HPLC, and the emulsion change and solution color change were observed by visual observation. The results are shown in Table 4.

[0097] Table 4: Stability of hydroxyl cinnamic acid alkoxyl alcohol ester derivatives in cosmetic formulations

[0098]

[0099] The results show that the hydroxyl cinnamic acid alkoxyl alcohol ester derivatives have good stability in the formulation. Although the comparative compounds also have good solubility in the oil phase, they are not stable and tend to precipitate or discolor in the emulsion system.

[0100] Example 4:

[0101] Radical scavenging ability of alkoxyl alcohol ester derivatives

[0102] DPPH, also known as 1,1-diphenyl-2-picrylhydrazyl, is a stable free radical with a nitrogen center. Its stability is mainly due to the steric hindrance of the three benzene rings, which makes the unpaired electrons on the nitrogen atom in the middle unable to play their due role in electron pairing. The DPPH anhydrous ethanol solution is purple, and has a maximum absorption at a wavelength of 517 nm. The absorbance is linearly related to the concentration. When a free radical scavenger is added to the DPPH anhydrous ethanol solution, it can bind or replace DPPH·, reducing the number of free radicals and reducing the absorbance, and the solution color becomes lighter. Therefore, the ability to scavenge free radicals can be evaluated. That is, by detecting the effect of the sample on DPPH at a wavelength of 517 nm, the antioxidant capacity can be calculated.

[0103] Test method:

[0104] Accurately weigh 5.0 mg of DPPH standard, dissolve in about 100 ml of anhydrous ethanol solvent, ultrasonic for 5 min, shake well, and make sure that the upper and lower parts are uniform. The solution is stored in the dark and used within 3.5 h. Accurately weigh 0.01 g of vitamin C standard, dissolve in anhydrous ethanol and dilute to 10 ml to obtain a 1000 mg / L vitamin C standard stock solution, which is stored in the dark. Take 0.05 mL, 0.10 mL, 0.15 mL, 0.20 mL, 0.25 mL, 0.50 mL, 0.75 mL, 1.0 mL, and 2.0 mL of the vitamin C standard stock solution into a 10 mL volumetric flask and dilute to the mark with anhydrous ethanol. The hydroxycinnamic acid alkoxyl alcohol ester derivative sample obtained from Example 1 is diluted with ethanol to prepare a gradient concentration sample of 1000, 500, 200, 100, 50, 10, 5, and 1 ppm.

[0105] Take 3.5 mL of DPPH anhydrous ethanol solution and add it to a small test tube, add 0.5 ml of anhydrous ethanol, mix well, and set the zero at 517 nm with anhydrous ethanol as the reference to measure the absorbance value A0. Take 3.5 mL of DPPH anhydrous ethanol solution and add it to a small test tube, add 0.5 ml of sample liquid, mix well, and avoid light for 30 min. After centrifugation at 8000 r / min for 5 min on a high-speed centrifuge, take the supernatant and set the zero at 517 nm with anhydrous ethanol as the reference to measure the absorbance value Ai. Take 3.5 ml of anhydrous ethanol and add it to a small test tube, add 0.5 ml of sample liquid, mix well, and avoid light for 30 min. After centrifugation at 8000 r / min for 5 min on a high-speed centrifuge, take the supernatant and set the zero at 517 nm with anhydrous ethanol as the reference to measure the absorbance value Aj. At the same time, use vitamin C as a positive control. Each experimental group sets 3 parallel samples.

[0106] Result calculation: clearance SR / % = [1-(Ai-Aj) / Ao]x100%, the concentration corresponding to the clearance of 50% is IC50value determined by fitting curve. The corresponding results are shown in Table 5:

[0107] Table 5: Free radical scavenging ability of alkoxyl alcohol ester derivatives

[0108]

[0109] The results show that the alkoxyl alcohol ester derivatives of hydroxycinnamic acid have good DPPH scavenging ability, and can achieve skin protection effect by reducing ROS generated by external stimulation.

[0110] Example 5:

[0111] Tyrosinase inhibitory activity of alkoxyl alcohol ester derivatives

[0112] Tyrosinase is a copper-containing oxidase that plays a key role in melanin biosynthesis. It catalyzes two key reactions: one is the hydroxylation of tyrosine to 3,4-dihydroxyphenylalanine (dopa), and the other is the oxidation of dopa to dopaquinone. Dopaquinone is then converted to melanin spontaneously or under the action of other enzymes. The activity of tyrosinase directly affects the amount of melanin produced, and its expression and activity are regulated by various factors, including ultraviolet radiation, hormone levels, and cell signaling pathways. In the skin, tyrosinase mainly exists in melanocytes, and its increased activity leads to increased melanin synthesis, causing skin pigmentation to darken, such as freckles, chloasma, etc. Therefore, tyrosinase is an important target for the development of whitening cosmetics, and its activity can be inhibited to reduce melanin production and achieve whitening effect. The inhibition of tyrosinase activity by cinnamic acid sugar was detected according to T / SHRH 015-2018 "Cosmetics - Tyrosinase activity inhibition test".

[0113] Test method:

[0114] 14.33 g of disodium hydrogen phosphate dodecahydrate was dissolved in 200 mL of water with a glass rod until dissolved to obtain solution a; 2.1 g of citric acid monohydrate was dissolved in 100 mL of water with a glass plate until dissolved to obtain solution b; 154.5 mL of solution a and 45.5 mL of solution b were mixed to obtain a disodium hydrogen phosphate-citric acid buffer solution. Tyrosinase (activity ≥1000 unit / mg solid) was dissolved in the buffer solution to 100 u / mL for immediate use; L-dopa (purity ≥98%) was dissolved in the buffer solution to 1 mg / mL and stored in the dark. The positive control of kojic acid and the hydroxycinnamic acid derivative samples were prepared into gradient concentration samples of 1000, 500, 200, 100, 50, 10, 5, 1 ppm with the buffer solution.

[0115] The sample group T, sample background group T0, blank group C, blank background group C0 were set. 1 mL of sample solution and 0.5 mL of tyrosinase solution were added to the sample group, 1 mL of sample solution and 0.5 mL of buffer solution were added to the sample background group, 1 mL of buffer solution and 0.5 mL of tyrosinase solution were added to the blank group, and 1.5 mL of buffer solution was added to the blank background group. After thoroughly mixing, incubate in a 37°C water bath for 10 minutes. Add 2 mL of levodopa solution to each tube, control the reaction time of each tube to be consistent for 5 min, and immediately measure the absorbance at 475 nm. Three groups of parallel samples were set for each sample. According to the following formula, the tyrosinase activity inhibition rate is calculated: SR / % = [1-(T-T0) / (C-C0)]x100%. According to the inhibition rate of the gradient concentration, the curve is fitted, and the concentration when the inhibition rate is 50% is calculated as IC 50 The results are shown in Table 6.

[0116] Table 6: Tyrosinase inhibition activity of alkoxy alcohol ester derivatives

[0117]

[0118] Example 6:

[0119] The test compound was dissolved in DMSO and diluted with ethanol to prepare a solution with a concentration of 20 ppm. The absorption spectrum between 250-400 nm was analyzed and scanned by a UV-visible spectrometer, and the results are shown in Figure 1

[0120] The results show that the test sample has good ultraviolet absorption effect in the UVA and UVB regions. It shows that the hydroxycinnamic acid alkoxy alcohol ester derivative proposed in the present application can reduce the photoaging damage of the skin by absorbing ultraviolet rays.​

Claims

1. A hydroxycinnamic acid alkoxyl alcohol ester derivative, characterized by, which is a compound of Formula I, ； wherein the wavy line directly connected to the double bond indicates that the double bond is in the E or Z configuration; X is a polymer residue having 1, 2, or 3 repeating units, the monomers of the polymer residue being one or more of ethylene glycol, 1,2-propanediol, 1,3-propanediol, and glycerol; the monomers of the polymer residue being connected by ether linkages; both ends of the polymer residue being -O-; R1is C 2-20 alkyl.

2. The hydroxycinnamic acid alkoxy alcohol ester derivative as described in claim 1, characterized in that, which satisfies one or more of the following conditions: (1) the number of carbons of the polymer residue is no more than 12; (2) the double bond is in the E configuration; and, (3) the monomers of the polymer residue are ethylene glycol, 1,2-propanediol, 1,3-propanediol, or glycerol.

3. The hydroxycinnamic acid alkoxy alcohol ester derivative as described in claim 1, characterized in that, which satisfies one or two of the following conditions: (1) X is , , , , , , , or ; the terminal is connected with R1; and, (2) R1is ethyl, , , , , , or .

4. The hydroxycinnamic acid alkoxy alcohol ester derivative as described in claim 1, characterized in that, The hydroxycinnamic acid alkoxyl alcohol ester derivative is: , , , , , , , , , or .

5. The hydroxycinnamic acid alkoxy alcohol ester derivative as described in claim 1, characterized in that, The hydroxycinnamic acid alkoxyl alcohol ester derivative is: , , , , , , , , , or .

6. A method for preparing the alkoxylated alcohol derivative of hydroxycinnamic acid according to any one of claims 1 to 5, characterized in that, which comprises the following steps: ； condensation of a compound of Formula II and R1-X-H to form a compound of Formula I; wherein R1 and X are as defined in any one of claims 1-5.

7. A cosmetic comprising the hydroxycinnamic acid alkoxyl alcohol ester derivative of any one of claims 1-5.

8. Use of the hydroxycinnamic acid alkoxyl alcohol ester derivative of any one of claims 1-5 in a cosmetic.

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