WO2024251138A1 - 1,3-dibenzyl phenol derivative, and preparation method therefor and use thereof - Google Patents

Abstract

The present application relates to the use of a compound as represented by formula I, wherein the compound as represented by formula I is as below: formula I, where each R₁, each R₂ and each R₃ are independently selected from one of or a combination of several of hydrogen, a hydroxyl, halogen, a phenyl, a halomethoxy, a methylamino, a methyl, and a linear or branched, saturated or unsaturated hydrocarbyl having 2-4 carbon atoms; R₄, R₅, R₆ and R₇ are each independently selected from one of or a combination of several of hydrogen, a methyl, and a linear or branched, saturated or unsaturated hydrocarbyl having 2-5 carbon atoms; and m, n and k are each independently an integer of 1-3.

Description

1,3-Bis-benzylphenol derivatives, preparation method and application thereof

Related Applications

This application claims priority to Chinese patent application number 2023106574780, filed on June 5, 2023, entitled “1,3-Bisbenzylphenol compounds, preparation methods and their application in whitening and anti-aging cosmetics”, the entire text of which is hereby incorporated by reference.

Technical Field

The present application belongs to the field of cosmetics and pharmaceutical technology, and relates to a 1,3-bisbenzylphenol derivative, a preparation method and an application thereof.

Background Art

Oxygen free radicals produced during cell metabolism can cause cumulative damage to intracellular biomacromolecules, causing cell aging and loss of proliferation capacity. This imbalance of oxidation and antioxidant systems is considered to be an important cause of skin aging. Tyrosinase, also known as polyphenol oxidase, is an oxidoreductase widely found in animals, plants, microorganisms and the human body. It is the key rate-limiting enzyme in melanin synthesis and is closely related to the occurrence of excessive melanin deposition such as freckles and brown spots on human skin. In recent years, its application in the fields of medicine and beauty has attracted widespread attention. At present, most of the skin whitening and brightening agents on the market are based on the inhibition of tyrosinase, such as α-arbutin, kojic acid, 4-butylresorcinol, etc., or based on antioxidants, such as vitamin C, vitamin E and its derivatives, to achieve whitening effects. α-arbutin is a hydroquinone derivative, which has a cytotoxic effect on melanocytes and a strong irritant to the skin. Long-term use may cause permanent white spots on the skin and has been included in the list of banned ingredients for cosmetics in many countries. Kojic acid inhibits the catalytic activity of tyrosinase by chelating the copper ions of tyrosinase. Its use in commercialized skin and hair lighteners can easily lead to contact allergies, and may also cause skin lesions or liver cancer. Vitamin C and vitamin E are important antioxidants for the human body. They do not directly inhibit tyrosinase, but reduce the colored intermediates in the biosynthesis of melanin, and have only an insufficient whitening and brightening effect on the skin. These unfavorable factors limit their widespread application in the whitening and anti-freckle cosmetics market.

Earlier, Xu Gang's research group isolated a series of diarylheptanoids from Ottelia acuminata var. acuminata, an edible vegetable of the Bai nationality in Dali, Yunnan, China, which have significant α-glucosidase inhibitory activity and potential therapeutic value for diabetes (Liu HX, Ma JZ, Ye YS, Zhao JJ, Wan SJ, Hu XY, Xu G. α-Glucosidase inhibitory diarylheptanoids from Ottelia acuminata var. acuminata, a traditional vegetable of Bai Nationality in Yunnan, Natural Products and Bioprospecting 2022, 12:22). Studies have shown that tyrosinase is a protein with sugar chains. During its maturation process, its original sugar chains must undergo a series of modification and cleavage before it can be converted into mature tyrosinase and exert its normal biological function. α-glucosidase I and α-glucosidase II are the key enzymes in the sugar chain modification and cleavage process (Mehta A, Zitzmann N, Rudd PM, Block TM, Dwek RA. α-Glucosidase inhibitors as potential broad-based anti-viral agents, FEBS Letters, 1998, 430(1): 17-22). When α-glucosidase is inhibited, the sugar chain modification on the glycoprotein is blocked, and active tyrosinase cannot be produced, and the formation of melanin is also reduced accordingly (Takahashi H, Parsons PG, Rapid and reversible inhibition of tyrosinase activity by glucosidase inhibitors in human melanoma cells, the Journal of Investigative Dermatology, 1992, 98 (4): 481-487.). Therefore, inhibiting α-glucosidase to reduce the maturation of tyrosinase in order to reduce the formation of melanin and skin pigmentation is a new possible way to whiten and remove spots. However, the content of diarylheptene polyphenol compounds from natural sources is low, and its structural characteristics are cis- and trans-olefin structures, poor molecular stability, easy double bond shift isomerization through ene reaction, difficult to synthesize, and relatively flexible molecules.

Summary of the invention

Some embodiments of the present application provide a 1,3-bisbenzylphenol derivative, a preparation method and application thereof.

The first aspect of the technical solution of the present application is to provide an application of a compound represented by formula I, wherein the compound represented by formula I is as follows:

Each R ₁ , each R ₂ and each R ₃ is independently selected from one or a combination of hydrogen, hydroxyl, halogen, phenyl, halomethoxy, methylamino, methyl and a linear or branched, saturated or unsaturated hydrocarbon group having 2 to 4 carbon atoms;

R ₄ , R ₅ , R ₆ and R ₇ are each independently selected from one or a combination of hydrogen, methyl and a linear or branched, saturated or unsaturated hydrocarbon group having 2 to 5 carbon atoms;

m, n and k are each independently an integer from 1 to 3;

The applications include one or more of the following: preparing tyrosinase inhibitors, preparing α-glucosidase inhibitors, preparing drugs for treating diabetes, preparing whitening products, preparing anti-skin oxidation products, preparing anti-aging products, preparing skin care products for reducing melanin production, preparing drugs for treating skin diseases that reduce melanin production, preparing skin care products for preventing pigmentation diseases, preparing drugs for treating skin diseases that prevent pigmentation diseases, preparing skin care products for treating pigmentation diseases, preparing drugs for treating skin diseases that treat pigmentation diseases, and inhibiting food browning.

In some embodiments, at least one of each R ₁ and each R ₃ is hydroxyl.

In some embodiments, at least one of each R ₁ is a hydroxyl group, and at least one of each R ₃ is a hydroxyl group.

In some embodiments, the compound represented by formula I is selected from one or more of the following structures:

The application includes one or more of the following: preparing α-glucosidase inhibitors, preparing drugs for treating diabetes, preparing anti-skin oxidation, preparing anti-aging products, preparing skin care products that reduce melanin production, preparing drugs for treating skin diseases that reduce melanin production, preparing skin care products that prevent pigmentation diseases, preparing drugs for treating skin diseases that prevent pigmentation diseases, preparing skin care products for treating pigmentation diseases, and preparing drugs for treating skin diseases for treating pigmentation diseases.

In some embodiments, the compound represented by formula I is selected from The application includes the preparation of tyrosinase inhibitors.

In some embodiments, the compound represented by formula I is selected from The application includes one or more of the following: preparing tyrosinase inhibitors, preparing α-glucosidase inhibitors, preparing drugs for treating diabetes, preparing anti-skin oxidation products, preparing anti-aging products, preparing skin care products for reducing melanin production, preparing drugs for treating skin diseases that reduce melanin production, preparing skin care products for preventing pigmentation diseases, preparing drugs for treating skin diseases that prevent pigmentation diseases, preparing skin care products for treating pigmentation diseases, and preparing drugs for treating skin diseases that treat pigmentation diseases.

In some embodiments, the pigmentation disease is selected from one or more of freckles, chloasma, stretch marks, age spots and melanoma.

In some embodiments, the anti-skin oxidation and anti-aging effects refer to the removal of active oxygen free radicals in cells.

The second aspect of the present application provides a 1,3-bis-benzylphenol compound, the structural formula of which is selected from one or more of the following structural formulas of compound 2 and compound 3:

The third aspect of the present application provides a method for preparing 1,3-bis-benzylphenol compounds, the preparation method comprising the following steps: mixing raw material A and raw material B in a substance amount ratio of 1:(5-10), the raw material A being selected from 1,3-di(bromomethyl)benzene, 1,3-di(chloromethyl)benzene and a combination thereof, the raw material B being selected from o-cresol, 1,2-benzenediol and a combination thereof, using aluminum chloride as a catalyst, heating the reaction at 100-120°C under nitrogen protection for a period of time, and then purifying by column chromatography to obtain the compound.

The fourth aspect of the present application provides a composition, wherein the composition has one or more of the effects of whitening, anti-skin oxidation, anti-aging and inhibition of food browning, and the composition comprises a compound shown in formula I and a carrier, and the compound shown in formula I is as follows:

Each R ₁ , each R ₂ and each R ₃ is independently selected from one or a combination of hydrogen, hydroxyl, halogen, phenyl, halomethoxy, methylamino, methyl and a linear or branched, saturated or unsaturated hydrocarbon group having 2 to 4 carbon atoms;

R ₄ , R ₅ , R ₆ and R ₇ are each independently selected from one or a combination of hydrogen, methyl and a linear or branched, saturated or unsaturated hydrocarbon group having 2 to 5 carbon atoms;

m, n and k are each independently an integer from 1 to 3;

The carrier is selected from one or more acceptable carriers in the cosmetics field, the pharmaceutical field, the food field and combinations thereof.

In some embodiments, at least one of each R ₁ and each R ₃ is hydroxyl.

In some embodiments, at least one of each R ₁ is a hydroxyl group, and at least one of each R ₃ is a hydroxyl group.

In some embodiments, the compound represented by formula I is selected from one or more of the following structures:

In some embodiments, the composition has at least one of whitening, anti-skin oxidation and anti-aging effects, including an effective amount of compound 1 as an active ingredient. Compound 2 Compound 3 At least one of, and one or more acceptable carriers in the field of cosmetics.

In some of the embodiments, whitening refers to one or more of inhibiting tyrosinase activity, inhibiting α-glucosidase activity, inhibiting cellular melanin production and inhibiting pigmentation; anti-skin oxidation and anti-aging refer to removing active oxygen free radicals in cells.

In some embodiments, the pigmentation is selected from one or more of freckles, chloasma, stretch marks, age spots and melanoma.

In some embodiments, the composition is selected from one or more of a tyrosinase inhibitor composition and an α-glucosidase inhibitor composition.

In some embodiments, the carrier includes one or more of a fragrance, a compound for skin care, a compound for skin cleansing, and an ultraviolet absorber.

In some embodiments, the composition includes a flavor and a compound of formula I, wherein the flavor is present in an amount effective to provide a sensory effect, and the compound of formula I is present in an amount having one or both of the effects of inhibiting tyrosinase and inhibiting α-glucosidase.

In some embodiments, in the composition, the compound represented by Formula I is present in an amount of about 3% to about 30% by weight.

In some embodiments, the composition includes a UV absorber and a compound shown in Formula I, wherein the amount of the UV absorber is effective to provide UV protection with a protection factor of at least greater than 2, and the amount of the compound shown in Formula I has one or both of the effects of inhibiting tyrosinase and inhibiting α-glucosidase.

In some of the embodiments, the composition includes one or more of a compound for skin care and a compound for skin cleansing, and a compound of formula I, wherein the amount of the compound of formula I has one or both of the effects of inhibiting tyrosinase and inhibiting α-glucosidase.

The fifth aspect of the present application provides a use of the above-mentioned composition in the preparation of whitening skin care products, whitening skin disease treatment drugs, anti-aging skin care products, anti-aging skin disease treatment drugs and combinations thereof.

In some embodiments, the composition is selected from one of a skin care composition and a pharmaceutical composition, and the composition includes an effective amount of compound 1 as an active ingredient. Compound 2 and compound 3 One or more of the .

In some of the embodiments, whitening refers to one or more of inhibiting tyrosinase activity, inhibiting α-glucosidase activity, inhibiting cellular melanin production and inhibiting pigmentation; anti-skin oxidation and anti-aging refer to removing active oxygen free radicals in cells.

In some embodiments, the pigmentation is selected from one or more of freckles, chloasma, stretch marks, age spots and melanoma.

The sixth aspect of the present application provides a product, which is one of a cosmetic and a drug for treating skin diseases, and which comprises the above-mentioned composition or a compound represented by formula I,

Each R ₁ , each R ₂ and each R ₃ is independently selected from one or a combination of hydrogen, hydroxyl, halogen, phenyl, halomethoxy, methylamino, methyl and a linear or branched, saturated or unsaturated hydrocarbon group having 2 to 4 carbon atoms;

R ₄ , R ₅ , R ₆ and R ₇ are each independently selected from one or a combination of hydrogen, methyl and a linear or branched, saturated or unsaturated hydrocarbon group having 2 to 5 carbon atoms;

m, n and k are each independently an integer of 1 to 3. In some embodiments, the mass percentage of the compound represented by formula I in the product is 0.0001% to 10%.

In some of the embodiments, the mass percentage of the compound represented by formula I in the product is 0.01% to 2%.

In some embodiments, the mass percentage of the compound represented by formula I in the product is 0.1% to 1%.

The seventh aspect of the present application provides a pharmaceutical composition for treating diabetes, which comprises an effective amount of a compound used as an active ingredient and a carrier, wherein the effective amount of the compound used as an active ingredient is selected from one or more of the compounds shown in Formula I, and the compound shown in Formula I is as follows:

Each R ₁ , each R ₂ and each R ₃ is independently selected from one or a combination of hydrogen, hydroxyl, halogen, phenyl, halomethoxy, methylamino, methyl and a linear or branched, saturated or unsaturated hydrocarbon group having 2 to 4 carbon atoms;

R ₄ , R ₅ , R ₆ and R ₇ are each independently selected from one or a combination of hydrogen, methyl and a linear or branched, saturated or unsaturated hydrocarbon group having 2 to 5 carbon atoms;

m, n and k are each independently an integer from 1 to 3;

The carrier is selected from one or more acceptable carriers in the pharmaceutical field.

In some embodiments, the effective amount of the compound used as the active ingredient is selected from compound 1 Compound 2 and compound 3 One or more of the .

The seventh aspect of the present application provides a use of the above-mentioned pharmaceutical composition in the preparation of a drug for treating diabetes.

In some embodiments, an effective amount of a compound selected from compound 1 is used as an active ingredient. Compound 2 and compound 3 One or more of the .

The ninth aspect of the present application provides a pharmaceutical preparation, which includes one or more compounds for treating diabetes and one or more compounds of formula I in an amount that has an α-glucosidase inhibitory effect; the compounds of formula I are as follows:

Each R ₁ , each R ₂ and each R ₃ is independently selected from one or a combination of hydrogen, hydroxyl, halogen, phenyl, halomethoxy, methylamino, methyl and a linear or branched, saturated or unsaturated hydrocarbon group having 2 to 4 carbon atoms;

R ₄ , R ₅ , R ₆ and R ₇ are each independently selected from one or a combination of hydrogen, methyl and a linear or branched, saturated or unsaturated hydrocarbon group having 2 to 5 carbon atoms;

m, n and k are each independently an integer of 1-3.

In some embodiments, at least one of each R ₁ and each R ₃ is hydroxyl.

In some embodiments, at least one of each R ₁ is a hydroxyl group, and at least one of each R ₃ is a hydroxyl group.

In some embodiments, the compound represented by formula I is selected from one or more of the following structures:

The tenth aspect of the present application provides a method for whitening human skin and combating age spots on human skin, comprising administering an effective amount of the above composition or the above product to a person in need.

The eleventh aspect of the present application provides a method for inhibiting browning of food, comprising applying an effective amount of the composition as described above to the food.

The twelfth aspect of the present application provides a method for treating diabetes, comprising administering an effective amount of the above-mentioned pharmaceutical composition or the above-mentioned pharmaceutical preparation to a person in need.

The details of one or more embodiments of the present application are set forth in the following description. Other features, objects, and advantages of the present application will become apparent from the specification and claims.

BRIEF DESCRIPTION OF THE DRAWINGS

In order to more clearly illustrate the embodiments of the present application or the technical solutions in the conventional technology, the drawings required for use in the embodiments or the conventional technology descriptions are briefly introduced below. Obviously, the drawings described below are merely embodiments of the present application, and ordinary technicians in this field can obtain other drawings based on the disclosed drawings without paying any creative work.

FIG1 : ¹ H NMR spectrum of compound 1 provided in the examples of the present application (500 MHz, DMSO-d ₆ ).

FIG2 : ¹³ C NMR spectrum of compound 1 provided in the examples of the present application (125 MHz, DMSO-d ₆ ).

FIG3 : ¹ H NMR spectrum of compound 2 provided in the examples of the present application (600 MHz, DMSO-d ₆ ).

FIG4 : ¹³ C NMR spectrum of compound 2 provided in the examples of the present application (150 MHz, DMSO-d ₆ ).

FIG5 : ¹ H NMR spectrum of compound 3 provided in the examples of the present application (500 MHz, DMSO-d ₆ ).

FIG6 : ¹³ C NMR spectrum of compound 3 provided in the examples of the present application (125 MHz, DMSO-d ₆ ).

FIG. 7 : ¹ H NMR spectrum (600 MHz, DMSO-d ₆ ) of compound 4 provided in the examples of the present application.

FIG8 : ¹³ C NMR spectrum of compound 4 provided in the examples of the present application (150 MHz, DMSO-d ₆ ).

FIG9 : ¹ H NMR spectrum of compound 5 provided in the examples of the present application (500 MHz, DMSO-d ₆ ).

FIG10 : ¹³ C NMR spectrum of compound 5 provided in the examples of the present application (125 MHz, DMSO-d ₆ ).

FIG. 11 : ¹ H NMR spectrum (600 MHz, MeOD) of compound 6 provided in the Examples of the present application.

FIG. 12 : ¹³ C NMR spectrum (150 MHz, MeOD) of compound 6 provided in the examples of the present application.

FIG. 13 : ¹ H NMR spectrum (500 MHz, CDCl ₃ ) of compound 7 provided in the examples of the present application.

FIG. 14 : ¹³ C NMR spectrum (125 MHz, CDCl ₃ ) of compound 7 provided in the examples of the present application.

FIG. 15 : ¹ H NMR spectrum (500 MHz, CDCl ₃ ) of compound 8 provided in the examples of the present application.

FIG. 16 : ¹³ C NMR spectrum (125 MHz, CDCl ₃ ) of compound 8 provided in the examples of the present application.

FIG. 17 : ¹ H NMR spectrum (500 MHz, CDCl ₃ ) of compound 9 provided in the examples of the present application.

FIG. 18 : ¹³ C NMR spectrum (125 MHz, CDCl ₃ ) of compound 9 provided in the examples of the present application.

FIG. 19 : ¹ H NMR spectrum (500 MHz, CDCl ₃ ) of compound 10 provided in the examples of the present application.

FIG. 20 : ¹³ C NMR spectrum (125 MHz, CDCl ₃ ) of compound 10 provided in the examples of the present application.

FIG. 21 : ¹ H NMR spectrum (600 MHz, CDCl ₃ ) of compound 11 provided in the examples of the present application.

FIG. 22 : ¹³ C NMR spectrum (150 MHz, CDCl ₃ ) of compound 11 provided in the examples of the present application.

FIG. 23 : ¹ H NMR spectrum (500 MHz, CDCl ₃ ) of compound 12 provided in the examples of the present application.

FIG. 24 : ¹³ C NMR spectrum (125 MHz, CDCl ₃ ) of compound 12 provided in the examples of the present application.

FIG. 25 : ¹ H NMR spectrum (600 MHz, MeOD) of compound 13 provided in the Examples of the present application.

FIG. 26 : ¹³ C NMR spectrum (150 MHz, MeOD) of compound 13 provided in the Examples of the present application.

FIG. 27 : ¹ H NMR spectrum (500 MHz, CDCl ₃ ) of compound 14 provided in the examples of the present application.

FIG. 28 : ¹³ C NMR spectrum (125 MHz, CDCl ₃ ) of compound 14 provided in the examples of the present application.

FIG. 29 : ¹ H NMR spectrum (600 MHz, CDCl ₃ ) of compound 15 provided in the examples of the present application.

FIG30 : ¹³ C NMR spectrum (150 MHz, CDCl ₃ ) of compound 15 provided in the examples of the present application.

FIG31 : ¹ H NMR spectrum (600 MHz, CDCl ₃ ) of compound 16 provided in the examples of the present application.

FIG32 : ¹³ C NMR spectrum (150 MHz, CDCl ₃ ) of compound 16 provided in the examples of the present application.

FIG33 : ¹ H NMR spectrum of compound 17 provided in the examples of the present application (500 MHz, DMSO-d ₆ ).

FIG34 : ¹³ C NMR spectrum of compound 17 provided in the examples of the present application (125 MHz, DMSO-d ₆ ).

FIG35 : ¹ H NMR spectrum (500 MHz, CDCl ₃ ) of compound 18 provided in the examples of the present application.

FIG36 : ¹³ C NMR spectrum (125 MHz, CDCl ₃ ) of compound 18 provided in the examples of the present application.

FIG37 : ¹ H NMR spectrum (600 MHz, CDCl ₃ ) of compound 19 provided in the examples of the present application.

FIG38 : ¹ H NMR spectrum (600 MHz, CDCl ₃ ) of compound 20 provided in the examples of the present application.

FIG39 : ¹ H NMR spectrum (600 MHz, MeOD) of compound 21 provided in the Examples of the present application.

FIG40 : ¹³ C NMR spectrum (150 MHz, MeOD) of compound 21 provided in the Examples of the present application.

FIG41 : ¹ H NMR spectrum (600 MHz, CDCl ₃ ) of compound 22 provided in the examples of the present application.

FIG. 42 : ¹³ C NMR spectrum (150 MHz, CDCl ₃ ) of compound 22 provided in the examples of the present application.

FIG. 43 : ¹ H NMR spectrum (600 MHz, CDCl ₃ ) of compound 23 provided in the examples of the present application.

FIG. 44 : ¹³ C NMR spectrum (150 MHz, CDCl ₃ ) of compound 23 provided in the examples of the present application.

FIG. 45 : ¹ H NMR spectrum (600 MHz, CDCl ₃ ) of compound 24 provided in the examples of the present application.

FIG. 46 : ¹³ C NMR spectrum (150 MHz, CDCl ₃ ) of compound 24 provided in the examples of the present application.

FIG. 47 : ¹ H NMR spectrum of compound 25 provided in the Examples of the present application (500 MHz, DMSO-d ₆ ).

FIG. 48 : ¹³ C NMR spectrum (125 MHz, CDCl ₃ ) of compound 25 provided in the examples of the present application.

FIG. 49 : ¹ H NMR spectrum of compound 26 provided in the Examples of the present application (500 MHz, DMSO-d ₆ ).

FIG50 : ¹³ C NMR spectrum of compound 26 provided in the examples of the present application (125 MHz, DMSO-d ₆ ).

FIG51 : ¹ H NMR spectrum of compound 27 provided in Examples of the present application (600 MHz, DMSO-d ₆ ).

FIG52 : ¹³ C NMR spectrum of compound 27 provided in Examples of the present application (150 MHz, DMSO-d ₆ ).

FIG53 : ¹ H NMR spectrum of compound 28 provided in the examples of the present application (500 MHz, DMSO-d ₆ ).

FIG54 : ¹³ C NMR spectrum of compound 28 provided in Examples of the present application (125 MHz, DMSO-d ₆ ).

FIG55 : ¹ H NMR spectrum of compound 29 provided in the examples of the present application (600 MHz, DMSO-d ₆ ).

FIG56 : ¹³ C NMR spectrum of compound 29 provided in the examples of the present application (150 MHz, DMSO-d ₆ ).

FIG57 : ¹ H NMR spectrum of compound 30 provided in Examples of the present application (500 MHz, DMSO-d ₆ ).

FIG58 : ¹³ C NMR spectrum of compound 30 provided in Examples of the present application (125 MHz, DMSO-d ₆ ).

FIG59 : ¹ H NMR spectrum (600 MHz, DMSO-d ₆ ) of compound 31 provided in the Examples of the present application.

FIG60 : ¹³ C NMR spectrum of compound 31 provided in Examples of the present application (150 MHz, DMSO-d ₆ ).

Figure 61: Effects of the three compounds provided in the examples of the present application and the positive drug kojic acid on tyrosinase activity.

Figure 62: Inhibitory effects of the three compounds provided in the examples of the present application and positive acarbose on α-glucosidase activity.

Figure 63: The scavenging effects of the three compounds provided in the examples of the present application and the positive drug vitamin E on ABTS free radicals.

Figure 64: Effects of the three compounds provided in the examples of the present application and the positive drug phenethylresorcinol on the activity of B16 cells.

Figure 65: Effects of Compound 1, Compound 2, Compound 3 and phenethylresorcinol provided in the Examples of the present application on melanin synthesis in B16 cells.

Figure 66: Typical images of zebrafish whitening of Compound 1 and Compound 2 provided in the Examples of the present application (the dotted line area is the quantitative area).

Figure 67: Schematic diagram of the location of the hair removal area on animal skin.

DETAILED DESCRIPTION

The following will be combined with the drawings in the embodiments of the present application to clearly and completely describe the technical solutions in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.

In this document, room temperature refers to a temperature of 10°C to 30°C. For example, the temperature is 10°C, 12°C, 15°C, 18°C, 20°C, 22°C, 25°C, 28°C, 30°C, or a range consisting of any two of these values. Optionally, room temperature refers to a temperature of 20°C to 30°C, for example, room temperature refers to a temperature of 20°C to 25°C.

As described in the background technology, diarylheptene polyphenol compounds have significant α-glucosidase inhibitory activity, and reduce the maturation of tyrosinase by inhibiting α-glucosidase, so as to achieve the purpose of reducing the production of melanin and skin pigmentation, which is a new possible way to whiten and remove spots. However, diarylheptene polyphenol compounds from natural sources have low content, poor molecular stability, easy double bond shift isomerization through ene reaction, difficult to synthesize, and large molecular flexibility. In order to solve the drug source problem, this application uses this type of natural product as a lead compound, and uses it as a template to simplify and replace its open-chain flexible molecular structure with a rigid benzene ring polyphenol structure analog by using conformational restriction and bioelectronic isosteric replacement strategy. At the same time, in order to improve the antioxidant activity, the phenolic hydroxyl group on the benzene ring is increased, and a series of 1,3-bisbenzylphenol derivatives are synthesized, and their tyrosinase inhibitory activity, α-glucosidase inhibitory activity, antioxidant activity and inhibition of cell melanogenesis activity are studied. Among them, although compound 1 is a known compound (Larry Q. Reyes, Salumeh Issazadeh, Jane Zhang, Buu Dao, and Russell J. Varley, Synthesis of Tri-Aryl Methane Epoxy Resin Isomers and Their Cure with Aromatic Amines, Macromolecular Materials and Engineering, Macromol. Mater. Eng. 2020, 305 (2), 1900546.), there is no report on its biological activity. The antioxidant activity, tyrosinase inhibitory activity, and α-glucosidase inhibitory activity of compounds 1, 2, and 3 were discovered for the first time, and compounds 2 and 3 are new compounds. This type of ingredient has a higher cell melanin synthesis inhibition rate than the classic whitening ingredient phenylethyl resorcinol on the market, and has a good application prospect in whitening, anti-aging and diabetes treatment.

In a first aspect, an application of a compound represented by formula I is provided, wherein the compound represented by formula I is as follows:

Each R ₁ , each R ₂ and each R ₃ is independently selected from one or a combination of hydrogen, hydroxyl, halogen, phenyl, halomethoxy, methylamino, methyl and a linear or branched, saturated or unsaturated hydrocarbon group having 2 to 4 carbon atoms;

R ₄ , R ₅ , R ₆ and R ₇ are each independently selected from one or a combination of hydrogen, methyl and a linear or branched, saturated or unsaturated hydrocarbon group having 2 to 5 carbon atoms;

m, n and k are each independently an integer from 1 to 3;

The applications include one or more of the following: preparing tyrosinase inhibitors, preparing α-glucosidase inhibitors, preparing drugs for treating diabetes, preparing whitening products, preparing anti-skin oxidation products, preparing anti-aging products, preparing skin care products for reducing melanin production, preparing drugs for treating skin diseases that reduce melanin production, preparing skin care products for preventing pigmentation diseases, preparing drugs for treating skin diseases that prevent pigmentation diseases, preparing skin care products for treating pigmentation diseases, preparing drugs for treating skin diseases that treat pigmentation diseases, and inhibiting food browning.

In the general formula shown in Formula I, (R ₁ ) _m represents that m R ₁ groups are connected to the benzene ring, m is 1, 2 or 3, each R ₁ can be the same or different, and each is independently selected from one or a combination of hydrogen, hydroxyl, halogen, methyl and a straight chain or branched, saturated or unsaturated hydrocarbon group having 2 to 4 carbon atoms. And the m R ₁ groups can be connected to any position on the benzene ring without special limitation. (R ₂ ) _n and (R ₃ ) _k have similar meanings and are not repeated here.

The applicant's activity study on the compound shown in Formula I confirms that the compound shown in Formula I and a mixture containing one or more compounds shown in Formula I have strong tyrosinase inhibition and α-glucosidase inhibition, and are therefore very suitable for use as skin whitening agents and anti-senile plaque agents, etc. And due to their high stability to light, they are very suitable for use as skin whitening agents in products such as cosmetics, as a substitute or supplement for known skin whitening active compounds (such as hydroquinone, arbutin or ascorbic acid). Tyrosinase inhibition usually occurs in beauty, but in some cases it can also have therapeutic characteristics, therefore, the compound shown in the above Formula I can also be used in dermatological drug treatment. For example, the compound shown in Formula I, especially when they are used as skin whitening agents or anti-senile plaque agents, is usually applied topically in the form of a solution, cream, lotion, gel, spray or the like.

In addition, the compound shown in formula I can also be used as an anti-browning additive in the food industry. α-glucosidase inhibition can also block the modification of sugar chains on glycoproteins to produce active tyrosinase, and melanin formation is correspondingly reduced. In addition, the compound shown in formula I can also be used as an antidiabetic drug in the pharmaceutical industry. For example, it is used as an oral antidiabetic drug.

In some embodiments, the pigmentation disease is selected from one or more of freckles, chloasma, stretch marks, age spots and melanoma.

In some embodiments, the anti-skin oxidation and anti-aging effects refer to the removal of active oxygen free radicals in cells.

In some embodiments, at least one of each R ₁ and each R ₃ is hydroxyl. In some embodiments, at least one of each R ₁ is hydroxyl, and at least one of each R ₃ is hydroxyl.

In some embodiments, R ₄ , R ₅ , R ₆ and R ₇ are each independently selected from hydrogen or methyl.

In some embodiments, the compound represented by Formula I is selected from one or more of the following structural formulas:

At least one of each R ₁ is a hydroxyl group, at least one of each R ₃ is a hydroxyl group, and R ₄ , R ₅ , R ₆ and R ₇ are each independently selected from hydrogen or methyl.

In some embodiments, the compound represented by formula I is selected from one or more of the following structures:

In some embodiments, the compound represented by formula I is selected from one or more of the following structures:

Among them, the name of compound 1 is 4,4’-(1,3-phenylenebis(methylene))diphenol; the name of compound 2 is 4,4’-(1,3-phenylenebis(methylene))bis-2-methylphenol; the name of compound 3 is 3,3’-(1,3-phenylenebis(methylene))bis-1,2-benzenediphenol.

In some embodiments, the application of the compound represented by Formula I includes:

(1) Use of one or both of Compound 2 and Compound 3 in the preparation of α-glucosidase inhibitors;

(2) Use of one or both of Compound 2 and Compound 3 in the preparation of drugs for treating diabetes.

(3) Use of one or both of Compound 2 and Compound 3 in the preparation of anti-skin oxidation products, anti-aging products and combinations thereof. The anti-oxidation mainly refers to the removal of intracellular reactive oxygen free radicals;

(4) Use of one or both of Compound 2 and Compound 3 in the preparation of skin care products for reducing melanin production, skin care products for preventing pigmentation diseases, skin care products for preventing pigmentation diseases, skin care products for treating pigmentation diseases, skin care products for treating pigmentation diseases, and skin care products for treating pigmentation diseases, and combinations thereof. The pigmentation diseases are selected from freckles, chloasma, stretch marks, age spots, melanoma, and combinations thereof.

(5) Use of the above compound 2 in the preparation of tyrosinase inhibitors.

In some other embodiments, the application of the compound represented by Formula I includes:

(1) Use of compound 1 in the preparation of tyrosinase inhibitors.

(2) Use of compound 1 in the preparation of α-glucosidase inhibitors.

(3) Use of compound 1 in the preparation of drugs for treating diabetes.

(4) Use of compound 1 in the preparation of anti-skin oxidation products, anti-aging products and combinations thereof, wherein the anti-oxidation mainly refers to the removal of intracellular reactive oxygen free radicals.

(5) Use of compound 1 in the preparation of skin care products for reducing melanin production, drugs for treating skin diseases for reducing melanin production, skin care products for preventing pigmentation diseases, drugs for treating skin diseases for preventing pigmentation diseases, skin care products for treating pigmentation diseases, drugs for treating skin diseases for treating pigmentation diseases, and combinations thereof. Wherein, the pigmentation diseases are selected from freckles, chloasma, stretch marks, age spots, melanoma, and combinations thereof.

Compound 1, Compound 2 and Compound 3 have good skin lightening and whitening effects (i.e., for example, they have strong α-glucosidase and/or tyrosinase inhibitory effects in an in vitro cell test system, reducing the production of cellular melanin); they also have good antioxidant effects (i.e., for example, they have strong free radical scavenging effects in an in vitro cell test system).

In some of the embodiments, the above effects are manifested as follows: Compound 1 and Compound 2 have high tyrosinase inhibitory activity, α-glucosidase inhibitory activity and antioxidant activity, and also have a significantly higher cell melanin synthesis inhibition rate than the classic whitening ingredient phenethyl resorcinol on the market; Compound 3 has extremely excellent α-glucosidase inhibitory activity and antioxidant activity, and also has a slightly better cell melanin synthesis inhibition rate than the classic whitening ingredient phenethyl resorcinol on the market. Compound 1, Compound 2 and Compound 3 can be prepared in a highly pure form; are acceptable to dermatology and toxicology; and also show good stability to light effects, so they can be used as functional ingredients of whitening and anti-aging cosmetics.

Experiments have shown that compounds 1 and 2 can effectively inhibit tyrosinase in specific cell-free or cell-based in vitro test systems, as well as in zebrafish in vivo experiments. For example, zebrafish experiments have shown that compound 1 at concentrations of 0.0002% and 0.0001%, and compound 2 at a concentration of 0.0001% have whitening effects and can inhibit melanin production, while the classic whitening ingredient phenylethyl resorcinol 377 has no whitening effect at a concentration of 0.0002%.

The applicant has found that the compounds in Formula I, especially Compound 1 and Compound 2, have stronger tyrosinase inhibitory activity than the known whitening active compound kojic acid, so they can be used in cosmetics at particularly low concentrations and are therefore toxicologically and dermatologically acceptable. Among them, Compound 1 has a tyrosinase inhibitory effect that is about 4 times stronger than kojic acid. Compound 2 has a tyrosinase inhibitory effect that is about 10 times stronger than kojic acid.

In addition, the in vitro mammalian cell micronucleus test proved that neither compound 1 nor compound 2 showed potential genetic toxicity. The bacterial reverse mutation test proved that compound 1 and compound 2 were tested with standard strains TA97a, TA98, TA100, and TA102, and the results showed no potential genetic toxicity. The skin phototoxicity test proved that compound 1 and compound 2 did not show skin phototoxicity in the guinea pig phototoxicity test.

This application has the following advantages and beneficial effects:

1. Based on the diarylheptene polyphenol compounds with α-glucosidase inhibitory activity in sea cauliflower, a series of 1,3-bisbenzylphenol derivatives were designed and synthesized for the first time, including but not limited to: 4,4'-(1,3-phenylenebis(methylene))bis-2-methylphenol (Compound 2), 3,3'-(1,3-phenylenebis(methylene))bis-1,2-benzenediol (Compound 3).

2. It was disclosed for the first time that 1,3-bisbenzylphenol compounds 1-3 have significant activity in inhibiting α-glucosidase and scavenging free radicals, compounds 1 and 2 have significant activity in inhibiting tyrosinase, and compounds 1, 2 and 3 have a higher cell melanin synthesis inhibition rate than the classic whitening ingredient phenethyl resorcinol on the market.

3. Compounds 1, 2 and 3 reported in this application have simple synthesis steps, high yields, low manufacturing costs, good safety and stability, and have good development and application prospects in the field of whitening, brightening and anti-aging cosmetics.

The second aspect of the present application provides a 1,3-bis-benzylphenol compound, the structural formula of which is selected from one or more of the following structural formulas of compound 2 and compound 3:

Among them, the name of compound 2 is 4,4'-(1,3-phenylenebis(methylene))bis-2-methylphenol.

The name of compound 3 is 3,3'-(1,3-phenylenebis(methylene))bis-1,2-benzenediol.

The third aspect of the present application provides a method for preparing 1,3-bis-benzylphenol compounds, the preparation method comprising the following steps: mixing raw material A and raw material B in a substance amount ratio of 1:(5-10), the raw material A being selected from 1,3-di(bromomethyl)benzene, 1,3-di(chloromethyl)benzene and a combination thereof, the raw material B being selected from o-cresol, 1,2-benzenediol and a combination thereof, using aluminum chloride as a catalyst, heating the reaction at 100-120°C under nitrogen protection for a period of time, and then purifying by column chromatography to obtain the compound.

In some embodiments, the reaction is heated at 110° C. for 2 h.

The fourth aspect of the present application provides a composition, wherein the composition has one or more of the effects of whitening, anti-skin oxidation, anti-aging and inhibiting food browning, and the composition comprises a compound shown in formula I and a carrier, and the compound shown in formula I is as follows:

Each R ₁ , each R ₂ and each R ₃ is independently selected from one or a combination of hydrogen, hydroxyl, halogen, phenyl, halomethoxy, methylamino, methyl and a linear or branched, saturated or unsaturated hydrocarbon group having 2 to 4 carbon atoms;

R ₄ , R ₅ , R ₆ and R ₇ are each independently selected from one or a combination of hydrogen, methyl and a linear or branched, saturated or unsaturated hydrocarbon group having 2 to 5 carbon atoms;

m, n and k are each independently an integer from 1 to 3;

The carrier is selected from one or more acceptable carriers in the cosmetics field, the pharmaceutical field, the food field and combinations thereof.

In some embodiments, at least one of each R ₁ and each R ₃ is hydroxyl.

In some embodiments, at least one of each R ₁ is a hydroxyl group, and at least one of each R ₃ is a hydroxyl group.

It should be noted that in the context of this article, for compounds represented by formula I having phenyl radicals with different substitutions and different R ₄ , R ₅ , R ₆ and R ₇ , pure S enantiomers, R enantiomers and any mixture of S and R enantiomers are included. In some embodiments, since racemic mixtures are easily obtained by synthesis, racemic mixtures of compounds represented by formula I are used for whitening and/or combating age spots. In other embodiments, pure enantiomers or non-racemic mixtures of these enantiomers are also suitable for whitening and/or combating age spots.

In some embodiments, the compound represented by formula I is selected from one or more of the following structures:

In some embodiments, the composition has at least one of whitening, anti-skin oxidation and anti-aging effects, and the composition is selected from a skin care composition, a pharmaceutical composition and a combination thereof, and the composition includes an effective amount of compound 1 as an active ingredient. Compound 2 Compound 3 At least one of, and one or more acceptable carriers in the field of cosmetics.

In some embodiments, the above-mentioned pharmaceutical composition is a pharmaceutical composition for treating skin diseases.

The skin care composition or the skin disease treatment pharmaceutical composition is related to whitening, anti-skin oxidation, anti-aging and their combination effects. Wherein: whitening refers to inhibiting tyrosinase activity, inhibiting α-glucosidase activity, inhibiting cellular melanin production, inhibiting pigmentation and their combination; anti-skin oxidation and anti-aging refer to removing active oxygen free radicals in cells. In some embodiments, anti-skin oxidation and anti-aging refer to removing active oxygen free radicals generated in cells due to ultraviolet light.

In some embodiments, acceptable carriers in the cosmetic field refer to conventional cosmetic carriers in the cosmetic field, including emulsifiers (e.g., oil-in-water, water-in-oil, water-in-silicone oil, water-in-water silicone oil, water-in-oil-in-water, oil-in-water-in-oil, silicone oil-in-water-in-oil, etc.), creams, lotions, liquids (e.g., aqueous or aqueous-alcoholic solutions), anhydrous bases (e.g., lipsticks or powders, etc.), gels, ointments, milks, creams, sprays, solids, eye creams, etc.

In some embodiments, the cosmetic composition of the present application can be made into various forms of cosmetics, including sunscreen, sunless tanning products, hair care products (such as shampoo, conditioner, hair dye, bleach, hair straightener and perm), nail polish, moisturizer, skin lotion and skin cream, lipstick and lip balm, cleanser, toner, mask, deodorant, antiperspirant, keratin exfoliant, shaving products (cream, aftershave), wet wipes, tanning lotion, bath gel, body oil, foot care products (powder, spray), foundation cream, rouge, eye shadow and eyeliner, lip gloss, mascara, baby products (baby skin cream, body oil, shampoo, talcum powder, wet wipes). In addition, these cosmetics can also be used as resident cosmetics or makeup remover cream.

In some embodiments, the pharmaceutically acceptable carrier comprises one or more anesthetics, antiallergens, antifungals, antimicrobials, anti-inflammatory agents, antioxidants, preservatives, chelating agents, colorants, decolorizing agents, softeners, emulsifiers, exfoliants, film formers, fragrances, wetting agents, insect repellents, lubricants, moisturizers, pharmaceutical agents, photostabilizers, preservatives, skin protectants, skin penetration enhancers, sunscreens, stabilizers, surfactants, thickeners, viscosity regulators, vitamins, or any combination thereof.

In some of the embodiments, whitening refers to one or more of inhibiting tyrosinase activity, inhibiting α-glucosidase activity, inhibiting cellular melanin production and inhibiting pigmentation; anti-skin oxidation and anti-aging refer to removing active oxygen free radicals in cells.

In some embodiments, the pigmentation is selected from one or more of freckles, chloasma, stretch marks, age spots and melanoma.

In some embodiments, the composition is selected from one or more of a tyrosinase inhibitor composition and an α-glucosidase inhibitor composition.

In some embodiments, the carrier includes one or more of a fragrance, a compound for skin care, a compound for skin cleansing, and an ultraviolet absorber.

In some embodiments, the composition includes a fragrance and a compound shown in formula I, the fragrance is present in an amount effective to provide a sensory effect, and the compound shown in formula I is present in an amount having one or both of the effects of inhibiting tyrosinase and inhibiting α-glucosidase. In some embodiments, in the composition, the compound shown in formula I is present in a mass percentage of about 3% to about 30%. Optionally, one or more excipients, additives, etc. may also be included in the above composition. It has been proven that the substances in the compounds shown in formula I have no odor themselves, or no odor at all, and this property determines that they can be used in perfume compositions. Since the content of perfume compositions in cosmetic final products is usually in the range of about 1% (m/m), the perfume composition containing the compound shown in formula I contains about 3% to 30% (m/m) of the compound shown in formula I. In one embodiment, the perfume composition contains 3% to 20% (m/m) of the compound shown in formula I.

In some embodiments, the composition includes a UV absorber and a compound of formula I, the amount of the UV absorber is effective to provide UV protection with a protection factor of at least greater than 2, and the amount of the compound of formula I has one or both of the effects of inhibiting tyrosinase and inhibiting α-glucosidase. In some embodiments, the amount of the UV absorber is effective to provide UV protection with a protection factor of at least greater than 5.

In some of the embodiments, the composition includes one or more of a compound for skin care and a compound for skin cleansing, and a compound of formula I, wherein the amount of the compound of formula I has one or both of the effects of inhibiting tyrosinase and inhibiting α-glucosidase.

In addition, the composition containing the compound shown in Formula I of the present application can also be used in foods, especially those foods that are prone to spontaneous browning reactions during processing due to their naturally occurring phenolic compound content under the influence of endogenous polyphenol oxidase. For example, foods include fruit and vegetable products, especially apples, pears or potatoes, or crustaceans, especially crabs, lobsters or shrimps. It will be understood that the above only lists some common foods, but is not limited to this.

The fifth aspect of the present application provides a use of the above-mentioned composition in the preparation of whitening skin care products, whitening skin disease treatment drugs, anti-aging skin care products, anti-aging skin disease treatment drugs and combinations thereof.

In some embodiments, the composition is selected from one of a skin care composition and a pharmaceutical composition, and the composition includes an effective amount of compound 1 as an active ingredient. Compound 2 and compound 3 One or more of the .

Skin care products or skin disease treatment drugs are related to whitening, anti-skin oxidation, anti-aging and their combination effects. Among them: whitening refers to inhibiting tyrosinase activity, inhibiting α-glucosidase activity, inhibiting cellular melanin production, inhibiting pigmentation and their combination; anti-skin oxidation and anti-aging refer to removing active oxygen free radicals in cells. In some embodiments, anti-skin oxidation and anti-aging refer to removing active oxygen free radicals generated in cells due to ultraviolet light.

The skin care products or dermatological treatments described herein can improve the aesthetic and/or cosmetic appearance of the skin. These improvements can be manifested in any of the following ways: reduction of dermatological aging symptoms, which are attributed to, for example, chronological aging, hormonal aging and/or photoaging; reduction of skin fragility; reduction of pore size; prevention and/or reversal of collagen and/or elastin loss; improvement of the effects of estrogen imbalance; prevention of skin atrophy; prevention and/or reduction of the appearance and/or depth of lines and/or wrinkles, including fine lines and/or wrinkles; prevention, reduction and/or treatment of hyperpigmentation; improvement of liver color, skin clarity and/or firmness; prevention, reduction and improvement of skin sagging; promotion of antioxidant activity; improvement of skin toughness, plumpness, elasticity, suppleness and/or softness; increase of procollagen and/or collagen production; improvement of skin texture and/or promotion of restoration of original texture state; promotion of skin barrier repair and/or function; improvement of skin contour appearance; restoration of skin radiance and/or brightness; minimization of fatigue and stress response of dermatological symptoms, such as skin rashes and/or resistance to stress reactions caused by environmental influences (pollution, temperature changes); replenishing essential nutrients and/or components in the skin that are reduced due to aging and/or menopause; enhancing the connection between skin cells; increasing cell proliferation and/or multiplication; enhancing skin cell metabolism that is reduced due to aging and/or menopause; delaying cell aging; inhibiting enzymes in the skin that accelerate skin cell aging; minimizing skin dryness and/or increasing skin moisture; minimizing skin discoloration, including dark circles; promoting and/or accelerating cell renewal; increasing skin thickness; increasing skin elasticity and/or resilience; increasing epidermal exfoliation with or without the help of alpha-hydroxy acids or other peeling agents; preventing and reversing the loss of glycosaminoglycans (GAGs), collagen and/or elastin; improving microcirculation; reducing and/or preventing the formation of fat deposits; reducing acne formation; can be used as a skin and hair lightener or anti-age spot agent.

In particular, the pharmaceutical composition of the present application can improve the aesthetic appearance, health and vitality of the skin. Such an improvement can be manifested in at least one of the following: reduction of melanin production, treatment of pigmentation diseases, including freckles, melasma, stretch marks, age spots or melanoma; prevention and/or reversal of collagen and/or elastin loss; improvement of skin texture; improvement of skin tone, clarity, and/or firmness; promotion/acceleration of cell renewal; and increase of skin thickness.

In some of the embodiments, whitening refers to one or more of inhibiting tyrosinase activity, inhibiting α-glucosidase activity, inhibiting cellular melanin production and inhibiting pigmentation; anti-skin oxidation and anti-aging refer to removing active oxygen free radicals in cells.

In some embodiments, the pigmentation is selected from one or more of freckles, chloasma, stretch marks, age spots and melanoma.

The sixth aspect of the present application provides a product, which is one of a cosmetic and a skin disease treatment drug, and the product includes the composition of the fourth aspect or includes the compound shown in Formula I.

In some embodiments, the mass percentage of the compound shown in Formula I in the product (especially the product for local application) is 0.0001% to 10%. Or the mass percentage of the compound shown in Formula I in the product is 0.01% to 2%. Or the mass percentage of the compound shown in Formula I in the product is 0.1% to 1%. Tyrosinase inhibitory active compounds such as compounds shown in Formula I in the product can be used preventively or as needed. For example, the concentration of active compounds used daily varies, depending on the physiological condition of the test subject and personal parameters such as age or weight. The compound shown in Formula I can be used alone or in combination with other tyrosinase inhibitors.

The compound shown in the formula I used in the present application can be used in conventional cosmetics or dermatological treatment drugs, such as but not limited to: pump sprays, aerosol sprays, creams, ointments, tinctures, lotions, nail care products (such as nail polish, nail polish remover, nail balm) etc. In some embodiments, in the above-mentioned products, the compound shown in the formula I used in the present application can also be combined with other active compounds, such as with skin whitening effects or other substances active against senile plaques. In this case, the product containing the compound shown in the formula I can be used for skin treatment in the sense of dermatological treatment or treatment in the sense of nursing cosmetics. Of course, it can also be used for decorative cosmetics in makeup products.

In some of the embodiments, the product containing the compound shown in Formula I also contains an active compound with whitening effect. It can be understood that there is no particular limitation on the active compound with whitening effect, and all skin whitening active compounds suitable or customarily used for cosmetic and/or dermatological applications can be used. For example, active compounds with whitening effects include kojic acid, kojic acid derivatives, arbutin, ascorbic acid, ascorbic acid derivatives, aloesin, ellagic acid, azelaic acid, thiamine, 4-n-butylresorcinol, diphenylmethane derivatives, sulfur-containing molecules (e.g., glutathione, l-ergothioneine), α-hydroxy acids (e.g., citric acid, lactic acid, malic acid) and their derivatives, nitrogen oxide synthesis inhibitors (e.g., l-nitroarginine and its derivatives), metal chelators (e.g., c-hydroxy fatty acids, palmitic acid, phytic acid, lactoferrin, humic acid, bile acid, bile extracts, bilirubin, biliverdin, EDTA, EGTA and its derivatives), flavonoids, chalcones, phenylpropanoids, coumarins, retinoids, alkaloids (e.g., diacetylcholine), niacinamide, soy milk, serine protease inhibitors, lipoic acid or other synthetic or natural active compounds for whitening. Among them, natural active compounds for whitening may also be used in the form of plant extracts, for example, bearberry extract, licorice root extract or components enriched therein, such as glycyrrhizin or lychee A, cinnamon extract, Polygonaceae and Garcinia plant extracts, Pinus (pine) extracts and Vitis plant extracts or stilbene derivatives enriched therein.

In some embodiments, the product may also contain preservatives, such as benzoic acid, benzoic acid esters and benzoic acid salts, propionic acid and its salts, salicylic acid and its salts, 2,4-hexanoic acid (also known as sorbic acid) and its salts, formaldehyde and polyformaldehyde, 2-hydroxyphenyl ether and its salts, 2-zincthiopyridine-N-oxide, inorganic sulfites and bisulfites, sodium iodate, chlorobutanol, 4-ethylmercury-(II) 5-amino-1,3-bis(2-hydroxybenzoic acid) acid and its salts and esters, dehydrated acid, formic acid, 1,6-bis(4-amino-2-bromo-phenoxy)-n-hexane and its salts, ethylmercury-(II)-thiosalicylic acid sodium salt, phenylmercury and its salts, 10-undecenoic acid and its salts, 5- Amino-1,3-di(2-ethylhexyl)-5-methyl-hexahydropyrimidine, 5-bromo-5-nitro-1,3-dioxadiene, 2-bromo-2-nitro-1,3-propanediol, 2,4-dichlorobenzene alcohol, N-(4-chloro)-N'-(3,4-dichlorophenyl)-urea, 4-chloro-m-cresol, 2,4,4'-trichloro-2'-hydroxydiphenyl ether, 4-chloro-3,5-dimethylphenol, 1,1'-methylene-bis(3-(1-hydroxymethyl-2,4-dioxoimidazol-5-yl)urea), poly(hexamethylene biguanide) hydrochloride, 2-phenoxyethanol, hexamethylenetetramine, 1-(3-chloropropenyl)-3,5,7-triazine -1-nitrogen-chloroadamantane, 1(4-chlorophenoxy)-1(1H-imidazol-1-yl)-3,3-dimethyl-2-butanone, 1,3-bis(hydroxymethyl)-5,5-dimethyl-2,4-imidazolidinedione, benzyl alcohol, pyridone ethanolamine salt, 1,2-dibromo-2,4-dicyanobutane, 2,2'-methylenebis(6-bromo-4-chlorophenol), bromo-chlorophenol, 5-chloro-2-methyl-3(2H)-isothiazolinone and 2-methyl-3(2H)-isothiazolinone mixed with magnesium chloride and magnesium nitrate, 2-benzyl-4-chlorophenol, 2-chloroacetamide, chlorhexidine, chlorhexidine acetate, chlorhexidine gluconate, salt Chlorhexidine acid, 1-phenoxy-2-propanol, N-alkyltrimethylammonium bromide and chloride, 4,4-dimethyl-1,3-oxazolidine, N-hydroxymethyl-N'-hydroxymethylurea, 1,6-bis(4-aminophenoxy)-n-hexane and its salts, glutaraldehyde-5-ethyl-1-aza-3,7-dioxycyclooctane, 3-(4-chlorophenoxy)-1,2-propylene glycol, quaternary ammonium salts, alkyl-dimethylbenzyl ammonium chloride, alkyl-dimethylbenzyl ammonium bromide, alkyl-dimethylbenzyl ammonium glycosylation, formaldehyde benzyl alcohol hemiacetal, 3-iodo-2-propylcarbamate, sodium hydroxymethylaminoacetate and sodium hydroxymethylaminoacetate.

When used, the product containing the compound represented by formula I is applied to the skin in a sufficient amount according to the usual manner of cosmetics and skin products.

In some of the embodiments, the product is a sunscreen product. The product contains one or more of a UVA filter, a UVB filter, and an inorganic pigment. It is understood that the sunscreen product can have various forms, such as those commonly used in sunscreen preparations. Therefore, the sunscreen product can be a solution, an emulsion or multiple emulsion of an oil-in-water (W/O) type or an oil-in-water (O/W) type, for example, an emulsion of an oil-in-water (W/O/N) type, a gel, a hydrogen dispersion, a solid stick, or an aerosol. In one example, the sunscreen product contains a UVB filter, which can be oil-soluble or water-soluble.

In one example, in a sunscreen product, the total mass percentage of the filter is, for example, 0.01% to 20%, optionally 0.1% to 10%, optionally 1.0% to 5.0%, so that the sunscreen product can protect the skin from ultraviolet radiation.

In one example, the sunscreen product is capable of achieving a protection factor of at least > 2. Alternatively, the sunscreen product is capable of achieving a protection factor of > 5.

In some embodiments, in cosmetics, the compound shown in Formula I can also be combined with cosmetic adjuvants, for example, antioxidants, perfume oils, anti-foaming agents, colorants, pigments with coloring effects, thickeners, surfactants, emulsifiers, plasticizers, humectants, fats, oils, waxes, and other conventional ingredients of cosmetic formulations, such as monohydric alcohols, polyols, polymers, foam stabilizers, electrolytes, organic solvents or silicone derivatives.

In some of these embodiments, the product containing the compound shown in Formula I is used for local prevention or cosmetic treatment of the skin, and generally contains a high content of therapeutic substances. In one example, the product containing the compound shown in Formula I contains one or more animal therapeutic fats and oils, plant therapeutic fats and oils, such as olive oil, sunflower seed oil, purified soybean oil, palm oil, sesame oil, rapeseed oil, almond oil, borage oil, evening primrose oil, coconut oil, shea butter, jojoba oil, whale oil, tallow, neatsfoot oil and lard, and optionally contains other therapeutic ingredients, such as fatty alcohols with 8-30 carbon atoms. Wherein, the fatty alcohol can be saturated or unsaturated, and can be straight chain or branched. For example, decyl alcohol, decenol, octanol, octenol, dodecanol, dodeenol, octadienol, decadienol, dodecadienol, oleyl alcohol, ricinoleyl alcohol, sinapyl alcohol, stearyl alcohol, isostearyl alcohol, hexadecanol, dodecanol, myristyl alcohol, arachidonic alcohol, decyl alcohol, linolenic alcohol, linseed alcohol and behenyl alcohol, and Guerbet alcohol can be used. It is to be understood that fatty alcohols are not limited to those listed above, and can also be alcohols related to other structural chemistry. In one example, the fatty alcohols are derived from natural fatty acids, usually prepared by reduction of the corresponding esters of the fatty acids. In addition, the fatty alcohol fractions formed by reduction of naturally occurring fats and fatty oils can be used, for example, tallow, peanut oil, rapeseed oil, cottonseed oil, soybean oil, sunflower seed oil, palm kernel oil, linseed oil, corn oil, castor oil, rapeseed oil, sesame oil, cocoa butter and cocoa butter.

In some embodiments, in the product containing the compound shown in Formula I, the therapeutic substance may also include: (1) ceramide, which is understood to be N-acyl sphingosine (fatty acid amide of sphingosine) or synthetic analogs of such lipids (so-called pseudoceramides), which significantly improve the water retention of the stratum corneum. (2) phospholipids, such as soybean lecithin, egg lecithin and cephalin. (3) petrolatum, paraffin and silicone oil. Among them, silicone oil includes dialkyl and alkyl aryl siloxanes, such as dimethyl polysiloxane and methylphenyl polysiloxane, and their alkoxylated and quaternized derivatives. (4) animal hydrolyzed protein and plant hydrolyzed protein, such as elastin, collagen, keratin, milk protein, soy protein, oat protein, pea protein, almond protein and wheat protein fractions or corresponding hydrolyzed proteins, and their condensation products with fatty acids, and quaternized hydrolyzed proteins. In one example, plant hydrolyzed protein is used.

In some embodiments, the product containing the compound shown in Formula I can be a solution or lotion, wherein the solvent can be: (1) water or an aqueous solution; (2) fatty oils, fats, waxes and other natural and synthetic fat bodies, such as fatty acid esters formed by fatty acids and alcohols with a low carbon number, wherein the alcohol with a low carbon number can be isopropanol, propylene glycol or glycerol, or fatty alcohols and alkane acids or fatty acids with a low carbon number. Formed fatty acid esters; (3) monohydric alcohols, dihydric alcohols or polyhydric alcohols with a low carbon number, and ethers thereof, such as ethanol, isopropanol, propylene glycol, glycerol, ethylene glycol, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol monobutyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether and the like. It is understood that the solvent can be a mixture of the above-mentioned multiple solvents. In the case of an alcohol solvent, water may be another component.

In some embodiments, the product containing the compound shown in Formula I may also contain an antioxidant, and all antioxidants suitable or customary for cosmetic and/or dermatological applications may be used. For example, the antioxidant is selected from the following substances: amino acids (e.g., glycine, histidine, tyrosine, tryptophan) and derivatives thereof, imidazoles (e.g., uric acid) and derivatives thereof, peptides such as D, L-carnosine, D-carnosine, L-carnosine and derivatives thereof (e.g., pilose antler), carotenoids, carotenes (e.g., c-carotene, b-carotene, lycopene) and derivatives thereof, lipoic acid and derivatives thereof (e.g., dihydrolipoic acid), gold thioglucose, propylthiouracil and other thiols (e.g., thioredoxime, thiourea ... Protein, glutathione, cysteine, cystine, succinyl and their glycosyl, N-acetyl, methyl, ethyl, propyl, pentyl, butyl, dodecyl, palmitoyl, oleyl, γ-linoleyl, cholesterol and their glycerides) and their salts, dinaphthoylthiodipropionic acid, distearoylthiodipropionic acid, thiodipropionic acid and its derivatives (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts) and very low tolerated doses of sulfoximine compounds (such as buthionine sulfoxide, homocysteine sulfoxide, buthionine sulfoxides, pentathionine sulfoxides, hexathionine sulfoxides, heptathionine sulfoxides), and (metal) chelators, such as α-hydroxy fatty acids, palmitic acid, phytic acid, lactoferrin, α-hydroxy acids (such as citric acid, lactic acid, malic acid), humic acid, bile acid, bile extracts, bilirubin, biliverdin, EDTA, EGTA and its derivatives, unsaturated fatty acids and their derivatives (such as gamma-linolenic acid, linoleic acid, oleic acid), folic acid and its derivatives, ubiquinone and ubiquinol and their derivatives, vitamin C and its derivatives Bioagents (e.g. ascorbyl palmitate, ascorbyl phosphate, ascorbyl acetate), tocopherol and its derivatives (e.g. vitamin E acetate), vitamin A and its derivatives (vitamin A palmitate) and coniferyl benzoate of benzoin resin, rutinic acid and its derivatives, ferulic acid and its derivatives, butylated hydroxytoluene, butylated hydroxyanisole, nordihydroguaiaretic acid, trihydroxybutyrophenone, uric acid and its derivatives, mannose and its derivatives, zinc and its derivatives (e.g. ZnO, ZnSO ₄ ), selenium and its derivatives (e.g. methionine selenium), stilbene and its derivatives (e.g. stilbene oxide, trans-stilbene oxide) and derivatives (salts, esters, ethers, sugars, nucleotides, nucleosides, peptides and lipids) of the active compounds.

In some embodiments, the product containing the compound of formula I may also contain vitamins and vitamin precursors, and all vitamins and vitamin precursors suitable or customary for cosmetic and/or dermatological applications may be used. For example, tocopherol, vitamin A, niacin and niacinamide, B vitamins such as biotin and vitamin C, pantothenic acid alcohol and its derivatives, which may be esters and ethers of pantothenic acid alcohol, and cationic pantothenic acid alcohol derivatives, such as triacetate pantothenic acid alcohol, pantothenic acid alcohol, monoethyl ether and monoacetic acid ester thereof, and cationic panthenic acid alcohol derivatives.

In certain embodiments, the product containing the compound shown in Formula I can also contain a wetting agent. For example, the wetting agent used is the following material: hyaluronic acid, glycerol, panthenol, pyrrolidone carboxylic acid, urea, glycolic acid, salicylic acid, brazilflavonoid class A, sodium lactate, sorbitol, propylene glycol, collagen, elastin, diester of adipic acid, urocanic acid, lecithin, phytantriol, lycopene, algae extract, ceramide, cholesterol, glycolipid, chitosan, chondroitin sulfate, polyamino acids and sugars, lanolin, lanolin, amino acids, alpha-hydroxy acids (e.g., citric acid, lactic acid, malic acid) and derivatives thereof, monodisaccharides and oligosaccharides, alpha-hydroxy fatty acids, phytosterols, triterpene acids such as betulinic acid or ursolic acid, algae extract.

In some embodiments, the product containing the compound shown in Formula I may also contain one or more of an anti-inflammatory active compound, an active compound that reduces redness, and an active compound that reduces itching. It is understood that all anti-inflammatory active compounds, active compounds that reduce redness, and active compounds that reduce itching that are suitable or customary for use in cosmetics and dermatological treatment drugs can be used.

In certain embodiments, the product containing the compound shown in Formula I can also contain plant extract, which is usually prepared by extracting complete plants, but in certain embodiments, it is also possible to extract and prepare separately from the flower, leaf, timber, bark or root of plants.Plant extract can come from aloe, seaweed, avocado, chamomile, coconut, green tea, ginseng, grapefruit, grapefruit seed, rosemary, sunflower, oak bark, willow herb, stinging nettle, wild nettle, hops, marigold, burdock root, hawthorn, linden flower, almond, pine needle, sandalwood, juniper, mango, apricot, orange, lemon, lime, apple, wheat, oat, barley, sage, thyme, basil, birch, mallow, vallisneria, willow bark, asparagus, okra, azalea, ginger root etc.In some embodiments, plant extract comes from aloe, algae, avocado, chamomile, coconut, green tea, ginseng, grapefruit, grapefruit seed, rosemary, sunflower. It is understood that in some embodiments, the plant extract may also be a mixture of two or more plant extracts. The extractant that can be used to prepare the plant extract may be water, alcohol, and a mixture thereof.

In certain embodiments, the product containing the compound shown in Formula I can also contain one or more of anionic surfactants, cationic surfactants, nonionic surfactants and amphoteric surfactants. For example, when crystallization or microcrystalline solids (such as inorganic micro-pigment) are incorporated into the product, a surfactant can be added. Surfactant is an amphipathic substance that can dissolve organic non-polar substances in water. In this case, the hydrophilic part of the surfactant molecule is generally a polar functional group, such as-COO,-OSO,-SO, and the hydrophobic part is generally a non-polar hydrocarbon radical. Surfactant is generally classified according to the properties and charge of the hydrophilic part of the molecule. Here can be divided into four categories: anionic surfactants, cationic surfactants, amphoteric surfactants and nonionic surfactants.

In some embodiments, the anionic surfactant is an acyl amino acid (and its salts), such as: (1) acyl glutamate, such as sodium acyl glutamate, sodium bis-TEA-palmitoyl aspartate, and sodium octyl/decyl glutamate; (2) acyl peptides, such as palmitoyl hydrolyzed milk protein, sodium coconut hydrolyzed soy protein, and sodium/potassium coconut hydrolyzed collagen; (3) sarcosinate, such as myristoyl sarcosine, TEA lauroyl sarcosinate, sodium lauroyl sarcosinate, and sodium coconut sarcosinate; (4) taurate, such as sodium lauroyl taurate and sodium methyl cocoyl taurate; (5) acyl lactylates, lauroyl lactylates, alanine carboxylates, capryloyl lactylates and derivatives, such as lauric acid, aluminum stearate, magnesium alkanoate and zinc undecylenate, ester carboxylates, such as calcium stearoyl lactylate, laureth-6 citrate and sodium PEG-4 lauroyl carboxylate; (6) ether carboxylic acids, such as sodium lauryl-13 carboxylate and sodium PEG-6 cocamide carboxylate, phosphate esters and salts, such as DEA-10 phosphate and diurea-4 phosphate, sulfonic acids and salts, such as acyl isosulfates, such as cocoyl Isosulfates, alkylaryl sulfonates, alkyl sulfonates, such as sodium coconut monoglyceride sulfate, sodium colein-sulfonate, sodium lauryl sulfoacetate and PEG-3 cocamide magnesium sulfate, for example, sulfosuccinate; sodium dioctyl sulfosuccinate, disodium lauroyl sulfosuccinate, disodium dodecyl sulfosuccinate and disodium undecylamine-methanesulfonate sulfosuccinate and sulfates, such as alkyl ether sulfates, such as sodium, ammonium, magnesium, MIPA, TIPA lauryl ether sulfate, sodium Mei's sulfate and sodium C _12-13 terephthalate, alkyl sulfates, such as sodium, ammonium and TEA lauryl sulfate.

In some of these embodiments, the cationic surfactant is an alkylamine, an alkylimidazole, an ethoxylated amine and a quaternary ammonium salt surfactant. The quaternary ammonium salt surfactant contains at least one N atom covalently bonded to 4 alkyl or aryl groups. Regardless of the pH value, this will result in a positive charge. In some of these embodiments, the cationic surfactant is one or more of alkyl betaine, alkyl amidopropyl betaine and alkyl amidopropyl hydroxysulfonic acid. In other embodiments, the cationic surfactant used can also be selected from the group comprising quaternary ammonium compounds, such as benzene trialkyl ammonium chloride or ammonium bromide, such as phenyl dimethyl stearyl ammonium chloride, and alkyl trialkyl ammonium salts, such as hexadecyl trimethyl ammonium chloride or ammonium bromide, alkyl dimethyl hydroxyethyl chloride or ammonium bromide, dialkyl dimethyl chloride or ammonium bromide, alkyl amidoethyl-trimethyl ammonium ether sulfate, alkyl pyridinium salt, such as dodecyl or hexadecyl pyridinium chloride, imidazoline derivatives and compounds of cationic nature, such as alkyl dimethylamine oxide or alkyl ethyl dimethylamine oxide. In one of these examples, hexadecyl trimethyl ammonium salt is used as a cationic surfactant.

In some of these embodiments, the amphoteric surfactant may include: (1) acyl/dialkylethylenediamines, such as sodium acylamide acetate, disodium acylamide dipropionate, disodium alkylamide diacetate, sodium acylamide hydroxypropyl sulfonate, disodium acylamide diacetate and sodium acylamide propionate; (2) N-alkylamino acids, such as aminopropyl alkylpentanediamine, alkylaminopropionic acid, sodium alkylaminodipropionate and laurin ampoulecarboxyglycine.

In some of these embodiments, the nonionic surfactant is an alcohol, an alkanolamide (e.g., cocamide MEA/DEA/MIPA), an amine oxide (e.g., cocamide propylamine oxide), an ester (these esters are esterified by carboxylic acids with ethylene oxide, glycerol, sorbitol or other alcohols), an ether (e.g., ethoxylated/propoxylated alcohols, ethoxylated/propoxylated esters, ethoxylated/propoxylated glycerides, ethoxylated/propoxylated cholesterol, ethoxylated/propoxylated triglycerides, ethoxylated/propoxylated lanolin, ethoxylated/propoxylated silicones, propoxylated POE ethers and alkyl polyglycosides such as dodecyl glucoside, decyl glucoside and coconut glucoside), sucrose esters and ethers, polyglycerol esters, diglycerides, monoglycerides, methyl glucose esters, hydroxy acid esters, and the like.

In some of these embodiments, anionic surfactants and amphoteric surfactants can be used in combination with one or more nonionic surfactants. The surfactant can be present in the product containing the compound shown in Formula I in a mass percentage of 1% to 90% (m/m), based on the total weight of the product.

In certain embodiments, the product containing the compound shown in Formula I can also exist in the form of emulsion.Oil phase can be selected from the following material groups: mineral oil, mineral wax, fat, wax and other natural and synthetic fat bodies, such as fatty acid and the fatty acid ester formed by alcohol with low carbon number, wherein, the alcohol with low carbon number can be isopropanol, propylene glycol or glycerine, or fatty alcohol and the fatty acid ester formed by alkane acid or fatty acid with low carbon number; Alkyl benzoate; Silicone oil, such as dimethylpolysiloxane, diethylpolysiloxane, diphenylpolysiloxane and mixed form thereof.In some of these embodiments, (a) chain length can be used for saturated and/or unsaturated, branched and/or straight-chain alkane carboxylic acid with 3 to 30 carbon atoms and ester formed by saturated and/or unsaturated, branched and/or straight-chain alcohol with 3 to 30 carbon atoms, (b) aromatic carboxylic acid and chain length are ester formed by saturated and/or unsaturated, branched and/or straight-chain alcohol with 3 to 30 carbon atoms. In one example, the ester oils include isopropyl myristate, isopropyl palmitate, isopropyl stearate, n-butyl stearate, n-hexyl laurate, n-decyl oleate, isooctyl stearate, isononyl isononyl, 2-ethylhexyl palmitate, 2-ethylhexyl laurate, 2-hexyldecyl stearate, 2-octyldodecyl palmitate, oleyl oleate, oleyl erucate, erucyl erucate, and synthetic, semi-synthetic, and natural mixtures of these esters, such as jojoba oil.

In addition, the oil phase can be selected from the set consisting of branched and straight-chain hydrocarbons and waxes, silicone oils, dialkyl ethers, saturated or unsaturated, branched or straight-chain alcohols and fatty acid triglycerides, specifically, triglycerides of saturated and/or unsaturated, branched and/or straight-chain alkane carboxylic acids with 8 to 24 carbon atoms, for example, 12 to 18 carbon atoms. Fatty acid triglycerides can be selected from the group including synthetic, semi-synthetic and natural oils, such as olive oil, sunflower seed oil, soybean oil, peanut oil, rapeseed oil, almond oil, palm oil, coconut oil, palm kernel oil, etc. In other embodiments, any mixture of this oil and wax component can also be used. In certain embodiments, it is also possible to use wax (e.g., hexadecyl palmitate) as the only lipid component of the oil phase; for example, the oil phase is selected from the set consisting of 2-ethylhexyl isostearate, octyl dodecanol, isononanoic acid isotriadecanoate, isoeicosane, 2-ethylhexyl coconut acid ester, C2-s alkyl benzoate, capric acid triglyceride and dialkyl ether. For example, a mixture of C2-S-alkyl benzoate and 2-ethylhexyl isostearate, a mixture of C2-S-alkyl benzoate and isotriacontanoic acid isotriacontanoic acid and a mixture of C2-S-alkyl benzoate, 2-ethylhexyl isostearate and isotriacontanoic acid isotriacontanoic acid. Hydrocarbon paraffin oil, squalane and squalene can also be used in the oil phase of the present application. In some of these embodiments, the oil phase can also contain cyclic or linear silicone oil or be composed of such oils completely, however, the additional content of other oil phase components except silicone oil or silicone oil-like substances can also be used. Silicone oil can for example be cyclomethicone (for example, decamethylcyclopentasiloxane).

However, other silicone oils may also be used, such as undecamethylcyclotrisiloxane, polydimethylsiloxane and polymethylphenylsiloxane. The oil phase may also be a mixture of cyclomethicone with isotrialkyl isononanoate and cyclomethicone with 2-ethylhexyl isostearate.

In certain embodiments, the product containing the compound shown in Formula I exists in the form of emulsion, and water may include: monohydric alcohol, dihydric alcohol or polyhydric alcohol and ether thereof with low carbon number, such as ethanol, isopropanol, propylene glycol, glycerine, ethylene glycol, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, propylene glycol monoethyl ether, propylene glycol monobutyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether and analogue, and one or more thickeners, the thickener may be selected from the group comprising silicon dioxide, aluminum silicate, polysaccharide and derivatives thereof, such as hyaluronic acid, xanthan gum, hydroxypropyl methylcellulose. For example, selected from the group comprising polyacrylate, in one of the examples, polyacrylate may be selected from the polyacrylate comprising so-called carbomer.

In certain embodiments, the product containing the compound shown in Formula I exists in emulsion form, can also contain one or more emulsifiers.For example, from the set comprising polyethoxylation or polypropoxylation or polyethoxylation and polypropoxylation product, select O/W emulsifier, for example emulsifier can be: fatty alcohol ethoxylate, ethoxylated wool wax alcohol, polyethylene glycol ether, fatty acid ethoxylate, polyethylene glycol glycerol fatty acid ester, polyethoxylated sorbitol ester, cholesterol ethoxylate, polyethoxylated triglyceride, alkyl ether carboxylic acid, alkyl ether sulfate, fatty alcohol propoxylate, polypropylene glycol ether.In some of these embodiments, fatty alcohol ethoxy ether is selected from the group consisting of ethoxylated stearyl alcohol, hexadecyl stearyl alcohol, hexadecyl stearyl alcohol (hexadecyl alcohol).

The following can be used as oil/water emulsifiers: monoglycerol esters of saturated and/or unsaturated fatty alcohols having 8 to 30 carbon atoms, diglycerol esters of branched and/or linear saturated and/or unsaturated alkanecarboxylic acids having 8 to 24 carbon atoms (e.g. 12 to 18 carbon atoms), monoglycerol ethers of branched and/or linear saturated and/or unsaturated alkanecarboxylic acids having 8 to 24 carbon atoms (e.g. 12 to 18 carbon atoms), diglycerol ethers of branched and/or linear saturated or unsaturated alcohols having 8 to 24 carbon atoms (e.g. 12 to 18 carbon atoms), propylene glycol esters of branched and/or linear saturated or unsaturated alkanecarboxylic acids having 8 to 24 carbon atoms (e.g. 12 to 18 carbon atoms) and sorbitan esters of branched and/or linear saturated or unsaturated alkanecarboxylic acids having 8 to 24 carbon atoms (e.g. 12 to 18 carbon atoms).

In some embodiments, the oil/water emulsifier includes glyceryl monostearate, glyceryl monoisostearate, glyceryl monomyristate, glyceryl monooleate, diglyceryl monostearate, propylene glycol monostearate, propylene glycol monoisostearate, propylene glycol monocaprylate, propylene glycol monolaurate, sorbitol monoisostearate, sorbitol monolaurate, sorbitol monocaprylate, sorbitol monoisostearate, sucrose distearate, cetyl alcohol, stearyl alcohol, arachidyl alcohol, behenyl alcohol, isobehenyl alcohol, squalane alcohol, glyceryl monolaurate, glyceryl monocaprate, glyceryl monocaprylate. The seventh aspect of the present application provides a pharmaceutical composition for treating diabetes, wherein, including a compound and a carrier used as an effective ingredient, the compound used as an effective ingredient is selected from one or more of the compounds shown in Formula I, and the compound shown in Formula I is as follows:

Each R ₁ , each R ₂ and each R ₃ is independently selected from one or a combination of hydrogen, hydroxyl, halogen, phenyl, halomethoxy, methylamino, methyl and a linear or branched, saturated or unsaturated hydrocarbon group having 2 to 4 carbon atoms;

R ₄ , R ₅ , R ₆ and R ₇ are each independently selected from one or a combination of hydrogen, methyl and a linear or branched, saturated or unsaturated hydrocarbon group having 2 to 5 carbon atoms;

m, n and k are each independently an integer from 1 to 3;

The carrier is selected from one or more acceptable carriers in the pharmaceutical field.

In some embodiments, the effective amount of the compound used as the active ingredient is selected from compound 1 Compound 2 and compound 3 One or more of the .

In some embodiments, the pharmaceutical composition for treating diabetes exerts its effect by inhibiting the activity of α-glucosidase.

The eighth aspect of the present application provides a use of the above-mentioned pharmaceutical composition for treating diabetes in the preparation of a drug for treating diabetes.

In some embodiments, an effective amount of a compound selected from compound 1 is used as an active ingredient. Compound 2 and compound 3 One or more of the .

The ninth aspect of the present application provides a pharmaceutical preparation, which includes one or more compounds for treating diabetes and one or more compounds of formula I in an amount that has an α-glucosidase inhibitory effect; the compounds of formula I are as follows:

Each R ₁ , each R ₂ and each R ₃ is independently selected from one or a combination of hydrogen, hydroxyl, halogen, phenyl, halomethoxy, methylamino, methyl and a linear or branched, saturated or unsaturated hydrocarbon group having 2 to 4 carbon atoms;

R ₄ , R ₅ , R ₆ and R ₇ are each independently selected from one or a combination of hydrogen, methyl and a linear or branched, saturated or unsaturated hydrocarbon group having 2 to 5 carbon atoms;

m, n and k are each independently an integer of 1-3.

In some embodiments, at least one of each R ₁ and each R ₃ is hydroxyl.

In some embodiments, at least one of each R ₁ is a hydroxyl group, and at least one of each R ₃ is a hydroxyl group.

In some embodiments, the compound represented by formula I is selected from one or more of the following structures:

The tenth aspect of the present application provides a method for whitening human skin and combating age spots on human skin, comprising administering an effective amount of the composition of the fourth aspect or the product of the sixth aspect to a person in need.

The eleventh aspect of the present application provides a method for inhibiting browning of food, comprising applying an effective amount of the composition according to the fourth aspect to the food.

The twelfth aspect of the present application provides a method for treating diabetes, comprising administering an effective amount of the pharmaceutical composition of the seventh aspect or the pharmaceutical preparation of the ninth aspect to a person in need thereof.

The following is the embodiment part:

Example 1: Synthesis of compounds

1. Synthesis of compound 1: 1,3-di(bromomethyl)benzene (1.5 g, 5.73 mmol/L), phenol (6.2 mL, 70 mmol/L), and aluminum chloride (195 mg, 1.5 mmol/L) were weighed in sequence, heated at 110°C under nitrogen protection until the raw materials disappeared, reacted for 2 hours, cooled to room temperature, extracted with saturated sodium carbonate aqueous solution and ethyl acetate three times each, then dried over sodium sulfate, filtered and dried by suction, passed through a silica gel column, and purified with ethyl acetate/petroleum ether (EA:PE=1:200, v/v) to obtain the product compound 1 (473.3 mg, yield 42%, white solid).

4,4'-(1,3-phenylenebis(methylene))diphenol (Compound 1): white solid, ¹ H NMR (600 MHz, CD ₃ OD, δ, ppm, J/Hz): 9.17 (s, 2H), 7.15 (t, J＝10, 1H), 7.04 (s, 1H), 6.98-6.95 (m, 6H), 6.66-6.64 (m, 4H), 3.76 (s, 4H). ¹³ C NMR (150 MHz, DMSO-d6, δ, ppm): 155.9, 142.4, 131.8, 130.0, 129.3, 128.8, 126.5, 115.6, 40.7. HRMS (ESI-) calculated for C ₂₀ H ₁₇ O ₂ [MH] ^- = 289.1234, found 289.1246. ^{The 1} H NMR spectrum and the ¹³ C NMR spectrum are shown in Figures 1-2.

2. Synthesis of compound 2: Weigh 1,3-di(bromomethyl)benzene (0.3 g, 1.15 mmol/L), o-cresol (0.6 g, 5.75 mmol/L), and aluminum chloride (39 mg, 0.29 mmol/L) in sequence, and heat to 110°C under nitrogen protection until the raw materials disappear. React for 2 hours, cool to room temperature, and directly pass through a silica gel column chromatography with ethyl acetate/petroleum ether (EA:PE=1:7.5, v/v) as eluent to obtain the product compound 2 (40.7 mg, yield 26%, brown solid).

4,4'-(1,3-phenylenebis(methylene))bis(2-methylphenol) (Compound 2): brown solid, ¹ H NMR (600 MHz, DMSO-d6, δ, ppm, J/Hz): 9.05 (s, 2H), 7.15 (t, J = 7.6 Hz, 1H), 7.05 (s, 1H), 6.97 (d, J = 7.6 Hz, 2H), 6.87 (s, 2H), 6.80 (dd, J = 8.2, 2.3 Hz, 2H), 6.67 (d, J = 8.1 Hz, 2H), 3.73 (s, 4H), 2.06 (s, 6H). ¹³ C NMR (150 MHz, DMSO-d6, δ, ppm): 153.5, 142.0, 131.3, 130.9, 128.8, 128.3, 126.7, 126.0, 123.6, 114.5, 40.4, 16.0. HRMS (ESI-) calcd for C ₂₂ H ₂₁ O ₂ [MH] ^- = 317.1547, found 317.1561. The ¹ H NMR spectrum and the ¹³ C NMR spectrum are shown in FIGS. 3-4 .

3. Synthesis of compound 3: Weigh 1,3-di(bromomethyl)benzene (1.5 g, 5.73 mmol/L), 1,2-benzenediol (0.63 g, 5.72 mmol/L), and aluminum chloride (195 mg, 1.5 mmol/L) in sequence, heat at 110°C under nitrogen protection until the raw materials disappear, react for 2 hours, cool to room temperature, and directly pass through a silica gel column chromatography with ethyl acetate/petroleum ether (EA:PE=1:2, v/v) as eluent to obtain the product compound 3 (124.8 mg, yield 32%, light yellow solid).

3,3'-(1,3-phenylenebis(methylene))bis(benzene-1,2-diol) (Compound 3): pale yellow solid, ¹ H NMR (500 MHz, DMSO-d ₆ , δ, ppm, J/Hz): 8.74 (s, 2H), 8.64 (s, 2H), 7.15 (t, J＝7.6 Hz, 1H), 7.01 (s, 1H), 6.95 (dd, J＝7.6, 1.7 Hz, 2H), 6.61 (d, J＝8.0 Hz, 2H), 6.53 (d, J＝2.1 Hz, 2H), 6.44 (dd, J＝8.0, 2.1 Hz, 2H), 3.69 (s, 4H). ¹³ C NMR (125 MHz, DMSO-d ₆ , δ, ppm): 145.5, 143.9, 142.4, 132.5, 129.4, 128.7, 126.6, 119.8, 116.5, 115.9, 41.0. HRMS (ESI) calcd for C ₂₀ H ₁₈ NaO ₄ [M+Na] ⁺ ＝345.1097, found 345.1097. The ¹ H NMR spectrum and the ¹³ C NMR spectrum are shown in FIGS. 5-6 .

4. Synthesis of compound 4-22:

In a dry round-bottom flask, a phenol compound (5.0 equiv) was dissolved in a mixed solution of methanol and water (the volume ratio of the two was 2:1), H ₂ SO ₄ (0.3 equiv) was slowly added dropwise to the solution, and then 2-hydroxy-5-methylisoxylene glycol was added to the flask. The temperature was raised to 45°C under nitrogen and monitored by a spot plate until the raw material reacted completely. After cooling to room temperature, the product was directly chromatographed on a silica gel column using ethyl acetate/petroleum ether (EA:PE=1:20-1:1, v/v) as the eluent to obtain the product.

5,5'-((2-hydroxy-5-methyl-1,3-phenylene)bis(methylene))bis(benzene-1,2,3-triol) (Compound 4): white solid, ¹ H NMR (600 MHz, DMSO-d ₆ , δ, ppm, J/Hz): 8.80 (s, 3H), 8.20 (s, 4H), 6.53 (s, 2H), 6.30 (d, J＝8.3 Hz, 2H), 6.21 (d, J＝8.2 Hz, 2H), 3.68 (s, 4H), 2.02 (s, 3H); ¹³ C NMR (150 MHz, DMSO-d ₆ ,δ,ppm):172.1,149.7,144.3,143.8,132.9,128.1,127.8,127.2,119.7,118.6,106.6,29.5,20.5. The ¹ H NMR spectrum and the ¹³ C NMR spectrum are shown in FIGS. 7-8.

4,4'-((2-hydroxy-5-methyl-1,3-phenylene)bis(methylene)diphenol (Compound 5): white solid, ¹ H NMR (500 MHz, DMSO-d ₆ , δ, ppm, J/Hz): 9.23 (s, 2H), 8.15 (s, 1H), 6.98 (d, J＝8.5 Hz, 4H), 6.65 (d, J＝8.5 Hz, 4H), 6.61 (s, 2H), 3.77 (s, 4H), 2.07 (s, 3H); ¹³ C NMR (125 MHz, DMSO-d ₆ , δ, ppm): 155.81, 150.25, 131.66, 130.07, 129.41, 128.90, 128.16, 115.44, 35.10, 20.77. Among them, ¹ H NMR spectrum and ¹³ C NMR spectrum are shown in Figures 9 and 10 .

4,4'-((2-hydroxy-5-methyl-1,3-phenylene)bis(methylene))bis(benzene-1,3-diol)(Compound 6): white solid, ¹ H NMR (600 MHz, MeOD, δ, ppm, J/Hz): 6.87 (d, J = 8.2 Hz, 2H), 6.72 (s, 2H), 6.31 (d, J = 2.5 Hz, 2H), 6.24 (dd, J = 8.2, 2.4 Hz, 2H), 3.75 (s, 4H), 2.12 (s, 3H). ¹³ C NMR (150 MHz, MeOD, δ, ppm): 157.60, 155.93, 150.33, 132.00, 130.20, 129.66, 129.42, 119.99, 108.06, 103.32, 30.67, 20.72. HRMS (ESI) m/z: [M+H] ⁺ Calcd for C ₂₁ H ₂₁ O ₅ 353.1389, found 353.1382. The ¹ H NMR spectrum and the ¹³ C NMR spectrum are shown in FIGS. 11-12 .

2-(3-bromo-2-hydroxybenzyl)-6-(3-bromo-4-hydroxybenzyl)-4-methylphenol (Compound 7): yellow solid, ¹ H NMR (500 MHz, CDCl ₃ , δ, ppm, J/Hz): 7.36–7.29 (m, 2H), 7.19 (dd, J＝7.6, 1.6 Hz, 1H), 7.07 (dd, J＝8.3, 2.1 Hz, 1H), 6.94–6.91 (m, 2H), 6.81–6.74 (m, 2H), 6.19 (d, J＝19.0 Hz, 2H), 5.43 (s, 1H), 3.92 (s, 2H), 3.86 (s, 2H), 2.22 (s, 3H). ¹³ C NMR (125 MHz, CDCl ₃ ,δ,ppm):150.45,149.23,148.72,134.32,131.87,130.38,130.07,129.94,129.84,129.51,128.10,127.75,125.98,122.45,115.90,110.42,110.17,35.28,31.26,20.51. HRMS (ESI) m/z:[M+H] ⁺ Calcd for C ₂₁ H ₁₉ Br ₂ O ₃ 476.9701,found 476.9551. The ¹ H NMR spectrum and the ¹³ C NMR spectrum are shown in FIGS. 13-14.

4,4'-((2-hydroxy-5-methyl-1,3-phenylene)bis(methylene))bis(2-bromophenol) (Compound 8): yellow solid, ¹ H NMR (500MHz, CDCl ₃ ,δ,ppm,J/Hz):7.32–7.29(m,2H),7.06(dd,J＝8.2,2.1Hz,2H),6.94(d,J＝8.3Hz,2H),6.85(s,2H),5.66(s,2H),4.57(s,1H),3.86(s,4H),2.28(d,J＝3.1Hz,3H). ¹³ C NMR (125MHz,CDCl ₃ ,δ,ppm):150.65,149.46,133.43,131.73,130.06,129.89,129.23,126.73,116.11,110.30,35.31,20.50.HRMS(ESI)m/z:[M+H] ⁺ Calcd for C ₂₁ H ₁₉ Br ₂ O ₃ 476.9701,found 476.9551. The ¹ H NMR spectrum and ¹³ C NMR spectrum are shown in FIGS. 15-16.

2-(2-hydroxy-3-methylbenzyl)-6-(4-hydroxy-3-methylbenzyl)-4-methylphenol (Compound 9): white solid, ¹ H NMR (500 MHz, CDCl ₃ , δ, ppm, J/Hz): 7.15 (d, J = 7.5 Hz, 1H), 7.03–6.94 (m, 3H), 6.91 (dd, J = 8.0 and 2.3 Hz, 1H), 6.82 (t, J = 4.4 Hz, 2H), 6.68 (dd, J = 8.1 and 1.9 Hz, 1H), 5.87 (s, 1H), 5.12 (s, 1H), 3.87 (d, J = 9.0 Hz, 4H), 2.25 (s, 3H), 2.22 (d, J = 6.1 Hz, 6H). ¹³ C NMR (125 MHz, CDCl ₃ ,δ,ppm):153.07,151.89,148.84,131.66,131.48,131.29,130.87,130.14,129.87,129.60,128.57,127.54,127.37,126.78,124.79,124.73,120.85,115.50,35.89,30.66,20.16,15.73,15.37.HRMS(ESI)m/z:[MH] ^- Calcd for C ₂₁ H ₂₃ O ₃ 347.1647,found 347.1669. The ¹ H NMR spectrum and the ¹³ C NMR spectrum are shown in FIGS. 17-18.

4,4'-((2-hydroxy-5-methyl-1,3-phenylene)bis(methylene))bis(2-methylphenol)(Compound 10): white solid, ¹ H NMR (500MHz,CDCl ₃ ,δ,ppm,J/Hz):δ6.99(s,2H),6.94–6.87(m,4H),6.65(d,J＝8.1Hz,2H),5.53(s,2H),4.78(s,1H),3.87(s,4H),2.30(s,3H),2.21(s,6H). ¹³ C NMR (125MHz,CDCl ₃ ,δ,ppm):152.32,149.87,131.82,131.15,129.64,129.59,127.41,127.08,124.02,115.07,35.85,20.55,15.77.HRMS(ESI)m/z:[MH] ^- Calcd for C ₂₃ H ₂₃ O ₃ 347.1647,found 347.1669. The ¹ H NMR spectrum and ¹³ C NMR spectrum are shown in Figures 19-20.

3-(2-hydroxy-3-((6-hydroxy-[1,1'-biphenyl]-3-yl)methyl)-5-methylbenzyl)-[1,1'-biphenyl]-2-ol (Compound 11): white solid, ¹ H NMR (600MHz, CDCl ₃ ,δ,ppm,J/Hz):7.51–7.46(m,2H),7.46–7.42(m,6H),7.41–7.35(m,2H),7.29(dd,J＝7.6and 1.7Hz,1H),7.14–7.10(m,3H),

7.00(d,J＝2.2Hz,1H),6.96(t,J＝7.6Hz,1H),6.89(d,J＝8.9Hz,1H),6.80(d,J＝2.2Hz ,1H),6.49(s,1H),6.09(s,1H),5.13(s,1H),3.95(s,2H),3.92(s,2H),2.24(s,3H). ¹³ C NMR (150MHz, CDCl ₃ ,δ,ppm):151.16,149.75,149.26,137.52,137.28,133.04,130.74,130.53,130.05,130.03,129.72,129.69,129.65,129.48,129 .43,129.37,128.92,128.70,128.35,128.31,128.02,127.49,126.84,121.66,116.09,35.44,30.72,20.22.HRMS(ESI)m/z:[MH] ^- Calcd for C ₃₃ H ₂₇ O ₃ 471.1960,found 471.1988. The ¹ H NMR spectrum and ¹³ C NMR spectrum are shown in Figures 21-22.

5,5"-((2-hydroxy-5-methyl-1,3-phenylene)bis(methylene))bis(([1,1'-biphenyl]-2-ol))(Compound 12): white solid, ¹ H NMR (500 MHz, CDCl ₃ , δ, ppm, J/Hz): 7.51–7.35 (m, 10H), 7.13–7.05 (m, 4H), 6.92–6.85 (m, 4H), 5.22 (d, J＝14.6 Hz, 2H), 4.60 (s, 1H), 3.92 (s, 4H), 2.25 (s, 3H). ¹³ C NMR (125 MHz, CDCl ₃ ,δ,ppm):151.40,150.31,137.39,132.39,130.57,130.11,130.05,129.50,129.37,128.51,128.11,127.45,116.31,35.61,20.21.HRMS(ESI)m/z:[MH] ^- Calcd for C ₃₃ H ₂₇ O ₃ 471.1960,found 471.1988. The ¹ H NMR spectrum and the ¹³ C NMR spectrum are shown in FIGS. 23-24.

4,4'-((2-hydroxy-5-methyl-1,3-phenylene)bis(methylene))bis(benzene-1,2-diol)(Compound 13): white solid, ¹ H NMR (500 MHz, MeOD, δ, ppm, J/Hz): 6.68–6.64 (m, 4H), 6.61 (d, J＝2.1 Hz, 2H), 6.53 (dd, J＝8.0 and 2.1 Hz, 2H), 3.78 (s, 4H), 2.12 (s, 3H). ¹³ C NMR (125 MHz, MeOD, δ, ppm): 150.97, 146.02, 144.24, 134.04, 130.19, 130.15, 129.90, 121.26, 117.10, 116.15, 36.23, 20.73. HRMS (ESI) m/z: [MH] ^- Calcd for C ₂₁ H ₂₁ O ₅ 353.1389, found 353.1381. ^{The 1} H NMR spectrum and the ¹³ C NMR spectrum are shown in FIGS. 25-26 .

2-(2-hydroxy-3-(trifluoromethoxy)benzyl)-6-(4-hydroxy-3-(trifluoromethoxy)benzyl)-4-methylphenol (Compound 14): yellow solid, ¹ H NMR (500MHz, CDCl ₃ ,δ,ppm,J/Hz):7.07–7.04(m,2H),7.01(dd,J＝8.4and 2.1Hz,2H),6.95(s,1H),6.93(s,1H),6.83(s,2H),5.41(s,2H),4.39(s,1H),3.87(s,4H),2.25(s,3H). ¹³ C NMR (125MHz,CDCl ₃ ,δ,ppm):150.00,146.63,136.69,133.00,130.51,130.30,128.38,126.83,121.80,117.64,35.34,20.15. The ¹ H NMR spectrum and the ¹³ C NMR spectrum are shown in FIGS. 27-28.

2-(3-ethyl-2-hydroxybenzyl)-6-(3-ethyl-4-hydroxybenzyl)-4-methylphenol (Compound 15): white solid, ¹ H NMR (600 MHz, CDCl ₃ , δ, ppm, J/Hz): 7.15 (dt, J＝7.6 and 1.2 Hz, 1H), 7.01 (td, J＝10.5, 10.0, 2.0 Hz, 3H), 6.90 (dd, J＝8.1 and 2.3Hz,1H),6.84(ddd,J＝16.1,8.1,1.6Hz,2H),6.68(d,J＝8.1Hz,1H),6.64(s,1H),5.70(s,1 H),5.02(s,1H),3.88(d,J＝3.2Hz,3H),2.61(p,J＝7.4Hz,4H),2.25(s,3H),1.21(td,J＝7.5and 2.0Hz, 6H). ¹³ C NMR (150MHz, CDCl ₃ ,δ,ppm):152.72,151.62,148.83,131.19,130.94,130.91,130.16,129.93,129.83,128.47,127.76,127.38,127.31,127.23,126.84,120.87,115.81,36.10,30.71,22.82,22.69,20.19,13.61,13.53.HRMS(ESI)m/z:[M+H] ⁺ Calcd for C ₂₅ H ₂₉ O ₃ 377.2117,found 377.2112.其中¹ H NMR谱图、 ¹³ C NMR谱图如图29～30所示。

4,4'-((2-hydroxy-5-methyl-1,3-phenylene)bis(methylene))bis(2-ethylphenol) (Compound 16): white solid, ¹ H NMR (500 MHz, CDCl ₃ , δ, ppm, J/Hz): 7.01 (d, J = 2.2 Hz, 2H), 6.89 (dd, J = 8.1 and 2.3 Hz, 2H), 6.86 (s, 2H), 6.65 (d, J = 8.0 Hz, 2H), 4.96 (s, 1H), 4.64 (s, 1H), 3.87 (s, 4H), 2.60 (d, J = 7.5 Hz, 4H), 2.26 (d, J = 6.6 Hz, 3H), 1.21 (t, J = 7.6 Hz, 6H). ¹³ C NMR (150 MHz, CDCl ₃ ,δ,ppm):151.83,149.84,131.91,130.19,129.63,129.60,129.51,127.40,126.90,115.33,35.92,22.98,20.55,14.00.HRMS(ESI)m/z:[M+H]+Calcd for C25H29O3 377.2117,found 377.2112. ^The1H NMR spectrum and ^13C NMR spectrum are shown in Figures 31-32.

2-(3-allyl-2-hydroxybenzyl)-6-(3-allyl-4-hydroxybenzyl)-4-methylphenol (Compound 17): white solid, ¹ H NMR (500 MHz, DMSO-d ₆ , δ, ppm, J/Hz): 9.14 (s, 1H), 8.45 (d, J＝55.5 Hz, 2H), 6.92–6.87 (m, 2H), 6.85–6.80 (m, 2H), 6.72–6.65 (m, 2H), 6.65–6.60 (m, 2H), 6.02–5.86 (m, 2H), 5.09–4.92 (m, 4H), 3.84 (s, 2H), 3.76 (s, 2H), 3.34 (dd, J＝6.6 and 1.6 Hz, 2H). 1.6Hz,2H),2.05(s,3H). ¹³ C NMR(125MHz,DMSO-d ₆ ,

δ, ppm): 152.97, 152.05, 149.66, 137.31, 137.22, 131.33, 130.17, 128.97, 128.65, 128.55, 128.20, 128.07, 127.84, 127.66, 127.36, 126.73, 125.63, 119.76, 115.49, 115.26, 114.77, 34.75, 34.21, 34.02, 30.41, 20.42. HRMS (ESI) m/z: [M+H]+ Calcd for C ₂₇ H ₂₉ O ₃ 401.2117, found 401.2115. Among them, ¹ H NMR spectrum, ¹³ C The NMR spectra are shown in Figures 33 and 34.

4,4'-((2-hydroxy-5-methyl-1,3-phenylene)bis(methylene))bis(2-allylphenol) (Compound 18): white solid, ¹ H NMR (500 MHz, CDCl ₃ , δ, ppm, J/Hz): 6.98 (d, J = 2.3 Hz, 2H), 6.95 (dd, J = 8.2 and 2.4 Hz, 2H), 6.84 (s, 2H), 6.72 (d, J = 8.2 Hz, 2H), 6.05–5.95 (m, 2H), 5.32 (s, 1H), 5.16 (dd, J = 6.9 and 1.7 Hz, 2H), 5.13 (t, J = 1.6 Hz, 2H), 3.86 (s, 4H), 3.37 (dt, J = 6.4, Hz, 4H), 2.26 (s, 3H). ¹³ C NMR (125 MHz, CDCl ₃ , δ, ppm): 153.07, 136.75, 132.27, 130.88, 129.92, 128.10, 127.64, 116.53, 116.18, 35.53, 34.76, 20.17. HRMS (ESI) m/z: [M+H]+ Calcd for C ₂₇ H ₂₉ O ₃ 401.2117, found 401.2112. The ¹ H NMR spectrum and the ¹³ C NMR spectrum are shown in FIGS. 35-36 .

4,4'-((2-hydroxy-5-methyl-1,3-phenylene)bis(methylene))bis(2-(methylamino)phenol)(Compound 19): white solid, ¹ H NMR (600 MHz, CDCl ₃ , δ, ppm, J/Hz): 7.09–7.03 (m, 1H), 6.91–6.84 (m, 2H), 6.83–6.75 (m, 2H), 6.71 (d, J＝13.2 Hz, 2H), 6.56 (d, J＝9.1 Hz, 1H), 4.07–3.76 (m, 4H), 2.58 (d, J＝10.8 Hz, 3H), 2.28–2.13 (m, 6H). HRMS (ESI) m/z: [M+H] ⁺ Calcd for C ₂₃ H ₂₇ N ₂ O ₃ 379.2022, found 379.2016. The ¹ H NMR spectrum is shown in Figure 37.

2-(2-hydroxy-3-(methylamino)benzyl)-6-(4-hydroxy-3-(methylamino)benzyl)-4-methylphenol (Compound 20): yellow solid, ¹ H NMR (600 MHz, CDCl ₃ , δ, ppm, J/Hz): 6.86 (d, J＝2.1 Hz, 2H), 6.77 (d, J＝7.9 Hz, 2H), 6.73 (s, 2H), 6.58 (d, J＝7.9 Hz, 2H), 4.75 (s, 3H), 3.82 (s, 3H), 2.82 (s, 4H), 2.20 (s, 3H). HRMS (ESI) m/z: [M+H] ⁺ Calcd for C ₂₃ H ₂₇ N ₂ O ₃ 379.2022, found 379.2017. The ¹ H NMR spectrum is shown in Figure 38.

2-(4-(tert-butyl)-2-hydroxybenzyl)-6-(2-(tert-butyl)-4-hydroxybenzyl)-4-methylphenol (Compound 21): white solid, ¹ H NMR (600 MHz, MeOD, δ, ppm, J/Hz): 7.05 (d, J = 7.9 Hz, 1H), 6.90 (d, J = 2.6 Hz, 1H), 6.86 (d, J = 1.9 Hz, 1H), 6.82–6.79 (m, 2H), 6.76 (d, J = 8.3 Hz, 1H), 6.54 (dd, J = 8.3 and 13 ^C NMR (150 MHz, MeOD, δ, ppm): 155.99, 154.17, 151.85, 150.67, 150.63, 135.06, 131.26, 131.11, 130.39, 129.81, 129.63, 129.40, 128.50, 125.66, 118.36, 114.27, 113.41, 112.99, 36.51, 35.14, 35.00, 31.97, 31.79, 31.22, 20.82. HRMS (ESI) m/z: [M+H] ⁺ Calcd for C ₂₉ H ₃₇ O ₃ 433.2743, found 377.2736. Among them, ¹ H NMR spectrum, ¹³ C NMR spectra are shown in Figures 39-40.

4,4'-((2-hydroxy-5-methyl-1,3-phenylene)bis(methylene))bis(2-ethylphenol) (Compound 22): white solid, ¹ H NMR (600 MHz, CDCl ₃ , δ, ppm, J/Hz): 7.01 (d, J = 2.2 Hz, 2H), 6.89 (dd, J = 8.1 and 2.3 Hz, 2H), 6.86 (s, 2H), 6.65 (d, J = 8.0 Hz, 2H), 4.96 (s, 1H), 4.64 (s, 1H), 3.87 (s, 4H), 2.60 (d, J = 7.5 Hz, 4H), 2.26 (d, J = 6.6 Hz, 3H), 1.21 (t, J = 7.6 Hz, 6H). ¹³ C NMR (150 MHz, CDCl ₃ ,δ,ppm):151.83,149.84,131.91,130.19,129.63,129.60,129.51,127.40,126.90,115.33,35.92,22.98,20.55,14.00.HRMS(ESI)m/z:[M+H] ⁺ Calcd for C ₂₅ H ₂₉ O ₃ 377.2117,found 377.2112. The ¹ H NMR spectrum and the ¹³ C NMR spectrum are shown in FIGS. 41-42.

5. Synthesis of Compounds 23-31:

In a dry round-bottom flask, phenylboronic acid compounds (2.4 eq) and 1,3-dibromomethylbenzene (1 eq) were added and dissolved in 25 mL of 1,4-dioxane, potassium carbonate (4.8 eq) and 13 mL of water were added, and after bubbling degassing, tetrakis(triphenylphosphine)palladium (0.025 eq) was added under nitrogen protection, and the mixture was heated to 100° C. and monitored by TLC spot plate until the raw material disappeared. After cooling to room temperature, the solvent was removed by rotation, and the mixture was directly chromatographed on a silica gel column with ethyl acetate/petroleum ether (EA:PE=1:20-1:1, v/v) as the eluent to obtain the first step product. The first step product (1 eq) was dissolved in dichloromethane, cooled to 0°C, and BBr ₃ (1M, 4.8 eq) was slowly added dropwise under nitrogen protection. The TLC spot plate was monitored until the raw material disappeared, and the reaction was quenched in water. The organic phases were combined, dried, spin-dried, and chromatographed on a silica gel column with ethyl acetate/petroleum ether (EA:PE=1:5, v/v) as the eluent to obtain the product.

2,2'-(1,3-phenylenebis(methylene))diphenol (Compound 23): white solid, ¹ H NMR (600 MHz, CDCl ₃ , δ, ppm, J/Hz): 7.23 (t, J＝7.6 Hz, 1H), 7.18 (s, 1H), 7.17–7.11 (m, 4H), 7.08 (d, J＝7.8 Hz, 2H), 6.94–6.89 (m, 2H), 6.77 (d, J＝7.8 Hz, 2H), 5.10 (s, 2H), 3.98 (s, 4H). ¹³ C NMR (150 MHz, CDCl ₃ ,δ,ppm):153.59,140.16,130.88,129.14,128.89,127.75,126.97,126.63,120.87,115.68,36.25. The ¹ H NMR spectrum and the ¹³ C NMR spectrum are shown in FIGS. 43-44.

3,3'-(1,3-phenylenebis(methylene))diphenol (Compound 24): white solid, ¹ H NMR (600 MHz, CDCl ₃ , δ, ppm, J/Hz): 7.19 (t, J = 7.6 Hz, 1H), 7.14 (t, J = 7.8 Hz, 2H), 7.04 (s, 1H), 7.02 (dd, J = 7.5 and 1.8 Hz, 2H), 6.78 (d, J = 7.5 Hz, 2H), 6.68 (dd, J = 8.2 and 2.3 Hz, 2H), 6.61 (t, J = 2.0 Hz, 2H), 6.22 (s, 2H), 3.88 (s, 4H). ¹³ C NMR (150 MHz, CDCl ₃ ,δ,ppm):171.94,155.66,143.02,140.80,129.77,129.50,128.57,126.79,121.14,115.74,113.03,41.51. ^{The 1} H NMR spectrum and the ¹³ C NMR spectrum are shown in FIGS. 45-46.

4,4'-(1,3-phenylenebis(methylene))bis(benzene-1,3-diol) (Compound 25): white solid, ¹ H NMR (500 MHz, DMSO-d ₆ , δ, ppm, J/Hz): 9.15 (s, 2H), 8.99 (s, 2H), 7.08 (t, J＝7.5 Hz, 1H), 7.04 (d, J＝2.1 Hz, 1H), 6.90 (dd, J＝7.5, 1.9 Hz, 2H), 6.73 (dd, J＝8.2, 1.7 Hz, 2H), 6.27 (s, 2H), 6.11 (dt, J＝8.2, 2.2 Hz, 2H), 3.67 (s, 4H); ¹³ C NMR (125 MHz, CDCl ₃ ,δ,ppm):156.5,155.6,141.7,130.6,128.9,127.8,125.7,118.0,106.0,102.4,34.6. The ¹ H NMR spectrum and the ¹³ C NMR spectrum are shown in FIGS. 47-48.

4,4'-(1,3-phenylenebis(ethane-1,1-diyl))bis(benzene-1,3-diol) (compound 26): white solid, ¹ H NMR (500MHz, DMSO-d ₆ ,δ,ppm,J/Hz):9.11(d,J＝5.0Hz,2H),8.96(s,2H),7.15–7.04(m,2H),6.93(d,J＝7.5Hz,2H), 6.79(dd,J＝8 .4,3.9Hz,2H),6.23(s,2H),6.13(d,J＝8.3Hz,2H),4.31–4.22(m,2H),3.35(s,6H),1.40(d,J＝ 7.6Hz,6H); ¹³ C NMR (125MHz, DMSO-d ₆ ,δ,ppm):156.53,156.52,155.46,155.44,146.93,146.88,128.15,128.01,127.96,127.37,127.07,124.93,124.78,123.69,123.61,106.43,106.40,102.75,36.75,36.70,21.69,21.62. The ¹ H NMR spectrum and the ¹³ C NMR spectrum are shown in FIGS. 49-50 .

4,4'-(1,3-phenylenebis(methylene))bis(2,6-dimethylphenol)(Compound 27): white solid, ¹ H NMR (600 MHz, DMSO-d ₆ , δ, ppm, J/Hz): 8.01 (s, 2H), 7.14 (t, J＝7.6 Hz, 1H), 7.05 (s, 1H), 6.96 (dd, J＝7.6, 1.3 Hz, 2H), 6.73 (s, 4H), 3.70 (s, 4H), 2.11 (s, 12H); ¹³ C NMR (150 MHz, DMSO-d ₆ ,δ,ppm):151.76,142.46,132.08,129.32,128.88,128.73,126.47,124.50,40.89,17.12. The ¹ H NMR spectrum and the ¹³ C NMR spectrum are shown in FIGS. 51-52 .

4,4'-(1,3-phenylenebis(methylene))bis(3,5-dimethylphenol)(Compound 28): white solid, ¹ H NMR (500 MHz, DMSO-d ₆ , δ, ppm, J/Hz): 9.01 (s, 2H), 7.06 (t, J＝7.6 Hz, 1H), 6.76 (s, 1H), 6.70 (d, J＝7.5 Hz, 2H), 6.45 (s, 4H), 3.79 (s, 4H), 2.06 (s, 12H); ¹³ C NMR (125 MHz, DMSO-d ₆ ) δ155.59, 140.82, 137.90, 128.67, 127.98, 127.76, 125.23, 115.23, 34.14, 20.45. Among them, ¹ H NMR spectrum, The ¹³ C NMR spectra are shown in FIGS. 53-54 .

5,5'-(1,3-phenylenebis(methylene))bis(2-methylphenol) (Compound 29): white solid, ¹ H NMR (600 MHz, DMSO-d ₆ , δ, ppm, J/Hz): 9.13 (s, 2H), 7.18 (t, J＝7.5 Hz, 1H), 7.05 (s, 1H), 6.99 (d, J＝7.3 Hz, 2H), 6.94 (d, J＝7.4 Hz, 2H), 6.63–6.51 (m, 4H), 3.76 (s, 4H), 2.06 (s, 6H); ¹³ C NMR (150 MHz, DMSO-d ₆ ,δ,ppm):155.74,141.96,140.13,130.90,129.53,128.81,126.77,121.79,119.68,115.38,

41.32, 16.11. The ¹ H NMR spectrum and ¹³ C NMR spectrum are shown in Figures 55-56.

6,6'-(1,3-phenylenebis(methylene))bis(2-methylphenol) (Compound 30): white solid, ¹ H NMR (500 MHz, DMSO-d ₆ , δ, ppm, J/Hz): 8.27 (s, 2H), 7.18–7.09 (m, 2H), 6.95 (d, J＝7.4 Hz, 2H), 6.91 (d, J＝6.9 Hz, 2H), 6.83 (d, J＝7.4 Hz, 2H), 6.65 (t, J＝7.4 Hz, 2H), 3.86 (s, 4H), 2.16 (s, 6H); ¹³ C NMR (125 MHz, DMSO-d ₆ ,δ,ppm):153.18,141.48,129.72,129.09,128.47,128.46,128.41,126.52,124.96,119.78. The ¹ H NMR spectrum and the ¹³ C NMR spectrum are shown in FIGS. 57-58 .

3,3'-(1,3-phenylenebis(methylene))bis(2-methylphenol) (Compound 31): white solid, ¹ H NMR (600 MHz, DMSO-d ₆ , δ, ppm, J/Hz): 9.21 (s, 2H), 7.14 (t, J＝7.6 Hz, 1H), 6.98 (d, J＝12.8 Hz, 1H), 6.95–6.87 (m, 4H), 6.69 (d, J＝7.9 Hz, 2H), 6.57 (d, J＝7.4 Hz, 2H), 3.85 (s, 4H), 1.99 (s, 6H); ¹³ C NMR (150 MHz, DMSO-d ₆ ,δ,ppm):155.84,141.03,140.69,129.33,128.69,126.40,126.25,122.78,121.11,113.27,39.41,11.95. The ¹ H NMR spectrum and the ¹³ C NMR spectrum are shown in FIGS. 59-60.

Example 2: Study on the inhibition of tyrosinase activity by compound 1, compound 2 and compound 3

1. Solution preparation

Phosphate buffer (0.2M, pH 6.8): Accurately weigh 2.84 g of Na ₂ HPO ₄ and 2.4 g of NaH ₂ PO ₄ , dissolve them in purified water to make up to 100 mL respectively, mix them in equal volumes and adjust the pH to 6.8.

L-DOPA solution: Accurately weigh 3.95 mg of L-DOPA and dissolve it in 10 mL of phosphate buffer (0.2 M, pH 6.8) to prepare a 2 mmol/L L-DOPA solution.

Tyrosinase solution: Accurately weigh 1 mg of tyrosinase (enzyme activity is 500 U/mg) and dissolve it in 5 mL of phosphate buffer (0.2 M, pH 6.8) to prepare a tyrosinase solution with an enzyme activity of 100 U/mL.

Sample working solution: Accurately weigh 10 mg each of compound 1, compound 2, compound 3, and kojic acid and place them in 500 μL of ultrapure water. Then slowly add 1 M NaOH until the solution is clear and transparent. Finally, make up to 1 mL with purified water to prepare a 10 mg/mL stock solution. Then use the above-mentioned phosphate buffer to dilute the test compounds and the positive control drug kojic acid to the concentrations of 31.2 μg/mL, 62.5 μg/mL, 125 μg/mL, 250.00 μg/mL and 500.00 μg/mL of sample working solution.

2. Tyrosinase activity assay

Four test groups were set up: sample group A ₁ , sample negative control group A ₂ , enzyme standard group B ₁ and enzyme negative control group B ₂ ; 3 parallels were set for each sample, and a 200 μL reaction system was prepared according to Table 1. The corresponding volume of phosphate buffer, the sample solution of each concentration (final concentration was 3.12 μg/mL, 6.25 μg/mL, 12.5 μg/mL, 25 μg/mL and 50 μg/mL), tyrosinase solution (final concentration was 20 U/mL) and reaction substrate L-DOPA (final concentration was 1.2 mmol/L) were added to the 96-well plate in sequence, and incubated in a microplate constant temperature oscillator at 37°C for 30 minutes, and then the absorbance of each test group at 475 nm was measured in a multifunctional microplate reader (SPARK 10M, TECAN). The inhibition rate of the test compound on tyrosinase was calculated as follows:

Tyrosinase inhibition rate (%)=[1-(A ₁ -A ₂ )/(B ₁ -B ₂ )]×100.

Table 1 Tyrosinase activity inhibition test reaction system preparation (volume/μL)

As shown in FIG61 , in FIG61 , when the concentrations are 3.12 μg/mL, 6.25 μg/mL, 12.5 μg/mL and 25 μg/mL, each concentration contains four groups of data, and the four groups of data are compound 3, kojic acid, compound 1 and compound 2 from left to right; when the concentration is 50 μg/mL, there are three groups of data, and from left to right they are compound 3, kojic acid and compound 1. As can be seen from FIG61 , compound 1, compound 2 and the positive control drug kojic acid all exhibit a dose-dependent inhibitory effect on tyrosinase activity. After nonlinear fitting using Graphpad Prism 8.0 software, it is calculated that the half-inhibitory concentrations IC ₅₀ of compound 1, compound 2 and kojic acid on tyrosinase are 10.43 μg/mL (i.e. 35.96 μmol/L), 4.36 μg/mL (i.e. 13.68 μmol/L) and 18.61 μg/mL (i.e. 131.6 μmol/L), respectively. Compound 3 showed no relevant activity at any tested concentration (IC ₅₀ >50 μg/mL). The results showed that Compound 1 and Compound 2 had good inhibitory activity against tyrosinase, and their tyrosinase inhibitory activity was 3.7 times and 9.6 times that of kojic acid, respectively, and they are expected to be used as browning inhibitors for skin whitening and brightening.

Example 3: Study on the inhibition of α-glucosidase activity by compound 1, compound 1 and compound 3

1. Solution preparation

Phosphate buffer (0.2M, pH 6.8): Accurately weigh 2.84 g of Na ₂ HPO ₄ and 2.4 g of NaH ₂ PO ₄ , dissolve them in purified water to 100 mL respectively, mix equal volumes of the two and adjust the pH to 6.8.

α-Glucosidase solution: α-glucosidase powder from Saccharomyces cerevisiae was prepared into 1U/mL α-glucosidase solution with phosphate buffer (0.2M, pH 6.8) and stored at -20℃.

Substrate PNPG solution: 211 mg of 4-nitrobenzene-α-D-pyranoglucoside (PNPG) was accurately weighed using an analytical balance, and 70 mL of the above phosphate buffer was added to dissolve evenly, and a 10 mmol/L substrate storage solution was prepared and stored at -20°C away from light. "mmol/L" in this application refers to millimoles per liter, and "μmol/L" in this application refers to micromoles per liter.

Positive control working solution: Acarbose was selected as the positive control in this experiment. 103.3 mg of acarbose powder was accurately weighed and fully dissolved and mixed with 1 mL of the above phosphate buffer to prepare a 160 mmol/L acarbose mother solution. The mother solution was then diluted with the above phosphate buffer to a positive control working solution with a concentration of 2.5 mmol/L, 5 mmol/L, 10 mmol/L, 20 mmol/L, 40 mmol/L, 80 mmol/L and 160 mmol/L.

Test compound working solution: Accurately weigh 2.90 mg of compound 1, 3.19 mg of compound 2, and 3.23 mg of compound 3, respectively, and place them in 500 μL of ultrapure water. Slowly add 1 M NaOH until the solution becomes clear and transparent. Finally, fill up to 1 mL with purified water to prepare a 10 mmol/L compound stock solution. Then dilute it with the above-mentioned phosphate buffer to a working solution of compound 1 with a concentration of 0.062mmol/L, 0.125mmol/L, 0.25mmol/L, 0.5mmol/L, 1mmol/L and 2mmol/L, a working solution of compound 2 with a concentration of 0.025mmol/L, 0.05mmol/L, 0.1mmol/L, 0.2mmol/L, 0.4mmol/L and 0.8mmol/L, and a working solution of compound 3 with a concentration of 3.12μmol/L, 6.25μmol/L, 12.5μmol/L, 25μmol/L, 50μmol/L and 100μmol/L.

2. α-glucosidase activity assay

Four test groups were set up: blank group A, enzyme standard group B, sample negative control group C, sample group D; 3 parallels were set for each sample. According to Table 2, 600 μL of reaction system was prepared, and the corresponding volume of phosphate buffer, working solution of each concentration of the sample to be tested (the final concentration was 20 times diluted by the working solution of the test compound), α-glucosidase solution (final concentration 0.005U/mL) and reaction substrate PNPG (final concentration 0.5mmol/L) were added to the 96-well plate in turn, and mixed thoroughly. After the reaction system was incubated at 37°C for 50 minutes, 60 μL of 0.1mol/L Na ₂ CO ₃ solution was added to terminate the reaction. The 96-well plate to be tested was placed in a multifunctional microplate reader (SPARK 10M, TECAN) to measure the absorbance of each test group at 405nm. The inhibition rate of α-glucosidase was calculated as follows:

α-Glucosidase inhibition rate (%) = [1-(D-C)/(B-A)] × 100.

Table 2 α-glucosidase activity inhibition test reaction system preparation (volume/μL)

As shown in Figure 62, the three compounds and the positive control drug acarbose all have a dose-dependent inhibitory effect on the activity of α-glucosidase. In Figure 62, from left to right, the α-glucosidase inhibition rates of compound 1, compound 2, compound 3 and acarbose at different concentrations are respectively corresponding. After nonlinear fitting using Graphpad Prism 8.0 software, it was calculated that the half-inhibitory concentration IC ₅₀ of compound 1, compound 2, compound 3 and acarbose on α-glucosidase were 21.77μmol/L, 8.91μmol/L, 0.95μmol/L and 481.7μmol/L, respectively. The above experimental results show that the three compounds all have good inhibitory activity on α-glucosidase, and the inhibitory effect is significantly better than that of the positive control drug acarbose. It is expected to achieve the purpose of reducing skin pigmentation by effectively inhibiting α-glucosidase to reduce the production of mature active tyrosinase.

Example 4: Study on the Antioxidant Activity of Compound 1, Compound 2 and Compound 3

Mix equal volumes of 7.4mmol/L ABTS solution and 2.6mmol/L K ₂ S ₂ O ₈ solution and let stand at room temperature in the dark for 16h to prepare ABTS free radical stock solution. Dilute the ABTS free radical stock solution with phosphate buffer solution (pH 7.4, 10mmol/L) to make the absorbance at 734nm reach 0.70±0.05 to prepare ABTS working solution. Take 200μL ABTS working solution and mix it with 10μL phosphate buffer solution (pH7.4, 10mmol/L), and measure the absorbance at 734nm as A0. Accurately weigh 10mg of compound 1 and dissolve it in 500μL purified water, slowly add 1mol/L NaOH until the solution is clear and transparent, and finally make up to 1mL with purified water to prepare a 10mg/mL mother solution. Then dilute the mother solution to be tested to the corresponding concentration with phosphate buffer solution (pH7.4, 10mmol/L). The positive control drug Trolox (water-soluble vitamin E) was directly prepared into a 10 mg/mL stock solution with pure water, and then diluted with water to the corresponding concentration. 10 μL of sample solutions of different concentrations were mixed with 200 μL of ABTS working solution to make the final concentration of the positive drug vitamin E 0.9 μg/mL, 1.79 μg/mL, 3.58 μg/mL, 7.15 μg/mL, 10.73 μg/mL, 14.30 μg/mL, 25 μg/mL and 50 μg/mL, the final concentration of compound 1 was 0.62 μg/mL, 1.25 μg/mL, 2.50 μg/mL, 5.00 μg/mL, 10 μg/mL, 20 μg/mL, 40 μg/mL and 50 μg/mL, and the final concentrations of compounds 2 and 3 were 0.78 μg/mL, 1.56 μg/mL, 3.12 μg/mL, 6.25 μg/mL, 12.5 μg/mL, 25 μg/mL and 50 μg/mL. The mixed sample solution was allowed to stand at room temperature for 10 minutes, and the absorbance (Ai) was measured at a wavelength of 734 nm. At the same time, 10 μL of the sample solution of the corresponding concentration was mixed with 200 μL of 10 mmol/L pH 7.4 phosphate buffer solution, and the background absorbance Aj at a wavelength of 734 nm was measured. Three parallels were set for each sample concentration. The formula for calculating the scavenging rate of the sample for ABTS free radicals is as follows:

ABTS free radical scavenging rate (%) = [1-(Ai-Aj)/A0]×100.

As shown in Figure 63, within the test concentration range, the tested compounds all showed good scavenging effects on ABTS free radicals. Using Graphpad Prism 8.0 software for nonlinear fitting, it was calculated that the IC _{50 (half maximal inhibitory concentration) of compound 1, compound 2 and compound 3 for scavenging ABTS free radicals were 6.78μg/mL (i.e. 23.22μmol/L), 2.56μg/mL (i.e. 8.02μmol/L) and 2.10μg/mL (i.e. 6.49μmol/L), respectively; the IC 50 value} of the positive control drug vitamin E was 4.75μg/mL (i.e. 11.05μmol/L). The above experimental results show that compound 1, compound 2 and compound have good free radical scavenging ability, among which the antioxidant activity of compound 2 and compound 3 is better than that of the positive control drug vitamin E, and is expected to help cells resist oxidative stress damage and delay skin aging.

Table 3 _IC50 values of the half-inhibitory concentrations of the three compounds

Example 5: Cell activity test of compound 1, compound 2 and compound 3

Treatment of test samples:

Sample group: Compound 1, Compound 2, Compound 3 and phenethyl resorcinol were respectively dissolved in DMSO and diluted with 1640 culture medium to form a mother solution with a concentration of 38.6 μmol/L. The mother solution was then diluted with 1640 culture medium to form a series of concentration samples of 19.3 μmol/L, 9.65 μmol/L, 4.825 μmol/L and 2.413 μmol/L for use.

Negative control group: 1640 basal culture medium.

Cell viability test:

B16 cells were plated in 96-well plates. After 24 hours, the culture medium was discarded and basal culture medium containing test samples at different concentrations was added. After 24 hours, OD490 nm was detected by MTT method, and the effects of test samples on B16 cell activity were analyzed by t-test.

The statistical analysis software was SPSS, and the comparison between the test sample and the negative control was performed using an independent sample t-test. The above statistical analyses were all two-tailed tests, with a significance level of α = 0.05. *P < 0.05, * indicates that the test sample was significantly different from the negative control group at this concentration, and the experimental results are shown in Figure 64. In each category corresponding to the horizontal axis of Figure 64, there are four groups of data. The four groups of data are, from left to right, the cell survival rate data of compound 1, compound 2, compound 3, and phenethylresorcinol.

As shown in Figure 64, when the concentration of the three compounds was 19.3 μmol/L, the cell activity was >90% and there was no cytotoxicity.

Example 6: Experiment on the inhibition of cell melanin synthesis by compound 1, compound 2 and compound 3

19.3 μmol/L of compound 1, compound 2 and compound 3, phenethyl resorcinol were used as experimental samples, 1640 basal medium was used as negative control, B16 cells were plated on 6-well plates, cultured for 24 hours, replaced with 1640 basal medium containing different concentrations of test samples, and then washed twice with PBS after two changes of medium, 200 μL of 0.25% trypsin was added to each well to digest the cells, and the cells were collected into a centrifuge tube and centrifuged for 5 minutes. 200 μL of 1M NaOH containing 10% DMSO was added to each tube to lyse the cells, shaken evenly, and transferred to a 96-well plate. The absorbance at 405 nm of each well was detected by an ELISA instrument. The formula for calculating the inhibition rate of cell melanin synthesis is:

Where: T—absorbance of test sample well;

C—average of three absorbance values of the negative control group;

The statistical analysis software was SPSS, and the comparison between the test sample and the negative control was performed using the independent sample t test. The above statistical analyses were all two-tailed tests, and the significance level was α = 0.05. *P < 0.05; **P < 0.01, * indicates that the test sample has a significant difference compared with the negative control group at this concentration. The results are shown in Figure 65.

As can be seen from Figure 65, the inhibition rates of 19.3 μmol/L of compound 1, compound 2, compound 3 and phenethyl resorcinol on B16 cell melanin synthesis were 52.230%, 40.881%, 34.798% and 32.791%, respectively, which had a significant effect on inhibiting cellular melanin synthesis (P<0.05). Moreover, the inhibition rates of compound 1, compound 2 and compound 3 on B16 cell melanin synthesis were significantly higher than that of phenethyl resorcinol, a classic whitening ingredient on the market, indicating that compound 1, compound 2 and compound 3 have excellent whitening effects.

Example 7: Whitening efficacy experiment of compound 1 and compound 2 in zebrafish

Zebrafish are transparent in the early stages of development, and melanin begins to grow from the retinal epithelium at 24 hours of embryonic development. Pigment cells originate from neural crest cells, which are a group of cells differentiated from the dorsal ectoderm, and then proliferate, migrate, and differentiate into pigment stem cells. Intervention in the melanin formation process can inhibit the formation of melanin. The whiteness of zebrafish skin can be used to evaluate the whitening effect of the sample.

The experimental system uses wild AB zebrafish. The zebrafish used are 6 hpf (6 hours after fertilization). The sample size of each group is 15 fish (N=10). The adult fish are raised and bred according to laboratory standard methods, which meet the requirements of international AAALAC certification.

Randomly select zebrafish in a 6-well plate, 15 per well. Prepare the sample into a suspension that can be evenly dispersed in water, with the concentration shown in Table 4. At the same time, set up a normal control group with a volume of 3 mL per well and incubate at 28°C in the dark for 45 hours. After the incubation, randomly select 10 zebrafish from each sample group and place them under a dissecting microscope to take pictures. Use advanced image processing software to analyze and collect data, analyze the melanin signal intensity (S) of the zebrafish head, and calculate and judge whether the sample has whitening effect according to the formula. The calculation formula is:

Whitening effect = S (normal control group) - S (sample group) / S (normal control group) × 100%.

From Table 4 and Figure 66, it was observed that the melanin signal intensity of the zebrafish head of the sample compound 1 (0.0002% group), compound 1 (0.0001% group), and compound 2 (0.0001% group) was significantly reduced compared with the normal control group, revealing that the sample has a whitening effect; the melanin signal intensity of the zebrafish head of the sample compound 1 (0.00001% group), compound 2 (0.00001% group), and phenethylresorcinol 377 group was similar to that of the normal control group, revealing that the sample did not have a whitening effect at this concentration. Therefore, under the conditions of this experiment, compound 1 (0.0002%), compound 1 (0.0001%), and compound 2 (0.0001%) have a whitening effect, while compound 1 (0.00001%), compound 2 (0.00001%), and phenethylresorcinol 377 (0.0002%) do not have a whitening effect.

Table 4 Zebrafish whitening efficacy test results

Note: Statistical analysis p < 0.05 and efficacy value ≥ 20% were considered effective.

Example 8: In vitro mammalian cell micronucleus assay

The in vitro micronucleus (MNvit) test is a genetic toxicity test used to detect micronuclei in the cytoplasm during interphase of cell division.

The test process is as follows:

Using DMSO as solvent, weigh a certain amount of sample to dissolve, add 1% of the sample into DMEM medium containing serum, and the final concentrations of the sample in the medium are IC ₅₀ , 1/2IC ₅₀ and 1/4IC ₅₀ , respectively.

Mouse lymphoma cells L5178Y with a passage number of no more than 32 were used to prepare a cell suspension, which was seeded into a 24-well cell culture plate at a seeding volume of 1 mL/well and a cell number of 4×10 ⁵ /well. The plate was placed in a carbon dioxide incubator and cultured for 24 hours at 37°C and 5% CO ₂ .

Add 1 mL of prepared solvent control solution, positive control solution, and different doses of test sample solution containing cells and culture medium to the corresponding wells of the culture plate. The solvent control solution is the same as the test sample solution except that it does not contain the test sample. The positive control solution is 0.25 μg/mL mitomycin, 10 μg/mL cyclophosphamide, and 0.3 μg/mL colchicine. The cells in the cell culture plate are exposed in three ways, including: short-term exposure without metabolic activation system (S9 mixture), short-term exposure with metabolic activation system (S9 mixture), and long-term exposure without metabolic activation system (S9 mixture). The culture plate is placed in a carbon dioxide incubator for incubation according to the requirements of different groups.

After the incubation, collect the cell suspension in the cell culture plate into a centrifuge tube for hypotonic treatment. After the hypotonic treatment, fix the cells. Drop the fixed cell suspension on the slide. One slide should be dropped for each well of culture. After the prepared micronucleus slide is stained, observe 1000 cells under a microscope and record the number of micronucleus cells.

Result evaluation criteria:

(1) Determination of positive results

① Compared with the solvent control group, the micronucleus rate at at least one tested dose showed a statistically significant increase (p value < 0.05 was considered a significant increase); ② The increase in micronucleus rate was dose-dependent; ③ The test results at any dose were not within the distribution range of the historical negative control data (within 95%).

(2) Negative result determination

① Compared with the solvent control group, the micronucleus rate did not show a statistically significant increase at any tested dose; ② The micronucleus rate was not dose-dependent; ③ All test results were within the range of historical solvent control data (95% range).

Experimental conclusion: In the micronucleus test, compared with the solvent control group, the micronucleus rates of compound 1 and compound 2 at IC ₅₀ (22.5, 19.76 μg/mL), 1/2 IC ₅₀ (11.28, 9.88 μg/mL) and 1/4 IC ₅₀ (5.64, 4.96 μg/mL) did not show a statistically significant increase, and there was no dose dependence, indicating that neither compound 1 nor compound 2 exhibited potential genotoxicity.

Example 9: Bacterial reverse mutation

Principle of the test: The bacterial reverse mutation test uses amino acid-requiring strains of Salmonella typhimurium and Escherichia coli to detect point mutations that involve the substitution, addition, or deletion of one or several DNA base pairs. The principle of this bacterial reverse mutation test is that it detects the presence of the reverse mutation in the test strain and restores the functional ability of the bacteria to synthesize the essential amino acids. Reverse transfecting bacteria are detected by their ability to grow in the absence of the amino acids required by the parent test strain.

The test process is as follows:

Dissolve the sample in DMSO at a concentration of 5 mg/dish, 2.5 mg/dish, 1.6 mg/dish, 0.8 mg/dish, and 0.4 mg/dish, filter, and prepare the sample for use. Select Salmonella typhimurium TA97a, TA98, TA100, and TA102. Take an appropriate amount of nutrient broth medium, add it to a test tube, inoculate the main plate strain into the nutrient broth medium, shake and culture at 37°C, 150 rpm for 10 hours, and the number of viable bacteria in each milliliter of culture medium is not less than 1×10 ⁹ /mL, and then measure OD ₆₅₀ .

Prepare the bottom culture medium and top agar, add 0.1 mL of fresh bacterial solution of the test strain, the test sample (the specific amount of the test sample to be added is determined according to the set concentration of the test sample), and 0.5 mL of 10% S9 mixed solution to 2 mL of the insulated top culture medium, shake evenly, and then quickly pour it onto the bottom culture medium, rotate the plate to make the top culture medium evenly distributed on the bottom culture medium, and lay it flat to solidify. Take the test concentrations of 5 mg/dish, 2.5 mg/dish, 1.6 mg/dish, 0.8 mg/dish, and 0.4 mg/dish, and set 3 parallels for each concentration. At the same time, set up positive controls, solvent controls, and blank controls, with 3 parallels for each group. Place the solidified plate in an incubator and culture it at 37°C for 48 hours, observe the results and record the number of colonies.

Result evaluation criteria:

(1) Determination of positive results: Directly count the number of reverse mutant colonies growing on the culture medium. If, under conditions of good background growth, the number of reverse mutant colonies of the test substance TA97a, TA98, TA100, and TA102 should increase by more than 1 time (i.e., the number of reverse mutant colonies is equal to or greater than 2 times that of the solvent control) in at least one or more strains, and there is a dose-response relationship, the test substance mutagenicity test can be considered positive. If, in at least one or more strains, there is a significant difference in the number of reverse mutant colonies at at least one test substance concentration, but there is no dose-response relationship, and if the data can be repeated and there is a statistically significant positive reaction, the test substance mutagenicity test can be considered positive.

(2) Negative result judgment: The above positive reaction is not consistent. Under any strain or whether the S9 activation system is added, at any test sample concentration, the number of reverted mutant colonies of the test sample does not increase significantly relative to spontaneous reversion, and there is no dose-response relationship, that is, the test sample mutagenesis experiment is negative. Under this experimental condition, the test sample does not induce gene mutation in the test strain.

Experimental conclusion: Compound 1 and compound 2 were dissolved in DMSO at concentrations of 5 mg/dish, 2.5 mg/dish, 1.6 mg/dish, 0.8 mg/dish and 0.4 mg/dish, respectively. The filtered samples were tested with standard strains TA97a, TA98, TA100 and TA102, and the results showed no potential genetic toxicity.

Example 10: Skin phototoxicity detection

Adult albino guinea pigs were selected, half male and half female. Six animals were selected for formal testing. The animals were allowed to adapt to the experimental animal room environment for 3 days before the test. 24 hours before the formal phototoxicity test, the skin on both sides of the animal spine was depilated, and the skin at the test site was intact, without damage or abnormality. According to China's "Safety Technical Specifications for Cosmetics" (2015 Edition) (hereinafter referred to as the Specifications), P501 Figure 1, 4 depilated areas (Figure 67), each depilated area is about 2cm×2cm.

The animal was fixed, and 0.2 mL of the sample was applied to the hair removal area 1 and hair removal area 2 of the animal as shown in Table 1 of Specification P501. After 30 minutes, the left side (hair removal area 1 and hair removal area 3) was covered with aluminum foil and fixed with tape, and the right side (hair removal area 2 and hair removal area 4) was irradiated with UVA. The average light intensity was about 7.011 mW/cm ² , the irradiation dose was 10 J/cm ² , and the time was 1426 seconds. After the end, the skin reaction was observed at 1h, 24h, 48h and 72h, and the skin reaction score of each animal was determined according to Table 2 of Specification P501-P502. If no skin reaction occurred in the non-irradiated area after the sample was simply applied, and the number of animals with a skin reaction score of 2 or more in the irradiated area after the sample was applied was 1 or more, the sample was judged to be phototoxic.

Experimental conclusion: In the phototoxicity experiment of test compound 1 and compound 2 on guinea pigs, no skin phototoxicity was observed.

The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

The above-described embodiments only express several implementation methods of the present application, and the descriptions thereof are relatively specific and detailed, but they cannot be construed as limiting the scope of the patent application. It should be pointed out that, for a person of ordinary skill in the art, several variations and improvements can be made without departing from the concept of the present application, and these all belong to the protection scope of the present application. Therefore, the protection scope of the patent application shall be subject to the attached claims.

Claims (42)

An application of a compound represented by formula I, wherein the compound represented by formula I is as follows:
Each R ₁ , each R ₂ and each R ₃ is independently selected from one or a combination of hydrogen, hydroxyl, halogen, phenyl, halomethoxy, methylamino, methyl and a linear or branched, saturated or unsaturated hydrocarbon group having 2 to 4 carbon atoms; R ₄ , R ₅ , R ₆ and R ₇ are each independently selected from one or a combination of hydrogen, methyl and a linear or branched, saturated or unsaturated hydrocarbon group having 2 to 5 carbon atoms; m, n and k are each independently an integer from 1 to 3; The applications include one or more of the following: preparing tyrosinase inhibitors, preparing α-glucosidase inhibitors, preparing drugs for treating diabetes, preparing whitening products, preparing anti-skin oxidation products, preparing anti-aging products, preparing skin care products for reducing melanin production, preparing drugs for treating skin diseases that reduce melanin production, preparing skin care products for preventing pigmentation diseases, preparing drugs for treating skin diseases that prevent pigmentation diseases, preparing skin care products for treating pigmentation diseases, preparing drugs for treating skin diseases that treat pigmentation diseases, and inhibiting food browning. The use according to claim 1, wherein at least one of each R ₁ and each R ₃ is a hydroxyl group. The use according to any one of claims 1 to 2, wherein at least one of each R ₁ is a hydroxyl group, and at least one of each R ₃ is a hydroxyl group. The use according to any one of claims 1 to 3, wherein the compound represented by formula I is selected from one or more of the following structures: The application includes one or more of the following: preparing α-glucosidase inhibitors, preparing drugs for treating diabetes, preparing anti-skin oxidation, preparing anti-aging products, preparing skin care products that reduce melanin production, preparing drugs for treating skin diseases that reduce melanin production, preparing skin care products that prevent pigmentation diseases, preparing drugs for treating skin diseases that prevent pigmentation diseases, preparing skin care products for treating pigmentation diseases, and preparing drugs for treating skin diseases for treating pigmentation diseases. The use according to any one of claims 1 to 4, wherein the compound represented by formula I is selected from The application includes the preparation of tyrosinase inhibitors. The use according to any one of claims 1 to 3, wherein the compound represented by formula I is selected from The application includes one or more of the following: preparing tyrosinase inhibitors, preparing α-glucosidase inhibitors, preparing drugs for treating diabetes, preparing anti-skin oxidation products, preparing anti-aging products, preparing skin care products for reducing melanin production, preparing drugs for treating skin diseases that reduce melanin production, preparing skin care products for preventing pigmentation diseases, preparing drugs for treating skin diseases that prevent pigmentation diseases, preparing skin care products for treating pigmentation diseases, and preparing drugs for treating skin diseases that treat pigmentation diseases. The use according to any one of claims 1 to 6, wherein the pigmentation disease is selected from one or more of freckles, chloasma, stretch marks, age spots and melanoma. The use according to any one of claims 1 to 7, wherein the anti-skin oxidation and anti-aging refers to the removal of active oxygen free radicals in cells. A 1,3-bisbenzylphenol compound, whose structural formula is selected from one or more of the following structural formulas of compound 2 and compound 3:
The method for preparing 1,3-bis-benzylphenol compounds according to claim 9, wherein the preparation method comprises the following steps: mixing raw material A and raw material B in a substance ratio of 1: (5 to 10), wherein raw material A is selected from 1,3-di(bromomethyl)benzene, 1,3-di(chloromethyl)benzene and a combination thereof, and raw material B is selected from o-cresol, 1,2-benzenediol and a combination thereof, using aluminum chloride as a catalyst, heating the reaction at 100-120°C under nitrogen protection for a period of time, and then purifying by column chromatography to obtain the obtained product. A composition, wherein the composition has one or more of the effects of whitening, anti-skin oxidation, anti-aging and inhibiting food browning, and the composition comprises a compound shown in formula I and a carrier, and the compound shown in formula I is as follows:
Each R ₁ , each R ₂ and each R ₃ is independently selected from one or a combination of hydrogen, hydroxyl, halogen, phenyl, halomethoxy, methylamino, methyl and a linear or branched, saturated or unsaturated hydrocarbon group having 2 to 4 carbon atoms; R ₄ , R ₅ , R ₆ and R ₇ are each independently selected from one or a combination of hydrogen, methyl and a linear or branched, saturated or unsaturated hydrocarbon group having 2 to 5 carbon atoms; m, n and k are each independently an integer from 1 to 3; The carrier is selected from one or more acceptable carriers in the cosmetics field, the pharmaceutical field, the food field and combinations thereof. The composition according to claim 11, wherein at least one of each R ₁ and each R ₃ is a hydroxyl group. The composition according to any one of claims 11 to 12, wherein at least one of each R ₁ is a hydroxyl group, and at least one of each R ₃ is a hydroxyl group. The composition according to any one of claims 11 to 13, wherein the compound represented by formula I is selected from one or more of the following structures: The composition according to any one of claims 11 to 14, wherein the composition has at least one of whitening, anti-skin oxidation and anti-aging effects, comprising an effective amount of compound 1 as an active ingredient Compound 2 Compound 3 At least one of, and one or more acceptable carriers in the field of cosmetics. The composition according to claim 15, wherein whitening refers to one or more of inhibiting tyrosinase activity, inhibiting α-glucosidase activity, inhibiting cellular melanin production and inhibiting pigmentation; anti-skin oxidation and anti-aging refer to removing active oxygen free radicals in cells. The composition according to claim 16, wherein the pigmentation is selected from one or more of freckles, chloasma, stretch marks, age spots and melanoma. The composition according to any one of claims 11 to 17, wherein the composition is selected from one or more of a tyrosinase inhibitor composition and an α-glucosidase inhibitor composition. The composition according to any one of claims 11 to 18, wherein the carrier comprises one or more of a fragrance, a compound for skin care, a compound for skin cleansing and an ultraviolet absorber. The composition according to claim 19, wherein the composition comprises a flavor and the compound of formula I, the flavor is present in an amount effective to provide a sensory effect, and the compound of formula I is present in an amount having one or both of an inhibitory effect on tyrosinase and an inhibitory effect on α-glucosidase. The composition according to claim 20, wherein, in the composition, the compound represented by formula I is present in a mass percentage of about 3% to about 30%. The composition of claim 19, wherein the composition comprises a UV absorber and a compound of formula I, wherein the amount of the UV absorber is effective to provide UV protection with a protection factor of at least greater than 2, and the amount of the compound of formula I has one or both of the effects of inhibiting tyrosinase and inhibiting α-glucosidase. The composition according to claim 19, wherein the composition comprises one or more of a compound for skin care and a compound for skin cleansing, and a compound represented by formula I, wherein the amount of the compound represented by formula I has one or both of the effects of inhibiting tyrosinase and inhibiting α-glucosidase. Use of the composition according to any one of claims 11 to 23 in the preparation of whitening skin care products, whitening skin disease treatment drugs, anti-aging skin care products, anti-aging skin disease treatment drugs and combinations thereof. The use according to claim 24, wherein the composition is selected from one of a skin care composition and a skin disease treatment pharmaceutical composition, and the composition comprises an effective amount of compound 1 as an active ingredient Compound 2 and compound 3 One or more of the . According to the use of claim 25, whitening refers to one or more of inhibiting tyrosinase activity, inhibiting α-glucosidase activity, inhibiting cellular melanin production and inhibiting pigmentation; anti-skin oxidation and anti-aging refer to removing active oxygen free radicals in cells. The use according to claim 26, wherein the pigmentation is selected from one or more of freckles, chloasma, stretch marks, age spots and melanoma. A product, wherein the product is one of a cosmetic and a drug for treating skin diseases, and the product comprises the composition according to any one of claims 11 to 23 or comprises the compound shown in formula I, Each R ₁ , each R ₂ and each R ₃ is independently selected from one or a combination of hydrogen, hydroxyl, halogen, phenyl, halomethoxy, methylamino, methyl and a linear or branched, saturated or unsaturated hydrocarbon group having 2 to 4 carbon atoms; R ₄ , R ₅ , R ₆ and R ₇ are each independently selected from one or a combination of hydrogen, methyl and a linear or branched, saturated or unsaturated hydrocarbon group having 2 to 5 carbon atoms; m, n and k are each independently an integer of 1-3. The product according to claim 28, wherein the mass percentage of the compound represented by formula I in the product is 0.0001% to 10%. The product according to claim 29, wherein the mass percentage of the compound represented by formula I in the product is 0.01% to 2%. The product according to claim 30, wherein the mass percentage of the compound represented by formula I in the product is 0.1% to 1%. A pharmaceutical composition for treating diabetes, comprising an effective amount of a compound as an active ingredient and a carrier, wherein the effective amount of the compound as an active ingredient is selected from one or more of the compounds shown in Formula I, and the compounds shown in Formula I are as follows:
Each R ₁ , each R ₂ and each R ₃ is independently selected from one or a combination of hydrogen, hydroxyl, halogen, phenyl, halomethoxy, methylamino, methyl and a linear or branched, saturated or unsaturated hydrocarbon group having 2 to 4 carbon atoms; R ₄ , R ₅ , R ₆ and R ₇ are each independently selected from one or a combination of hydrogen, methyl and a linear or branched, saturated or unsaturated hydrocarbon group having 2 to 5 carbon atoms; m, n and k are each independently an integer from 1 to 3; The carrier is selected from one or more acceptable carriers in the pharmaceutical field. The pharmaceutical composition for treating diabetes according to claim 32, wherein the effective amount of the compound used as the active ingredient is selected from compound 1 Compound 2 and compound 3 One or more of the . Use of the pharmaceutical composition according to any one of claims 32 to 33 in the preparation of a drug for treating diabetes. The use according to claim 34, wherein the effective amount of the compound used as the active ingredient is selected from compound 1 Compound 2 and compound 3 One or more of the . A pharmaceutical preparation, comprising one or more compounds for treating diabetes, and one or more compounds of formula I in an amount that inhibits α-glucosidase; the compounds of formula I are as follows:
Each R ₁ , each R ₂ and each R ₃ is independently selected from one or a combination of hydrogen, hydroxyl, halogen, phenyl, halomethoxy, methylamino, methyl and a linear or branched, saturated or unsaturated hydrocarbon group having 2 to 4 carbon atoms; R ₄ , R ₅ , R ₆ and R ₇ are each independently selected from one or a combination of hydrogen, methyl and a linear or branched, saturated or unsaturated hydrocarbon group having 2 to 5 carbon atoms; m, n and k are each independently an integer of 1-3. The pharmaceutical preparation according to claim 36, wherein at least one of each R ₁ and each R ₃ is a hydroxyl group. The pharmaceutical preparation according to any one of claims 36 to 37, wherein at least one of each R ₁ is a hydroxyl group, and at least one of each R ₃ is a hydroxyl group. The pharmaceutical preparation according to any one of claims 36 to 38, wherein the compound represented by formula I is selected from one or more of the following structures: A method for whitening human skin and combating age spots on human skin, comprising administering an effective amount of the composition of any one of claims 11 to 23 or the product of any one of claims 28 to 31 to a person in need thereof. A method for inhibiting browning of food, comprising applying an effective amount of the composition according to any one of claims 11 to 23 to the food. A method for treating diabetes, comprising administering an effective amount of the pharmaceutical composition according to any one of claims 32 to 33 or the pharmaceutical preparation according to any one of claims 36 to 39 to a person in need thereof.