Oil-soluble bosaicin ester with antioxidant, firming and anti-wrinkle effects, preparation method and application thereof

Abstract

The present invention relates to bosaicin esters and their preparation methods and applications. The bosaicin esters have a structural formula as shown in formula (I), wherein each R1 is independently selected from: hydrogen, -C(=O)R, and at least one R1 is -C(=O)R; R is selected from: C7~C 21 Alkyl, C7~C 21 Unsaturated chain hydrocarbon group. The bosaicin ester of the present invention has a significant DPPH free radical scavenging effect and can significantly increase the expression of elastin, hyaluronic acid and type I collagen in cells. When added as an effective ingredient in cosmetics, it has excellent antioxidant, moisturizing and / or firming and anti-wrinkle effects.

Description

Technical Field

[0001] The present invention belongs to the technical field of cosmetics and relates to skin care products, in particular to bosaicin ester and a preparation method and application thereof. Background Art

[0002] Pro-Xylane, also known as (2S,3R,4S,5R)-2-(2-hydroxypropyl)tetrahydro-2H-pyran-3,4,5-triol (CAS No. 439685-79-7), is a xylose derivative derived from natural xylose with anti-wrinkle properties. It can induce the biosynthesis of GAGs and PG proteoglycans in the superficial epidermis, promoting the production of hyaluronic acid. It also improves dermal-epidermal adhesion, promotes collagen and elastin synthesis, regenerates damaged tissue, maintains dermal elasticity, and prevents skin aging. Therefore, Pro-Xylane is widely used in cosmetics, food, biology, medicine, and other technical fields.

[0003] Currently, research on bosaicin mainly focuses on its synthesis, extraction, composition, and application. Studies on the relationship between bosaicin structure modification and efficacy are limited. Currently, only L'Oréal has disclosed research on the activity of bosaicin esters in patent document FR2999076A1. The bosaicin esters disclosed in the patent document are used for anti-aging skin. Their structural formula is shown in Formula (1):

[0004]

[0005] Wherein, X is selected from hydrogen atom or C1-C 18 Alkyl, etc., R' is independently selected from H or -COR", R" independently represents a hydrogen atom or C1-C 18 and the four groups R' are not hydrogen atoms at the same time.

[0006] FR2999076A1 discloses a method for preparing bosaicin esters, which are obtained by reacting bosaicin with acyl chlorides in a specific ratio. Because all four hydroxyl groups of bosaicin are secondary alcohols, their reactivity is minimal when esterified with acyl chlorides, and the position of esterification cannot be determined. The resulting esterification product is a complex mixture, and the ratio of different esters in the mixture cannot be guaranteed, which affects its actual efficacy in cosmetics. Summary of the Invention

[0007] Based on this, the present invention provides an oil-soluble bosaicin ester, which has better antioxidant, moisturizing and firming and anti-wrinkle effects than bosaicin.

[0008] The present invention includes the following technical solutions.

[0009] In a first aspect, the present invention provides a bosaicin ester or a stereoisomer thereof, wherein the bosaicin ester has a structural formula as shown in formula (I):

[0010]

[0011] wherein each R1 is independently selected from: hydrogen, -C(=O)R, and at least one R1 is -C(=O)R;

[0012] R is selected from: C7~C 17 Alkyl, C7~C 17 Unsaturated chain hydrocarbon group.

[0013] In a second aspect, the present invention provides a bosaicin ester composition, which is composed of two or more compounds of the bosaicin ester or its stereoisomers described in the present invention.

[0014] In a third aspect, the present invention provides the use of the bosaicin ester or its stereoisomers, or the bosaicin ester composition, as an effective ingredient in the preparation of antioxidant cosmetics.

[0015] In a fourth aspect, the present invention provides the use of the bosaicin ester or its stereoisomers, or the bosaicin ester composition, as an effective ingredient in the preparation of cosmetics capable of moisturizing, firming the skin and / or anti-wrinkle.

[0016] In a fifth aspect, the present invention provides a cosmetic, wherein the effective ingredients of the cosmetic contain the bosaicin ester or its stereoisomers, or the bosaicin ester composition described in the present invention.

[0017] In a sixth aspect, the present invention provides a method for preparing the bosaicin ester, comprising the following steps:

[0018] (1) Compound 1 reacts with compound 2 to obtain compound 3;

[0019] (2) Esterifying compound 3 to obtain compound 4;

[0020] (3) Reducing the carbonyl group in compound 4 to obtain the bosaicin ester of the structure shown in formula (I);

[0021] The reaction formula is as follows:

[0022] ;

[0023] wherein each R1 is independently selected from: hydrogen, -C(O)R, and at least one R1 is -C(O)R;

[0024] R is selected from: C7~C 21 Alkyl, C7~C 21 Unsaturated chain hydrocarbon group.

[0025] The present invention has the following beneficial effects:

[0026] The bosaiin ester prepared by the present invention has an unesterified hydroxyl group at the 8th position, retaining the hydroxypropyl group. Through extensive experimental research, the present invention has found that by modifying the hydroxyl group on the bosaiin tetrahydropyran ring with a specific carbon chain while retaining the hydroxypropyl group (i.e., the 8th-position hydroxyl group is not esterified), the resulting bosaiin ester has better antioxidant, moisturizing, and firming and anti-wrinkle effects than bosaiin and bosaiin esters with an esterified 8th-position hydroxyl group.

[0027] The bosaicin ester of the present invention has a significant DPPH free radical scavenging effect and can significantly increase the expression of elastin, hyaluronic acid and type I collagen in cells. When added to cosmetics as an effective ingredient, it has excellent antioxidant, moisturizing and / or firming and anti-wrinkle effects.

[0028] The bosaicin ester of the present invention has good oil solubility and can be well dissolved in commonly used oils and fats in cosmetics, such as isopropyl myristate, squalane, isohexadecane, etc. DETAILED DESCRIPTION

[0029] To facilitate understanding of the present invention, the present invention will be described more fully below. The present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the understanding of the present disclosure more thorough and comprehensive.

[0030] In the following examples, the experimental methods without specific conditions are generally carried out under conventional conditions or conditions recommended by the manufacturers. The various commonly used chemical reagents used in the examples are all commercially available products.

[0031] Unless otherwise defined, all technical and scientific terms used herein have the same meanings as commonly understood by those skilled in the art to which this invention pertains. The terms used in this specification are for the purpose of describing specific embodiments only and are not intended to limit the invention. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

[0032] Furthermore, as used herein, the term "or" is inclusive and equivalent to the term "and / or," unless the context clearly dictates otherwise. The term "based on" is not exclusive and allows for being based on other factors not described, unless the context clearly dictates otherwise. Furthermore, throughout this specification, the meanings of "a," "an," and "the" include plural referents. The meaning of "in" includes "in" and "on."

[0033] The term "alkyl" herein refers to a saturated aliphatic hydrocarbon group, including both branched and straight-chain groups, having a specified number of carbon atoms. For example, the definition of "C1-C6 alkyl" includes groups having 1, 2, 3, 4, 5, or 6 carbon atoms in a straight or branched chain. For example, "C1-C6 alkyl" specifically includes methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, pentyl, and hexyl.

[0034] The term "unsaturated chain hydrocarbon group" in the present invention refers to branched and straight-chain unsaturated aliphatic hydrocarbon groups having a specific number of carbon atoms, that is, non-cyclic chain hydrocarbon groups, and the carbon chain contains one or more carbon-carbon double bonds, or carbon-carbon triple bonds, such as: -(CH2)7(CH=CH)(CH2)7CH3, -(CH2)8(CH=CH)(CH2)7CH3, -(CH2)8(CH=CH)(CH2)5CH3, -(CH2)8(CH=CH)(CH2)7CH3, -(CH2)8(CH=CH)(CH2)6CH3, -(CH2)8(CH=CH)CH2(CH=CH)(CH2)2CH3, -(CH2)8(CH=CH)CH2(CH=CH)(CH2)4CH3, -(CH2)8(CH=CH)CH2(CH=CH)(CH2)6CH3, etc.

[0035] In some embodiments, a bosaicin ester or a stereoisomer thereof is involved, wherein the structural formula of the bosaicin ester is shown in formula (I):

[0036]

[0037] wherein each R1 is independently selected from: hydrogen, -C(=O)R, and at least one R1 is -C(=O)R;

[0038] R is selected from: C7~C 17 Alkyl, C7~C 17 Unsaturated chain hydrocarbon group.

[0039] In some embodiments, the three R1s in formula (I) are all -C(O)R.

[0040] In some embodiments, any two R1 in formula (I) are -C(O)R, and one R1 is hydrogen.

[0041] In some embodiments, any one R1 in formula (I) is -C(O)R, and two R1s are hydrogen.

[0042] In some embodiments, the structural formula of the bosaicin ester is shown in Formula (I-1), Formula (I-2), Formula (I-3), Formula (I-4), Formula (I-5), Formula (I-6) or Formula (I-7):

[0043]

[0044] In some embodiments, R is selected from the group consisting of: C7 alkyl, C8 alkyl, C9 alkyl, C 10 Alkyl, C 11 Alkyl, C 12 Alkyl, C 13 Alkyl, C 14 Alkyl, C 15 Alkyl, C 16 Alkyl, C 17 Alkyl, C7 unsaturated chain hydrocarbon group containing one or two carbon-carbon double bonds, C8 unsaturated chain hydrocarbon group containing one or two carbon-carbon double bonds, C9 unsaturated chain hydrocarbon group containing one or two carbon-carbon double bonds, C 10 Unsaturated chain hydrocarbon group, C containing one or two carbon-carbon double bonds 11 Unsaturated chain hydrocarbon group, C containing one or two carbon-carbon double bonds 12 Unsaturated chain hydrocarbon group, C containing one or two carbon-carbon double bonds 13 Unsaturated chain hydrocarbon group, C containing one or two carbon-carbon double bonds 14 Unsaturated chain hydrocarbon group, C containing one or two carbon-carbon double bonds 15 Unsaturated chain hydrocarbon group, C containing one or two carbon-carbon double bonds 16 Unsaturated chain hydrocarbon group, C containing one or two carbon-carbon double bonds 17 Unsaturated chain hydrocarbon group.

[0045] In some embodiments, R is selected from: n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, n-tridecyl, n-tetradecyl, n-pentadecyl, n-hexadecyl, n-heptadecyl, 1-hexyl-nonyl, -(CH2)8(CH=CH)(CH2)5CH3, -(CH2)7(CH=CH)(CH2)7CH3, -(CH2)9(CH=CH)(CH2)5CH3.

[0046] In some preferred embodiments, R is selected from: C 15 Branched alkyl, C containing a carbon-carbon double bond 17 Unsaturated chain hydrocarbon group.

[0047] In some embodiments, the bosaicin ester is selected from the following compounds:

[0048] ;

[0049] ;

[0050] ; ;

[0051] ;

[0052] ;

[0053] ;

[0054] ;

[0055] ; .

[0056] The bosaiin ester prepared by the present invention has an unesterified hydroxyl group at the 8th position, retaining the hydroxypropyl group. Through extensive experimental research, the present invention has found that by modifying the hydroxyl group on the bosaiin tetrahydropyran ring with a specific carbon chain while retaining the hydroxypropyl group (i.e., the 8th-position hydroxyl group is not esterified), the resulting bosaiin ester has better antioxidant, moisturizing, and firming and anti-wrinkle effects than bosaiin and bosaiin esters with an esterified 8th-position hydroxyl group.

[0057] The bosaicin ester of the present invention has a significant DPPH free radical scavenging effect and can significantly increase the expression of elastin, hyaluronic acid and type I collagen in cells. When added to cosmetics as an effective ingredient, it has excellent antioxidant, moisturizing and / or firming and anti-wrinkle effects.

[0058] The bosaicin ester of the present invention has good oil solubility and can be well dissolved in commonly used oils and fats in cosmetics, such as isopropyl myristate, squalane, isohexadecane, etc.

[0059] The bosaicin ester of the present invention can be added to cosmetics in the form of a composition of two or more, which can significantly increase the expression of elastin, hyaluronic acid and type I collagen in cells, and have excellent antioxidant, moisturizing and / or firming and anti-wrinkle effects.

[0060] In some embodiments of the present invention, a bosaicin ester composition is provided, comprising two or more bosaicin esters or stereoisomers thereof described herein. For example, the bosaicin ester composition of the present invention may contain component A, component B, and component C, wherein component A is a bosaicin ester or stereoisomer thereof represented by formula (I-1), component B is a bosaicin ester or stereoisomer thereof represented by formula (I-2), formula (I-3), and / or formula (I-4), and component C is a bosaicin ester or stereoisomer thereof represented by formula (I-5), formula (I-6), and / or formula (I-7).

[0061] For another example, the bosaicin ester composition of the present invention may contain bosaicin esters represented by formula (I-2), formula (I-3) and formula (I-4) or stereoisomers thereof.

[0062] For another example, the bosaicin ester composition of the present invention may contain bosaicin esters represented by formula (I-5), formula (I-6) and formula (I-7) or stereoisomers thereof.

[0063] In some embodiments, the bosaicin ester composition contains a bosaicin ester having a structure represented by formula (I-1) or a stereoisomer thereof, and the molar ratio of the bosaicin ester having a structure represented by formula (I-1) or a stereoisomer thereof in the bosaicin ester composition is 2% or more, preferably 5% or more, more preferably 10% or more, more preferably 15% or more, more preferably 20% or more, more preferably 25% or more, more preferably 30% or more, more preferably 35% or more, more preferably 40% or more, more preferably 45% or more, more preferably 50% or more, more preferably 55% or more, more preferably 60% or more, more preferably 65% ​​or more, more preferably 70% or more, more preferably 75% or more, more preferably 80% or more, more preferably 85% or more, more preferably 90% or more, more preferably 95% or more, more preferably 98% or more.

[0064] In some embodiments, the bosaicin ester composition contains bosaicin ester or its stereoisomers having structures represented by formula (I-2), formula (I-3) and / or formula (I-4), and the total amount of bosaicin ester or its stereoisomers having structures represented by formula (I-2), formula (I-3) and formula (I-4) in the bosaicin ester composition has a molar ratio of 5% or more, more preferably 9% or more, more preferably 10% or more, more preferably 15% or more, more preferably 20% or more, more preferably 25% or more, more preferably 30% or more, more preferably 35% or more, more preferably 40% or more, more preferably 45% or more, more preferably 50% or more, more preferably 55% or more, more preferably 60% or more, more preferably 65% ​​or more, more preferably 70% or more, more preferably 75% or more, more preferably 80% or more.

[0065] In some embodiments, the total amount of the bosaicin esters or their stereoisomers represented by the structures of formula (I-2), formula (I-3) and formula (I-4) in the bosaicin ester composition has a molar ratio of 75% to 95%.

[0066] In some embodiments, the total amount of the bosaicin esters or their stereoisomers represented by the structures of formula (I-2), formula (I-3) and formula (I-4) in the bosaicin ester composition has a molar ratio of 80% to 90%.

[0067] In some embodiments of the present invention, a cosmetic is further provided, wherein the effective ingredients of the cosmetic contain the bosaicin ester or its stereoisomers, or the bosaicin ester composition of the present invention.

[0068] The cosmetics described in the present invention include but are not limited to daily cleaning or skin care products such as cleansers, lotions, emulsions, facial masks, creams and essences.

[0069] The amount of the bosaicin ester or its stereoisomer, or the bosaicin ester composition, added to the cosmetic product is determined based on its ability to produce antioxidant, moisturizing, and / or firming and anti-wrinkle effects without causing significant toxicity. Because the bosaicin ester or its stereoisomer has significant skin-improving effects and low cytotoxicity, its addition amount can be within a relatively large range, for example, 0.01 wt% to 0.5 wt%.

[0070] Some embodiments of the present invention also relate to a method for preparing the bosaicin ester of the present invention, comprising the following steps:

[0071] (1) Compound 1 reacts with compound 2 to obtain compound 3;

[0072] (2) Esterifying compound 3 to obtain compound 4;

[0073] (3) Reducing the carbonyl group in compound 4 to obtain the bosaicin ester of the structure shown in formula (I);

[0074] The reaction formula is as follows:

[0075] ;

[0076] wherein each R1 is independently selected from: hydrogen, -C(O)R, and at least one R1 is -C(O)R;

[0077] R is selected from: C7~C 21 Alkyl, C7~C 21 Unsaturated chain hydrocarbon group.

[0078] The present invention uses xylose (compound 1) as a raw material, which is first reacted with acetylacetone (compound 2) to obtain compound 3, which is then esterified to obtain compound 4. Compound 4 is then reduced to obtain a bosaicin ester (compound (I). This specific reaction route can retain the 8-hydroxyl group from being esterified. The retention of the 8-hydroxyl group can significantly improve the antioxidant, moisturizing and / or firming and anti-wrinkle effects of the obtained bosaicin ester.

[0079] The preparation steps of compound 3 include: mixing xylose and acetylacetone in a solvent, adding a base to carry out a condensation reaction, and obtaining compound 3.

[0080] In the reaction for preparing compound 3, the base used includes inorganic bases and organic bases. The inorganic base is selected from sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, etc., and the organic base is selected from piperidine, tetrahydropyrrole, diethylamine, triethylamine, diisopropylethylamine, etc.

[0081] In some embodiments, step (1) of preparing compound 3 comprises: mixing compound 1 and compound 2 in a solvent, adding dropwise an alkali solution dissolved in the solvent (the solvent is the same as the reaction solvent, and the concentration can be 15wt%-25wt%) at a temperature of 20°C-30°C, controlling the dropping speed so that the temperature of the reaction solution is not higher than 40°C, and after the dropping is completed, continuing to keep the temperature at 40°C-50°C for 1-2 hours to obtain compound 3.

[0082] In some embodiments, the molar ratio of compound 1, compound 2 and base is 1:1-1.2:1-1.2.

[0083] There are many methods for preparing compound 4, including the acyl chloride method, catalytic esterification method, transesterification method, and condensation agent method. Among them, the acyl chloride method and catalytic esterification method are the most commonly used.

[0084] The acyl chloride method uses compound 3 and fatty acyl chloride (R-(C=O)-Cl) as reactants, and after the reaction is completed in a solvent, compound 4 is obtained by post-treatment. The R group in the fatty acyl chloride is selected from: C7~C 21 Alkyl, C7~C 21 Unsaturated chain hydrocarbon groups, for example, the fatty acid chloride can be selected from lauroyl chloride, myristoyl chloride, octanoyl chloride, decanoyl chloride, oleoyl chloride, linoleoyl chloride, linolenoyl chloride, palmitoyl chloride, stearoyl chloride, isostearoyl chloride, isononanoyl chloride, cocoyl chloride, 2-hexyldecanoyl chloride, Guerbet C12 acid chloride, Guerbet C16 acid chloride, and the like.

[0085] In some embodiments, step (2) of esterifying compound 3 includes: dissolving compound 3 in a solvent, cooling the temperature to 0°C-10°C, adding the fatty acid chloride dropwise, maintaining the temperature of the reaction solution at no more than 15°C during the addition, heating the reaction solution to 20°C-30°C after the addition, reacting for 1h-2h, and obtaining compound 4 through post-treatment.

[0086] Among them, the molar ratio of compound 3 to the fatty acid chloride is determined by the expected target product. If the main purpose is to obtain a triester in which all three hydroxyl groups on the tetrahydropyran ring are esterified (i.e., the bosaiin ester shown in formula (I-1)), the molar ratio of compound 3 to the fatty acid chloride is 1:3-3.5; if the main purpose is to obtain a diester in which two hydroxyl groups on the tetrahydropyran ring are esterified (i.e., the bosaiin ester shown in formula (I-2), formula (I-3) and formula (I-4)), the molar ratio of compound 3 to the fatty acid chloride is 1:2-2.2; if the main purpose is to obtain a monoester in which one hydroxyl group on the tetrahydropyran ring is esterified (i.e., the bosaiin ester shown in formula (I-5), formula (I-6) and formula (I-7)), the molar ratio of compound 3 to the fatty acid chloride is 1:1-1.2.

[0087] The catalytic esterification method uses compound 3 and a fatty acid as reactants. After complete reaction in a solvent, compound 4 is obtained through post-treatment. Catalytic esterification methods include acid-catalyzed esterification, base-catalyzed esterification, and enzyme-catalyzed esterification. Catalysts for acid-catalyzed esterification include sodium bisulfate, p-toluenesulfonic acid, aminosulfonic acid, Lewis acids, and solid superacids; catalysts for base-catalyzed esterification include sodium hydroxide, potassium hydroxide, or sodium methoxide; and catalysts for enzyme-catalyzed esterification include various fat esterification / hydrolysis enzymes. Fatty acids used include lauric acid, myristic acid, caprylic acid, capric acid, oleic acid, linoleic acid, linolenic acid, palmitic acid, stearic acid, isostearic acid, isononanoic acid, coconut acid, 2-hexyldecanoic acid, Guerbet C12 acid, and Guerbet C16 acid.

[0088] In the transesterification method, compound 3 reacts with fatty methyl ester / ethyl ester using alkali or lipase as catalyst, and methanol / ethanol is removed to obtain compound 4.

[0089] The condensation method uses compound 3 and fatty acid as substrates, and carries out a condensation reaction under the action of a condensation agent and a condensation auxiliary to prepare compound 4.

[0090] Compound 4 is reduced to obtain compound (I), the target product of the present invention, bosyl ester. Reduction methods include reduction with a boron reducing agent or catalytic hydrogenation. The boron reducing agent is selected from sodium borohydride, potassium borohydride, etc.; the catalyst used in catalytic hydrogenation is a metal catalyst such as Pt, Ni, or Pd.

[0091] In some embodiments, the step (3) of reducing the carbonyl group in compound 4 comprises: dissolving compound 4 in a solvent, adding a boron reducing agent, and reacting for 1 hour to 3 hours to obtain a bosyl ester having the structure shown in formula (I).

[0092] In some embodiments, the molar ratio of compound 4 to the boron reducing agent is 1:1-1.5.

[0093] The present invention is further described in detail below with reference to specific embodiments.

[0094] The general synthesis reaction formula of bosaicin ester in the following examples is as follows:

[0095] ;

[0096] Among them, one, two or three of the three R1s are -C(O)R2, and the remaining R1s are hydrogen; R2 is selected from: C7~C 21 Alkyl, C7~C 21 Unsaturated chain hydrocarbon group.

[0097] The saponification values ​​in the following examples were determined according to the acid value determination method in the Chinese Pharmacopoeia Part IV General Chapter 0713 Fats and Fatty Oils Determination Method.

[0098] The room temperature in the examples refers to a room temperature of 15°C to 30°C.

[0099] Example 1 Synthesis of Intermediate Compound 3

[0100] A 10 L reactor equipped with nitrogen protection, mechanical stirring, a thermometer, and a dropping funnel was added with methanol (300 mL), D-xylose (300.0 g, 2.0 mol), and acetylacetone (210.0 g, 2.1 mol). The temperature was controlled at 20°C-30°C in a cold bath. 20 wt% sodium hydroxide-methanol solution (440.0 g, 2.2 mol) was added dropwise with vigorous stirring. The addition rate was controlled so that the temperature of the reaction solution did not exceed 40°C. After completion of the addition, the reaction was continued at 40°C-50°C for 1 hour. Acetic acid (6.0 g, 0.1 mol) was added to neutralize the excess sodium hydroxide, and the mixture was concentrated to dryness to obtain a crude product of compound 3. The crude product was purified by column chromatography to obtain 340.0 g of compound 3 in a yield of 90%.

[0101] The NMR analysis data of compound 3 are as follows:

[0102] 1 H-NMR (500MHz, D2O): δ 2.15 (s, 3H), 2.57-2.63 (m, 1H), 2.92-2.96 (m, 1H), 3.09-3.13 (t, 1H), 3.16-3.21 ( t, 1H), 3.30-3.34 (t, 1H), 3.45-3.51 (m, 1H), 3.60-3.64 (m, 1H), 3.78-3.82 (m, 1H).

[0103] Example 2 Synthesis of Intermediate Compound 3

[0104] Potassium hydroxide was used instead of sodium hydroxide. The remaining raw materials, reagents and synthesis steps were the same as those in Example 1, and the yield was 80%.

[0105] Example 3 Synthesis of lauric acid benzoin ester (5-12-3)

[0106]

[0107] Anhydrous pyridine (300 mL) was added to a reaction flask, and compound 3 (19.0 g, 0.1 mol) was added with stirring to dissolve the mixture. The temperature was then cooled to 10°C, and lauroyl chloride (67.6 g, 0.31 mol) was added dropwise. The reaction temperature was maintained below 15°C during the addition. After completion, the temperature was raised to 25°C and the reaction was allowed to proceed for 1 h. Pyridine was removed by distillation under reduced pressure, and ethyl acetate (300 mL) was added. The mixture was stirred thoroughly, and the lower layer was separated. The upper layer was washed sequentially with 1M aqueous sulfuric acid (200 mL), purified water (200 mL), and saturated brine (200 mL). The mixture was then dried over anhydrous sodium sulfate, filtered, and concentrated to yield 70.0 g of crude compound 4 in a 95% yield.

[0108] The crude compound 4 was dissolved in isopropanol (1 L) and sodium borohydride (3.8 g, 0.1 mol) was added. After reacting at room temperature for 2 hours, the isopropanol was removed under reduced pressure, and ethyl acetate (300 mL) was added. The mixture was stirred evenly, and the lower layer was separated. The upper layer was washed sequentially with 1M aqueous sulfuric acid (200 mL) and saturated brine (300 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 69.5 g of compound 5-12-3 in a yield of 99.0%. The HPLC purity was 98.5%.

[0109] 1 H-NMR (500MHz, CDCl3): δ5.30-5.26(m,1H), 5.00-4.87(m,2H), 4.20-4.12(m,1H), 4.10-3.95(m ,1H), 3.70-3.50(m,2H), 3.28-3.16(m,1H), 2.30-2.15(m,6H), 1.76-1.12(m,59H), 0.87(s,9H).

[0110] Saponification value: 231 (theoretical value: 228).

[0111] Example 4 Synthesis of lauric acid bis(5-12-2)

[0112]

[0113] Anhydrous pyridine (250 mL) was added to a reaction flask, and compound 3 (19.0 g, 0.1 mol) was added with stirring to dissolve the mixture. The temperature was then cooled to 10°C, and lauroyl chloride (45.8 g, 0.21 mol) was added dropwise. The reaction temperature was maintained below 15°C during the addition. After completion, the temperature was raised to 25°C and the reaction was allowed to proceed for 1 h. Pyridine was removed by distillation under reduced pressure, and ethyl acetate (300 mL) was added. The mixture was stirred thoroughly, and the lower layer was separated. The upper layer was washed sequentially with 1M aqueous sulfuric acid (200 mL), purified water (200 mL), and saturated brine (200 mL). The mixture was then dried over anhydrous sodium sulfate, filtered, and concentrated to yield 50.0 g of compound 4 in a 90% yield.

[0114] The obtained compound 4 was dissolved in isopropanol (1 L), and sodium borohydride (3.8 g, 0.1 mol) was added. After reacting at room temperature for 2 hours, the isopropanol was removed under reduced pressure, and ethyl acetate (300 ml) was added. The mixture was stirred evenly, and the lower layer solution was separated. The upper layer solution was washed with 1M sulfuric acid aqueous solution (200 mL) and saturated brine (300 ml) in sequence, and then dried over anhydrous sodium sulfate, filtered, and concentrated to obtain compound 549.1 g with a yield of 98.0%.

[0115] HPLC analysis results showed that in the product, the molar proportion of triester (5-12-3) was 5%, the molar proportion of diester (5-12-2) was 85%, and the molar proportion of monoester (5-12-1) was 10%.

[0116] 1 H-NMR (500 MHz, CDCl3): δ 5.00-4.50 (m, 2H, hydrogen on the same carbon as the ester), 4.15-3.90 (m, 2H), 3.80-3.10 (m, 9H), 2.40-2.25 (m, 4H), 1.90-1.12 (m, 41H), 0.87 (s, 6H).

[0117] Saponification value: 205 (theoretical value: 202).

[0118] Example 5 Synthesis of lauric acid monolaurate (5-12-1)

[0119]

[0120] Add 150 mL of anhydrous pyridine to a reaction flask, then add compound 3 (19.0 g, 0.1 mol) with stirring to dissolve the mixture. Cool the mixture to 10°C, then add lauroyl chloride (24.1 g, 0.11 mol) dropwise. Maintain the reaction temperature below 15°C during the addition. After completion, warm the mixture to 25°C and react for 1 h. Remove the pyridine by distillation under reduced pressure, then add ethyl acetate (200 mL), stir thoroughly, and separate the lower layer. Wash the upper layer sequentially with 1M aqueous sulfuric acid (100 mL), purified water (100 mL), and saturated brine (100 mL). Dry the mixture over anhydrous sodium sulfate, filter, and concentrate to yield 31.7 g of compound 4 (85% yield).

[0121] The obtained compound 4 was dissolved in isopropanol (300 L), and sodium borohydride (3.8 g, 0.1 mol) was added. After reacting at room temperature for 2 hours, the isopropanol was removed under reduced pressure, and ethyl acetate (200 ml) was added. The mixture was stirred evenly, and the lower layer solution was separated. The upper layer solution was washed with 1M aqueous sulfuric acid solution (100 mL) and saturated brine (100 ml), dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 30.2 g of compound 5 with a yield of 95.0%.

[0122] HPLC analysis results showed that in the product, the molar proportion of triester (5-12-3) was 2%, the molar proportion of diester (5-12-2) was 15%, and the molar proportion of monoester (5-12-1) was 83%.

[0123] 1 H-NMR (500 MHz, CDCl3) δ 5.00-4.50 (m, 1H, hydrogen on the same carbon as the ester), 4.15-3.90 (m, 3H), 3.80-3.10 (m, 5H), 2.40-2.25 (m, 2H), 1.90-1.12 (m, 24H), 0.87 (s, 3H).

[0124] Saponification value: 155 (theoretical value: 150).

[0125] Example 6-8 Synthesis of trioctanoic acid benzoin ester (5-8-3), dioctanoic acid benzoin ester (5-8-2), and monooctanoic acid benzoin ester (5-8-1)

[0126] According to the steps of Example 3-5, octanoyl chloride was used instead of lauroyl chloride to synthesize trioctanoic acid benzoyl ester (5-8-3), dioctanoic acid benzoyl ester (5-8-2), and monooctanoic acid benzoyl ester (5-8-1).

[0127] ;

[0128] Trioctanoate bosaicin (5-8-3): Two-step yield 92%, HPLC purity 98.6%.

[0129] 1 H-NMR (500MHz, CDCl3): δ5.30-5.26(m,1H), 5.00-4.87(m,2H), 4.20-4.12(m,1H), 4.10-3.95(m ,1H), 3.70-3.50(m,2H), 3.28-3.16(m,1H), 2.30-2.15(m,6H), 1.86-1.12(m,35H), 0.87(s,9H).

[0130] Saponification value: 300 (theoretical value: 294).

[0131] Bosaicin dioctanoate (5-8-2): The two-step yield was 88%. HPLC analysis showed that the molar proportion of triester (5-8-3) was 6%, the molar proportion of diester (5-8-2) was 86%, and the molar proportion of monoester (5-8-1) was 8%.

[0132] 1 H-NMR (500 MHz, CDCl3): δ 5.00-4.50 (m, 2H, hydrogen on the same carbon as the ester), 4.15-3.90 (m, 2H), 3.80-3.10 (m, 4H), 2.40-2.25 (m, 4H), 1.90-1.12 (m, 26H), 0.87 (s, 6H).

[0133] Saponification value: 255 (theoretical value: 252).

[0134] Monooctanoic acid bosaicin ester (5-8-1): two-step yield 82%. HPLC analysis showed that the molar proportion of triester (5-8-3) was 3%, the molar proportion of diester (5-8-2) was 12%, and the molar proportion of monoester (5-8-1) was 85%.

[0135] 1 H-NMR (500 MHz, CDCl3): δ 5.00-4.50 (m, 1H, hydrogen on the same carbon as the ester), 4.15-3.90 (m, 3H), 3.80-3.10 (m, 6H), 2.40-2.25 (m, 2H), 1.90-1.12 (m, 17H), 0.87 (s, 3H).

[0136] Saponification value: 179 (theoretical value: 176).

[0137] Example 9-11 Synthesis of tripalmitoyl benzoate (5-16-3), dipalmitoyl benzoate (5-16-2), and monopalmitoyl benzoate (5-16-1)

[0138] According to the steps of Example 3-5, palmitoyl chloride was used instead of lauroyl chloride to synthesize tripalmitoyl bosaicin (5-16-3), dipalmitoyl bosaicin (5-16-2), and monopalmitoyl bosaicin (5-16-1).

[0139] ;

[0140] Bosaicin tripalmitate (5-16-3): Two-step yield 94%, HPLC purity 98.5%.

[0141] 1 H-NMR (500MHz, CDCl3): δ5.30-5.26(m,1H), 5.00-4.87(m,2H), 4.20-4.12(m,1H), 4.10-3.95(m ,1H), 3.70-3.50(m,2H), 3.28-3.16(m,1H), 2.30-2.15(m,6H), 1.86-1.12(m,83H), 0.87(s,9H).

[0142] Saponification value: 187 (theoretical value: 185).

[0143] Bosaicin dipalmitate (5-16-2): Two-step yield 85%. HPLC analysis showed that the molar proportion of triester (5-16-3) was 10%, the molar proportion of diester (5-16-2) was 84%, and the molar proportion of monoester (5-16-1) was 6%.

[0144] 1 H-NMR (500 MHz, CDCl3): δ 5.00-4.50 (m, 2H, hydrogen on the same carbon as the ester), 4.15-3.90 (m, 2H), 3.80-3.10 (m, 5H), 2.40-2.25 (m, 4H), 1.90-1.12 (m, 55H), 0.87 (s, 6H).

[0145] Saponification value: 170 (theoretical value: 167).

[0146] Monopalmitic acid bosaicin ester (5-16-1): The two-step yield is 85%. HPLC analysis shows that the molar proportion of triester (5-16-3) is 3%, the molar proportion of diester (5-16-2) is 10%, and the molar proportion of monoester (5-16-1) is 87%.

[0147] 1H-NMR (500 MHz, CDCl3): δ 5.00-4.50 (m, 1H, hydrogen on the same carbon as the ester), 4.15-3.90 (m, 3H), 3.80-3.10 (m, 5H), 2.40-2.25 (m, 2H), 1.90-1.12 (m, 30H), 0.87 (s, 3H).

[0148] Saponification value: 131 (theoretical value: 130).

[0149] Example 12-14 Synthesis of trioleyl bosaicin (5-18o-3), dioleyl bosaicin (5-18o-2), and monooleyl bosaicin (5-18o-1)

[0150] According to the steps of Example 3-5, oleoyl chloride was used instead of lauroyl chloride to synthesize trioleyl bosaicin (5-18o-3), dioleyl bosaicin (5-18o-2), and monooleyl bosaicin (5-18o-1).

[0151] ;

[0152] Bosaicin trioleate (5-18o-3): Two-step yield 90%, HPLC purity 98.7%.

[0153] 1 H-NMR (500MHz, CDCl3): δ5.4-5.35(m,6H), 5.30-5.26(m,1H), 5.00-4.87(m,2H), 4.20-4.12(m,1H), 4.10 -3.95(m,1H), 3.70-3.50(m,2H), 3.28-3.16(m,1H), 2.40-2.00(m,18H), 1.86-1.12(m,71H), 0.87(s,9H).

[0154] Saponification value: 175 (theoretical value: 170).

[0155] Bosaicin dioleate (5-18o-2): Two-step yield 87%. HPLC analysis showed that the molar proportion of triester (5-18o-3) was 12%, the molar proportion of diester (5-18o-2) was 80%, and the molar proportion of monoester (5-18o-1) was 8%.

[0156] 1H-NMR (500 MHz, CDCl3) δ 5.4-5.30 (m, 4H), 5.00-4.50 (m, 2H, hydrogen on the same carbon as the ester), 4.15-3.90 (m, 2H), 3.80-3.10 (m, 5H), 2.40-2.00 (m, 12H), 1.86-1.12 (m, 49H), 0.87 (s, 6H).

[0157] Saponification value: 158 (theoretical value: 156).

[0158] Bosaiin monooleate (5-18o-1): Two-step yield 87%. HPLC analysis showed that the molar proportion of triester (5-18o-3) was 4%, the molar proportion of diester (5-18o-2) was 10%, and the molar proportion of monoester (5-18o-1) was 86%.

[0159] 1 H-NMR (500 MHz, CDCl3) δ 5.4-5.30 (m, 2H), 5.00-4.50 (m, 1H, hydrogen on the same carbon as the ester), 4.15-3.90 (m, 3H), 3.80-3.10 (m, 5H), 2.40-2.00 (m, 6H), 1.86-1.12 (m, 29H), 0.87 (s, 3H).

[0160] Saponification value: 128 (theoretical value: 123).

[0161] Example 15-17 Synthesis of tris(2-hexyldecanoate) bosaiin ester (5-16g-3), bis(2-hexyldecanoate) bosaiin ester (5-16g-2), and mono(2-hexyldecanoate) bosaiin ester (5-16g-1)

[0162] According to the steps of Example 3-5, tri(2-hexyldecanoate) bosaicin (5-16g-3), bis(2-hexyldecanoate) bosaicin (5-16g-2), and mono(2-hexyldecanoate) bosaicin (5-16g-1) were synthesized using 2-hexyldecanoyl chloride instead of lauroyl chloride.

[0163] ;

[0164] Tris(2-hexyldecanoate) bosaicin (5-16g-3): two-step yield 87%, HPLC 98.2%.

[0165] 1H-NMR (500MHz, CDCl3): δ5.30-5.26(m,1H), 5.00-4.87(m,2H), 4.20-4.12(m,1H), 4.10-3.95(m, 1H), 3.70-3.50(m,2H), 3.28-3.16(m,1H), 2.35-2.15(m,3H), 1.86-1.12(m,77H), 0.87(s,18H).

[0166] Saponification value: 189 (theoretical value: 185).

[0167] Bis(2-hexyldecanoate) bosaicin ester (5-16g-2): The two-step yield is 86%. HPLC analysis shows that the molar proportion of triester (5-16g-3) is 5%, the molar proportion of diester (5-16g-2) is 90%, and the molar proportion of monoester (5-16g-1) is 5%.

[0168] 1 H-NMR (500 MHz, CDCl3): δ 5.00-4.50 (m, 2H, hydrogen on the same carbon as the ester), 4.15-3.90 (m, 2H), 3.80-3.10 (m, 5H), 2.40-2.25 (m, 2H), 1.90-1.12 (m, 53H), 0.87 (s, 12H).

[0169] Saponification value: 169 (theoretical value: 167).

[0170] Mono(2-hexyldecanoate) bosaicin ester (5-16g-1): two-step yield 82%. HPLC analysis showed that the molar proportion of triester (5-16g-3) was 3%, the molar proportion of diester (5-16g-2) was 9%, and the molar proportion of monoester (5-16g-1) was 88%.

[0171] 1 H-NMR (500 MHz, CDCl3): δ 5.00-4.50 (m, 1H, hydrogen on the same carbon as the ester), 4.15-3.90 (m, 3H), 3.80-3.10 (m, 5H), 2.40-2.25 (m, 1H), 1.90-1.12 (m, 30H), 0.87 (s, 6H).

[0172] Saponification value: 134 (theoretical value: 130).

[0173] Comparative Example 1 Synthesis of lauric acid laurate (S-12-3) using lauric acid as raw material

[0174] S-12-3 is a mixture of the following four types of bosaicin trilaurate:

[0175]

[0176] Anhydrous pyridine (300 mL) was added to a reaction flask. Bosylamine (19.2 g, 0.1 mol) was added with stirring to dissolve the mixture. The temperature was then cooled to 10°C. Lauryl chloride (67.6 g, 0.3 mol) was added dropwise, maintaining the reaction temperature below 15°C. After addition, the temperature was raised to 25°C and the reaction was allowed to proceed for 1 h. Pyridine was removed by distillation under reduced pressure. Ethyl acetate (300 mL) was added and stirred thoroughly. The lower layer was separated. The upper layer was washed sequentially with 1M aqueous sulfuric acid (200 mL), purified water (200 mL), and saturated brine (200 mL). The mixture was then dried over anhydrous sodium sulfate, filtered, and concentrated to yield 62.8 g of bosylamine trilaurate (85% yield).

[0177] HPLC analysis showed that the molar proportion of triester (S-12-3) was 88% (of which 5-12-3 was 18%), the molar proportion of tetraester was 4%, the molar proportion of diester (S-12-2) was 5%, and the molar proportion of monoester (S-12-1) was 3%.

[0178] Saponification value: 231 (theoretical value: 228).

[0179] 1 H-NMR (500MHz, CDCl3) δ5.30-4.50(m,3H), 4.25-3.10(m,5H), 2.40-2.10(m,6H), 1.80-1.12(m,59H), 0.87(s,9H).

[0180] Comparative Example 2: Synthesis of bis(lauric acid) bis(lauric acid) ester (S-12-2) using bis(lauric acid) as raw material

[0181] S-12-2 is a mixture of the following six types of bosaicin dilaurate esters:

[0182]

[0183] Anhydrous pyridine (250 mL) was added to a reaction flask. Bosylamine (19.2 g, 0.1 mol) was added with stirring to dissolve the mixture. The temperature was lowered to 10°C, and lauroyl chloride (45.8 g, 0.2 mol) was added dropwise. The reaction temperature was maintained below 15°C during the addition. After completion, the temperature was raised to 25°C and the reaction was allowed to proceed for 1 h. Pyridine was removed by distillation under reduced pressure. Ethyl acetate (300 mL) was added and stirred thoroughly. The lower layer was separated and the upper layer was washed sequentially with 1M aqueous sulfuric acid (200 mL), purified water (200 mL), and saturated brine (200 mL). The mixture was then dried over anhydrous sodium sulfate, filtered, and concentrated to yield 44.5 g of bosylamine dilaurate (80% yield).

[0184] HPLC analysis showed that the molar proportion of diesters 5-12-2-a to 5-12-2-c was 42%, the molar proportion of 5-12-2-p1 to 5-12-2-p3 was 45%, the molar proportion of tetraester was 2%, the molar proportion of triester (S-12-3) was 5%, and the molar proportion of monoester (S-12-1) was 6%.

[0185] 1 H-NMR (500 MHz, CDCl3) δ 5.10-4.30 (m, 2H, hydrogen on the same carbon as the ester), 4.15-3.10 (m, 6H), 2.40-2.25 (m, 5H), 1.90-1.12 (m, 41H), 0.87 (s, 6H).

[0186] Saponification value: 210 (theoretical value: 202).

[0187] Comparative Example 3: Synthesis of lauric acid botoxime ester (S-12-1) using botoxime as raw material

[0188] S-12-1 is a mixture of the following four types of monolaurate esters:

[0189]

[0190] Add 150 mL of anhydrous pyridine to a reaction flask, then add borax (19.2 g, 0.1 mol) with stirring to dissolve the mixture. Cool the mixture to 10°C, then add lauroyl chloride (24.1 g, 0.1 mol) dropwise. Maintain the reaction temperature below 15°C during the addition. After completion, warm the mixture to 25°C and react for 1 hour. Remove the pyridine by distillation under reduced pressure, add ethyl acetate (200 mL), stir thoroughly, and separate the lower layer. Wash the upper layer sequentially with 1M aqueous sulfuric acid (100 mL), purified water (100 mL), and saturated brine (100 mL). Dry the mixture over anhydrous sodium sulfate, filter, and concentrate to obtain 31.7 g of borax monolaurate (78% yield).

[0191] HPLC analysis showed that the molar proportion of 5-12-1-a to 5-12-1-c was 80%, the molar proportion of 5-12-1-p was 15%, the molar proportion of tetraester was 0.5%, the molar proportion of triester (S-12-3) was 1.5%, and the molar proportion of diester (S-12-2) was 3.0%.

[0192] 1 H-NMR (500 MHz, CDCl3) δ 5.00-4.30 (m, 1H, hydrogen on the same carbon as the ester), 4.15-3.85 (m, 3H), 3.80-3.10 (m, 5H), 2.40-2.25 (m, 2H), 1.90-1.12 (m, 24H), 0.87 (s, 3H).

[0193] Saponification value: 154 (theoretical value: 150).

[0194] Comparative Example 4-6: Using bosin as raw material, trioctanoic acid bosin ester (S-8-3), dioctanoic acid bosin ester (S-8-2) and monooctanoic acid bosin ester (S-8-1) were synthesized.

[0195] According to the steps of Comparative Examples 1-3, octanoyl chloride was used instead of lauroyl chloride to synthesize trioctanoate (S-8-3), dioctanoate (S-8-2) and monooctanoate (S-8-1).

[0196] ;

[0197] Trioctanoic acid bosaicin ester (S-8-3): yield 92%. HPLC analysis showed that the molar proportion of triester (S-8-3) was 84% ​​(of which 5-8-3 was 12%), the molar proportion of tetraester was 6%, the molar proportion of diester (S-8-2) was 8%, and the molar proportion of monoester (S-8-1) was 2%.

[0198] 1 H-NMR (500MHz, CDCl3) δ5.35-3.12(m,8H), 2.50-2.00(m,6H), 1.86-1.12(m,35H), 0.87(s,9H).

[0199] Saponification value: 297 (theoretical value: 294).

[0200] Bosaicin dioctanoate (S-8-2): Yield 88%. HPLC analysis showed that the molar proportion of the tetraester was 2%, the molar proportion of the triester (S-8-3) was 8%, the molar proportion of the diester (S-8-2) was 80% (of which 5-8-2 was 45%), and the molar proportion of the monoester (S-8-1) was 10%.

[0201] 1 H-NMR (500 MHz, CDCl3) δ 5.00-4.50 (m, 2H, hydrogen on the same carbon as the ester), 4.16-3.80 (m, 2H), 3.80-3.00 (m, 4H), 2.40-2.25 (m, 4H), 1.90-1.12 (m, 26H), 0.87 (s, 6H).

[0202] Saponification value: 257 (theoretical value: 252).

[0203] Monooctanoic acid bosaicin ester (S-8-1): yield 82%, the molar proportion of the analysis was 2% for the tetraester, 4% for the triester (S-8-3), 8% for the diester (S-8-2), and 86% for the monoester (S-8-1) (of which 5-8-1 accounted for 62%).

[0204] 1 H-NMR (500 MHz, CDCl3) δ 5.00-4.50 (m, 1H, hydrogen on the same carbon as the ester), 4.15-3.90 (m, 3H), 3.80-3.10 (m, 6H), 2.40-2.25 (m, 2H), 1.90-1.12 (m, 17H), 0.87 (s, 3H).

[0205] Saponification value: 179 (theoretical value: 176).

[0206] Comparative Example 7-9: Using phosphene as raw material, phosphene tripalmitate (S-16-3), phosphene dipalmitate (S-16-2) and phosphene monopalmitate (S-16-1) were synthesized.

[0207] According to the steps of Comparative Examples 1-3, palmitoyl chloride was used instead of lauroyl chloride to synthesize tripalmitoyl bosaicin (S-16-3), dipalmitoyl bosaicin (S-16-2) and monopalmitoyl bosaicin (S-16-1).

[0208] ;

[0209] Bosaiin tripalmitate (S-16-3): yield 88%. HPLC analysis showed that the molar proportion of triester (S-16-3) was 87% (of which 5-16-3 was 14%), the molar proportion of tetraester was 5%, the molar proportion of diester (S-16-2) was 7%, and the molar proportion of monoester (S-16-1) was 1%.

[0210] 1 H-NMR (500MHz, CDCl3): δ5.30-5.26(m,1H), 5.00-4.87(m,2H), 4.20-4.12(m,1H), 4.10-3.95(m ,1H), 3.70-3.50(m,2H), 3.28-3.16(m,1H), 2.30-2.15(m,6H), 1.86-1.12(m,83H), 0.87(s,9H).

[0211] Saponification value: 187 (theoretical value: 185).

[0212] Bosaicin dipalmitate (S-16-2): yield 85%. HPLC analysis showed that the molar proportion of the tetraester was 2%, the molar proportion of the triester (S-16-3) was 7%, the molar proportion of the diester (S-16-2) was 84% ​​(of which 5-16-2 was 42%), and the molar proportion of the monoester (S-16-1) was 11%.

[0213] 1 H-NMR (500 MHz, CDCl3) δ 5.00-4.50 (m, 2H, hydrogen on the same carbon as the ester), 4.20-3.90 (m, 2H), 3.80-3.10 (m, 5H), 2.40-2.25 (m, 4H), 1.90-1.12 (m, 55H), 0.87 (s, 6H).

[0214] Saponification value: 170 (theoretical value: 167).

[0215] Monopalmitic acid bosaicin ester (S-16-1): yield 80%. HPLC analysis showed that the molar proportion of the tetraester was 1%, the molar proportion of the triester (S-16-3) was 3%, the molar proportion of the diester (S-16-2) was 10%, and the molar proportion of the monoester (S-16-1) was 86% (of which 5-16-1 accounted for 64.5%).

[0216] 1 H-NMR (500 MHz, CDCl3) δ 5.00-4.50 (m, 1H, hydrogen on the same carbon as the ester), 4.25-3.90 (m, 3H), 3.80-3.00 (m, 5H), 2.40-2.25 (m, 2H), 1.90-1.12 (m, 30H), 0.87 (s, 3H).

[0217] Saponification value: 131 (theoretical value: 130).

[0218] Comparative Examples 10-12: Using bosin as raw material, trioleate bosin (S-18o-3), dioleate bosin (S-18o-2) and monooleate bosin (S-18o-1) were synthesized.

[0219] According to the steps of Comparative Examples 1-3, oleoyl chloride was used instead of lauroyl chloride to synthesize trioleyl bosaicin (S-18o-3), dioleyl bosaicin (S-18o-2) and monooleyl bosaicin (S-18o-1).

[0220] ;

[0221] Bosaiin trioleate (S-18o-3): yield 92%. HPLC analysis showed that the molar proportion of triester (S-18o-3) was 84% ​​(of which 5-18o-3 was 11%), the molar proportion of tetraester was 6%, the molar proportion of diester (S-18o-2) was 8%, and the molar proportion of monoester (S-18o-1) was 2%.

[0222] 1 H-NMR (500MHz, CDCl3) δ5.5-3.16(m,14H), 2.50-2.00(m,18H), 1.86-1.12(m,71H), 0.87(s,9H).

[0223] Saponification value: 178 (theoretical value: 170).

[0224] Bosaicin dioleate (S-18o-2): yield 90%. HPLC analysis showed that the molar proportion of tetraester was 2%, the molar proportion of triester (S-18o-3) was 10%, the molar proportion of diester (S-18o-2) was 85% (of which 5-18o-2 was 45%), and the molar proportion of monoester (S-18o-1) was 3%.

[0225] 1 H-NMR (500MHz, CDCl3) δ5.4-3.10(m,13H), 2.45-2.00(m,12H), 1.86-1.12(m,49H), 0.87(s,6H).

[0226] Saponification value: 159 (theoretical value: 156).

[0227] Monooleic acid bosacein ester (S-18o-1): yield 87%. HPLC analysis showed that the molar proportion of tetraester was 2%, the molar proportion of triester (S-18o-3) was 6%, the molar proportion of diester (S-18o-2) was 10%, and the molar proportion of monoester (S-18o-1) was approximately 82% (of which 5-18o-1 was 62%).

[0228] 1 H-NMR (500MHz, CDCl3) δ5.4-3.10(m,11H), 2.40-2.00(m,6H), 1.86-1.12(m,29H), 0.87(s,3H).

[0229] Saponification value: 130 (theoretical value: 123).

[0230] Comparative Examples 13-15: Tris(2-hexyldecanoate) bosaicin (S-16g-3), bis(2-hexyldecanoate) bosaicin (S-16g-2), and mono(2-hexyldecanoate) bosaicin (S-16g-1) were synthesized using bosaicin as a raw material.

[0231] According to the steps of Comparative Examples 1-3, tri(2-hexyldecanoate) bosaicin (S-16g-3), bis(2-hexyldecanoate) bosaicin (S-16g-2), and mono(2-hexyldecanoate) bosaicin (S-16g-1) were synthesized using 2-hexyldecanoyl chloride instead of lauroyl chloride.

[0232] ;

[0233] Tris(2-hexyldecanoate) bosacene ester (S-16g-3): yield 87%. HPLC analysis showed that the molar proportion of the tetraester was 3%, the molar proportion of the triester (S-16g-3) was 85% (of which 5-16g-3 was 18%), the molar proportion of the diester (S-16g-2) was 5%, and the molar proportion of the monoester (S-16g-1) was 7%.

[0234] 1 H-NMR (500MHz, CDCl3) δ5.40-3.16(m,8H), 2.40-2.10(m,3H), 1.90-1.12(m,77H), 0.87(s,18H).

[0235] Saponification value: 187 (theoretical value: 185).

[0236] Bis(2-hexyldecanoate) bosacene ester (S-16g-2): yield 86%. HPLC analysis showed that the molar proportion of the tetraester was 1%, the molar proportion of the triester (S-16g-3) was 8%, the molar proportion of the diester (S-16g-2) was 85% (of which 5-16g-2 was 40%), and the molar proportion of the monoester (S-16g-1) was 6%.

[0237] 1 H-NMR (500MHz, CDCl3) δ5.20-3.10(m,9H), 2.40-2.15(m,2H), 1.90-1.12(m,53H), 0.87(s,12H).

[0238] Saponification value: 171 (theoretical value: 167).

[0239] Mono(2-hexyldecanoate) bosacene ester (S-16g-1): yield 83%. HPLC analysis showed that the molar proportion of the tetraester was 1%, the molar proportion of the triester (S-16g-3) was 6%, the molar proportion of the diester (S-16g-2) was 8%, and the molar proportion of the monoester (S-16g-1) was 85% (of which 5-16g-1 accounted for 60.1%).

[0240] 1 H-NMR (500MHz, CDCl3) δ5.40-3.10(m,9H), 2.40-2.25(m,1H), 1.90-1.12(m,30H), 0.87(s,6H).

[0241] Saponification value: 135 (theoretical value: 130).

[0242] Comparative Example 16

[0243] Commercially available bosine, purity ≥99%.

[0244] The following efficacy tests were conducted on the bosaicin esters prepared in Examples 3-17 and Comparative Examples 1-15, as well as the commercially available bosaicin in Comparative Example 16:

[0245] 1. Antioxidant activity detection.

[0246] Weigh 3.9 mg of DPPH and dissolve it in an appropriate amount of anhydrous ethanol. Solubilize it in the dark and completely dissolve it. Use anhydrous ethanol to dilute it to 100 ml to prepare a DPPH working solution with a concentration of 0.1 mmol / L. Prepare a test solution with a concentration of 24 mM using the bosaicin ester or bosaicin of each example and comparative example. The solvent for Examples 3 to 17 and Comparative Examples 1 to 15 is isopropyl myristate, and the solvent for Comparative Example 16 is pure water. First, add 50 μl of the test solution to each sample group in a 96-well plate (add 50 μl of solvent to the blank control group) and then add 200 μl of DPPH working solution (set up a blank background group in which the DPPH working solution is replaced with an equal amount of ethanol). Mix well and react at room temperature in the dark for 2 h. Detect the absorbance of each group at a wavelength of 517 nm using a microplate reader. Calculate the DPPH free radical scavenging rate according to formula (1) based on the absorbance. Set up three replicates for each concentration. The results are shown in Table 1.

[0247] DPPH free radical scavenging rate (%) = (1)

[0248] Where: C1—OD value of blank control group containing DPPH system

[0249] C2—blank background group without DPPH system OD value

[0250] T1—OD value of the sample group containing DPPH system

[0251] T2—OD value of sample group without DPPH system

[0252] Table 1 DPPH free radical scavenging rate of each sample

[0253]

[0254] As shown in Table 1, bosaicin itself has no antioxidant activity, while bosaicin esters connected to the carbon chain have DPPH free radical scavenging ability and antioxidant activity; and different side chains connected to the carbon chain exhibit different DPPH free radical scavenging abilities, among which the bosaicin esters prepared in Examples 12 to 17 exhibited significant DPPH free radical scavenging effects.

[0255] At the same time, the comparison found that the ability of the bosaiin esters prepared in the examples to scavenge DPPH free radicals was better than that of the corresponding comparative examples, and the antioxidant activity was more significantly improved. Compared with the comparative examples, the 8-hydroxyl group of the bosaiin esters prepared in the examples was not esterified, and the structure of the hydroxypropyl group was retained. It can be seen that modifying the hydroxyl group on the bosaiin tetrahydropyran ring with a specific carbon chain while retaining its hydroxypropyl group from being esterified can more significantly improve the antioxidant activity of the obtained bosaiin ester.

[0256] In addition, the more three hydroxyl groups on the tetrahydropyran ring are esterified, the better the antioxidant activity of the resulting bosaicin ester, that is, the antioxidant activity of triester is better than that of diester, and diester is better than that of monoester.

[0257] Detection of zebrafish elastin, hyaluronic acid and type I collagen content (ELISA method)

[0258] The bosaiin esters prepared in Examples 3 to 17 and Comparative Examples 1 to 15, and the bosaiin of Comparative Example 16 were dissolved in an aqueous solution containing 5% isopropyl myristate, 10% Tween 80, 2% polyoxyethylene ether-40 hydrogenated castor oil, and 30% glycerol, and diluted with embryo culture medium (containing 10% NaCl, 0.3% KCl, 0.3% CaCl2, 0.79% MgSO4) to a final concentration of 100 μM to obtain a bosaiin ester solution or a bosaiin solution.

[0259] Normally developed wild-type zebrafish embryos (AB) at 72 hpf were randomly selected and plated in 48-well plates. Three parallel groups were set up per well, with 15 embryos per well. 500 μl of either borax ester solution or borax solution was added to each well of each sample group. The blank control group was treated with 500 μl of embryo culture medium containing an equal amount of solvent. The cells were then incubated in a dark incubator at 28 ± 1°C for 24 h. The embryos were collected and washed with embryo culture medium. Each group was then ground with 1 ml of phosphate buffer solution and centrifuged at 1000 rpm for 20 min. The supernatant was then assayed for elastin, hyaluronic acid, and type I collagen levels according to the ELISA kit instructions. The expression upregulation rate (%) of each indicator was calculated using formula (2).

[0260] Expression upregulation rate (%) = (2)

[0261] In formula (2):

[0262] Ve—the content of elastin, hyaluronic acid or type I collagen in the sample group;

[0263] Vc—the content of elastin, hyaluronic acid or type I collagen in the blank control group.

[0264] Table 2 Up-regulation rate of elastin expression in embryos of each group (%)

[0265] ;

[0266] Table 3 Up-regulation rate of hyaluronic acid expression in embryos of each group (%)

[0267]

[0268] Table 4 Up-regulation rate of type Ⅰ collagen expression in embryos of each group (%)

[0269]

[0270] The experimental results in Tables 2 to 4 show that compared with benzophenone (Comparative Example 16), benzophenone esters that are connected to one or more carbon chains through esterification of the hydroxyl group on the tetrahydropyran ring of benzophenone can increase the expression of elastin, hyaluronic acid and type I collagen, among which benzophenone esters containing oleate and 2-hexyldecanoate side chains have the most obvious upregulation effect.

[0271] Compared with Comparative Examples 1 to 15, the bosaicin esters prepared in Examples 3 to 17 in which the hydroxypropyl groups were not esterified had stronger abilities to promote the expression of elastin, hyaluronic acid and type I collagen.

[0272] In addition, the more three hydroxyl groups on the tetrahydropyran ring are esterified, the more significant the effect of the resulting bosaicin ester on increasing the expression of elastin, hyaluronic acid and type I collagen, that is, the effect of triester is better than diester, and diester is better than monoester.

[0273] The above results show that the prepared bosaicin ester of the present invention has better antioxidant, moisturizing and firming and anti-wrinkle effects than bosaicin and bosaicin ester with hydroxypropyl ester.

[0274] The above-described embodiments merely illustrate several implementations of the present invention, and while their descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the patent. It should be noted that a person skilled in the art would be able to make numerous variations and improvements without departing from the spirit of the present invention, all of which fall within the scope of protection of the present invention. Therefore, the scope of protection of the patent for this invention shall be determined by the appended claims.

Claims

1. A bosaicin ester, characterized in that The structural formula of the bosaicin ester is shown in formula (I): （I） wherein each R1 is independently selected from: hydrogen, -C(=O)R, and at least one R1 is -C(=O)R; R is selected from: C 15 Branched alkyl, C containing a carbon-carbon double bond 17 Unsaturated chain hydrocarbon group.

2. The bosaicin ester according to claim 1, characterized in that The structural formula of the bosaicin ester is shown in Formula (I-1), Formula (I-2), Formula (I-3), Formula (I-4), Formula (I-5), Formula (I-6) or Formula (I-7): 。 3. The bosaicin ester according to claim 1 or 2, characterized in that R is selected from: 1-hexyl-nonyl, -(CH2)7(CH=CH)(CH2)7CH3.

4. The bosaicin ester according to claim 1, characterized in that The bosaicin ester is selected from the following compounds: 。 5. A bosaicin ester composition, characterized in that The invention is composed of two or more compounds of the bosaicin ester according to any one of claims 1 to 4.

6. The bosaicin ester composition according to claim 5, characterized in that The bosaicin ester composition contains a bosaicin ester having a structure represented by formula (I-1), and the molar ratio of the bosaicin ester having a structure represented by formula (I-1) in the bosaicin ester composition is greater than 2%.

7. The bosaicin ester composition according to claim 6, characterized in that The molar ratio of the bosaicin ester having the structure represented by formula (I-1) in the bosaicin ester composition is greater than 90%.

8. The bosaicin ester composition according to claim 5, characterized in that The bosaicin ester composition contains bosaicin esters having structures represented by formula (I-2), formula (I-3) and / or formula (I-4), and the total amount of bosaicin esters having structures represented by formula (I-2), formula (I-3) and formula (I-4) in the bosaicin ester composition has a molar ratio of greater than 70%.

9. The bosaicin ester composition according to claim 8, characterized in that The total amount of the bosaicin esters having the structures represented by formula (I-2), formula (I-3) and formula (I-4) in the bosaicin ester composition has a molar ratio of 75% to 95%.

10. Use of the bosaicin ester according to any one of claims 1 to 4, or the bosaicin ester composition according to any one of claims 5 to 9, as an effective ingredient in the preparation of antioxidant cosmetics.

11. Use of the bosaicin ester according to any one of claims 1 to 4, or the bosaicin ester composition according to any one of claims 5 to 9, as an effective ingredient in the preparation of cosmetics capable of moisturizing, firming the skin and / or anti-wrinkle.

12. Use of the bosaicin ester according to any one of claims 1 to 4, or the bosaicin ester composition according to any one of claims 5 to 9 as an effective ingredient in the preparation of cosmetics, characterized in that: The cosmetic can increase the content of elastin, hyaluronic acid and / or type I collagen in cells.

13. A cosmetic, characterized in that: The effective ingredients of the cosmetics contain the bosaicin ester according to any one of claims 1 to 4, or the bosaicin ester composition according to any one of claims 5 to 9.

14. A method for preparing the bosaicin ester according to any one of claims 1 to 4, characterized in that: The steps include: (1) Compound 1 reacts with compound 2 to obtain compound 3; (2) Esterifying compound 3 to obtain compound 4; (3) Reducing the carbonyl group in compound 4 to obtain the bosaicin ester of the structure shown in formula (I); The reaction formula is as follows: wherein R1 is as described in any one of claims 1 to 4.

Images