Oil-soluble glassine ester with anti-oxidation, firming and anti-wrinkle effects as well as preparation method and application of oil-soluble glassine ester

Abstract

The invention relates to glassine ester as well as a preparation method and application thereof. The structural formula of the glassine ester is shown as a formula (I), each R1 is independently selected from hydrogen and-C (= O) R, and at least one R1 is-C (= O) R; r is selected from C7-C21 alkyl groups and C7-C21 unsaturated chain alkyl groups. The glassine ester has a remarkable DPPH free radical scavenging effect, can remarkably improve expression of elastin, hyaluronic acid and I-type collagen in cells, and has excellent effects of oxidation resistance, moisturizing and / or tightening and wrinkle resistance when being added into cosmetics as a functional component. # imgabs0 #

Description

Technical Field

[0001] The present invention belongs to the technical field of cosmetics, relates to skin care products, and specifically relates to hydroxyproxylane esters, their preparation methods and applications. Background Art

[0002] Hydroxyproxylane (Pro-Xylane), whose full name is (2S,3R,4S,5R)-2-(2-hydroxypropyl)tetrahydro-2H-pyran-3,4,5-triol, also known as hydroxypropyltetrahydropyran triol (CAS No. 439685-79-7), is a xylose derivative derived from natural xylose and having anti-wrinkle activity. It can induce the biosynthesis of GAGs mucopolysaccharides and PG proteoglycans in the superficial epidermis, and promote the production of hyaluronic acid. In addition, it can also improve the adhesion between the dermis and the epidermis, promote the synthesis of collagen and elastin, regenerate damaged tissues, maintain the elasticity of the dermis, and prevent skin aging. Therefore, hydroxyproxylane is widely used in technical fields such as cosmetics, food, biology, and medicine.

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

[0004] Among them, X is selected from a hydrogen atom or C 1 -C 18 alkyl, etc., R' independently is selected from H or -COR", and R" independently represents a hydrogen atom or C 1 -C 18 alkyl; and the four groups R' are not simultaneously hydrogen atoms.

[0005] FR2999076A1 discloses a preparation method of hydroxyproxylane esters, which is obtained by reacting hydroxyproxylane and acyl chloride in a certain proportion. Since the 4 hydroxyl groups of hydroxyproxylane are all secondary alcohols, the reaction activities are less different when esterifying with acyl chloride, the esterification position cannot be determined, and the obtained esterification product is a mixture with complex components, and the ratio of different esters in the mixture cannot be guaranteed, which will affect its actual efficacy in cosmetics. Summary of the Invention

[0006] Based on this, the present invention provides an oil-soluble hydroxyproxylane ester, which has better antioxidant, moisturizing and firming and anti-wrinkle effects compared with hydroxyproxylane.

[0007] The present invention includes the following technical solutions.

[0008] In the first aspect, the present invention provides a bosicain ester or its stereoisomer, and the structural formula of the bosicain ester is shown as formula (I):

[0009] wherein each R 1 is independently selected from: hydrogen, -C(=O)R, and at least one R 1 is -C(=O)R; R is selected from: C 7 ~C 17 alkyl, C 7 ~C 17 unsaturated hydrocarbon radical.

[0010] In the second aspect, the present invention provides a bosicain ester composition, which is composed of two or more compounds of the bosicain ester or its stereoisomer described in the present invention.

[0011] In the third aspect, the present invention provides the use of the bosicain ester or its stereoisomer described in the present invention, or the bosicain ester composition as an active ingredient in the preparation of antioxidant cosmetics.

[0012] In the fourth aspect, the present invention provides the use of the bosicain ester or its stereoisomer described in the present invention, or the bosicain ester composition as an active ingredient in the preparation of cosmetics capable of moisturizing, firming the skin and / or anti-wrinkle.

[0013] In the fifth aspect, the present invention provides a cosmetic, and the active ingredient of the cosmetic contains the bosicain ester or its stereoisomer described in the present invention, or the bosicain ester composition.

[0014] In the sixth aspect, the present invention provides a preparation method of the bosicain ester, including the following steps: (1) React compound 1 with compound 2 to obtain compound 3; (2) Esterify compound 3 to obtain compound 4; (3) Reduce the carbonyl group in compound 4 to obtain the bosicain ester with the structure shown in formula (I); The reaction formula is as follows: ;

[0015] wherein each R 1 is independently selected from: hydrogen, -C(O)R, and at least one R 1 is -C(O)R; R is selected from: C 7 ~C 21 alkyl, C 7 ~C 21 unsaturated hydrocarbon radical.

[0016] The present invention has the following beneficial effects: For the hydroxyprogesterone acetate prepared by the present invention, the hydroxyl group at the 8th position is not esterified, and the hydroxypropyl group is retained. Through a large number of experimental studies, the present invention has found that while modifying the hydroxyl group on the tetrahydropyran ring of hydroxyprogesterone with a specific carbon chain, the hydroxypropyl group is retained without being esterified (i.e., the hydroxyl group at the 8th position is not esterified). The obtained hydroxyprogesterone acetate has better antioxidant, moisturizing, and firming and anti-wrinkle effects compared to hydroxyprogesterone and hydroxyprogesterone acetate with the hydroxyl group at the 8th position esterified.

[0017] The hydroxyprogesterone acetate of the present invention has a significant DPPH free radical scavenging effect, can significantly increase the expression of elastin, hyaluronic acid, and type I collagen in cells, and has excellent antioxidant, moisturizing, and / or firming and anti-wrinkle effects when added as an active ingredient to cosmetics.

[0018] The hydroxyprogesterone acetate of the present invention has good oil solubility and can be well dissolved in common oils used in cosmetics, such as isopropyl myristate, squalane, isocetane, etc. Detailed implementation manners

[0019] To facilitate the understanding of the present invention, the present invention will be described more comprehensively 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 disclosed content of the present invention more thorough and comprehensive.

[0020] For the experimental methods without specific conditions noted in the following embodiments, they are usually in accordance with conventional conditions or the conditions recommended by the manufacturer. All kinds of common chemical reagents used in the embodiments are commercially available products.

[0021] Unless otherwise defined, all technical and scientific terms used in the present invention have the same meaning as commonly understood by those skilled in the technical field to which the present invention belongs. The terms used in the description of the present invention are only for the purpose of describing specific embodiments and are not used to limit the present invention. The term "and / or" used in the present invention includes any and all combinations of one or more of the related listed items.

[0022] In addition, as used in the present invention, the term "or" is an inclusive "or" symbol and is equivalent to the term "and / or", unless the context clearly stipulates otherwise. The term "based on" is not exclusive and allows for other factors not described, unless the context clearly stipulates otherwise. In addition, throughout the specification, the meanings of "a", "an", and "the" include plural referents. The meaning of "in..." includes "in..." and "on...".

[0023] The term "alkyl" in the present invention refers to branched and straight-chain saturated aliphatic hydrocarbon groups including those having a specific number of carbon atoms. For example: "C 1 -C 6 alkyl" in which the definition of "C 1 -C 6 " includes groups having 1, 2, 3, 4, 5 or 6 carbon atoms arranged in a straight-chain or branched-chain manner. For example: "C 1 -C 6 alkyl" specifically includes methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, pentyl, hexyl.

[0024] The term "unsaturated 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 containing one or more carbon-carbon double bonds or carbon-carbon triple bonds in the carbon chain, such as: -(CH 2 ) 7 (CH=CH)(CH 2 ) 7 CH 3 ,-(CH 2 ) 8 (CH=CH)(CH 2 ) 5 CH 3 ,-(CH 2 ) 8 (CH=CH)(CH 2 ) 7 CH 3 ,-(CH 2 ) 8 (CH=CH)(CH 2 ) 6 CH 3 ,-(CH 2 ) 8 (CH=CH)CH 2 (CH=CH)(CH 2 ) 2 CH 3 ,-(CH 2 ) 8 (CH=CH)CH 2 (CH=CH)(CH 2 ) 4 CH 3 ,-(CH 2 ) 8 (CH=CH)CH 2 (CH=CH)(CH 2 ) 6 CH 3 etc.

[0025] In some of these embodiments, it relates to a bosicerin ester or its stereoisomer, and the structural formula of the bosicerin ester is shown as formula (I):

[0026] Wherein each R 1 is independently selected from: hydrogen, -C(=O)R, and at least one R 1 is -C(=O)R; R is selected from: C 7 ~C 17 alkyl, C 7 ~C 17 unsaturated hydrocarbon group.

[0027] In some of these embodiments, the 3 Rs in formula (I) 1 are all -C(O)R.

[0028] In some of these embodiments, any 2 Rs in formula (I) 1 are all -C(O)R, and 1 R 1 is hydrogen.

[0029] In some of these embodiments, any 1 R in formula (I) 1 is -C(O)R, and 2 Rs 1 are hydrogen.

[0030] In some of these embodiments, the structural formula of the bosicerin ester is shown as formula (I-1), formula (I-2), formula (I-3), formula (I-4), formula (I-5), formula (I-6) or formula (I-7):

[0031] In some of these embodiments, R is selected from: C 7 alkyl, C 8 alkyl, C 9 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, C 7 unsaturated hydrocarbon group containing one or two carbon-carbon double bonds, C 8 unsaturated hydrocarbon group containing one or two carbon-carbon double bonds, C 9 unsaturated hydrocarbon group containing one or two carbon-carbon double bonds, C 10 unsaturated hydrocarbon group containing one or two carbon-carbon double bonds, C 11Unsaturated hydrocarbon group, C with one or two carbon-carbon double bonds 12 Unsaturated hydrocarbon group, C with one or two carbon-carbon double bonds 13 Unsaturated hydrocarbon group, C with one or two carbon-carbon double bonds 14 Unsaturated hydrocarbon group, C with one or two carbon-carbon double bonds 15 Unsaturated hydrocarbon group, C with one or two carbon-carbon double bonds 16 Unsaturated hydrocarbon group, C with one or two carbon-carbon double bonds 17 Unsaturated hydrocarbon group.

[0032] 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, -(CH 2 ) 8 (CH=CH)(CH 2 ) 5 CH 3 、-(CH 2 ) 7 (CH=CH)(CH 2 ) 7 CH 3 、-(CH 2 ) 9 (CH=CH)(CH 2 ) 5 CH 3 。

[0033] In some preferred embodiments, R is selected from: C 15 Branched alkyl group, C with one carbon-carbon double bond 17 Unsaturated hydrocarbon group.

[0034] In some embodiments, the bosic acid ester is selected from the following compounds: ; ; ; ; ; ; ; ; ; 。

[0035] The hydroxy group at the 8-position of the hydroxyproline ester prepared by the present invention is not esterified, and the hydroxypropyl group is retained. Through a large number of experimental studies, the present invention finds that while modifying the hydroxy group on the tetrahydropyran ring of hydroxyproline with a specific carbon chain, the hydroxypropyl group is retained without being esterified (i.e., the hydroxy group at the 8-position is not esterified). The obtained hydroxyproline ester has better antioxidant, moisturizing, and firming and anti-wrinkle effects compared to hydroxyproline and the hydroxyproline ester with the 8-position hydroxy group esterified.

[0036] The hydroxyproline ester of the present invention has a significant DPPH free radical scavenging effect, can significantly increase the expression of elastin, hyaluronic acid, and type I collagen in cells, and has excellent antioxidant, moisturizing, and / or firming and anti-wrinkle effects when added as an active ingredient to cosmetics.

[0037] The hydroxyproline ester of the present invention has good oil solubility and can be well dissolved in common oils used in cosmetics, such as isopropyl myristate, squalane, isocetane, etc.

[0038] The hydroxyproline ester of the present invention can be added to cosmetics in the form of two or more compositions, can significantly increase the expression of elastin, hyaluronic acid, and type I collagen in cells, and has excellent antioxidant, moisturizing, and / or firming and anti-wrinkle effects.

[0039] In some embodiments of the present invention, a hydroxyproline ester composition is provided. The composition is composed of two or more compounds of the hydroxyproline ester or its stereoisomers described in the present invention. For example, the hydroxyproline ester composition of the present invention can simultaneously contain component A, component B, and component C. Component A is the hydroxyproline ester shown in (I-1) or its stereoisomer, component B is the hydroxyproline ester shown in formula (I-2), formula (I-3), and / or formula (I-4) or its stereoisomer, and component C is the hydroxyproline ester shown in formula (I-5), formula (I-6), and / or formula (I-7) or its stereoisomer.

[0040] For another example, the hydroxyproline ester composition of the present invention can simultaneously contain the hydroxyproline esters shown in (I-2), formula (I-3), and formula (I-4) or their stereoisomers.

[0041] For another example, the hydroxyproline ester composition of the present invention can simultaneously contain the hydroxyproline esters shown in (I-5), formula (I-6), and formula (I-7) or their stereoisomers.

[0042] In some of these embodiments, the hydroxypinacolone retinoate composition contains a hydroxypinacolone retinoate having the structure shown in formula (I-1) or a stereoisomer thereof, and the molar ratio of the hydroxypinacolone retinoate having the structure shown in formula (I-1) or a stereoisomer thereof in the hydroxypinacolone retinoate composition is more than 2%, preferably more than 5%, more preferably more than 10%, more preferably more than 15%, more preferably more than 20%, more preferably more than 25%, more preferably more than 30%, more preferably more than 35%, more preferably more than 40%, more preferably more than 45%, more preferably more than 50%, more preferably more than 55%, more preferably more than 60%, more preferably more than 65%, more preferably more than 70%, more preferably more than 75%, more preferably more than 80%, more preferably more than 85%, more preferably more than 90%, more preferably more than 95%, more preferably more than 98%.

[0043] In some of these embodiments, the hydroxypinacolone retinoate composition contains a hydroxypinacolone retinoate having the structure shown in formula (I-2), formula (I-3) and / or formula (I-4) or a stereoisomer thereof, and the total molar ratio of the hydroxypinacolone retinoate having the structure shown in formula (I-2), formula (I-3) and formula (I-4) or a stereoisomer thereof in the hydroxypinacolone retinoate composition is more than 5%, more preferably more than 9%, more preferably more than 10%, more preferably more than 15%, more preferably more than 20%, more preferably more than 25%, more preferably more than 30%, more preferably more than 35%, more preferably more than 40%, more preferably more than 45%, more preferably more than 50%, more preferably more than 55%, more preferably more than 60%, more preferably more than 65%, more preferably more than 70%, more preferably more than 75%, more preferably more than 80%.

[0044] In some of these embodiments, the total molar ratio of the hydroxypinacolone retinoate having the structure shown in formula (I-2), formula (I-3) and formula (I-4) or a stereoisomer thereof in the hydroxypinacolone retinoate composition is 75% - 95%.

[0045] In some of these embodiments, the total molar ratio of the hydroxypinacolone retinoate having the structure shown in formula (I-2), formula (I-3) and formula (I-4) or a stereoisomer thereof in the hydroxypinacolone retinoate composition is 80% - 90%.

[0046] In some embodiments of the present invention, a cosmetic is also provided, and the active ingredient of the cosmetic contains the hydroxypinacolone retinoate or a stereoisomer thereof, or the hydroxypinacolone retinoate composition of the present invention.

[0047] The cosmetic of the present invention includes but is not limited to daily commonly used cleansing or skin care products such as facial cleanser, lotion, emulsion, facial mask, cream and essence.

[0048] The addition amount of the hydroxypinacolone ester or its stereoisomer, or the hydroxypinacolone ester composition in the cosmetics is based on the effect of antioxidation, moisturizing and / or firming and anti-wrinkle without obvious toxicity. Since the hydroxypinacolone ester or its stereoisomer of the present invention has a significant improvement effect on the skin and low cytotoxicity, its addition amount can be in a relatively large range, for example, it can be 0.01wt% - 0.5wt%.

[0049] Some embodiments of the present invention also relate to a preparation method of the hydroxypinacolone ester of the present invention, including the following steps: (1) Reacting compound 1 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 hydroxypinacolone ester with the structure shown in formula (I); The reaction formula is as follows: ;

[0050] Wherein each R 1 is independently selected from: hydrogen, -C(O)R, and at least one R 1 is -C(O)R; R is selected from: C 7 ~C 21 alkyl, C 7 ~C 21 unsaturated hydrocarbon radical.

[0051] The present invention uses xylose (compound 1) as a raw material, first reacts with acetylacetone (compound 2) to obtain compound 3, then esterifies compound 3 to obtain compound 4, and compound 4 is reduced to obtain hydroxypinacolone ester (compound (I)). This specific reaction route can retain the 8-position hydroxyl group without esterification, and the retention of the 8-position hydroxyl group can significantly improve the antioxidation, moisturizing and / or firming and anti-wrinkle effects of the obtained hydroxypinacolone ester.

[0052] The preparation step of compound 3 includes: mixing xylose and acetylacetone in a solvent, adding a base for condensation reaction to obtain compound 3.

[0053] In the reaction for preparing compound 3, the bases used include inorganic bases and organic bases. The inorganic bases are selected from sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, etc., and the organic bases are selected from piperidine, pyrrolidine, diethylamine, triethylamine, diisopropylethylamine, etc.

[0054] In some of these embodiments, step (1) of preparing Compound 3 includes: mixing Compound 1 and Compound 2 in a solvent, dropping 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 rate so that the temperature of the reaction solution does not exceed 40°C. After the dropping is complete, continue to keep the temperature at 40°C - 50°C and react for 1 - 2 hours to obtain Compound 3.

[0055] In some of these embodiments, the molar ratio of Compound 1, Compound 2, and the alkali is 1:1 - 1.2:1 - 1.2.

[0056] There are various methods for preparing Compound 4, including the acyl chloride method, the catalytic ester method, the transesterification method, and the condensing agent method. Among them, the acyl chloride method and the catalytic esterification method are the most commonly used.

[0057] The acyl chloride method uses Compound 3 and fatty acyl chloride (R-(C=O)-Cl) as reactants. After the reaction is complete in a solvent, Compound 4 is obtained through post-treatment. The R group in the fatty acyl chloride is selected from: C 7 ~C 21 alkyl, C 7 ~C 21 unsaturated hydrocarbon groups. For example, the fatty acyl 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, coconut oil acyl chloride, 2-hexyldecanoyl chloride, Guerbet C12 acyl chloride, Guerbet C16 acyl chloride, and so on.

[0058] In some of these embodiments, step (2) of esterifying Compound 3 includes: dissolving Compound 3 in a solvent, cooling to 0°C - 10°C, dropping the fatty acyl chloride, maintaining the temperature of the reaction solution not to exceed 15°C during the dropping process, and after the dropping is complete, raising the temperature to 20°C - 30°C and reacting for 1h - 2h, and obtaining Compound 4 through post-treatment.

[0059] Among them, the molar ratio of Compound 3 to the fatty acyl chloride depends on the expected target product. If mainly wanting to obtain a triester in which all 3 hydroxyl groups on the tetrahydropyran ring are esterified (i.e., the boswellin ester shown in formula (I-1)), then the molar ratio of Compound 3 to the fatty acyl chloride is 1:3 - 3.5; if mainly wanting to obtain a diester in which 2 hydroxyl groups on the tetrahydropyran ring are esterified (i.e., the boswellin esters shown in formula (I-2), formula (I-3), and formula (I-4)), then the molar ratio of Compound 3 to the fatty acyl chloride is 1:2 - 2.2; if mainly wanting to obtain a monoester in which 1 hydroxyl group on the tetrahydropyran ring is esterified (i.e., the boswellin esters shown in formula (I-5), formula (I-6), and formula (I-7)), then the molar ratio of Compound 3 to the fatty acyl chloride is 1:1 - 1.2.

[0060] The catalytic esterification method uses compound 3 and fatty acids as reactants. After the reaction is complete in a solvent, compound 4 is obtained through post-treatment. The catalytic esterification method includes acid-catalyzed esterification, base-catalyzed esterification, and enzyme-catalyzed esterification. Among them, the catalysts for acid-catalyzed esterification include sodium bisulfate, p-toluenesulfonic acid, sulfamic acid, Lewis acids, and solid superacids, etc.; the catalysts for base-catalyzed esterification include sodium hydroxide, potassium hydroxide, sodium methoxide, etc.; the catalysts for enzyme-catalyzed esterification include various fatty acid esterification / hydrolysis enzymes. The 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 fatty acid, 2-ethylhexanoic acid, Guerbet C12 acid, Guerbet C16 acid, and so on.

[0061] The transesterification method uses a base or lipase as a catalyst, and compound 3 reacts with fatty acid methyl / ethyl esters to remove methanol / ethanol to obtain compound 4.

[0062] The condensation method uses compound 3 and fatty acids as substrates, and a condensation reaction is carried out under the action of a condensing agent and a condensation assistant to obtain compound 4.

[0063] Compound 4 is reduced to obtain compound (I), the target product hydroxyproline ester of the present invention. The reduction methods include reduction with boron reducing agents and catalytic hydrogenation reduction. The boron reducing agents are selected from sodium borohydride, potassium borohydride, etc.; the catalysts used for catalytic hydrogenation reduction are metal catalysts such as Pt, Ni, Pd, etc.

[0064] In some of the embodiments, step (3) of reducing the carbonyl group in compound 4 includes: dissolving compound 4 in a solvent, adding a boron reducing agent, and reacting for 1 hour to 3 hours to obtain the hydroxyproline ester with the structure shown in formula (I).

[0065] In some of the embodiments, the molar ratio of compound 4 to the boron reducing agent is 1:1 - 1.5.

[0066] The present invention will be further described in detail below with reference to specific embodiments.

[0067] The general formula for the synthesis reaction of hydroxyproline ester in the following examples is as follows: ;

[0068] Among them, one or two or three of the three Rs 1 are -C(O)R 2 , and the remaining Rs 1 are hydrogen; R 2 is selected from: C 7 ~C 21 alkyl, C 7 ~C 21 unsaturated hydrocarbon groups.

[0069] The saponification value in the following examples was determined according to the acid value determination method in the method for the determination of fats and fatty oils in the fourth part of the Chinese Pharmacopoeia, General Rules 0713.

[0070] In the examples, room temperature refers to the indoor temperature of 15°C - 30°C.

[0071] Example 1 Synthesis of Intermediate Compound 3 A 10L reactor was equipped with nitrogen protection, mechanical stirring, a thermometer and a dropping funnel. Methanol (300 mL), D-xylose (300.0 g, 2.0 mol) and acetylacetone (210.0 g, 2.1 mol) were added. The temperature was controlled at 20°C - 30°C with a cold bath. While stirring strongly, a 20wt% sodium hydroxide - methanol solution (440.0 g, 2.2 mol) was added dropwise for reaction. The dropping rate was controlled so that the temperature of the reaction solution did not exceed 40°C. After the addition was complete, 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 the crude product of compound 3. The crude product was purified by column chromatography to obtain 340.0 g of compound 3, with a yield of 90%.

[0072] The nuclear magnetic resonance analysis data of compound 3 are as follows: 1 H-NMR (500 MHz, D 2 O): 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).

[0073] Example 2 Synthesis of Intermediate Compound 3 Potassium hydroxide was used instead of sodium hydroxide, and the other raw materials, reagents and synthesis steps were the same as in Example 1, with a yield of 80%.

[0074] Example 3 Synthesis of Boswellia Serrata Ester (5 - 12 - 3)

[0075] Charge anhydrous pyridine (300 mL) into the reaction flask, dissolve compound 3 (19.0 g, 0.1 mol) with stirring, cool down to 10 °C, and dropwise add lauroyl chloride (67.6 g, 0.31 mol). During the dropping process, maintain the temperature of the reaction solution not higher than 15 °C. After dropping, warm up to 25 °C and react for 1 h. Distill off pyridine under reduced pressure, add ethyl acetate (300 ml), stir evenly, and separate the lower layer solution; wash the upper layer solution successively with 1M sulfuric acid aqueous solution (200 mL), purified water (200 ml), and saturated brine (200 ml), then dry with anhydrous sodium sulfate, filter, and concentrate to obtain 70.0 g of crude product of compound 4 with a yield of 95%.

[0076] Dissolve the obtained crude product of compound 4 in isopropanol (1 L), add sodium borohydride (3.8 g, 0.1 mol), react at room temperature for 2 hours, then remove isopropanol under reduced pressure, add ethyl acetate (300 ml), stir evenly, and separate the lower layer solution; wash the upper layer solution successively with 1M sulfuric acid aqueous solution (200 mL) and saturated brine (300 ml), then dry with anhydrous sodium sulfate, filter, and concentrate to obtain 369.5 g of compound 5-12-3 with a yield of 99.0%. HPLC purity is 98.5%.

[0077] 1 H-NMR (500 MHz, CDCl 3 ): δ 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), 2.30 - 2.15 (m, 6H), 1.76 - 1.12 (m, 59H), 0.87 (s, 9H).

[0078] Saponification value: 231 (theoretical value: 228).

[0079] Example 4 Synthesis of bis(lauroyl) hydroxyproline ester (5-12-2)

[0080] Charge anhydrous pyridine (250 mL) into the reaction flask. While stirring, add compound 3 (19.0 g, 0.1 mol) until it dissolves clearly. Cool the temperature to 10 °C and dropwise add lauroyl chloride (45.8 g, 0.21 mol). During the dropping process, maintain the temperature of the reaction solution not higher than 15 °C. After dropping, raise the temperature to 25 °C and react for 1 h. Remove pyridine by vacuum distillation, add ethyl acetate (300 ml), stir evenly, and separate the lower layer solution; wash the upper layer solution successively with 1M sulfuric acid aqueous solution (200 mL), purified water (200 ml), and saturated brine (200 ml), then dry with anhydrous sodium sulfate, filter, and concentrate to obtain 50.0 g of compound 4 with a yield of 90%.

[0081] Dissolve the obtained compound 4 in isopropanol (1 L), add sodium borohydride (3.8 g, 0.1 mol), react at room temperature for 2 hours, then remove isopropanol under reduced pressure, add ethyl acetate (300 ml), stir evenly, and separate the lower layer solution; wash the upper layer solution successively with 1M sulfuric acid aqueous solution (200 mL) and saturated brine (300 ml), then dry with anhydrous sodium sulfate, filter, and concentrate to obtain 49.1 g of compound 5 with a yield of 98.0%.

[0082] The HPLC analysis results show that: in the product, the molar ratio of triester (5-12-3) is 5%, the molar ratio of diester (5-12-2) is 85%, and the molar ratio of monoester (5-12-1) is 10%.

[0083] 1 H-NMR (500 MHz, CDCl 3 ): 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).

[0084] Saponification value: 205 (theoretical value: 202).

[0085] Example 5 Synthesis of hydroxyproline monocaprylate (5-12-1)

[0086] Add 150 mL of anhydrous pyridine to a reaction flask. While stirring, add compound 3 (19.0 g, 0.1 mol) until it dissolves completely. Cool the solution to 10 °C, and then dropwise add lauroyl chloride (24.1 g, 0.11 mol). During the addition, maintain the temperature of the reaction solution at no higher than 15 °C. After the addition is complete, raise the temperature to 25 °C and react for 1 h. Remove pyridine by vacuum distillation, add ethyl acetate (200 ml), stir well, and separate the lower layer solution. Wash the upper layer solution successively with 1 M sulfuric acid aqueous solution (100 mL), purified water (100 ml), and saturated brine (100 ml), then dry with anhydrous sodium sulfate, filter, and concentrate to obtain 31.7 g of compound 4 with a yield of 85%.

[0087] Dissolve the obtained compound 4 in isopropanol (300 L), add sodium borohydride (3.8 g, 0.1 mol), and react at room temperature for 2 h. Then remove isopropanol under reduced pressure, add ethyl acetate (200 ml), stir well, and separate the lower layer solution. Wash the upper layer solution successively with 1 M sulfuric acid aqueous solution (100 mL) and saturated brine (100 ml), then dry with anhydrous sodium sulfate, filter, and concentrate to obtain 30.2 g of compound 5 with a yield of 95.0%.

[0088] The HPLC analysis results show that in the product, the molar ratio of triester (5-12-3) is 2%, the molar ratio of diester (5-12-2) is 15%, and the molar ratio of monoester (5-12-1) is 83%.

[0089] 1 H-NMR (500 MHz, CDCl 3 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).

[0090] Saponification value: 155 (theoretical value: 150).

[0091] Synthesis of Pro-Xylane trioctanoate (5-8-3), Pro-Xylane dioctanoate (5-8-2), and Pro-Xylane monooctanoate (5-8-1) in Examples 6 - 8 According to the steps of Examples 3 - 5, use octanoyl chloride instead of lauroyl chloride to synthesize Pro-Xylane trioctanoate (5-8-3), Pro-Xylane dioctanoate (5-8-2), and Pro-Xylane monooctanoate (5-8-1).

[0092] ;

[0093] Pro-Xylane trioctanoate (5-8-3): The two-step yield is 92%, and the HPLC purity is 98.6%.

[0094] 1 H-NMR (500 MHz, CDCl 3 ): δ 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), 2.30 - 2.15 (m, 6H), 1.86 - 1.12 (m, 35H), 0.87 (s, 9H).

[0095] Saponification value: 300 (theoretical value: 294).

[0096] Boswellia bis-caprylate (5 - 8 - 2): Two-step yield 88%. By HPLC analysis, the molar ratio of the triester (5 - 8 - 3) is 6%, the molar ratio of the diester (5 - 8 - 2) is 86%, and the molar ratio of the monoester (5 - 8 - 1) is 8%.

[0097] 1 H-NMR (500 MHz, CDCl 3 ): 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).

[0098] Saponification value: 255 (theoretical value: 252).

[0099] Boswellia mono-caprylate (5 - 8 - 1): Two-step yield 82%. By HPLC analysis, the molar ratio of the triester (5 - 8 - 3) is 3%, the molar ratio of the diester (5 - 8 - 2) is 12%, and the molar ratio of the monoester (5 - 8 - 1) is 85%.

[0100] 1 H-NMR (500 MHz, CDCl 3 ): 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).

[0101] Saponification value: 179 (theoretical value: 176).

[0102] Synthesis of boswellia tripalmitate (5 - 16 - 3), boswellia bis-palmitate (5 - 16 - 2), and boswellia mono-palmitate (5 - 16 - 1) in Examples 9 - 11 According to the steps of Example 3-5, palmitoyl chloride was used instead of lauroyl chloride to synthesize tripalmitoyl hydroxyproline (5-16-3), dipalmitoyl hydroxyproline (5-16-2), and monopalmityl hydroxyproline (5-16-1).

[0103] ;

[0104] Tripalmitoyl hydroxyproline (5-16-3): The two-step yield was 94%, and the HPLC purity was 98.5%.

[0105] 1 H-NMR (500 MHz, CDCl 3 ): δ 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), 2.30 - 2.15 (m, 6H), 1.86 - 1.12 (m, 83H), 0.87 (s, 9H).

[0106] Saponification value: 187 (theoretical value: 185).

[0107] Dipalmitoyl hydroxyproline (5-16-2): The two-step yield was 85%. By HPLC analysis, the molar ratio of the triester (5-16-3) was 10%, the molar ratio of the diester (5-16-2) was 84%, and the molar ratio of the monoester (5-16-1) was 6%.

[0108] 1 H-NMR (500 MHz, CDCl 3 ): 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).

[0109] Saponification value: 170 (theoretical value: 167).

[0110] Monopalmityl hydroxyproline (5-16-1): The two-step yield was 85%. By HPLC analysis, the molar ratio of the triester (5-16-3) was 3%, the molar ratio of the diester (5-16-2) was 10%, and the molar ratio of the monoester (5-16-1) was 87%.

[0111] 1 H-NMR (500 MHz, CDCl 3): 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).

[0112] Saponification value: 131 (theoretical value: 130).

[0113] Synthesis of Boswellia serrata trioleate (5 - 18o - 3), Boswellia serrata dioleate (5 - 18o - 2), and Boswellia serrata monooleate (5 - 18o - 1) in Examples 12 - 14 According to the steps of Examples 3 - 5, oleoyl chloride was used instead of lauroyl chloride to synthesize Boswellia serrata trioleate (5 - 18o - 3), Boswellia serrata dioleate (5 - 18o - 2), and Boswellia serrata monooleate (5 - 18o - 1).

[0114] ;

[0115] Boswellia serrata trioleate (5 - 18o - 3): Two - step yield 90%, HPLC purity 98.7%.

[0116] 1 H - NMR (500 MHz, CDCl 3 ): δ 5.4 - 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).

[0117] Saponification value: 175 (theoretical value: 170).

[0118] Boswellia serrata dioleate (5 - 18o - 2): Two - step yield 87%. The molar ratio of the tri - ester (5 - 18o - 3) analyzed by HPLC is 12%, the molar ratio of the di - ester (5 - 18o - 2) is 80%, and the molar ratio of the mono - ester (5 - 18o - 1) is 8%.

[0119] 1 H - NMR (500 MHz, CDCl 3 ) 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).

[0120] Saponification value: 158 (theoretical value: 156).

[0121] Boswellia serrata oleate (5-18o-1): The two-step yield is 87%. The molar ratio of the triester (5-18o-3) analyzed by HPLC is 4%, the molar ratio of the diester (5-18o-2) is 10%, and the molar ratio of the monoester (5-18o-1) is 86%.

[0122] 1 H-NMR (500 MHz, CDCl 3 ) 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).

[0123] Saponification value: 128 (theoretical value: 123).

[0124] Synthesis of tris(2-hexyldecanoic acid) boswellia serrata ester (5-16g-3), bis(2-hexyldecanoic acid) boswellia serrata ester (5-16g-2), and mono(2-hexyldecanoic acid) boswellia serrata ester (5-16g-1) in Examples 15 - 17 According to the steps of Examples 3 - 5, 2-hexyldecanoyl chloride was used instead of lauroyl chloride to synthesize tris(2-hexyldecanoic acid) boswellia serrata ester (5-16g-3), bis(2-hexyldecanoic acid) boswellia serrata ester (5-16g-2), and mono(2-hexyldecanoic acid) boswellia serrata ester (5-16g-1).

[0125] ;

[0126] Tris(2-hexyldecanoic acid) boswellia serrata ester (5-16g-3): The two-step yield is 87%, and HPLC is 98.2%.

[0127] 1 H-NMR (500 MHz, CDCl 3 ) δ: 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), 2.35 - 2.15 (m, 3H), 1.86 - 1.12 (m, 77H), 0.87 (s, 18H).

[0128] Saponification value: 189 (theoretical value: 185).

[0129] Bis(2-hexyldecanoic acid) hydroxyproline ester (5-16g-2): The two-step yield is 86%. By HPLC analysis, the molar ratio of the triester (5-16g-3) is 5%, the molar ratio of the diester (5-16g-2) is 90%, and the molar ratio of the monoester (5-16g-1) is 5%.

[0130] 1 H-NMR (500 MHz, CDCl 3 ): 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).

[0131] Saponification value: 169 (theoretical value: 167).

[0132] Mono(2-hexyldecanoic acid) hydroxyproline ester (5-16g-1): The two-step yield is 82%. By HPLC analysis, the molar ratio of the triester (5-16g-3) is 3%, the molar ratio of the diester (5-16g-2) is 9%, and the molar ratio of the monoester (5-16g-1) is 88%.

[0133] 1 H-NMR (500 MHz, CDCl 3 ): 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).

[0134] Saponification value: 134 (theoretical value: 130).

[0135] Comparative Example 1 Synthesis of hydroxyproline trilaurate (S-12-3) using hydroxyproline as the raw material S-12-3 is a mixture. Theoretically, there are the following 4 kinds of hydroxyproline trilaurates:

[0136] Add anhydrous pyridine (300 mL) to the reaction flask, dissolve hydroxyproline (19.2 g, 0.1 mol) with stirring, cool down to 10 °C, and dropwise add lauroyl chloride (67.6 g, 0.31). During the dropping process, maintain the temperature of the reaction solution not higher than 15 °C. After dropping, raise the temperature to 25 °C and react for 1 h. Distill off pyridine under reduced pressure, add ethyl acetate (300 mL), stir evenly, and separate the lower layer solution; wash the upper layer solution successively with 1 M sulfuric acid aqueous solution (200 mL), purified water (200 mL), and saturated brine (200 mL), then dry with anhydrous sodium sulfate, filter, and concentrate to obtain 62.8 g of hydroxyproline trilaurate, with a yield of 85%.

[0137] The molar ratio of the triester (S-12-3) analyzed by HPLC is 88% (where 5-12-3 is 18%), the molar ratio of the tetraester is 4%, the molar ratio of the diester (S-12-2) is 5%, and the molar ratio of the monoester (S-12-1) is 3%.

[0138] Saponification value: 231 (theoretical value: 228).

[0139] 1 H-NMR (500 MHz, CDCl 3 ) δ 5.30 - 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).

[0140] In Comparative Example 2, hydroxyproline dilaurate (S-12-2) was synthesized using hydroxyproline as the raw material S-12-2 is a mixture, and theoretically there are the following 6 kinds of hydroxyproline dilaurates:

[0141] Add anhydrous pyridine (250 mL) to the reaction flask, dissolve hydroxyproline (19.2 g, 0.1 mol) with stirring, cool down to 10 °C, and dropwise add lauroyl chloride (45.8 g, 0.21). During the dropping process, maintain the temperature of the reaction solution not higher than 15 °C. After dropping, raise the temperature to 25 °C and react for 1 h. Distill off pyridine under reduced pressure, add ethyl acetate (300 mL), stir evenly, and separate the lower layer solution; wash the upper layer solution successively with 1 M sulfuric acid aqueous solution (200 mL), purified water (200 mL), and saturated brine (200 mL), then dry with anhydrous sodium sulfate, filter, and concentrate to obtain 44.5 g of hydroxyproline dilaurate, with a yield of 80%.

[0142] The molar ratio of diesters 5-12-2-a to 5-12-2-c in HPLC analysis is 42%, the molar ratio of 5-12-2-p1 to 5-12-2-p3 is 45%, the molar ratio of tetraesters is 2%, the molar ratio of triesters (S-12-3) is 5%, and the molar ratio of monoesters (S-12-1) is 6%.

[0143] 1 H-NMR (500 MHz, CDCl 3 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).

[0144] Saponification value: 210 (theoretical value: 202).

[0145] In Comparative Example 3, hydroxyprogesterone caproate (S-12-1) was synthesized using hydroxyprogesterone as the raw material S-12-1 is a mixture, and theoretically there are the following 4 kinds of hydroxyprogesterone caproates:

[0146] 150 mL of anhydrous pyridine was added to the reaction flask, and hydroxyprogesterone (19.2 g, 0.1 mol) was dissolved and clarified under stirring. The temperature was lowered to 10 °C, and lauroyl chloride (24.1 g, 0.11) was added dropwise. During the dropping process, the temperature of the reaction solution was maintained not higher than 15 °C. After the dropping was completed, the temperature was raised to 25 °C and reacted for 1 h. Pyridine was removed by distillation under reduced pressure, ethyl acetate (200 ml) was added, and the mixture was stirred evenly. The lower layer solution was separated; the upper layer solution was washed successively with 1 M sulfuric acid aqueous solution (100 mL), purified water (100 ml), and saturated brine (100 ml), then dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 31.7 g of hydroxyprogesterone caproate, with a yield of 78%.

[0147] The molar ratio of 5-12-1-a to 5-12-1-c in HPLC analysis is 80%, the molar ratio of 5-12-1-p is 15%, the molar ratio of tetraesters is 0.5%, the molar ratio of triesters (S-12-3) is 1.5%, and the molar ratio of diesters (S-12-2) is 3.0%.

[0148] 1 H-NMR (500 MHz, CDCl 3 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).

[0149] Saponification value: 154 (theoretical value: 150).

[0150] For Comparative Examples 4 - 6, boswellic acid was used as the raw material to synthesize boswellia trioctanoate (S - 8 - 3), boswellia dioctanoate (S - 8 - 2), and boswellia monooctanoate (S - 8 - 1). According to the steps of Comparative Examples 1 - 3, octanoyl chloride was used instead of lauroyl chloride to synthesize boswellia trioctanoate (S - 8 - 3), boswellia dioctanoate (S - 8 - 2), and boswellia monooctanoate (S - 8 - 1).

[0151] ;

[0152] Boswellia trioctanoate (S - 8 - 3): The yield was 92%. By HPLC analysis, the molar proportion of the tri - ester (S - 8 - 3) was 84% (where 5 - 8 - 3 was 12%), the molar proportion of the tetra - ester was 6%, the molar proportion of the di - ester (S - 8 - 2) was 8%, and the molar proportion of the mono - ester (S - 8 - 1) was 2%.

[0153] 1 H - NMR (500 MHz, CDCl 3 ) δ5.35 - 3.12(m, 8H), 2.50 - 2.00(m, 6H), 1.86 - 1.12(m, 35H), 0.87(s, 9H).

[0154] Saponification value: 297 (theoretical value: 294).

[0155] Boswellia dioctanoate (S - 8 - 2): The yield was 88%. By HPLC analysis, the molar proportion of the tetra - ester was 2%, the molar proportion of the tri - ester (S - 8 - 3) was 8%, the molar proportion of the di - ester (S - 8 - 2) was 80% (where 5 - 8 - 2 was 45%), and the molar proportion of the mono - ester (S - 8 - 1) was 10%.

[0156] 1 H - NMR (500 MHz, CDCl 3 ) δ5.00 - 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).

[0157] Saponification value: 257 (theoretical value: 252).

[0158] Boswellia octanoate (S-8-1): Yield 82%. The molar ratio of the tetraester was analyzed to be 2%, the molar ratio of the triester (S-8-3) was 4%, the molar ratio of the diester (S-8-2) was 8%, and the molar ratio of the monoester (S-8-1) was 86% (where 5-8-1 was 62%).

[0159] 1 H-NMR (500 MHz, CDCl 3 ): 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).

[0160] Saponification value: 179 (theoretical value: 176).

[0161] For Comparative Examples 7 - 9, boswellia was used as the raw material to synthesize boswellia tripalmitate (S-16-3), boswellia dipalmitate (S-16-2), and boswellia monopalmitate (S-16-1). According to the steps of Comparative Examples 1 - 3, palmitoyl chloride was used instead of lauroyl chloride to synthesize boswellia tripalmitate (S-16-3), boswellia dipalmitate (S-16-2), and boswellia monopalmitate (S-16-1).

[0162] ;

[0163] Boswellia tripalmitate (S-16-3): Yield 88%. By HPLC analysis, the molar ratio of the triester (S-16-3) was 87% (where 5-16-3 was 14%), the molar ratio of the tetraester was 5%, the molar ratio of the diester (S-16-2) was 7%, and the molar ratio of the monoester (S-16-1) was 1%.

[0164] 1 H-NMR (500 MHz, CDCl 3 ): δ 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), 2.30 - 2.15 (m, 6H), 1.86 - 1.12 (m, 83H), 0.87 (s, 9H).

[0165] Saponification value: 187 (theoretical value: 185).

[0166] Dipalmitoyl hydroxyproline (S-16-2): Yield 85%. By HPLC analysis, the molar ratio of tetraester is 2%, the molar ratio of triester (S-16-3) is 7%, the molar ratio of diester (S-16-2) is 84% (where 5-16-2 is 42%), and the molar ratio of monoester (S-16-1) is 11%.

[0167] 1 H-NMR (500 MHz, CDCl 3 ) 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).

[0168] Saponification value: 170 (theoretical value: 167).

[0169] Mono-palmitoyl hydroxyproline (S-16-1): Yield 80%. By HPLC analysis, the molar ratio of tetraester is 1%, the molar ratio of triester (S-16-3) is 3%, the molar ratio of diester (S-16-2) is 10%, and the molar ratio of monoester (S-16-1) is 86% (where 5-16-1 is 64.5%).

[0170] 1 H-NMR (500 MHz, CDCl 3 ) 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).

[0171] Saponification value: 131 (theoretical value: 130).

[0172] Comparative Examples 10 - 12 used hydroxyproline as the raw material to synthesize trioleoyl hydroxyproline (S-18o-3), dioleoyl hydroxyproline (S-18o-2), and monooleoyl hydroxyproline (S-18o-1). Following the steps of Comparative Examples 1 - 3, oleoyl chloride was used instead of lauroyl chloride to synthesize trioleoyl hydroxyproline (S-18o-3), dioleoyl hydroxyproline (S-18o-2), and monooleoyl hydroxyproline (S-18o-1).

[0173] ;

[0174] Boswellia trioleate (S-18o-3): Yield 92%. By HPLC analysis, the molar proportion of the triester (S-18o-3) is 84% (where 5-18o-3 is 11%), the molar proportion of the tetraester is 6%, the molar proportion of the diester (S-18o-2) is 8%, and the molar proportion of the monoester (S-18o-1) is 2%.

[0175] 1 H-NMR (500 MHz, CDCl 3 ) δ 5.5 - 3.16 (m, 14H), 2.50 - 2.00 (m, 18H), 1.86 - 1.12 (m, 71H), 0.87 (s, 9H).

[0176] Saponification value: 178 (theoretical value: 170).

[0177] Boswellia dioleate (S-18o-2): Yield 90%. By HPLC analysis, the molar proportion of the tetraester is 2%, the molar proportion of the triester (S-18o-3) is 10%, the molar proportion of the diester (S-18o-2) is 85% (where 5-18o-2 is 45%), and the molar proportion of the monoester (S-18o-1) is 3%.

[0178] 1 H-NMR (500 MHz, CDCl 3 ) δ 5.4 - 3.10 (m, 13H), 2.45 - 2.00 (m, 12H), 1.86 - 1.12 (m, 49H), 0.87 (s, 6H).

[0179] Saponification value: 159 (theoretical value: 156).

[0180] Boswellia monooleate (S-18o-1): Yield 87%. By HPLC analysis, the molar proportion of the tetraester is 2%, the molar proportion of the triester (S-18o-3) is 6%, the molar proportion of the diester (S-18o-2) is 10%, and the molar proportion of the monoester (S-18o-1) is approximately 82% (where 5-18o-1 is 62%).

[0181] 1 H-NMR (500 MHz, CDCl 3 ) δ 5.4 - 3.10 (m, 11H), 2.40 - 2.00 (m, 6H), 1.86 - 1.12 (m, 29H), 0.87 (s, 3H).

[0182] Saponification value: 130 (theoretical value: 123).

[0183] For Comparative Examples 13-15, hydroxyproline was used as the raw material to synthesize tricaprylyl hydroxyproline (S-16g-3), dicaprylyl hydroxyproline (S-16g-2) and monocaprylyl hydroxyproline (S-16g-1). According to the steps of Comparative Examples 1-3, tricaprylyl hydroxyproline (S-16g-3), dicaprylyl hydroxyproline (S-16g-2) and monocaprylyl hydroxyproline (S-16g-1) were synthesized by using 2-hexyldecanoyl chloride instead of lauroyl chloride.

[0184] ;

[0185] Tricaprylyl hydroxyproline (S-16g-3): The yield was 87%. The molar ratio of the tetraester analyzed by HPLC was 3%, the molar ratio of the triester (S-16g-3) was 85% (where 5-16g-3 was 18%), the molar ratio of the diester (S-16g-2) was 5%, and the molar ratio of the monoester (S-16g-1) was 7%.

[0186] 1 H-NMR (500 MHz, CDCl 3 ) δ 5.40 - 3.16 (m, 8H), 2.40 - 2.10 (m, 3H), 1.90 - 1.12 (m, 77H), 0.87 (s, 18H).

[0187] Saponification value: 187 (theoretical value: 185).

[0188] Dicaprylyl hydroxyproline (S-16g-2): The yield was 86%. The molar ratio of the tetraester analyzed by HPLC was 1%, the molar ratio of the triester (S-16g-3) was 8%, the molar ratio of the diester (S-16g-2) was 85% (where 5-16g-2 was 40%), and the molar ratio of the monoester (S-16g-1) was 6%.

[0189] 1 H-NMR (500 MHz, CDCl 3 ) δ 5.20 - 3.10 (m, 9H), 2.40 - 2.15 (m, 2H), 1.90 - 1.12 (m, 53H), 0.87 (s, 12H).

[0190] Saponification value: 171 (theoretical value: 167).

[0191] Boswellia serrata extract (S-16g-1): Yield 83%, HPLC analysis showed that the molar ratio of tetraester was 1%, the molar ratio of triester (S-16g-3) was 6%, the molar ratio of diester (S-16g-2) was 8%, and the molar ratio of monoester (S-16g-1) was 85% (of which 5-16g-1 was 60.1%).

[0192] 1 H-NMR (500 MHz, CDCl 3 ) δ 5.40 - 3.10 (m, 9H), 2.40 - 2.25 (m, 1H), 1.90 - 1.12 (m, 30H), 0.87 (s, 6H).

[0193] Saponification value: 135 (theoretical value: 130).

[0194] Comparative Example 16 Commercially available boswellia serrata extract, purity ≥ 99%.

[0195] The following efficacy tests were carried out on the boswellia serrata esters prepared in Examples 3-17 and Comparative Examples 1-15 and the commercially available boswellia serrata extract in Comparative Example 16: 1. Detection of antioxidant activity.

[0196] Weigh 3.9 mg of DPPH, dissolve it in an appropriate amount of absolute ethanol, and sonicate it in the dark until it is completely dissolved. Then, make up the volume to 100 ml with absolute ethanol to prepare a DPPH working solution with a concentration of 0.1 mmol / L. The boswellia serrata esters or boswellia serrata extract of each example and comparative example were prepared into a test solution with a concentration of 24 mM. The solvents for Examples 3-17 and Comparative Examples 1-15 were isopropyl myristate, and the solvent for Comparative Example 16 was pure water. In each sample group of the 96-well plate, first add 50 μl of the test solution (add 50 μl of the solvent to the blank control group), then add 200 μl of the DPPH working solution (set up another blank background group and replace the DPPH working solution with an equal volume of ethanol), mix well, react at room temperature in the dark for 2 h, and measure the absorbance of each group at a wavelength of 517 nm with an enzyme-linked immunosorbent assay (ELISA) reader. Calculate the DPPH radical scavenging rate according to formula (1) based on the absorbance, and set 3 replicates for each concentration. The results are shown in Table 1.

[0197] DPPH radical scavenging rate (%) = (1) Where: C1 - OD value of the DPPH-containing system in the blank control group C2 - OD value of the DPPH-free system in the blank background group T1 - OD value of the DPPH-containing system in the sample group T2 - OD value of the DPPH-free system in the sample group Table 1 DPPH radical scavenging rate of each sample

[0198] As can be seen from Table 1, pro-xylane itself has no antioxidant activity, while the pro-xylane ester with a carbon chain incorporated has the ability to scavenge DPPH free radicals and thus has antioxidant activity; and incorporating different side chains shows different DPPH free radical scavenging abilities, among which the pro-xylane esters prepared in Examples 12 - 17 exhibit significant DPPH free radical scavenging effects.

[0199] At the same time, it was found by comparison that the ability of the pro-xylane esters prepared in the examples to scavenge DPPH free radicals is better than that of the corresponding comparative examples, and can more significantly improve the antioxidant activity. Compared with the comparative examples, the 8-position hydroxyl group of the pro-xylane esters prepared in the examples is not esterified, and the structure of hydroxypropyl is retained. It can be seen that while modifying the hydroxyl group on the tetrahydropyran ring of pro-xylane with a specific carbon chain and retaining its hydroxypropyl group without esterification can more significantly improve the antioxidant activity of the obtained pro-xylane ester.

[0200] In addition, the more the number of the 3 hydroxyl groups on the tetrahydropyran ring is esterified, the better the antioxidant activity of the obtained pro-xylane ester, that is, the antioxidant activity of the tri-ester is better than that of the di-ester, and the di-ester is better than the mono-ester.

[0201] Detection of the contents of zebrafish elastin, hyaluronic acid and type I collagen (ELISA method) The pro-xylane esters prepared in Examples 3 - 17 and Comparative Examples 1 - 15 and the pro-xylane 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% CaCl 2 , 0.79% MgSO 4 ) to a final concentration of 100 μM to obtain a pro-xylane ester solution or a pro-xylane solution.

[0202] Wild-type AB zebrafish embryos at 72 hpf with normal development were randomly selected into 48-well plates, with 3 parallel groups set for each group and 15 embryos in each well. 500 μl of the pro-xylane ester solution or the pro-xylane solution was added to each well of each sample group, and 500 μl of embryo culture medium containing an equal amount of solvent was added to the blank control group. They were placed in a biochemical incubator at 28 ± 1 °C and incubated in the dark for 24 h. The embryos were collected, washed with embryo culture medium, and then 1 ml of phosphate buffer solution was added to each group for grinding, followed by centrifugation at 1000 rpm for 20 min. The supernatant was taken to detect the contents of elastin, hyaluronic acid and type I collagen according to the instructions of the ELISA kit. The up-regulation rate (%) of each index was calculated according to formula (2).

[0203] Up-regulation rate (%) = (2) In formula (2): Ve—the content of elastin, hyaluronic acid or type I collagen in the sample group; Vc—the content of elastin, hyaluronic acid or type I collagen in the blank control group.

[0204] Table 2 Up-regulation rate of elastin expression in embryos of each group (%) ; Table 3 Up-regulation rate of hyaluronic acid expression in embryos of each group (%)

[0205] Table 4 Up-regulation rate of type I collagen expression in embryos of each group (%)

[0206] The experimental results in Tables 2 - 4 show that compared with hydroxyprogesterone (Comparative Example 16), hydroxyprogesterone esters with one or more carbon chains attached through esterification of the hydroxyl groups on the tetrahydropyran ring of hydroxyprogesterone can all increase the expression of elastin, hyaluronic acid and type I collagen, and among them, the hydroxyprogesterone esters containing oleate and 2 - hexyl decanoate side chains have the most obvious up-regulation effect.

[0207] Compared with Comparative Examples 1 - 15, the hydroxyprogesterone esters without esterified hydroxypropyl groups prepared in Examples 3 - 17 have a stronger ability to promote the expression of elastin, hyaluronic acid and type I collagen.

[0208] In addition, the more the number of the 3 hydroxyl groups on the tetrahydropyran ring is esterified, the more significant the effect of the obtained hydroxyprogesterone ester on increasing the expression of elastin, hyaluronic acid and type I collagen, that is, the effect of the triester is better than that of the diester, and the diester is better than the monoester.

[0209] The above results show that the prepared hydroxyprogesterone esters of the present invention have better antioxidant, moisturizing and firming and anti-wrinkle effects compared with hydroxyprogesterone and hydroxyprogesterone esters with esterified hydroxypropyl groups.

[0210] The above-described embodiments only represent several implementation manners of the present invention, and their descriptions are relatively specific and detailed, but should not be construed as limiting the scope of the invention patent. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present invention, several modifications and improvements can still be made, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the invention patent should be subject to the appended claims.

Claims

1. A bosaicin ester or a stereoisomer thereof, 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: C7~C 17 Alkyl, C7~C 17 Unsaturated chain hydrocarbon group.

2. The bosaicin ester or its stereoisomer 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 or its stereoisomer according to claim 1 or 2, characterized in that: R is selected from: 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.

4. The bosaicin ester or its stereoisomer according to claim 3, characterized in that: 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.

5. The bosaicin ester or its stereoisomer according to claim 3, characterized in that: R is selected from: C 15 Branched alkyl, C containing a carbon-carbon double bond 17 Unsaturated chain hydrocarbon group.

6. The bosaicin ester or its stereoisomer according to claim 1, characterized in that: The bosaicin ester is selected from the following compounds: ； ； ； ； ； ； ； ； ； 。 7. A bosaicin ester composition, characterized in that: The invention is composed of two or more compounds of the bosaicin ester or its stereoisomers as described in any one of claims 1 to 6.

8. The bosaicin ester composition according to claim 7, characterized in that: 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 greater than 2%.

9. The bosaicin ester composition according to claim 8, characterized in that: The molar ratio of the bosaicin ester having the structure represented by the formula (I-1) or its stereoisomer in the bosaicin ester composition is greater than 90%.

10. The bosaicin ester composition according to claim 7, characterized in that: 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 more than 70%.

11. The bosaicin ester composition according to claim 10, characterized in that: The total amount of the bosaicin esters or their 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 75% to 95%.

12. Use of the bosaicin ester or its stereoisomer according to any one of claims 1 to 6, or the bosaicin ester composition according to any one of claims 7 to 11 as an effective ingredient in the preparation of antioxidant cosmetics.

13. Use of the bosaicin ester or its stereoisomer according to any one of claims 1 to 6, or the bosaicin ester composition according to any one of claims 7 to 11 as an effective ingredient in the preparation of cosmetics capable of moisturizing, tightening the skin and / or anti-wrinkle.

14. Use of the bosaicin ester or its stereoisomer according to any one of claims 1 to 6, or the bosaicin ester composition according to any one of claims 7 to 11 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.

15. A cosmetic, characterized in that: The effective ingredients of the cosmetics contain the bosaicin ester or its stereoisomers as described in any one of claims 1 to 6, or the bosaicin ester composition as described in any one of claims 7 to 11.

16. A method for preparing the bosaicin ester according to any one of claims 1 to 6, 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 a bosaicin ester having a structure shown in formula (I); The reaction formula is as follows: ； Wherein, R1 is as described in any one of claims 1-6.

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