Ascorbic acid derivative and cosmetic containing same

Abstract

Provided is a novel ascorbic acid derivative which has excellent functions inherent to ascorbic acid, such as a collagen production promoting effect and a moisturizing effect, and which is stable even when stored for a long period of time and shows little decrease in activity, the present invention relates to an ascorbic acid derivative represented by the following general formula (1), (3) or (4): [in formula (1), (3) or (4), R1 is-(CH2) n-* (n is an integer of 2 to 4),-CH2CH (OH) CH2-* (* represents the position of O bonding to the second position of an ascorbic acid ring) or a dimethyloxetane group; r2 and R3 are hydrogen,-COR4, alkyl or benzyl; r4 is a C1 to 22 alkyl group; and in formula (3), R5 and R6 are hydrogen, methyl or phenyl].

Description

TECHNICAL FIELD

[0001] The present application relates to an ascorbic acid derivative suitable for use as a raw material for a cosmetic, and also relates to a cosmetic containing the ascorbic acid derivative. BACKGROUND

[0002] Ascorbic acid is a safe and useful antioxidant, and is known as a compound having excellent whitening properties. However, its application in the field of cosmetics has been hindered due to its instability to light, heat and oxidation, and its insufficient stability over time. Therefore, various ascorbic acid derivatives or salts thereof have been proposed as derivatives having improved stability over time compared to ascorbic acid, and have been proposed to be incorporated into topical skin whitening preparations (Patent Documents 1 and 2) and cosmetics (Patent Document 3).

[0003] However, many of the above-mentioned ascorbic acid derivatives and salts thereof still have insufficient stability over time, and have problems such as a decrease in the pH in the formulation over time, accelerated decomposition under alkaline conditions, etc. Furthermore, the duration of in vivo activity is insufficient, and improvements in this regard are desired.

[0004] The present inventors have addressed these problems by proposing an ascorbic acid derivative that is inhibited from decomposing under alkaline conditions (Patent Document 4). However, there is a need for an ascorbic acid derivative having further improved stability over time under alkaline conditions, and having high stability over a wide pH range.

[0005] PRIOR ART DOCUMENTS

[0006] PATENT DOCUMENTS

[0007] Patent Document 1: JP 1987-221611 A

[0008] Patent Document 2: JP 2005-060239 A

[0009] Patent Document 3: JP 1989-228978 A

[0010] Patent Document 4: JP 4681670 B1 SUMMARY

[0011] PROBLEMS TO BE SOLVED BY THE INVENTION

[0012] An object of the present application is to provide an ascorbic acid derivative which not only has the excellent properties inherent to ascorbic acid such as moisturizing properties, but also has high stability in a wide pH range and has excellent physiological activity effects. Another object of the present application is to provide a cosmetic and a pharmaceutical which contain the ascorbic acid derivative and exhibit excellent moisturizing activity and the like, high stability in a wide pH range, and excellent physiological activity effects.

[0013] Means for solving the problem

[0014] The present inventors have conducted intensive studies in view of the above-mentioned circumstances, and have found that novel ascorbic acid derivatives represented by the following formulae (1), (3), or (4) have excellent moisturizing properties, and some of them are highly stable in a wide pH range, and have excellent physiological activity effects such as an effect of promoting the production of hyaluronic acid. In addition, the present inventors have found that a cosmetic and a pharmaceutical which contain the ascorbic acid derivatives represented by the following formulae (1), (3), or (4) have excellent moisturizing properties, are stable in a wide pH range, and also have excellent physiological activity effects such as an effect of promoting the production of hyaluronic acid. Based on these findings, the present application has been accomplished.

[0015] The first aspect of the present application is an ascorbic acid derivative represented by the following general formula (1), (3), or (4) (claim 1).

[0016] [Chemical Formula 1]

[0017]

[0018] [Chemical Formula 2]

[0019]

[0020] [Chemical Formula 3]

[0021]

[0022] [In formulae (1), (3), or (4), R 1 is -(CH2) n - (n is an integer of 2 to 4), -CH2CH(OH)CH2- *, -CH2CH(CH2OH)- *, -CH(CH2OH)CH2- *, -C(CH3)2CH2- *, -CH2C(CH3)2- * (* indicates a position bonded to O at the 2-position of the ascorbic acid ring), or a divalent group represented by the following formula (2);

[0023] In formula (1), R 2 and R 3 are each hydrogen, -COR 4, a linear or branched alkyl group or a benzyl group having 1 to 22 carbon atoms, and R 4 is a linear or branched alkyl group having 1 to 22 carbon atoms; and

[0024] In formula (3), R 5 and R 6 each is a hydrogen atom, a methyl group or a phenyl group.

[0025] [Chemical Formula 4]

[0026]

[0027] In formulae (1), (3) and (4), carbon atoms and hydrogen atoms bonded to these carbon atoms are omitted. For example, in formula (1), the 1st, 2nd and 3rd positions are carbon atoms, the 4th and 5th positions are CH groups, and the 6th position is a CH2 group. In the following structural formulae, hydrogen atoms and carbon atoms are also omitted as in these formulae.

[0028] The ascorbic acid derivative represented by general formula (1) has excellent stability over time in a neutral to weakly basic range (pH range of about 6 to 10) compared to ascorbic acid and conventional ascorbic acid derivatives. In particular, even when stored for several weeks in a high-temperature environment higher than room temperature, the ascorbic acid derivative maintains a high residual rate in a wide pH range and inhibits problems such as odor generation and discoloration. In addition, the ascorbic acid derivative represented by general formula (1), (3) or (4) has excellent collagen production promoting effect and hyaluronic acid production promoting effect compared to conventional ascorbic acid derivatives such as glyceryl ascorbate.

[0029] A second aspect of the present application is a preferred embodiment of the first aspect of the present application, which is an ascorbic acid derivative represented by general formula (1), wherein R 1 is -(CH2)n-* (n is 3 or 4), -CH2CH(OH)CH2-*, -CH2CH(CH2OH)-*, -CH(CH2OH)CH2-* (* indicates a position bonded to O at the 2nd position of the ascorbic acid ring) or a divalent group represented by formula (2), and R 2 and R 3 are hydrogen; or R 1 is -(CH2)n- (n is 3 or 4), R 2 is -COR 4 , and R 3 is hydrogen or -COR 4 , and R 4is a linear or branched alkyl group having 4 to 18 carbon atoms. These compounds are preferred because they have particularly excellent stability over time in the neutral to weakly basic range.

[0030] A third aspect of the present application is a preferred embodiment of the second aspect of the present application, which is an ascorbic acid derivative represented by the general formula (1),

[0031] wherein R 1 in the general formula (1) is -(CH2) 3 -CH2CH(OH)CH2- (* indicates a position bonded to O at the 2-position of the ascorbic acid ring) or a divalent group represented by the formula (2), and R 2 and R 3 are each hydrogen, or R 1 is -(CH2)3-*, R 2 is -COR 4 , R 3 is hydrogen or -COR 4 , and R 4 is a linear or branched alkyl group having 8 to 18 carbon atoms. These compounds are preferred because they have particularly excellent effects of promoting collagen production and hyaluronic acid production. Among these, particularly preferred are ascorbic acid derivatives characterized in that R 1 is -(CH2)3- or a divalent group represented by the formula (2), and R 2 and R 3 are each hydrogen, or R 1 is -(CH2)3-*, R 2 is -COR 4 , R 3 is hydrogen or -COR 4 , and R 4 is a linear or branched alkyl group having 8 to 18 carbon atoms, because they have particularly excellent effects of promoting hyaluronic acid production.

[0032] The ascorbic acid derivative of the present application can be blended into a cosmetic. A fourth aspect of the present application is a cosmetic in which the ascorbic acid derivative of any one of the first to third aspects of the present application is blended. The fourth aspect of the present application is a cosmetic that has excellent moisturizing properties, is stable in a wide pH range, and exhibits excellent physiological activity effects such as collagen production promotion effects and hyaluronic acid production promotion effects.

[0033] The fifth aspect of the present application is a collagen production promoter comprising the ascorbic acid derivative of the third aspect of the present application. The collagen production promoter of the fifth aspect of the present application is stable in a wide pH range, exhibits excellent physiological activity, and exhibits particularly excellent collagen production promotion effects, and thus it is suitable for use as a collagen production promoter.

[0034] The sixth aspect of the present application is a hyaluronic acid production promoter comprising the ascorbic acid derivative of the first to third aspects of the present application. The sixth aspect of the present application is stable in a wide pH range, has excellent physiological activity, and exhibits excellent hyaluronic acid production promotion effects, and thus it is suitable for use as a hyaluronic acid production promoter.

[0035] Among the hyaluronic acid production promoters of the sixth aspect of the present application, the hyaluronic acid production promoter characterized by comprising the ascorbic acid derivative of the third aspect of the present application has particularly excellent hyaluronic acid production promotion effects, and thus it is even more preferably used as a hyaluronic acid production promoter.

[0036] Effects of the Invention

[0037] The ascorbic acid derivative represented by General Formula (1), (3), or (4) of the present application has the excellent functions of ascorbic acid as originally, such as moisturizing effects, is stable in a wide pH range even after long-term storage, has almost no discoloration, taste change, or activity reduction, and has high physiological activity, such as collagen production promotion effects and hyaluronic acid production promotion effects. Thus, by blending the ascorbic acid derivative represented by General Formula (1), (3), or (4) into a cosmetic, such as a skin external preparation and a hair cosmetic, it is possible to provide a cosmetic, such as a moisturizing cosmetic, that has excellent moisturizing effects, is stable even after long-term storage, and has high physiological activity. Furthermore, by blending the ascorbic acid derivative represented by General Formula (1), (3), or (4), it is possible to provide a collagen production promoter that exhibits excellent collagen production promotion effects and a hyaluronic acid production promoter that has excellent hyaluronic acid production promotion effects. DETAILED DESCRIPTION

[0038] Embodiments of the present application are described below, but the scope of the present application is not limited to the embodiments described below.

[0039] Specific examples of the ascorbic acid derivative represented by General Formula (1), (3) or (4) include 2,3-O-(l,2-ethanediyl) ascorbic acid, 2,3-O-(l,3-propanediyl) ascorbic acid, 2,3-O-(l,4-butanediyl) ascorbic acid, 2,3-O-(2-hydroxypropane-l,3-diyl) ascorbic acid, 2,3-O-(l-hydroxymethyl-l,2-ethanediyl) ascorbic acid, 2,3-O-(2-hydroxymethyl-l,2-ethanediyl) ascorbic acid, 2,3-O-(3,3-dimethyleneoxetane) ascorbic acid, 2,3-O-(2,2-dimethyl-l,2-ethanediyl) ascorbic acid, 2,3-O-(l,l-dimethyl-l,2-ethanediyl) ascorbic acid,

[0040] 6-O-butyryl-2,3-O-(l,4-butanediyl) ascorbic acid, 5,6-O-dibutyryl-2,3-O-(l,4-butanediyl) ascorbic acid, 6-O-octanoyl-2,3-O-(l,4-butanediyl) ascorbic acid, 5,6-O-dioctanoyl-2,3-O-(l,4-butanediyl) ascorbic acid, 6-O-lauroyl-2,3-O-(l,4-butanediyl) ascorbic acid, 5,6-O-dilauroyl-2,3-O-(l,4-butanediyl) ascorbic acid, 6-O-palmitoyl-2,3-O-(l,4-butanediyl) ascorbic acid, 5,6-O-dipalmitoyl-2,3-O-(l,4-butanediyl) ascorbic acid, 6-O-isostearoyl-2,3-O-(l,4-butanediyl) ascorbic acid, 5,6-O-diisostearoyl-2,3-O-(l,4-butanediyl) ascorbic acid, 5-O-butyryl-6-O-octanoyl-2,3-O-(l,4-butanediyl) ascorbic acid,

[0041] 6-O-butyryl-2,3-O-(l,3-propanediyl) ascorbic acid, 5,6-O-dibutyryl-2,3-O-(l,3- propanediyl) ascorbic acid, 6-O-octanoyl-2,3-O-(l,3-propanediyl) ascorbic acid, 5,6-O- dioctanoyl-2,3-O-(l,3-propanediyl) ascorbic acid, 6-O-lauroyl-2,3-O-(l,3-propanediyl) ascorbic acid, 5,6-O-dilauroyl-2,3-O-(l,3-propanediyl) ascorbic acid, 6-O-palmitoyl-2,3-O- (l,3-propanediyl) ascorbic acid, 5,6-O-dipalmitoyl-2,3-O-(l,3-propanediyl) ascorbic acid, 6-O- isostearoyl-2,3-O-(l,3-propanediyl) ascorbic acid, 5,6-O-diisostearoyl-2,3-O-(l,3- propanediyl) ascorbic acid, 5-butyryl-6-O-palmitoyl-2,3-O-(l,3-propanediyl) ascorbic acid,

[0042] 6-O-isostearoyl-2,3-O-(l,2-ethanediyl) ascorbic acid, 5,6-O-diisostearoyl-2,3-O-(l,2- ethanediyl) ascorbic acid,

[0043] 5,6-O-isopropylidene-2,3-O-(l,3-propanediyl) ascorbic acid, 5,6-O-isopropylidene-2,3-O- (l,4-butanediyl) ascorbic acid,

[0044] 5,6-O-(phenylmethylene)-2,3-O-(l,3-propanediyl) ascorbic acid, 5,6-O-(phenylmethylene)- 2,3-O-(l,4-butanediyl) ascorbic acid, 4-hydroxy-2,6,9,14-tetraoxatricyclo[6.6.0.0 1.5 ]tetradecan-7-one, 4-hydroxy-2,6,9,13-tetraoxatricyclo[6.5.0.0 1.5 ]tridecan-7-one, and 6-O-benzyl-2,3-O-(l,4-butanediyl) ascorbic acid.

[0045] The ascorbic acid derivatives represented by general formulae (1), (3) or (4) can be produced by various methods.

[0046] For example, a dihaloalkane, 2-halomethyl oxirane, bis-halomethyl oxetane, or the like can be allowed to react with the hydroxyl groups at the 2- and 3-positions of ascorbic acid to form a cyclic structure from the hydroxyl groups, and then acylation, alkylation, benzylation, or acetalization can be performed on the oxygen atoms bonded to the 5- and 6-positions by known means, thereby obtaining an ascorbic acid derivative represented by General Formula (1) or (3). Alternatively, acylation, alkylation, benzylation, or acetalization can be performed on the oxygen atoms bonded to the 5- and 6-positions of ascorbic acid by known means, and then a dihaloalkane or the like is used to form a cyclic structure from the hydroxyl groups at the 2- and 3-positions by known means, thereby obtaining an ascorbic acid derivative represented by General Formula (1) or (3).

[0047] An ascorbic acid derivative represented by General Formula (4) can be obtained by forming a cyclic structure from the hydroxyl groups at the 2- and 3-positions of ascorbic acid (as described above), followed by intramolecular reaction in the presence of a strong base and then in the presence of a strong acid.

[0048] Examples of compounds capable of reacting with the hydroxyl groups at the 2- and 3-positions of ascorbic acid to form a cyclic structure include, but are not limited to, dihaloalkanes, 2-halomethyl oxiranes, and bis-halomethyl oxetanes.

[0049] Examples of dihaloalkanes include dibromoethane, dibromopropane, dibromobutane, dichloroethane, dichloropropane, dichlorobutane, diiodoethane, diiodopropane, and diiodobutane.

[0050] Examples of 2-halomethyl oxiranes include 2-bromomethyl oxirane, 2-chloromethyl oxirane, and 2-iodomethyl oxirane.

[0051] Examples of bis-halomethyl oxetanes include bis-bromomethyl oxetane and bis-chloromethyl oxetane.

[0052] In the synthesis of the ascorbic acid derivative represented by General Formula (1), (3), or (4), the amount of the dihaloalkane, 2-halomethyl oxirane, or bis-halomethyl oxetane used to form a cyclic structure by reaction with the hydroxyl groups at the 2- and 3-positions of ascorbic acid is not particularly limited, but is preferably 0.5 to 2.0 mol, more preferably 1.0 to 1.5 mol, per 1 mol of ascorbic acid.

[0053] Specifically, an ascorbic acid derivative represented by General Formula (1), (3), or (4) in which R 1 is -(CH2) n * (n is an integer of 2 to 4) can be obtained by allowing ascorbic acid to react with a dihaloalkane (having 2 to 4 carbon atoms) to form a cyclic structure between the hydroxyl groups at the 2- and 3-positions of ascorbic acid and the dihaloalkane.

[0054] Further, the ascorbic acid derivative represented by general formula (1), (3) or (4) wherein R 1 is -CH2CH(OH)CH2-* or wherein R 1 is -CH2CH(CH2OH)-* or -CH(CH2OH)CH2-*.

[0055] Further, the ascorbic acid derivative represented by general formula (1), (3) or (4) wherein R 1 is a divalent group represented by general formula (2) can be obtained by reacting ascorbic acid with a dihalomethyloxetane to form a cyclic structure from the hydroxyl groups at the 2- and 3-positions of ascorbic acid.

[0056] The reaction described above for synthesizing the ascorbic acid derivative represented by general formula (1), (3) or (4) can be carried out in various solvents. Examples of the solvent include water, lower alcohols (such as methanol, ethanol and isopropanol), dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), dioxane, tetrahydrofuran (THF), N-methylpyrrolidone, acetonitrile and mixtures thereof, and are not particularly limited. The reaction temperature is not particularly limited, but is preferably in the range of 30 to 100°C, more preferably in the range of 50 to 90°C, and particularly preferably in the range of 60 to 90°C.

[0057] Examples of the pH adjuster used during the reaction include lactic acid, citric acid, glycolic acid, succinic acid, tartaric acid, malic acid, gluconic acid, sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, sodium bicarbonate, ammonium bicarbonate, triethylamine, diazabicycloundecene and p-toluenesulfonic acid monohydrate.

[0058] From the reaction product of the ascorbic acid derivative represented by general formula (1), (3) or (4) produced as described above, the desired compound can be isolated and purified by means of HPLC (liquid chromatography), column chromatography using silica gel, column chromatography using a resin (such as an ion exchange resin), activated carbon treatment, extraction, distillation, crystallization and the like.

[0059] Further, the ascorbic acid derivative having a cyclic structure formed from the hydroxyl groups at the 2- and 3-positions can be produced by synthesizing the ascorbic acid derivative having a cyclic structure formed from the hydroxyl groups at the 2- and 3-positions as described above, and then carrying out various known methods.

[0060] The ascorbic acid derivative represented by general formula (1) wherein R 1 is -(CH2) n - (n is an integer of 2 to 4) and R 2 and / or R3 Yes-COR 4 , a straight-chain or branched alkyl group or a benzyl group having 1 to 22 carbon atoms;

[0061] Ascorbic acid derivatives represented by the general formula (3), wherein R 1 Yes - (CH2) n -* (n is an integer from 2 to 4), and R 5 and / or R 6 is hydrogen, methyl or phenyl; and

[0062] Ascorbic acid derivatives represented by the general formula (4), wherein R 1 Yes - (CH2) n -* (n is an integer from 2 to 4).

[0063] For example, the ascorbic acid derivative having a cyclic structure can be mixed with various acid halides or various acid anhydrides, or by mixing the ascorbic acid derivative having a cyclic structure with various carboxylic acids in concentrated sulfuric acid to synthesize the compound wherein R 1 Yes - (CH2) n -* (n is an integer from 2 to 4) and R 2 and / or R 3 Yes-COR 4 Ascorbic acid derivatives represented by the general formula (1).

[0064] In addition, it can be synthesized by 5 is phenyl and R 6 is hydrogen, and then the ascorbic acid derivative represented by the general formula (3) is ring-opened using a reducing agent to produce an ascorbic acid derivative wherein R 1 Yes - (CH2) n -* (n is an integer from 2 to 4) and R 2 It is an ascorbic acid derivative represented by the general formula (1) which is a benzyl group.

[0065] Furthermore, an ascorbic acid derivative in which R is a ring structure formed by hydroxyl groups at the 2- and 3-positions can be produced by synthesizing an ascorbic acid derivative in which a ring structure is formed by hydroxyl groups at the 2- and 3-positions, and then reacting the resulting compound with a dialkoxyalkyl group, α,α-dialkoxytoluene, or the like under strong acid conditions. 1 Yes - (CH2) n -* (n is an integer from 2 to 4) and R 5 and / or R 6 An ascorbic acid derivative represented by the general formula (3) which is hydrogen, methyl or phenyl.

[0066] The compound wherein R can be produced by forming a ring structure from the 2- and 3-positions of ascorbic acid as described above, followed by an intramolecular reaction with a strong base, and then a reaction with a strong acid. 1 Yes - (CH2)n * (n is an integer of 2 to 4).

[0067] Examples of the acid halide which can be used in the above reaction include acetyl chloride, acetyl bromide, propionyl chloride, propionyl bromide, butyryl chloride, octanoyl chloride, nonanoyl chloride, decanoyl chloride, undecanoyl chloride, dodecanoyl chloride, tridecanoyl chloride, tetradecanoyl chloride, pentadecanoyl chloride, hexadecanoyl chloride, heptadecanoyl chloride, octadecanoyl chloride, nonadecanoyl chloride, eicosanoyl chloride, heneicosanoyl chloride, docosanoyl chloride, 2-ethylhexanoyl chloride, 3-ethylhexanoyl chloride, 5-methylheptanoyl chloride, isostearyl chloride (e.g., 2-octyldecanoyl chloride or 16-methylheptadecanoyl chloride), isononyl chloride, isodecyl chloride, isoundecyl chloride, isododecyl chloride, isotridecyl chloride, isotetradecyl chloride, isopentadecyl chloride, isohexadecyl chloride, isopentadecyl chloride, isononadecyl chloride, isoeicosyl chloride, isoheneicosyl chloride, and isodocosyl chloride.

[0068] When an acid halide derived from a branched fatty acid among the above acid halides is used, a commercially available product can contain a mixture of acid halides having different branching points, and thus a reaction product to which a fatty acid having a different branching point is added can be obtained as a by-product. For example, when a commercially available 16-methylheptadecanoyl chloride is used, a compound formed by reaction with 2-octyldecanoyl chloride having a different branching point can also be produced as a by-product. In this case, the ascorbic acid derivative of the present application also contains this by-product.

[0069] The amount of the acid halide to be used is not particularly limited. However, when the acid halide is mainly introduced into the 5-hydroxyl group or the 6-hydroxyl group, the amount thereof is preferably 0.5 to 2.0 mol, and particularly preferably 0.8 to 1.5 mol, per mol of the ascorbic acid derivative having a cyclic structure.

[0070] When the amount of the acid halide used is 1.5 to 5.0 mol, preferably 1.5 to 3.0 mol, per mol of the ascorbic acid derivative forming a cyclic structure, a mixture of a compound introduced into only one position and a compound introduced into both positions is obtained. Alternatively, after a compound having a hydroxyl group at the 5-position or the 6-position introduced under the above conditions is obtained, further reaction with an acid halide or the like can give a compound introduced into the hydroxyl groups at the 5-position and the 6-position.

[0071] As the dialkoxyalkyl or α,α-dialkoxytoluene used in the above reaction, dimethoxymethane, dimethoxypropane, α,α-dimethoxytoluene, or the like can be used. The amount of the dialkoxyalkyl or α,α-dialkoxytoluene used is not particularly limited, but is preferably 0.8 to 2.5 mol, and particularly preferably 1.0 to 2.0 mol, per mol of the ascorbic acid derivative having a cyclic structure.

[0072] The reaction with an acid halide, a dialkoxyalkyl group, or an α,α-dialkoxytoluene can be carried out by adjusting the solvent, the reaction temperature, and the pH in the same manner as in the reaction for forming the cyclic structure. Also, the ascorbic acid derivative of the present application having the desired structure can be obtained by purifying the reaction by means of chromatography using silica gel, column chromatography using a resin such as an ion exchange resin, activated carbon treatment, extraction, distillation, crystallization, and the like.

[0073] The ascorbic acid derivative of the present application can be suitably used as a component of various cosmetics such as skin external preparations and hair cosmetics, and also as a food additive, an animal feed, and the like.

[0074] When the ascorbic acid derivative of the present application is blended into various cosmetic preparations, the blending amount is preferably 1 to 20 mass% of the total amount of the cosmetic, and particularly preferably 3 to 10 mass%. If the blending amount is less than 1 mass%, the effect of the ascorbic acid derivative of the present application such as the hyaluronic acid production promoting effect cannot generally be sufficiently exerted. On the other hand, if the blending amount exceeds 20 mass%, the formulation system can be impaired, and even if the blending amount is increased, improvement of the effect can not be expected in many cases.

[0075] In addition to these essential ingredients, the cosmetic of the present application can contain, as needed, common ingredients such as an oily raw material, a surfactant, a moisturizer, a polymer compound, an antioxidant, a whitening agent, a drug, an ultraviolet absorber, a chelating agent, a protein, a protein hydrolysate or a derivative thereof, an amino acid or a derivative thereof, a pH adjuster, and a preservative. Although the ascorbic acid derivative of the present application also exhibits an effect as a moisturizer, other moisturizers can also be blended into the cosmetic of the present application as needed.

[0076] Examples of the oily raw material, the surfactant, the other moisturizer, the polymer compound, the antioxidant, the whitening agent, the other drug, the ultraviolet absorber, the chelating agent, the protein, the protein hydrolysate or a derivative thereof, the amino acid or a derivative thereof, the pH adjuster, and the preservative include substances similar to those described in WO2022 / 080287.

[0077] The cosmetic of the present application can be formulated in any formulation system including a solution system, a dissolution system, an emulsion system, a gel system, a powder dispersion system, and a water-oil double layer system. The cosmetic of the present application can be produced by blending the ascorbic acid derivative represented by the above general formula (1), (3), or (4) with the above optional ingredients according to the desired product.

[0078] Examples

[0079] Next, specific embodiments for implementing the present application will be described in detail with reference to the examples, but the scope of the present application is not limited to these examples. Before the examples, an example of production of the ascorbic acid derivative of the present application used in the examples will be shown as a synthesis example.

[0080] Synthesis Example 1

[0081] (Synthesis of 2,3-O-(l,2-ethanediyl) ascorbic acid)

[0082] DMF (9.0 g), ascorbic acid (0.88 g), potassium carbonate (0.76 g), and dibromoethane (1.03 g) were added to a flask and stirred at 80°C for 3 hours. After cooling, the mixture was filtered and concentrated under reduced pressure. The resulting residue (1.2 g) was subjected to silica gel chromatography and eluted with a mixture of chloroform / methanol / water (20 / 3 / 0.3). Further concentration under reduced pressure gave 2,3-O-(l,2-ethanediyl) ascorbic acid (0.505 g).

[0083] The resulting product was measured by mass spectrometry, 1 H-NMR, and 13 C-NMR, and the results confirmed that the product was 2,3-O-(l,2-ethanediyl) ascorbic acid represented by the following structural formula.

[0084] In the synthesis examples shown below, the obtained products were also measured by mass spectrometry, 1 H-NMR, and 13 C-NMR, and the results of these measurements confirmed that the products were ascorbic acid derivatives represented by the structural formulae or compound names shown in each synthesis example (including cases where the product is composed of two or more ascorbic acid derivatives), or that the products were mainly composed of ascorbic acid derivatives. The results of the mass spectrometry, 1 H-NMR, and 13 C-NMR measurements of the products obtained in each synthesis example are shown in Tables 1 to 9.

[0085] [Chemical Formula 5]

[0086]

[0087] Synthesis Example 2

[0088] (Synthesis of 2,3-O-(l,3-propanediyl) ascorbic acid)

[0089] DMF (35.0 g), ascorbic acid (3.50 g), potassium carbonate (3.0 g), and dibromopropane (4.4 g) were added to a flask and stirred at 80°C for 16 hours. After cooling, the mixture was filtered, and the filtrate was concentrated under reduced pressure. The resulting concentrate was dissolved in water. Extraction was performed using isobutanol, and the organic layer was recovered, to which magnesium sulfate was added. Subsequently, the mixture was filtered, and the filtrate was concentrated under reduced pressure. The resulting residue (4.2 g) was subjected to silica gel chromatography, eluted with a mixture of chloroform / methanol / water (20 / 3 / 0.3), and then concentrated under reduced pressure to obtain 2,3-O-(1,3-propanediyl) ascorbic acid represented by the following structural formula (0.56 g):

[0090] [Chemical Formula 6]

[0091]

[0092] Synthesis Example 3

[0093] (Synthesis of 2,3-O-(1,4-butanediyl) ascorbic acid)

[0094] DMF (35.0 g), ascorbic acid (3.50 g), potassium carbonate (3.0 g), and dibromopropane (4.4 g) were added to a flask and stirred at 80°C for 16 hours. After cooling, the mixture was filtered, and the filtrate was concentrated under reduced pressure. The resulting concentrate was dissolved in water. Extraction was performed using isobutanol, and the organic layer was recovered, to which magnesium sulfate was added. Subsequently, the mixture was filtered, and the filtrate was concentrated under reduced pressure. The resulting residue (4.2 g) was subjected to silica gel chromatography, eluted with a mixture of chloroform / methanol / water (20 / 3 / 0.3), and then concentrated under reduced pressure to obtain 2,3-O-(1,3-propanediyl) ascorbic acid represented by the following structural formula (0.56 g):

[0095] [Chemical Formula 7]

[0096]

[0097] Synthesis Example 4 and Synthesis Example 5

[0098] (Synthesis of 2,3-O-(2-hydroxypropane-1,3-diyl) ascorbic acid and 2,3-O-(1-hydroxymethyl-1,2-ethanediyl) ascorbic acid)

[0099] DMF (13.6 g), water (6.3 g), ascorbic acid (3.5 g), triethylamine (2.0 g), and 2-chloromethyloxirane (2.2 g) were added to a flask and stirred at 60°C for 3 hours. After cooling, the filtrate was concentrated under reduced pressure, and the resulting concentrate was dissolved in water. Extraction was performed using isobutyl alcohol, and the organic layer was recovered, to which magnesium sulfate was added. Subsequently, filtration was performed, and the filtrate was concentrated under reduced pressure. The resulting residue (2.4 g) was subjected to silica gel chromatography, eluted with a mixture of chloroform / methanol / water (15 / 3 / 0.3 to 10 / 3 / 0.3), and concentrated under reduced pressure to obtain a crude product (140 mg). The obtained crude product was separated and purified by HPLC to obtain 2,3-O-(2-hydroxypropane-l,3-diyl) ascorbic acid (58.0 mg) (Synthesis Example 4: represented by the structural formula on the left below) and 2,3-O-(l-hydroxymethyl-l,2-ethanediyl) ascorbic acid (6.6 mg) (Synthesis Example 5: represented by the structural formula on the right below).

[0100] [Chemical Formula 8]

[0101]

[0102] Synthesis Example 6

[0103] (Synthesis of 2,3-O-(3,3-dimethyleneoxetane) ascorbic acid)

[0104] DMF (5.0 g), ascorbic acid (0.528 g), potassium carbonate (0.456 g), and 3,3-bis(bromomethyl)oxetane (0.805 g) were added to a flask and stirred at 80°C for 7 hours. After cooling, the mixture was filtered, and the filtrate was concentrated under reduced pressure. The resulting concentrate was dissolved in water. Extraction was performed using isobutyl alcohol, and the organic layer was recovered, to which magnesium sulfate was added. Subsequently, the mixture was filtered, and the filtrate was concentrated under reduced pressure. The resulting residue (3.8 g) was subjected to silica gel chromatography, eluted with a chloroform / methanol / water mixture (20 / 3 / 0.3), and then concentrated under reduced pressure to obtain 2,3-O-(3,3-dimethyleneoxetane) ascorbic acid (0.144 g).

[0105] [Chemical Formula 9]

[0106]

[0107] Synthesis Example 7

[0108] (Synthesis of 2,3-O-(2,2-dimethyl-l,2-ethanediyl) ascorbic acid)

[0109] 2-O-(2-hydroxyisobutyl) ascorbic acid was synthesized by the method described in Synthesis Example 1 of JP 7267657 B1.

[0110] The synthesized 2-O-(2-hydroxyisobutyl) ascorbic acid (0.50 g), THF (5 ml), and p-toluenesulfonic acid monohydrate (0.52 g) were added to an eggplant-shaped flask and stirred at 80°C for 24 hours. After completion of the reaction, ion exchange water and isobutyl alcohol were added and the mixture was separated. The isobutyl alcohol layer was recovered and concentrated under reduced pressure. The obtained residue (0.60 g) was subjected to silica gel chromatography, eluted with a mixture of chloroform / methanol (10 / 0 to 9.5 / 0.5), and concentrated under reduced pressure to obtain 2,3-O-(2,2-dimethyl-1,2-ethanediyl) ascorbic acid (37.3 mg).

[0111] [Chemical Formula 10]

[0112]

[0113] Synthesis Example 8

[0114] (Synthesis of 2,3-O-(1,1-dimethyl-1,2-ethanediyl) ascorbic acid)

[0115] 3-O-(2-hydroxyisobutyl) ascorbic acid was synthesized by the method described in Synthesis Example 2 of JP 7267657 B1.

[0116] The synthesized 3-O-(2-hydroxyisobutyl) ascorbic acid (4.21 g), THF (25 ml), and p-toluenesulfonic acid monohydrate (4.19 g) were added to an eggplant-shaped flask and stirred at 90°C for 18 hours. After completion of the reaction, ion exchange water and ethyl acetate were added and the mixture was separated. The ethyl acetate was recovered and concentrated under reduced pressure. The obtained residue (0.21 g) was subjected to silica gel chromatography, eluted with a mixture of chloroform / methanol (10 / 0 to 9.5 / 0.5), and concentrated under reduced pressure to obtain 2,3-O-(1,1-dimethyl-1,2-ethanediyl) ascorbic acid (15.3 mg).

[0117] [Chemical Formula 11]

[0118]

[0119] Synthesis Example 9 and Synthesis Example 10

[0120] (Synthesis of 6-O-butyryl-2,3-O-(1,4-butanediyl) ascorbic acid and 5,6-O-dibutyryl-2,3-O-(1,4-butanediyl) ascorbic acid)

[0121] In a round-bottom flask was placed 2,3-O-(l,4-butanediyl) ascorbic acid (3.0 g) obtained in Synthesis Example 3, N-methylpyrrolidone (30.0 g), and triethylamine (5.1 g), and while stirring at 25°C, butyryl chloride (5.1 g) was added. After stirring at 25°C for 5 hours, the mixture was extracted with ethyl acetate. After washing with water three times, the organic layer was recovered, and magnesium sulfate was added thereto. Subsequently, the mixture was filtered and concentrated under reduced pressure. The obtained residue (2.5 g) was subjected to silica gel chromatography, eluted with a mixed solvent of hexane / ethyl acetate (4 / 1 to 1 / 1), and concentrated under reduced pressure, to obtain 6-O-butyryl-2,3-O-(l,4-butanediyl) ascorbic acid (0.9 g) (Synthesis Example 9: represented by the structural formula on the left below) and 5,6-O-dibutyryl-2,3-O-(l,4-butanediyl) ascorbic acid (1.4 g) (Synthesis Example 10: represented by the structural formula on the right below).

[0122] [Chemical Formula 12]

[0123]

[0124] Synthesis Examples 11 and 12

[0125] (Synthesis of 6-O-octanoyl-2,3-O-(l,4-butanediyl) ascorbic acid and 5,6-O-dioctanoyl-2,3-O-(l,4-butanediyl) ascorbic acid)

[0126] In a round-bottom flask was placed 2,3-O-(l,4-butanediyl) ascorbic acid (3.0 g) obtained in Synthesis Example 3, N-methylpyrrolidone (30.0 g), and triethylamine (5.1 g), and while stirring at 25°C, butyryl chloride (5.1 g) was added. After stirring at 25°C for 5 hours, the mixture was extracted with ethyl acetate. After washing with water three times, the organic layer was recovered, and magnesium sulfate was added thereto. Subsequently, the mixture was filtered and concentrated under reduced pressure. The obtained residue (2.5 g) was subjected to silica gel chromatography, eluted with a mixed solvent of hexane / ethyl acetate (4 / 1 to 1 / 1), and concentrated under reduced pressure, to obtain 6-O-butyryl-2,3-O-(l,4-butanediyl) ascorbic acid (0.9 g) (Synthesis Example 9: represented by the structural formula on the left below) and 5,6-O-dibutyryl-2,3-O-(l,4-butanediyl) ascorbic acid (1.4 g) (Synthesis Example 10: represented by the structural formula on the right below).

[0127] [Chemical Formula 13]

[0128]

[0129] Synthesis Example 13

[0130] Synthesis of 6-O-palmitoyl-2,3-O-(l,4-butanediyl) ascorbic acid

[0131] In a round-bottom flask was placed 2,3-O-(l,4-butanediyl) ascorbic acid (3.0 g) obtained in Synthesis Example 3, N-methylpyrrolidone (30.0 g), and triethylamine (1.7 g), and then lauroyl chloride (3.4 g) was added while stirring at 25°C. The mixture was stirred at 25°C for 4 hours and extracted with ethyl acetate. The mixture was washed with water three times, and the organic layer was recovered, to which magnesium sulfate was added. Then, the mixture was filtered and concentrated under reduced pressure. The resulting residue (6.1 g) was subjected to silica gel chromatography, eluted with a mixed solvent of hexane / ethyl acetate (8 / 3 to 1 / 1), and concentrated under reduced pressure to obtain 6-O-lauroyl-2,3-O-(l,4-butanediyl) ascorbic acid (3.1 g) represented by the following structural formula.

[0132] [Chemical Formula 14]

[0133]

[0134] Synthesis Example 14

[0135] Synthesis of 5,6-O-dilauroyl-2,3-O-(l,4-butanediyl) ascorbic acid

[0136] In a round-bottom flask was placed 6-O-lauroyl-2,3-O-(l,4-butanediyl) ascorbic acid (1.5 g) obtained in Synthesis Example 13, 4-dimethylaminopyridine (DMAP: 19.0 mg), and lauroyl chloride (1.2 g), followed by stirring at 25°C for 4 hours. The resulting residue (3.2 g) was subjected to silica gel chromatography, eluted with a mixed solvent of hexane / ethyl acetate (4 / 1), and concentrated under reduced pressure to obtain 5,6-O-dilauroyl-2,3-O-(l,4-butanediyl) ascorbic acid (0.9 g) represented by the following structural formula.

[0137] [Chemical Formula 15]

[0138]

[0139] Synthesis Example 15

[0140] Synthesis of 6-O-palmitoyl-2,3-O-(l,4-butanediyl) ascorbic acid

[0141] In a round-bottom flask was placed 2,3-O-(l,4-butanediyl) ascorbic acid (2.0 g) obtained in Synthesis Example 3, N-methylpyrrolidone (30.0 g), and triethylamine (1.1 g), and hexadecanoyl chloride (2.6 g) was added while stirring at 0°C. After stirring for 5 hours at 25°C, the mixture was extracted with ethyl acetate. The mixture was washed with water twice, and the organic layer was recovered, to which magnesium sulfate was added. Subsequently, the mixture was filtered and concentrated under reduced pressure. The resulting residue (4.7 g) was subjected to silica gel chromatography, eluted with a mixed solvent of hexane / ethyl acetate (5 / 1 to 1 / 1), and concentrated under reduced pressure to obtain 6-O-palmitoyl-2,3-O-(l,4-butanediyl) ascorbic acid (1.3 g) represented by the following structural formula.

[0142] [Chemical Formula 16]

[0143]

[0144] Synthesis Example 16

[0145] (Synthesis of 5,6-O-dipalmitoyl-2,3-O-(l,4-butanediyl) ascorbic acid)

[0146] In a round-bottom flask was placed 6-O-palmitoyl-2,3-O-(l,4-butanediyl) ascorbic acid (1.6 g) obtained in Synthesis Example 15, DMAP (22.0 mg), and hexadecanoyl chloride (1.8 g), followed by stirring for 4 hours at 60°C and then stirring for 16 hours at 25°C. The mixture was then extracted with a mixed solvent of hexane / ethyl acetate (1 / 1), and the organic layer was recovered, to which magnesium sulfate was added. The mixture was then filtered and concentrated under reduced pressure. The resulting residue (3.3 g) was subjected to silica gel chromatography, eluted with a mixed solvent of hexane / ethyl acetate (4 / 1), and then concentrated under reduced pressure to obtain 5,6-O-dipalmitoyl-2,3-O-(l,4-butanediyl) ascorbic acid (0.9 g) represented by the following structural formula.

[0147] [Chemical Formula 17]

[0148]

[0149] Synthesis Example 17 and Synthesis Example 18

[0150] (Synthesis of 6-O-isostearyl-2,3-O-(l,4-butanediyl) ascorbic acid and 5,6-O-diisostearyl-2,3-O-(l,4-butanediyl) ascorbic acid)

[0151] In a flask, 2,3-O-(l,4-butanediyl) ascorbic acid (3.0 g) obtained in Synthesis Example 3, N-methylpyrrolidone (30.0 g), and triethylamine (3.4 g) were added, and then isostearoyl chloride (9.4 g) was added while stirring at 25°C. After stirring at 25°C for 3 hours, the mixture was extracted with ethyl acetate. After washing with water twice, the organic layer was recovered, and magnesium sulfate was added thereto. Subsequently, the mixture was filtered and concentrated under reduced pressure. The obtained residue (9.8 g) was subjected to silica gel chromatography, eluted with a mixed solvent of hexane / ethyl acetate (4 / 1 to 1 / 1), and concentrated under reduced pressure, to obtain 6-O-isostearoyl-2,3-O-(l,4-butanediyl) ascorbic acid (2.5 g) (Synthesis Example 17: represented by the following upper structural formula) and 5,6-O-diisostearoyl-2,3-O-(l,4-butanediyl) ascorbic acid (1.8 g) (Synthesis Example 18: represented by the following lower structural formula).

[0152] [Chemical Formula 18]

[0153]

[0154] Synthesis Example 19

[0155] (Synthesis of 5-O-butyryl-6-O-octanoyl-2,3-O-(l,4-butanediyl) ascorbic acid)

[0156] In a flask, 6-O-octanoyl-2,3-O-(l,4-butanediyl) ascorbic acid (1.0 g) obtained in Synthesis Example 11, acetonitrile (5.0 g), and triethylamine (0.6 g) were added, and then butyryl chloride (0.5 g) was added while stirring at 25°C. The mixture was stirred at 25°C for 2 hours and extracted with ethyl acetate. The mixture was washed with water twice, and the organic layer was recovered, and magnesium sulfate was added thereto. Subsequently, the mixture was filtered and concentrated under reduced pressure. The obtained residue (1.5 g) was subjected to silica gel chromatography, eluted with a mixed solvent of hexane / ethyl acetate (4 / 1 to 3 / 1), and concentrated under reduced pressure, to obtain 5-O-butyryl-6-O-octanoyl-2,3-(l,4-butanediyl) ascorbic acid (0.8 g) represented by the following structural formula.

[0157] [Chemical Formula 19]

[0158]

[0159] Synthesis Example 20 and Synthesis Example 21

[0160] Synthesis of 6-O-butyryl-2,3-O-(l,3-propanediyl) ascorbic acid and 5,6-O-dibutyryl-2,3-O-(l,3-propanediyl) ascorbic acid

[0161] In a round-bottom flask was placed 2,3-O-(l,3-propanediyl) ascorbic acid (2.2 g) obtained in Synthesis Example 2, N-methylpyrrolidone (22.0 g), and triethylamine (5.0 g), and then butyryl chloride (2.6 g) was added while stirring at 25°C. The mixture was stirred at 25°C for 2 hours and extracted with ethyl acetate. The mixture was washed with water four times, and the organic layer was recovered, to which magnesium sulfate was added. Subsequently, the mixture was filtered and concentrated under reduced pressure. The resulting residue (4.2 g) was subjected to silica gel chromatography, eluted with a mixed solvent of hexane / ethyl acetate (3 / 1 to 2 / 3), and concentrated under reduced pressure to obtain 6-O-butyryl-2,3-O-(l,3-propanediyl) ascorbic acid (0.7 g) (Synthesis Example 20: represented by the structural formula on the left below) and 5,6-O-dibutyryl-2,3-O-(l,3-propanediyl) ascorbic acid (1.9 g) (Synthesis Example 21: represented by the structural formula on the right below).

[0162] [Chemical Formula 20]

[0163]

[0164] Synthesis Example 22 and Synthesis Example 23

[0165] Synthesis of 6-O-butyryl-2,3-O-(l,3-propanediyl) ascorbic acid and 5,6-O-dibutyryl-2,3-O-(l,3-propanediyl) ascorbic acid

[0166] In a round-bottom flask was placed 2,3-O-(l,3-propanediyl) ascorbic acid (2.2 g) obtained in Synthesis Example 2, N-methylpyrrolidone (22.0 g), and triethylamine (5.0 g), and then octanoyl chloride (6.0 g) was added while stirring at 25°C. The mixture was stirred at 25°C for 3 hours and extracted with ethyl acetate. The mixture was washed with water four times, and the organic layer was recovered, to which magnesium sulfate was added. Subsequently, the mixture was filtered and concentrated under reduced pressure. The resulting residue (7.6 g) was subjected to silica gel chromatography, eluted with a mixed solvent of hexane / ethyl acetate (4 / 1 to 1 / 1), and concentrated under reduced pressure to obtain 6-O-octanoyl-2,3-O-(l,3-propanediyl) ascorbic acid (1.3 g) (Synthesis Example 22: represented by the structural formula on the left below) and 5,6-O-dioctanoyl-2,3-O-(l,3-propanediyl) ascorbic acid (2.3 g) (Synthesis Example 23: represented by the structural formula on the right below).

[0167] [Chemical Formula 21]

[0168]

[0169] Synthesis Example 24 and Synthesis Example 25

[0170] (Synthesis of 6-O-palmitoyl-2,3-O-(l,3-propanediyl) ascorbic acid and 5,6-O-dipalmitoyl-2,3-O-(l,3-propanediyl) ascorbic acid)

[0171] In a pyrex flask was placed 2,3-O-(l,3-propanediyl) ascorbic acid (2.2 g) obtained in Synthesis Example 2, N-methylpyrrolidone (22.0 g) and triethylamine (11.0 g), and then lauroyl chloride (7.8 g) was added while stirring at room temperature. The mixture was stirred at 25°C for 3 hours and extracted with ethyl acetate. The mixture was washed with water three times, and the organic layer was recovered, to which was added magnesium sulfate. Subsequently, the mixture was filtered and concentrated under reduced pressure. The resulting residue (6.6 g) was subjected to silica gel chromatography, eluted with a mixed solvent of hexane / ethyl acetate (4 / 1 to 1 / 1), and concentrated under reduced pressure to obtain 6-O-lauroyl-2,3-O-(l,3-propanediyl) ascorbic acid (1.3 g) (Synthesis Example 24: represented by the following upper structural formula) and 5,6-O-dilauroyl-2,3-O-(l,3-propanediyl) ascorbic acid (2.3 g) (Synthesis Example 25: represented by the following lower structural formula).

[0172] [Chemical Formula 22]

[0173]

[0174] Synthesis Example 26 and Synthesis Example 27

[0175] (Synthesis of 6-O-palmitoyl-2,3-O-(l,3-propanediyl) ascorbic acid and 5,6-O-dipalmitoyl-2,3-O-(l,3-propanediyl) ascorbic acid)

[0176] In a flask, 2,3-O-(l,3-propanediyl) ascorbic acid (3.0 g) obtained in Synthesis Example 2, N-methylpyrrolidone (30.0 g), and triethylamine (1.8 g) were added, and then isostearoyl chloride (5.0 g) was added with stirring. The mixture was stirred at 25°C for 4 hours and extracted with ethyl acetate. The mixture was washed with water three times, and the organic layer was recovered, to which magnesium sulfate was added. Subsequently, the mixture was filtered and concentrated under reduced pressure. The obtained residue (8.6 g) was subjected to silica gel chromatography, eluted with a mixed solvent of hexane / ethyl acetate (4 / 1 to 1 / 1), and concentrated under reduced pressure, to obtain 6-O-isostearoyl-2,3-O-(l,3-propanediyl) ascorbic acid (2.4 g) represented by the following structural formula.

[0177] [Chemical Formula 23]

[0178]

[0179] Synthesis Example 28

[0180] (Synthesis of 6-O-isostearoyl-2,3-O-(l,3-propanediyl) ascorbic acid)

[0181] In a flask, 2,3-O-(l,3-propanediyl) ascorbic acid (3.0 g) obtained in Synthesis Example 2, N-methylpyrrolidone (30.0 g), and triethylamine (1.8 g) were added, and then isostearoyl chloride (5.0 g) was added with stirring. The mixture was stirred at 25°C for 4 hours and extracted with ethyl acetate. The mixture was washed with water three times, and the organic layer was recovered, to which magnesium sulfate was added. Subsequently, the mixture was filtered and concentrated under reduced pressure. The obtained residue (8.6 g) was subjected to silica gel chromatography, eluted with a mixed solvent of hexane / ethyl acetate (4 / 1 to 1 / 1), and concentrated under reduced pressure, to obtain 6-O-isostearoyl-2,3-O-(l,3-propanediyl) ascorbic acid (2.4 g) represented by the following structural formula.

[0182] [Chemical Formula 24]

[0183]

[0184] Synthesis Example 29

[0185] (Synthesis of 5,6-O-diisostearoyl-2,3-O-(l,3-propanediyl) ascorbic acid)

[0186] In a round-bottom flask was placed 6-isostearoyl-2,3-O-(l,3-propanediyl) ascorbic acid (1.4 g) obtained in Synthesis Example 28, DMAP (22.0 mg), and isostearoyl chloride (1.4 g). Then, N-methylpyrrolidone (14.0 g) was added, and the mixture was stirred at 25°C for 7 hours and concentrated under reduced pressure. The resulting residue (3.8 g) was subjected to silica gel chromatography, eluted with a mixed solvent of hexane / ethyl acetate (4 / 1), and concentrated under reduced pressure to obtain 5,6-O-diisostearoyl-2,3-O-(l,3-propanediyl) ascorbic acid (0.17 g) represented by the following structural formula.

[0187] [Chemical Formula 25]

[0188]

[0189] Synthesis Example 30

[0190] (Synthesis of 5-butyryl-6-O-palmitoyl-2,3-O-(l,3-propanediyl) ascorbic acid)

[0191] In a round-bottom flask was placed 6-O-palmitoyl-2,3-O-(l,3-propanediyl) ascorbic acid (0.8 g) obtained in Synthesis Example 26, acetonitrile (4.0 g), and triethylamine (0.36 g), and then butyryl chloride (0.3 g) was added while stirring at 25°C. The mixture was stirred at 25°C for 2 hours and extracted with ethyl acetate. The mixture was washed with water twice, and the organic layer was recovered, to which magnesium sulfate was added. Subsequently, the mixture was filtered and concentrated under reduced pressure. The resulting residue (0.9 g) was subjected to silica gel chromatography, eluted with a mixed solvent of hexane / ethyl acetate (4 / 1 to 3 / 1), and concentrated under reduced pressure to obtain 5-O-butyryl-6-O-palmitoyl-2,3-O-(l,3-propanediyl) ascorbic acid (0.6 g) represented by the following structural formula.

[0192] [Chemical Formula 26]

[0193]

[0194] Synthesis Example 31 and Synthesis Example 32

[0195] (Synthesis of 6-O-isostearoyl-2,3-O-(l,2-ethanediyl) ascorbic acid and 5,6-O-diisostearoyl-2,3-O-(l,2-ethanediyl) ascorbic acid)

[0196] In a flask, 2,3-O-(l,2-ethanediyl) ascorbic acid (1.9 g) obtained in Synthesis Example 1, N-methylpyrrolidone (20.0 g), and triethylamine (4.8 g) were added, and isostearoyl chloride (6.8 g) was added while stirring at 25°C. The mixture was stirred at 25°C for 3 hours and extracted with ethyl acetate. The mixture was washed with water four times, and the organic layer was recovered, to which magnesium sulfate was added. Subsequently, the mixture was filtered and concentrated under reduced pressure. The obtained residue (9.2 g) was subjected to silica gel chromatography, eluted with a mixed solvent of hexane / ethyl acetate (4 / 1 to 1 / 1), and concentrated under reduced pressure, to obtain 6-O-isostearoyl-2,3-O-(l,2-ethanediyl) ascorbic acid (1.0 g) (Synthesis Example 31: represented by the following upper structural formula) and 5,6-O-diisostearoyl-2,3-O-(l,2-ethanediyl) ascorbic acid (1.0 g) (Synthesis Example 32: represented by the following lower structural formula).

[0197] [Chemical Formula 27]

[0198]

[0199] Synthesis Example 33

[0200] Synthesis of (4-hydroxy-2,6,9,14-tetraoxatricyclo[6.6.0.0 1.5 ]tetradecan-7-one)

[0201] In a flask, 2,3-O-(l,4-butanediyl) ascorbic acid (1.3 g) obtained in Synthesis Example 3, water (8.0 g), and isopropyl alcohol (2.0 g) were added, and 10% sodium hydroxide aqueous solution (4.5 g) was added while stirring at 25°C, followed by stirring at 25°C for 30 minutes. Subsequently, 17% hydrochloric acid aqueous solution (2.4 g) was added, and the mixture was allowed to stand at 25°C for 16 hours, followed by extraction with ethyl acetate. The mixture was washed with water three times, and the organic layer was recovered, to which magnesium sulfate was added. Subsequently, the mixture was filtered and concentrated under reduced pressure. The obtained residue (0.4 g) was subjected to silica gel chromatography, eluted with a mixed solvent of hexane / ethyl acetate (3 / 1 to 1 / 1), and concentrated under reduced pressure, to obtain 4-hydroxy-2,6,9,14-tetraoxatricyclo[6.6.0.0 1.5 ]tetradecan-7-one (125 mg) represented by the following structural formula.

[0202] [Chemical Formula 28]

[0203]

[0204] Synthesis Example 34

[0205] (4-hydroxy-2,6,9, 13-tetraoxatricyclo[6.5.0.0 1.5 ]tridecan-7-one)

[0206] In a round-bottom flask, 2,3-O-(l,3-propanediyl) ascorbic acid (2.5 g) obtained in Synthesis Example 2, water (16.0 g), and isopropanol (4.0 g) were added. While stirring at 25°C, 10% sodium hydroxide aqueous solution (9.0 g) was added, followed by stirring at 25°C for 8 hours. Then, 17% hydrochloric acid aqueous solution (7.5 g) was added, and the mixture was allowed to stand at 25°C for 16 hours. Ethyl acetate was then added for extraction. The mixture was washed with water three times, and the organic layer was recovered, to which magnesium sulfate was added. Subsequently, the mixture was filtered and concentrated under reduced pressure. The resulting residue (1.7 g) was subjected to silica gel chromatography, eluted with a mixed solvent of hexane / ethyl acetate (1 / 1), and concentrated under reduced pressure, to obtain 4-hydroxy-2,6,9, 13-tetraoxatricyclo[6.5.0.0 1.5 ]tridecan-7-one (464 mg) represented by the following structural formula.

[0207] [Chemical Formula 29]

[0208]

[0209] Synthesis Example 35

[0210] (Synthesis of 5,6-O-isopropylidene-2,3-O-(l,4-butanediyl) ascorbic acid)

[0211] In a round-bottom flask, 2,3-O-(l,4-butanediyl) ascorbic acid (920 mg) obtained in Synthesis Example 3, acetonitrile (9.0 mL), 2,2-dimethoxypropane (824 mg), and p-toluenesulfonic acid monohydrate (76 mg) were sequentially added, and the mixture was stirred at 25°C for 2 hours. The mixture was neutralized with triethylamine and concentrated under reduced pressure. To the resulting concentrate, ethyl acetate was added for extraction. The mixture was washed with water once and with saturated brine twice, and magnesium sulfate was added to the recovered organic layer. The mixture was then filtered and concentrated under reduced pressure. The resulting residue (1.1 g) was dissolved in a mixed solvent of hexane / ethyl acetate (5 / 3) with heating, allowed to cool, and then allowed to stand at room temperature overnight. The precipitated solid was collected by filtration, washed with hexane, and vacuum-dried, to obtain 5,6-O-isopropylidene-2,3-O-(l,4-butanediyl) ascorbic acid (619 mg) represented by the following structural formula.

[0212] [Chemical Formula 30]

[0213]

[0214] Synthesis Example 36

[0215] Synthesis of (5,6-O-isopropylidene-2,3-O-(l,3-propanediyl) ascorbic acid

[0216] In a round-bottom flask, 2,3-O-(l,3-propanediyl) ascorbic acid (650 mg) obtained in Synthesis Example 2, acetone (6.0 mL), 2,2-dimethoxypropane (620 mg), and p-toluenesulfonic acid monohydrate (57 mg) were sequentially added, and the mixture was stirred at 25°C for 2.5 hours. The mixture was neutralized with an aqueous sodium hydroxide solution and concentrated under reduced pressure, and to the resulting concentrate was added ethyl acetate for extraction. The mixture was washed once with water and twice with saturated brine, and to the recovered organic layer was added magnesium sulfate. The mixture was then filtered and concentrated under reduced pressure. The resulting residue (750 mg) was dissolved in a mixture of isopropyl alcohol and methanol (3 / 2) with heating, allowed to cool, and then allowed to stand at room temperature overnight. The precipitated solid was collected by filtration, washed with isopropyl alcohol, and vacuum-dried to obtain 5,6-O-isopropylidene-2,3-O-(l,3-propanediyl) ascorbic acid (303 mg) represented by the following structural formula.

[0217] [Chemical Formula 31]

[0218]

[0219] Synthesis Example 37

[0220] Synthesis of (5,6-O-(phenylmethylidene)-2,3-O-(l,4-butanediyl) ascorbic acid

[0221] In a round-bottom flask, 2,3-O-(l,4-butanediyl) ascorbic acid (920 mg) obtained in Synthesis Example 3, acetonitrile (9.0 mL), α,α-dimethoxytoluene (669 mg), and p-toluenesulfonic acid monohydrate (76 mg) were sequentially added, and the mixture was stirred at 25°C for 19 hours. The mixture was neutralized with triethylamine and concentrated under reduced pressure. To the resulting concentrate were sequentially added water and ethyl acetate, and the concentrate was washed. The solid was recovered by filtration and vacuum-dried to obtain 5,6-O-(phenylmethylidene)-2,3-O-(l,4-butanediyl) ascorbic acid (226 mg) represented by the following structural formula.

[0222] [Chemical Formula 32]

[0223]

[0224] Synthesis Example 38

[0225] Synthesis of (5,6-O-(phenylmethylene)-2,3-O-(1,3-propanediyl) ascorbic acid)

[0226] In a round-bottom flask, 2,3-O-(1,3-propanediyl) ascorbic acid (650 mg) obtained in Synthesis Example 2, acetonitrile (6.0 mL), a,a-dimethoxytoluene (502 mg), and p-toluenesulfonic acid monohydrate (57 mg) were sequentially added, and the mixture was stirred at 25°C for 5 hours. The mixture was neutralized with triethylamine and concentrated under reduced pressure. The concentrate was washed with water, and then with a mixture of hexane / ethyl acetate (5 / 1). The solid was collected by filtration and vacuum-dried to obtain 5,6-O-(phenylmethylene)-2,3-O-(1,3-propanediyl) ascorbic acid (303 mg) represented by the following structural formula.

[0227] [Chemical Formula 33]

[0228]

[0229] Synthesis Example 39

[0230] Synthesis of (6-O-benzyl-2,3-O-(1,4-butanediyl) ascorbic acid)

[0231] In a round-bottom flask, 2,3-O-(1,4-butanediyl) ascorbic acid (318 mg) obtained in Synthesis Example 3 and DMF (5.0 mL) were added. While being cooled in an ice bath, 2-methylpyridine borane (1,000 mg) and trimethylchlorosilane (543 mg) were added, and then the mixture was stirred in a 50°C water bath for 1 hour. Ice water was added, followed by stirring for another 1 hour. Ethyl acetate (10 mL) was added and the mixture was separated. The organic layer was recovered, and the aqueous layer was extracted with ethyl acetate (50 mL). The recovered organic layer was washed twice with saturated brine (50 mL). Magnesium sulfate was added, followed by filtration and concentration under reduced pressure. The resulting residue (750 mg) was subjected to silica gel chromatography, eluted with a mixed solvent of hexane / ethyl acetate (1 / 1 to 1 / 2), and concentrated under reduced pressure to obtain 6-O-benzyl-2,3-O-(1,4-butanediyl) ascorbic acid (90 mg).

[0232] [Chemical Formula 34]

[0233]

[0234] The products obtained in Synthesis Examples 1 to 39 were subjected to mass spectrometric analysis using LCMS-2020 (manufactured by Shimadzu Corporation). The measurement results are shown in Tables 1 and 2.

[0235] [Table ]

[0236]

[0237] * Ionization was performed by electrospray ionization (ESI).

[0238] [Table 2]

[0239]

[0240] * Ionization was performed by electrospray ionization (ESI).

[0241] The product obtained in Synthesis Examples 1 to 39 was subjected to1H-NMR measurement using JNM-ECS400 (manufactured by JEOL Ltd.). 1 The measurement results are shown in Tables 3 to 6.

[0242] [Table 3]

[0243]

[0244] [Table 4]

[0245]

[0246] [Table 5]

[0247]

[0248] [Table 6]

[0249]

[0250] The product obtained in Synthesis Examples 1 to 39 was subjected to13C-NMR measurement using JNM-ECS400 (manufactured by JEOL Ltd.). 13 The measurement results are shown in Tables 7 to 9.

[0251] [Table 7]

[0252]

[0253] [Table 8]

[0254]

[0255] [Table 9]

[0256]

[0257] Test Example 1 [Stability Test-1]

[0258] For each sample of Synthesis Examples 1 to 6, a 1% aqueous solution was adjusted to pH 3, 5, 7, 8 and 9 with a dilute aqueous potassium hydroxide solution, then put into a 50 mL screw tube and sealed. After storage at 50°C for 4 weeks, HPLC measurement was performed (using a liquid chromatograph manufactured by Shimadzu Corporation), and the residual rate was calculated from the peak area. The results on the residual rate based on the following criteria are shown in Table 10. In addition, the odor and coloring of the sample adjusted to pH 7 were evaluated based on the following method and criteria, and the results are shown in Table 11.

[0259] Residual rate:

[0260] ◎: 80% or more

[0261] O: 50% or more, less than 80%

[0262] △: 30% or more, less than 50%

[0263] X: less than 30%

[0264] Odor:

[0265] The evaluation was performed by 10 panelists according to the following criteria.

[0266] 3: Almost no odor.

[0267] 2: Slight odor.

[0268] 1: Strong odor was detected.

[0269] Based on the results of the above evaluation, the following classification was made:

[0270] O: Total score of 10 panelists was 25 or more

[0271] △: Total score of 10 panelists was 16 to 24

[0272] X: Total score of 10 panelists was less than 15

[0273] Coloring:

[0274] The evaluation was performed by 10 panelists according to the following criteria.

[0275] 3: Almost no change compared to immediately after preparation.

[0276] 2: Color change compared to immediately after preparation.

[0277] 1: Strong coloring compared to immediately after preparation.

[0278] Based on the results of the above evaluation, the following classification was made:

[0279] O: Total score of 10 panelists was 25 or more

[0280] △: Total score of 10 judges is 16-24

[0281] X: Total score of 10 judges is 15 or less

[0282] [Table 10]

[0283]

[0284] [Table 11]

[0285]

[0286] Test Example 2 [Stability Test-2]

[0287] For each sample of Synthesis Examples 9 to 32, (a) and (b) shown in Table 12 were heated and mixed, respectively. After cooling, (c) shown in Table 12 was added to prepare a cream having a pH of 7 or 9. The sample was stored at 50°C for 4 weeks, and the residual rate was measured in the same manner as in Test Example 1, and evaluated according to the criteria described below. The odor and coloring were also evaluated according to the same method and criteria as in Test Example 1. The results on the residual rate are shown in Tables 13 and 14, and the results on the odor and coloring are shown in Tables 15 and 16.

[0288] Residual rate:

[0289] ◎: 95% or more

[0290] O: 85% or more and less than 95%

[0291] X: Less than 85%

[0292] [Table 12]

[0293]

[0294] [Table 13]

[0295]

[0296] [Table 14]

[0297]

[0298] [Table 15]

[0299]

[0300] [Table 16]

[0301]

[0302] The results of the above test examples show that the ascorbic acid derivative represented by the general formula (1) of the present application exhibits excellent stability over time, in which the residual rate does not decrease compared to ascorbic acid and conventional ascorbic acid derivatives when stored at 50°C, and also substantially no odor and coloring. In Test Example 1, in the neutral to weakly basic range of pH 7 to 9, the residual rates of ascorbic acid and conventional ascorbic acid derivatives decreased to less than 30% after two weeks, whereas the ascorbic acid derivative represented by the general formula (1) of the present application maintained a residual rate of 50% or more after two weeks, and even after four weeks, the residual rate thereof was much higher than that of ascorbic acid and conventional ascorbic acid derivatives.

[0303] Similarly, it is evident in Test Example 2 that the ascorbic acid derivative represented by the general formula (1) of the present application has higher stability than ascorbic acid tetrahexyldecyl ester, a conventional ascorbic acid derivative, in the neutral to weakly basic range of pH 7 to 9. The ascorbic acid derivative represented by the general formula (1) of the present application has excellent properties inherent to ascorbic acid, and the results shown in Tables 10, 11, and 13 to 16 further confirm that the stability over time, which is a problem of conventional ascorbic acid derivatives, is improved, thereby making it more suitable as a component material for cosmetics.

[0304] Test Example 3 [Collagen production promoting effect]

[0305] Normal human dermal fibroblasts were prepared to a cell density of 2.5 x 10 4 After removal of the culture medium, a sample prepared to a predetermined concentration in D-MEM containing 5% (v / v) fetal bovine serum was added to each well and cultured for 48 hours. After completion of the culture, the amount of free collagen in the supernatant was quantified by ELISA. The measurement was repeated three times (N = 3).

[0306] The amount of collagen produced when the sample was measured at a concentration of 10 mM or less was compared to that produced by the control group, and the results (% value when the control group was set to 100%) are shown in Table 17 based on the following criteria.

[0307] <100%: ±

[0308] 100-140%: +

[0309] 140%<: ++

[0310] [Table 17]

[0311]

[0312] The results in Table 17 clearly indicate that the ascorbic acid derivatives of the present application represented by General Formula (1) have the same or greater collagen production promoting effect as the known ascorbic acid derivatives (i.e., 2-O-glyceryl ascorbic acid and 3-O-glyceryl ascorbic acid).

[0313] Test Example 4 [Hyaluronic acid production promoting effect]

[0314] Normal human dermal fibroblasts (NHDF) were prepared to a cell density of 2.5 x 10 4 cells / well in D-MEM containing 5% (v / v) fetal bovine serum, and then pre-incubated for 24 hours in a 96-well plate. After removal of the culture medium, samples prepared in serum-free D-MEM were added to each well, and cultured for 48 hours. After completion of the culture, the amount of hyaluronic acid in the supernatant was quantified by ELISA. Measurement was repeated three times (N = 3).

[0315] The amount of hyaluronic acid produced when the sample was measured at a concentration of 10 mM or less was compared to the amount produced by the control group, and the results (% value when the control group was set to 100%) are shown in Tables 18 to 20 based on the following criteria.

[0316] <100%: ±

[0317] 100-120%: +

[0318] 120%<: ++

[0319] [Table 18]

[0320]

[0321] [Table 19]

[0322]

[0323] [Table 20]

[0324]

[0325] The results in Tables 18 to 20 clearly indicate that the ascorbic acid derivatives of the present application have a higher hyaluronic acid production promoting effect than ascorbic acid and known ascorbic acid derivatives.

[0326] Test Example 5 [Antioxidant effect]

[0327] Normal human dermal fibroblasts (NHDF) were prepared to a cell density of 2.0 x 10 4Cell density of 1 x 104 / well The normal human epidermal keratinocytes were seeded on a 96-well plate using KG2 medium. After pre-incubation for 24 hours, the sample adjusted to a predetermined concentration in KG2 medium was added to each well. After incubation for 24 hours, the medium was removed, followed by washing with HBSS(-), and incorporation of the ROS reactive fluorescent probe DCFHDA for 30 minutes. The cells were again washed with HBSS(-), treated with 0.2 mM H2O2, and incubated for 2 hours. The fluorescence intensity was measured, and the amount of ROS produced per unit of protein amount was calculated by dividing the fluorescence intensity by the amount of protein quantified by the BCA method, to give an assay value of 1. In addition, the amount of ROS production calculated using the above test method without the addition of the sample adjusted to a predetermined concentration was set as an assay value 2; and the amount of ROS production calculated without the addition of the sample or 0.2 mM H2O2 was set as an assay value 3.

[0328] The ROS production inhibition rate (%) was calculated using the following formula. The results are shown in Table 21. The higher the ROS production inhibition rate, the greater the antioxidant effect that can be evaluated.

[0329] ROS production inhibition rate (%) = [(assay value 2) - (assay value 1)] / [(assay value 2) - (assay value 3)] x 100

[0330] The ROS production inhibition rate when the sample was measured at a concentration of 10 mM or less was evaluated as follows. Note that the measurement was performed with N = 4.

[0331] <20%: +

[0332] 20-40%: ++

[0333] 40%: +++

[0334] [Table 21]

[0335]

[0336] The results in Table 21 indicate that the ascorbic acid derivative of the present application has an antioxidant effect equivalent to or greater than that of known ascorbic acid derivatives.

[0337] Example 122 Cream

[0338] The oil phase shown in Table 22 was heated to 70°C and dissolved with the raw materials (components (1) to (5)), and the water phase was heated to 70°C and dissolved with the raw materials (components (6) to (10)), and the oil phase and the water phase were prepared, respectively. Then, the oil phase was added to the water phase and pre-emulsified, and the mixture was homogenously emulsified using a homomixer. Thereafter, the mixture was cooled to room temperature while being sufficiently stirred to prepare a cream. In Table 22 and subsequent tables, the blending amount is parts by mass.

[0339] [Table 22]

[0340]

[0341] * means the amount required to make the total blending amount 100 mass. This applies equally to the following tables.

[0342] Example 123 Emulsion

[0343] The oil phase of the composition shown in Table 23 was heated to 70°C and dissolved with components (1) to (9), and the water phase was heated to 70°C and dissolved with components (10) to (13), and the oil phase and the water phase were prepared, respectively. Then, the oil phase was added to the water phase and pre-emulsified, and the mixture was homogenously emulsified using a homomixer. Thereafter, the mixture was cooled to room temperature while being sufficiently stirred to prepare an emulsion.

[0344] [Table 23]

[0345]

[0346] Example 124 Emulsion

[0347] The oil phase of the composition shown in Table 24 was heated to 70°C and dissolved with components (5) to (10), and the water phase was heated to 70°C and dissolved with components (1) to (4) and (11) to (12), and the oil phase and the water phase were prepared, respectively. Then, the oil phase was added to the water phase and pre-emulsified, and the mixture was homogenously emulsified using a homomixer. Thereafter, the mixture was cooled to room temperature while being sufficiently stirred to prepare an emulsion.

[0348] [Table 24]

[0349]

[0350] Example 125 Cream

[0351] The oil phase shown in Table 25 was heated to 70°C and dissolved with components (1) to (2), and the water phase was heated to 70°C and dissolved with components (3) to (10), and the oil phase and the water phase were prepared, respectively. Then, the oil phase was added to the water phase to pre-emulsify, and the mixture was homogenously emulsified using a homomixer. Thereafter, the mixture was cooled to room temperature while being sufficiently stirred to prepare a cream.

[0352] [Table 25]

[0353]

[0354] Example 126 Skin lotion

[0355] A skin lotion was prepared by mixing the ingredients (1) to (6) shown in Table 26 under sufficient stirring.

[0356] [Table 26]

[0357]

[0358] Example 127 Cream

[0359] The ingredients (1) to (6) and the ingredients (7) to (10) shown in Table 27 were each heated to 70°C and dissolved. The oil phase was added to the water phase and pre-emulsified. Then the mixture was emulsified using a homomixer, and cooled to room temperature while being sufficiently stirred to prepare a cream.

[0360] [Table 27]

[0361]

[0362] Example 128 Cream

[0363] The oil phase of the composition shown in Table 28 was heated to 70°C and dissolved with the ingredients (1) to (5) and the water phase was heated to 70°C and dissolved with the ingredients (6) to (10) to prepare the oil phase and the water phase, respectively. Then the oil phase was added to the water phase and pre-emulsified, and the mixture was homogeneously emulsified using a homomixer. Then the mixture was cooled to room temperature while being sufficiently stirred to prepare a cream.

[0364] [Table 28]

[0365]

[0366] Example 129 Cream

[0367] The oil phase shown in Table 29 was heated to 70°C and dissolved with the ingredients (1) to (2) and the water phase was heated to 70°C and dissolved with the ingredients (3) to (10) to prepare the oil phase and the water phase, respectively. Then the oil phase was added to the water phase and pre-emulsified, and the mixture was homogeneously emulsified using a homomixer. Then the mixture was cooled to room temperature while being sufficiently stirred to prepare a cream.

[0368] [Table 29]

[0369]

Claims

1. An ascorbic acid derivative represented by the following general formula (1), (3) or (4): [Chemical Formula 1] [Chemical Formula 2] [Chemical Formula 3] [In formula (1), (3) or (4), R 1 Yes - (CH2) n -* (n is an integer from 2 to 4), -CH2CH(OH)CH2-*, -CH2CH(CH2OH)-*, -CH(CH2OH)CH2-*, -C(CH3)2CH2-*, -CH2C(CH3)2-* (* represents the position of bonding to O at the second position of the ascorbic acid ring), or a divalent group represented by the following formula (2); In formula (1), R 2 and R 3 Each is hydrogen, -COR 4 , a linear or branched alkyl group or a benzyl group having 1 to 22 carbon atoms, and R 4 is a straight or branched chain alkyl group having 1 to 22 carbon atoms; and In formula (3), R 5 and R 6 are each a hydrogen atom, a methyl group or a phenyl group,] [Chemical Formula 4] 。 2. The ascorbic acid derivative according to claim 1, which is represented by the general formula (1), wherein R 1 Yes - (CH2) n -* (n is 3 or 4), -CH2CH(OH)CH2-*, -CH2CH(CH2OH)-*, -CH(CH2OH)CH2-* (* represents the position of bonding to O at the second position of the ascorbic acid ring) or a divalent group represented by formula (2), and R 2 and R 3 is hydrogen; or R 1 Yes - (CH2) n -* (n is 3 or 4), R 2 Yes-COR 4 , and R 3 is hydrogen or -COR 4 , and R 4 is a straight-chain or branched-chain alkyl group having 4 to 18 carbon atoms.

3. The ascorbic acid derivative according to claim 2, which is represented by the general formula (1), wherein R 1 is -(CH2)3-*, -CH2CH(OH)CH2-* (* represents the position of bonding to O at the second position of the ascorbic acid ring) or a divalent group represented by formula (2), and R 2 and R 3 Each is hydrogen, or R 1 It is -(CH2)3-*, R 2 Yes-COR 4 , R 3 is hydrogen or -COR 4 , and R 4 is a straight-chain or branched-chain alkyl group having 8 to 18 carbon atoms. 4 . A cosmetic comprising the ascorbic acid derivative according to claim 1 . 5 . A collagen production promoter comprising the ascorbic acid derivative according to claim 3 . 6 . A hyaluronic acid production promoter comprising the ascorbic acid derivative according to claim 1 . 7 . A hyaluronic acid production promoter comprising the ascorbic acid derivative according to claim 3 .

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