JPH0539284A - New kojic acid derivative - Google Patents
New kojic acid derivativeInfo
- Publication number
- JPH0539284A JPH0539284A JP3102858A JP10285891A JPH0539284A JP H0539284 A JPH0539284 A JP H0539284A JP 3102858 A JP3102858 A JP 3102858A JP 10285891 A JP10285891 A JP 10285891A JP H0539284 A JPH0539284 A JP H0539284A
- Authority
- JP
- Japan
- Prior art keywords
- kojic acid
- acid derivative
- formula
- aqueous solution
- solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Landscapes
- Pyrane Compounds (AREA)
- Cosmetics (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、チロシナーゼ酵素の活
性を抑制し、抗酸化作用を有する新規化合物であるコウ
ジ酸誘導体に関する。FIELD OF THE INVENTION The present invention relates to a kojic acid derivative which is a novel compound which suppresses the activity of tyrosinase enzyme and has an antioxidant effect.
【０００２】[0002]
【従来の技術】コウジ酸およびその誘導体がメラニン生
成を抑制することは知られており、それらを有効成分と
する色白化粧料も知られている（たとえば、特公昭６１
−１０４４７号公報、特公昭６２−５９０８４号公
報）。2. Description of the Related Art Kojic acid and its derivatives are known to inhibit melanin production, and whitening cosmetics containing them as active ingredients are also known (for example, Japanese Examined Patent Publication 61).
No. -10447 and Japanese Patent Publication No. 62-59084).
【０００３】また、式Also, the formula
【０００４】[0004]
【化２】 [Chemical 2]
【０００５】のコウジ酸誘導体は、コウジ酸とホルムア
ルデヒドから合成されることも知られている（大阪府立
大学紀要、農学、生物学、ｐｐ２０９−２６７、１２
巻、１９７０年）。It is also known that the kojic acid derivative (1) is synthesized from kojic acid and formaldehyde (Osaka Prefecture University Bulletin, Agriculture, Biology, pp. 209-267, 12).
Vol., 1970).
【０００６】[0006]
【発明が解決しようとする課題】本発明は、優れたチロ
シナーゼ活性を抑制する作用及び抗酸化作用を有する前
記式（１）で表されるコウジ酸誘導体を提供することを
目的とする。SUMMARY OF THE INVENTION It is an object of the present invention to provide a kojic acid derivative represented by the above formula (1), which has an excellent tyrosinase activity-suppressing action and antioxidant action.
【０００７】[0007]
【課題を解決するための手段】本発明によれば、式According to the invention, the formula
【０００８】[0008]
【化３】 [Chemical 3]
【０００９】で表される文献未載の新規なコウジ酸誘導
体が提供される。There is provided a novel kojic acid derivative represented by:
【００１０】本発明のコウジ酸誘導体は、コウジ酸水溶
液にアセトアルデヒドを加え、２０ないし９０℃で３０
分ないし２４時間攪拌することによって得ることができ
る。The kojic acid derivative of the present invention is prepared by adding acetaldehyde to an aqueous solution of kojic acid, and adding the acetaldehyde to the kojic acid solution at 30 ° C.
It can be obtained by stirring for minutes to 24 hours.
【００１１】本発明の反応は、下記の反応式で表される
２段階の反応で進行し、その結果、式（１）の新規なコ
ウジ酸誘導体が生成する。即ち、コウジ酸とアセトアル
デヒドが１：１のモル比で反応し、式（３）の中間化合
物が生成する。続いて、式（３）の中間化合物は残りの
未反応のコウジ酸と反応して、式（１）の新規化合物が
生成する。このように本発明の物質を得る反応は、式
（３）の中間化合物を単離することなしに、効率的に進
めることができる。The reaction of the present invention proceeds in a two-step reaction represented by the following reaction formula, and as a result, a novel kojic acid derivative of formula (1) is produced. That is, kojic acid and acetaldehyde react at a molar ratio of 1: 1 to produce an intermediate compound of formula (3). Subsequently, the intermediate compound of formula (3) reacts with the remaining unreacted kojic acid to form a new compound of formula (1). Thus, the reaction for obtaining the substance of the present invention can proceed efficiently without isolating the intermediate compound of formula (3).
【００１２】従って、上記の反応過程から明らかなよう
に、本反応にはコウジ酸２モルに対してアセトアルデヒ
ド１モルが必要となる。Therefore, as is clear from the above reaction process, 1 mol of acetaldehyde is required for 2 mol of kojic acid in this reaction.
【００１３】式Expression
【００１４】[0014]
【化４】 [Chemical 4]
【００１５】反応に際して、コウジ酸水溶液は、たとえ
ば、水酸化ナトリウム、水酸化カリウムなどの水溶液を
加えることによってｐＨ７ないし１０、好ましくはｐＨ
８に調整される。In the reaction, the aqueous solution of kojic acid is adjusted to pH 7 to 10, preferably pH by adding an aqueous solution of sodium hydroxide, potassium hydroxide or the like.
Adjusted to 8.
【００１６】アセトアルデヒドは、上記の反応工程を考
えた場合、コウジ酸の特に１／２モル量が好適に添加さ
れる。Considering the above reaction step, acetaldehyde is preferably added in an amount of 1/2 mol of kojic acid.
【００１７】反応条件は、２０ないし９０℃、好ましく
は５０ないし６０℃で０．５ないし２４時間、好ましく
は１ないし４時間攪拌下に行われる。The reaction conditions are 20 to 90 ° C., preferably 50 to 60 ° C., and stirring for 0.5 to 24 hours, preferably 1 to 4 hours.
【００１８】反応液は７ないし１０の範囲のｐＨを有す
るが、たとえば、硫酸、塩酸などでｐＨ２程度に調整さ
れる。かくして得られた溶液を濃縮し、低温で１ないし
２４時間放置した後、水、エタノールあるいは水とエタ
ノールの混合溶媒（任意の割合で使用し得る）を用いて
再結晶し、最終生成物を得る。The reaction solution has a pH in the range of 7 to 10, and is adjusted to about pH 2 with sulfuric acid, hydrochloric acid or the like. The solution thus obtained is concentrated, allowed to stand at a low temperature for 1 to 24 hours, and then recrystallized with water, ethanol or a mixed solvent of water and ethanol (which can be used in any proportion) to obtain a final product. ..
【００１９】[0019]
【実施例】以下、本発明のコウジ酸誘導体の具体的な製
造例を示す。EXAMPLES Hereinafter, specific production examples of the kojic acid derivative of the present invention will be shown.
【００２０】コウジ酸１０ｇ（０．０７ｍｏｌ）を水１
２０ｍｌに懸濁し、１Ｎ水酸化ナトリウム水溶液でｐＨ
８．０に調整した。この溶液にアセトアルデヒド１．５
５ｇ（０．０３５ｍｏｌ）を加え、５５℃で３時間攪拌
した。その後、反応溶液を１Ｎ硫酸でｐＨ２に調整し、
エバポレーターで約３０ｍｌまで濃縮した。一晩４℃に
放置し、析出した微黄色固体を濾過により得た。水とエ
タノールの混合溶媒（水／エタノール＝５０／５０ｖ／
ｖ）１４０ｍｌから再結晶し、白色粒状結晶７．８ｇを
得た。収率は７２％であった。10 g (0.07 mol) of kojic acid was added to 1 part of water.
Suspend in 20 ml and pH with 1N aqueous sodium hydroxide
It was adjusted to 8.0. Acetaldehyde 1.5 in this solution
5 g (0.035 mol) was added, and the mixture was stirred at 55 ° C. for 3 hours. Then, the reaction solution was adjusted to pH 2 with 1N sulfuric acid,
It was concentrated to about 30 ml with an evaporator. The mixture was allowed to stand overnight at 4 ° C., and a slightly yellow solid that precipitated was obtained by filtration. Mixed solvent of water and ethanol (water / ethanol = 50 / 50v /
v) Recrystallized from 140 ml to obtain 7.8 g of white granular crystals. The yield was 72%.
【００２１】得られた化合物は融点が２０６．５ないし
２１２．８℃（分解、未補正）で、水に僅かに溶解し、
エタノール、アセトニトリルに溶解した。The compound obtained has a melting point of 206.5 to 212.8 ° C. (decomposition, uncorrected) and is slightly soluble in water,
It was dissolved in ethanol and acetonitrile.
【００２２】図１にＵＶ吸収スペクトル（水溶液）、図
２にＩＲ吸収スペクトル（ＫＢｒ法）、図３にＰＭＲス
ペクトル（溶媒：ＤＭＳＯ）、図４にＣＭＲスペクトル
（溶媒：ＤＭＳＯ）、図５にＭＳスペクトル（ＭＷ３１
０）を示した。FIG. 1 shows a UV absorption spectrum (aqueous solution), FIG. 2 shows an IR absorption spectrum (KBr method), FIG. 3 shows a PMR spectrum (solvent: DMSO), FIG. 4 shows a CMR spectrum (solvent: DMSO), and FIG. 5 shows MS. Spectrum (MW31
0) was shown.
【００２３】本発明の実施例によって得られたコウジ酸
誘導体のキレート作用およびフェノール性水酸基による
抗酸化作用についての評価を下記に示す。The chelating action of the kojic acid derivative obtained in the examples of the present invention and the antioxidant action of the phenolic hydroxyl group are evaluated below.
【００２４】試験例１：チロシナーゼ活性阻害試験 ハムスター黒色腫由来Ｄ1 １７９細胞のホモジネートの
３０，０００Ｇ上清をチロシナーゼ酵素液として用い
た。緩衝液には０．１Ｍリン酸緩衝液（ｐＨ６．８）を
用いた。Test Example 1: Tyrosinase activity inhibition test A 30,000 G supernatant of a homogenate of D 1 179 cells derived from hamster melanoma was used as a tyrosinase enzyme solution. As the buffer, 0.1 M phosphate buffer (pH 6.8) was used.
【００２５】分光光度計のセルに、チロシナーゼ酵素液
３５μｌ、０．１Ｍリン酸緩衝液４３２μｌおよび５０
％ジメチルスルホキシド水溶液に溶解した本コウジ酸誘
導体２００μｌをそれぞれ添加した。In the spectrophotometer cell, 35 μl of tyrosinase enzyme solution, 432 μl of 0.1 M phosphate buffer and 50
% Of the kojic acid derivative dissolved in a dimethylsulfoxide aqueous solution were added.
【００２６】２分後、１０ｍＭ Ｌ−ＤＯＰＡ ３３３
μｌ（緩衝液に溶かしたもの）を添加し、３７℃におけ
る４７５ｎｍの吸光度（ΔＯＤ475nm ）の経時変化を追
跡した。なお、コントロールとして、５０％ジメチルス
ルホキシド水溶液を用いた。After 2 minutes, 10 mM L-DOPA 333
μl (dissolved in buffer) was added, and the time course of the absorbance at 475 nm (ΔOD 475 nm ) at 37 ° C. was traced. As a control, a 50% dimethyl sulfoxide aqueous solution was used.
【００２７】結果を表１に示した。本コウジ酸誘導体に
は、チロシナーゼ阻害作用が認められた。The results are shown in Table 1. This kojic acid derivative was confirmed to have a tyrosinase inhibitory action.
【００２８】[0028]
【表１】 [Table 1]
【００２９】試験例２：抗酸化能 評価試料として下記の試料を用いた。Test Example 2 Antioxidant Ability The following samples were used as evaluation samples.
【００３０】１）ビタミンＥのエタノール溶液（終濃度
４０μＭ） ２）コウジ酸誘導体のエタノール溶液（終濃度１．０ｍ
Ｍ、２．０ｍＭ） ５００ｍＭリノール酸のエタノール溶液１．０ｍｌ、
０．１Ｍリン酸緩衝液（ｐＨ７．０）１０．０ｍｌ、エ
タノール４．０ｍｌおよび精製水５．０ｍｌの混合溶液
に評価試料５．０ｍｌをそれぞれの終濃度となるように
添加した。1) Vitamin E ethanol solution (final concentration 40 μM) 2) Kojic acid derivative ethanol solution (final concentration 1.0 m
M, 2.0 mM) 1.0 mM ethanol solution of 500 mM linoleic acid,
5.0 ml of the evaluation sample was added to a mixed solution of 10.0 ml of 0.1 M phosphate buffer (pH 7.0), 4.0 ml of ethanol, and 5.0 ml of purified water so that each final concentration was obtained.
【００３１】各供試液を３７℃の暗所に放置し、１、
３、６、９および１２日後、過酸化物価の経時変化をロ
ダン鉄法により測定した。すなわち、供試液０．１ｍｌ
に７５％エタノール４．７ｍｌ、３０％ロダン酸アンモ
ニウム０．１ｍｌ、２×１０-2Ｍ塩化第一鉄の３．５％
塩酸溶液０．１ｍｌを加え、正確に３分後、５００ｎｍ
における吸光度を測定した。Each test solution was left in the dark at 37 ° C.
After 3, 6, 9 and 12 days, the change with time of the peroxide value was measured by the rodan iron method. That is, the test solution 0.1 ml
75% ethanol 4.7 ml, 30% ammonium rhodanate 0.1 ml, 2 × 10 -2 M ferrous chloride 3.5%
Add 0.1 ml of hydrochloric acid solution, exactly 3 minutes later, 500 nm
The absorbance at was measured.
【００３２】試験結果を図６に示した。本コウジ酸誘導
体にはきわめて優れた抗酸化能を有することが見出され
た。The test results are shown in FIG. It was found that this kojic acid derivative has an extremely excellent antioxidant ability.
【００３３】[0033]
【発明の効果】本発明の新規なコウジ酸誘導体は、色素
沈着症の予防および治療、ならびに金属イオンの定量、
抽出および画像診断用薬剤などキレート作用を利用した
種々の用途に使用される。またさらに、動植物抽出物の
酸化および褐変防止、ならびに塗料の酸化防止剤などの
抗酸化作用を利用した種々の用途に使用することができ
る。INDUSTRIAL APPLICABILITY The novel kojic acid derivative of the present invention is used for the prevention and treatment of pigmentation, and the determination of metal ions,
It is used for various applications utilizing the chelating action such as drugs for extraction and diagnostic imaging. Furthermore, it can be used for various applications utilizing the antioxidant and browning prevention of animal and plant extracts, and the antioxidant effect of paints.
【図１】 実施例で得られたコウジ酸誘導体のＵＶ吸収
スペクトルを示す。FIG. 1 shows a UV absorption spectrum of a kojic acid derivative obtained in an example.
【図２】 同化合物のＩＲ吸収スペクトルを示す。FIG. 2 shows an IR absorption spectrum of the same compound.
【図３】 同化合物のＰＭＲスペクトルを示す。FIG. 3 shows a PMR spectrum of the same compound.
【図４】 同化合物のＣＭＲスペクトルを示す。FIG. 4 shows a CMR spectrum of the same compound.
【図５】 同化合物のＭＳスペクトルを示す。FIG. 5 shows an MS spectrum of the same compound.
【図６】 同化合物の抗酸化能を示す。 ■FIG. 6 shows the antioxidant ability of the same compound. ■
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3102858A JPH0539284A (en) | 1991-05-08 | 1991-05-08 | New kojic acid derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3102858A JPH0539284A (en) | 1991-05-08 | 1991-05-08 | New kojic acid derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0539284A true JPH0539284A (en) | 1993-02-19 |
Family
ID=14338623
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3102858A Withdrawn JPH0539284A (en) | 1991-05-08 | 1991-05-08 | New kojic acid derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0539284A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100365072B1 (en) * | 2000-12-29 | 2002-12-18 | 주식회사 태평양 | Kojic acid dimer and preparation method thereof |
| EP3869255A1 (en) | 2020-02-21 | 2021-08-25 | Canon Kabushiki Kaisha | Optical system and image pickup apparatus having the same |
-
1991
- 1991-05-08 JP JP3102858A patent/JPH0539284A/en not_active Withdrawn
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100365072B1 (en) * | 2000-12-29 | 2002-12-18 | 주식회사 태평양 | Kojic acid dimer and preparation method thereof |
| EP3869255A1 (en) | 2020-02-21 | 2021-08-25 | Canon Kabushiki Kaisha | Optical system and image pickup apparatus having the same |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A300 | Withdrawal of application because of no request for examination |
Free format text: JAPANESE INTERMEDIATE CODE: A300 Effective date: 19980806 |