【発明の詳細な説明】［産業上の利用分野〕で示されるアスコルビン酸誘導体の製造法に関する。[Detailed description of the invention][Industrial application field]The present invention relates to a method for producing an ascorbic acid derivative shown in the following.
［従来技術］従来、アスコルごン酸はその強い酸化還元作用により、
細胞呼吸作用、酵素賦活作用、膠原形成作用を有し、か
つメラニン還元作用にもとづく美白効果のため各種の化
粧料に配合されている。しかしながら、アスコルビン酸
は熱、光、酵素、金属イオンまたはｐｌなどにより分解
や変成をおこしやすく、それゆえ安定性に乏しい。[Prior art] Conventionally, ascorgonic acid has a strong redox effect,
It has cellular respiration, enzyme activation, and collagen formation effects, and is included in various cosmetics for its whitening effect based on melanin reduction. However, ascorbic acid is easily decomposed or denatured by heat, light, enzymes, metal ions, pl, etc., and therefore has poor stability.
このようなアスコルビン酸の不安定性は、誘導体化、す
なわちその化学構造中のエンジオール基に置換基を導入
することによって軽減することが試みられており、具体
的にはアセチル化、ベンゾイル化、バルジ１ヘモは硫酸化などが検討されている。Attempts have been made to reduce the instability of ascorbic acid by derivatization, that is, by introducing substituents into the enediol group in its chemical structure, including acetylation, benzoylation, and bulging. Sulfation and other methods are being considered for hemo-1.
［発明が解決しようとしている問題点］しかしながら、
これらのいずれの誘導体も経日安定性に問題があったり
、変色、変臭の原因となるなど根本的な解決はなされて
いない。[Problem that the invention seeks to solve] However,
All of these derivatives have problems with stability over time, cause discoloration and odor, and no fundamental solution has been found.
［問題点を解決するための手段］本発明者らはかかる現状に鑑み種々研究を重ねた結果、
熱、光、酵素、金属イオンまたは０１１などによって分
解や変性をおこさず、安定性がきわめてすぐれた式（１
１で示されるアスコルビン酸誘導体の製造法を見出し、
本発明を完成するにいたった。[Means for solving the problem] The present inventors have conducted various studies in view of the current situation, and have found that
The formula (1
discovered a method for producing the ascorbic acid derivative shown in 1,
This led to the completion of the present invention.
［作用および実施例］本発明によれば、式（１）で示されるアスコルビン酸誘
導体はつぎの反応式によって製造される。[Function and Examples] According to the present invention, the ascorbic acid derivative represented by formula (1) is produced by the following reaction formula.
（Ｉ［） （Ｉこの反応式にしたがい、有機塩基の存在下、有機溶媒中
、室温にて式ｆｌ）で示される５、６−０−イソプロピ
リデン−Ｌ−アスコルビン酸と式Ｉで示されるアセチル
グルコサミノクロリドを反応させて所望の式（１）で示
されるし一アスコルビン酸誘導体をうる。(I[) (I According to this reaction formula, 5,6-0-isopropylidene-L-ascorbic acid of formula fl) and 5,6-0-isopropylidene-L-ascorbic acid of formula I in the presence of an organic base in an organic solvent at room temperature Acetylglucosaminochloride is reacted to obtain the desired monoascorbic acid derivative represented by formula (1).
この反応は、水の存在する条件下で行なうと式（Ｍｌで
示されるアセチルゲルコサミノクロリドの加水分解が優
先し、目的とする式［Ｉ）で示されるし一アスコルビン
酸誘導体の生成が極度に抑制されるので、水の存在しえ
ない反応系、すなわち有機塩基の存在下、有機溶媒中で
行なう。用いる有機塩基としては、ピリジン、１，８−
ジアザビシクロ［５，４，０ｌ−７−ウンデセン（ＤＢ
Ｕ）、トリエチルアミン、シクロヘキシルアミン、４−
ジメチルアミノピリジン、モノエタノールアミン、ジェ
タノールアミンまたはトリエタノールアミンなどがあげ
られる。また有機溶媒としては、アセトニトリル、ジメ
チルホルムアミドおよびジメチルスルホキシドのような
極性の大なる有機溶媒、またはアセトン、ｎ−プロパノ
ール、テトラヒドロフラン、ジオキサンおよびクロロホ
ルムのような極性の小なる有機溶媒があげられる。When this reaction is carried out in the presence of water, the hydrolysis of acetylgelcosamininochloride represented by the formula (Ml) takes precedence, and the production of the desired mono-ascorbic acid derivative represented by the formula [I] is extremely high. Therefore, the reaction is carried out in an organic solvent in the presence of an organic base in a reaction system in which water cannot be present. The organic base used is pyridine, 1,8-
Diazabicyclo[5,4,0l-7-undecene (DB
U), triethylamine, cyclohexylamine, 4-
Examples include dimethylaminopyridine, monoethanolamine, jetanolamine or triethanolamine. Examples of the organic solvent include highly polar organic solvents such as acetonitrile, dimethylformamide and dimethyl sulfoxide, and less polar organic solvents such as acetone, n-propanol, tetrahydrofuran, dioxane and chloroform.
式＋１）の化合物の収Ｉ（率）は、用いる溶媒の極性お
よびアミンの塩基性度の両方の影響を受けるため、極性
の大なる溶媒を用いたばあい、若干、塩基性度の低いア
ミンを用いても式（Ｉ）の化合物はかなりの収率（率）
でえられるが、より塩基性度の高いアミンを用いること
によりさらに収率（率）が増す。The yield I (rate) of the compound of formula +1) is affected by both the polarity of the solvent used and the basicity of the amine, so if a highly polar solvent is used, the amine with slightly lower basicity The compound of formula (I) can be obtained in considerable yield (rate) using
However, the yield can be further increased by using a more basic amine.
一方、極性の小なる溶媒を用いたばあい、塩基性度の低
いアミンを用いると収率〈率）も悪く実用的でないので
、塩基性度の高いアミンを用いる方が好ましいく第１表
参照）。On the other hand, if a less polar solvent is used, the yield will be poor and impractical if an amine with a low degree of basicity is used, so it is preferable to use an amine with a high degree of basicity.See Table 1. ).
用いる式（Ｉｔ）および（ｍｌで示される出発物質はい
ずれも公知である。The starting materials of formula (It) and (ml) used are all known.
かくして該反応は、式［１１［）で示される５、６−０
−イソプロピリデン−［−アスコルビンＭ１モルに対し
て、有機強塩基０５〜３５モル、式［１［１で示される
アセチルゲルコサミノクロリド０．５〜２モルを用いて
室温（１５〜３０℃）にて０．５〜２時間行なわれる。Thus, the reaction proceeds to 5,6-0 of formula [11[)
-Isopropylidene-[-To 1 mole of ascorbine M, 05 to 35 moles of a strong organic base and 0.5 to 2 moles of acetylgelcosamininochloride represented by the formula [1] were used at room temperature (15 to 30°C). The test is carried out for 0.5 to 2 hours.
生成した式ｆｉｌで示されるし一アスコルビン！ｉ１ｍ
導体は、常法によって反応系からＩＩＭ、精製できる。Ascorbine is shown by the generated formula fil! i1m
The conductor can be purified by IIM from the reaction system by conventional methods.
えられた式（１１で示されるし一アスコルビン酸誘導体
は非常に安定で、かつ生体内で容易にし一アスコルごン
酸に変るので各種の化粧料に配合するのにきわめて適し
ている。The mono-ascorbic acid derivative represented by formula (11) is very stable and easily converted to mono-ascorbic acid in vivo, making it extremely suitable for blending into various cosmetics.
また式（Ｉ）で示されるし一アスコルビン酸誘導体は、
たとえばメタノール中、室温にてアンモニアまたはナト
リウムメトキシドで処理すると容易に脱アセチル化し、
この脱アセチル化物または式ｆｌ）の化合物は、室温に
て６０〜８０％の酢酸水溶液で処理すると脱イソプロピ
リデン化される。Further, the monoascorbic acid derivative represented by formula (I) is
Easily deacetylated, for example, by treatment with ammonia or sodium methoxide in methanol at room temperature;
This deacetylated product or compound of formula fl) is deisopropylidened upon treatment with 60-80% aqueous acetic acid at room temperature.
これらの脱アセチル化物および／または脱イソプロピリ
デン化物も非常に安定であり、かつ生体内で容易に［−
アスコルビン酸に変るので各種の化粧料に配合するのに
適している。These deacetylated products and/or deisopropylidened products are also very stable and easily [-
Since it converts into ascorbic acid, it is suitable for inclusion in various cosmetics.
つぎに実施例をあげて本発明をさらに詳しく説明するが
、本発明はかかる実施例のみに限定されるものではない
。Next, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited to these Examples.
実施例１５．６−０−イソプロピリデン−し−アスコルビン酸４
．６ｇ（０，０２モル）をテトラアセチルゲルコサミノ
クロリド７．３ｇ（０，０２モル）および１．８−ジア
ザビシクロ［５，４，Ｏ］−７−ウンデセン３ｇ（０，
０２モル）を、１−プロパノール１０ｄ中において室温
で１時間反応させた。反応終了後、クロロホルム５０−
を加え、水で数回洗浄した。クロロホルム層を乾燥後、
減圧留去すると赤褐色粘稠物質４．７ｇをえたく収率４
３％）。Example 1 5.6-0-isopropylidene-di-ascorbic acid 4
．． 6 g (0.02 mol) of tetraacetylgelcosaminochloride 7.3 g (0.02 mol) and 3 g (0.02 mol) of 1,8-diazabicyclo[5,4,O]-7-undecene.
02 mol) were reacted for 1 hour at room temperature in 10d of 1-propanol. After the reaction is complete, chloroform 50-
was added and washed several times with water. After drying the chloroform layer,
Distillation under reduced pressure yielded 4.7 g of reddish-brown viscous substance, yield 4.
3%).
これを放置すると結晶化し、少】の酢酸エチルで洗浄し
て白色結晶をえた。えられた生成物の性質（ま以下のと
おりであった。When this was allowed to stand, it crystallized and was washed with a small amount of ethyl acetate to give white crystals. The properties of the product obtained were as follows.
融 点 ： １４４〜１４６℃ＩＲ： ３３００．１７５０ｃｍ−’ＮＨＲ（ＣＤＣｌ２ δ） ： ２．６０（６Ｈ）
、 １．９８．２．０６．２．１０（１２Ｈ）、４．６０（ＩＨ）、５４０〜５．２４（２Ｈ）、５．５０〜５．７０（２Ｈ）、６１０〜６．３０（ＩＨ）、７．４０〜７．６０（ＩＨ）［ＭＳ］ ： ５４５（Ｈ＋）実施例２〜２８実験条件を種々変更したほかは同様にして実験を行なっ
た。Melting point: 144-146°C IR: 3300.1750cm-' NHR (CDCl2 δ): 2.60 (6H)
, 1.98.2.06.2.10 (12H), 4.60 (IH), 540-5.24 (2H), 5.50-5.70 (2H), 610-6.30 (IH) ), 7.40 to 7.60 (IH) [MS]: 545 (H+) Examples 2 to 28 Experiments were conducted in the same manner except that the experimental conditions were variously changed.
実験条件および実験結果を第１表に示す。Experimental conditions and experimental results are shown in Table 1.
［以下余白］[Margin below]
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP17216685AJPS6233195A (en) | 1985-08-05 | 1985-08-05 | Production of ascorbic acid derivative |
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP17216685AJPS6233195A (en) | 1985-08-05 | 1985-08-05 | Production of ascorbic acid derivative |
| Publication Number | Publication Date |
|---|---|
| JPS6233195Atrue JPS6233195A (en) | 1987-02-13 |
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP17216685APendingJPS6233195A (en) | 1985-08-05 | 1985-08-05 | Production of ascorbic acid derivative |
| Country | Link |
|---|---|
| JP (1) | JPS6233195A (en) |
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0738508A1 (en)* | 1995-04-20 | 1996-10-23 | L'oreal | Skin whitening and/or anti ageing composition and its uses |
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0738508A1 (en)* | 1995-04-20 | 1996-10-23 | L'oreal | Skin whitening and/or anti ageing composition and its uses |
| FR2733148A1 (en)* | 1995-04-20 | 1996-10-25 | Oreal | COMPOSITION FOR FIGHTING AGAINST SPOTS AND / OR AGING OF THE SKIN, USES THEREOF |
| US5730972A (en)* | 1995-04-20 | 1998-03-24 | L'oreal | Composition for combating skin marks and/or ageing of the skin and uses thereof |
| Publication | Publication Date | Title |
|---|---|---|
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| ES2132609T3 (en) | ARILACETIC ACID DERIVATIVES AND THEIR USE AS FUNGICIDES. | |
| JPS6233195A (en) | Production of ascorbic acid derivative | |
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