JPS6233195A - Production of ascorbic acid derivative - Google Patents

Abstract

PURPOSE:To obtain the titled compound having extremely excellent stability and suitable for compounding to a cosmetic, by reacting isopropylidene-L- ascorbic acid with acetylglucosamino chloride in an organic solvent in the presence of an organic base. CONSTITUTION:The objective compound of formula III can be produced by reacting 5,6-o-isopropylidene-L-ascorbic acid of formula I with acetylglucosamino chloride of formula II in an organic solvent in the presence of an organic base usually at 15-30 deg.C for 0.5-2hr. The organic base is preferably an amine having high basicity, e.g. 1,8-diazabicyclo[5,4,0]-7-undecene, etc., and the amounts of the organic base and the compound of formula II are preferably 0.5-3.5mol and 0.5-2mol per 1mol of the compound of formula I, respectively.

Description

[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.

[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.

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.

[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.

[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.

[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 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).

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.

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.

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. ).

The starting materials of formula (It) and (ml) used are all known.

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.

Ascorbine is shown by the generated formula fil! i1m
The conductor can be purified by IIM from the reaction system by conventional methods.

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.

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.

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.

Next, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited to these Examples.

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%).

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.

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.

Experimental conditions and experimental results are shown in Table 1.

[Margin below]

Claims (1)

[Scope of Claims] 1 Formula (I
): ▲Mathematical formulas, chemical formulas, tables, etc. ▼(I) Production method of ascorbic acid derivatives shown in (I). 2. The manufacturing method according to claim 1, wherein the organic solvent is a highly polar organic solvent. 3. The production method according to claim 2, wherein the highly polar organic solvent is acetonitrile, dimethylformamide or dimethyl sulfoxide. 4. The manufacturing method according to claim 1, wherein the organic solvent is a less polar organic solvent. 5. The method according to claim 4, wherein the organic solvent with low polarity is acetone, 1-propanol, tetrahydrofuran, chloroform, or dioxane.