JPH0745489B2 - Method for producing tetrahydropyran derivative - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial field of use] The present invention relates to an improved method for producing arptin or a related compound thereof, which is useful as an industrial drug or a medicine.

[Conventional technology]

Conventionally, the following structural formula: Arbutin represented by is known to be a useful compound as a stabilizer for color photographic images, a diuretic, and a urinary tract fungicide [The Merck Index (The Merck Index).
Merck Index) 10th edition, page 112, item 792 (1983)].

Conventionally, various methods are known as a method for producing arbutin, and in any of these methods, a treatment for removing an acyl group by hydrolysis is performed from an intermediate in which the hydroxyl group of the glucopyranoside ring is acylated. Need that. Known hydrolysis methods include a method in which sodium and methanol are allowed to directly act, and a method in which barium hydroxide is present.

[Problems to be solved by the invention]

However, in the conventional method, since arbutin is easily soluble in water, it is difficult to separate it from the inorganic salt formed in the hydrolysis → neutralization process, and thus the yield is low and the hydroxyphenyl group is protected. However, there are various problems such that the number of steps increases due to desorption after hydrolysis, which is complicated, or barium hydroxide is bulky, difficult to handle, and expensive. Atsuta

An object of the present invention is to provide a method for easily producing arbutin or a related compound thereof, which does not have the conventional problems.

[Means for solving problems]

The present invention can be summarized by the following general formula I: (In the formula, R ^{1 to} R ³ are the same or different, and are hydrogen, a hydroxyl group, a lower alkoxy group, a lower acyloxy group or an aralkyloxy group, and R ⁴ is hydrogen, a lower alkyl group, a hydroxymethyl group, a lower alkoxymethyl group, a lower acyloxy group. A methyl group or an aralkyloxymethyl group, wherein at least one of R ^{1 to} R ⁴ is a group containing the lower acyl group) in the presence of sodium hydroxide or potassium hydroxide. The following general formula II is characterized in that it is hydrolyzed with and then treated with a cation exchange resin: (In the formula, Z ^{1 to} Z ⁴ are groups corresponding to R ^{1 to} R ⁴ in the formula I, and represent a group in which a lower acyloxy moiety is converted to a hydroxyl group. That is, Z ^{1 to} Z ⁴ are When any of R ^{1 to} R ⁴ is a group containing a lower acyloxy moiety, it is a group in which the lower acyloxy moiety is converted to a hydroxyl group, and contains a lower acyloxy moiety among R ^{1 to} R ^4. not group group are the compounds of formula I a process for preparing tetrahydropyran derivatives represented by the indicating) that the same group and as R ¹ to R ^4, among the groups represented by R ¹ to R ^4, a lower Examples of alkyl groups include groups such as methyl and ethyl, and examples of other common groups include groups such as methoxy, ethoxy, acetoxy, propionyloxy and benzyloxy. Among them, compounds in which R ^{1 to} R ³ are lower acyloxy groups and R ⁴ is a lower acyloxymethyl group are preferable.

Examples of bases that can be used in the present invention include sodium hydroxide and potassium hydroxide, unlike those which are expensive or require careful handling as in the conventional method. The method of the present invention makes it possible to use such an inexpensive base.

Examples of the cation exchange resin usable in the present invention include ion exchange resins having a sulfonic acid group and / or a carboxylic acid group, and examples thereof include Amberlyst. Since these ion exchange resins retain the inorganic cations formed as a by-product of hydrolysis, it is possible to prevent the inorganic ions from being mixed into the target compound. Then, these resins can be recovered, regenerated and reused.

In the method of the present invention, a solvent may or may not be used, and examples of the solvent include methanol, ethanol and ethylene glycol, which may be mixed.

The reaction temperature is 0 to 100 ° C, which is a conventional method for ester hydrolysis.
The reaction temperature under reflux is preferable.

〔Example〕

Hereinafter, the present invention will be described in more detail with reference to Examples.
The invention is not limited to these examples.

Example 1 Synthesis of 4-hydroxyphenyl β-D-glucopyranoside (1) 4-hydroxyphenyl tetra-0-acetyl-β-D
-1.0 g (23 mmol) of glucopyranoside (2) and 0.55 g (13.8 mmol) of sodium hydroxide were added to a mixed solution of 3 ml of water and 7 ml of methanol, and the mixture was heated with stirring at 60 ° C for 0.5 hour. After the reaction was completed, the reaction mixture was cooled to 5 ° C and amberlyst-15
Was added and the mixture was stirred at the same temperature for 0.5 hour. Then, after removing Amberlyst-15, the liquid was concentrated under reduced pressure,
0.61 g of compound (1) was obtained. Yield 98%, melting point 198-200 ° C
(Recrystallized from ethanol) Nuclear magnetic resonance spectrum (dimethyl sulfoxide-d
₆ middle) 3.1 to 3.3 (4H, m) 3.47 (1H, ddd, J = 12.2Hz, 6.0H
z, 6.0Hz) 3.69 (1H, ddd, J = 12.2Hz, 6.0Hz, 2.2H
z) * 4.38 (1H, t, J = 6Hz) 4.63 (1H, d, J = 7.6Hz)
* 4.79 (1H, d, J = 5.3Hz) * 4.84 (1H, d, J = 8.4Hz) * 5.05 (1H, d, J = 5.0)
Hz) 6.65 (2H, d, J = 8.4Hz) 6.88 (1H, d, J = 8.4
Hz) * 8.86 (1H, s) * hydroxyl group Examples 2 and 3 Instead of the compound (2) in Example 1, 3-hydroxyphenyl tetra-0-acetyl- (beta) -D- glucopyranoside (3) or 2-. Hydroxyphenyl tetra-0-
The same operation as in Example 1 was performed except that acetyl-β-D-glucopyranoside (4) was used, and the corresponding 3-hydroxyphenyl β-D-glucopyranoside (5) was obtained in a yield of 95%, respectively. 2-hydroxyphenyl β-D-
Glucopyranoside (6) was obtained with a yield of 92%.

〔The invention's effect〕

As explained above, according to the method of the present invention, the remarkable effect that arbutin and its related compounds can be obtained more easily and in a higher yield than the conventional method can be obtained.

Claims (1)

[Claims] 1. The following general formula I: (In the formula, R ^{1 to} R ³ are the same or different, and are hydrogen, a hydroxyl group, a lower alkoxy group, a lower acyloxy group or an aralkyloxy group, and R ⁴ is hydrogen, a lower alkyl group, a hydroxymethyl group, a lower alkoxymethyl group, a lower acyloxy group. A methyl group or an aralkyloxymethyl group, wherein at least one of R ^{1 to} R ⁴ is a group containing the lower acyl group), a compound represented by the presence of sodium hydroxide or potassium hydroxide. The following general formula II, characterized in that it is hydrolyzed underneath and then treated with a cation exchange resin: (In the formula, Z ^{1 to} Z ⁴ are groups corresponding to R ^{1 to} R ⁴ in the formula I, but a group in which a lower acyloxy moiety is converted to a hydroxyl group is shown) Production of a tetrahydropyran derivative Law.