JP2003113196A - Method for producing hinokitiol glycoside - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing hinokitiol glycoside having high solubility to water, inexpensively in an industrial scale with high yield, and to provide a method for producing hinokitiol acetyl glycoside utilizable for the production of the hinokitiol glycoside. SOLUTION: The invention includes, [1] a method for producing the hinokitiol glycoside by reacting hinokitiol and a polyacetylglycosyl halide in the presence of a chelating agent, a metal hydroxide and a phase transfer catalyst, [2] a method for producing the hinokitiol acetyl glycoside by reacting a metal salt of hinokitiol and the polyacetylglycosyl halide in the presence of a chelating agent and a phase transfer catalyst, and [3] a method for producing hinokitiol glycoside comprising a step which deacetylates the hinokitiol acetyl glycoside obtained in the methods prescribed in [1] or [2].

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a hinokitiol acetyl glycoside and a method for producing a hinokitiol glycoside.

[0002]

2. Description of the Related Art Hinokitiol is a natural tropolone contained in the essential oil components of trees such as Taiwan cypress and Aomori Hiba, and is currently known to have many antibacterial, antifungal, antiseptic and hair growth promoting effects. Is used for medicines, agricultural chemicals, hair products, food preservatives, cosmetics, etc. (for example, Japanese Patent Application Laid-Open Nos. 2-40304 and 4-1824).
08 gazette etc.). However, since hinokitiol is poorly soluble in water, the formulation of hinokitiol is limited in its dosage form, and as a result, the application of hinokitiol itself is limited.

Therefore, a method of reacting hinokitiol and glucose with β-glucosidase derived from almond (JP-A-7-17993) and Eucalyptus (Euca).
A method for obtaining hinokitiol glycosides by culturing cultured cells derived from plant tissue pieces of lyptus) in an iron-free medium and adding hinokitiol thereto (JP-A-7-8228).
No. 8) is disclosed, but all of these methods have poor productivity and are costly, so they cannot be said to be industrial.

On the other hand, little is known about a method for chemically synthesizing a hinokitiol glycoside, but a glycosylation reaction between a sugar acceptor and a sugar donor is used as a means for the chemical synthesis. Can be considered. As such a glycosylation reaction, the Koenigs-Knorr method, which uses a stoichiometric amount of silver salt, mercury salt, etc., has been the mainstream. For example, synthesis of terpene glycosides by reaction of terpene alcohol and brominated sugar derivative using silica gel supported silver carbonate (Oil Chemistry Vol. 43, No. 1), synthesis of tropolone glycoside using silver carbonate as catalyst ( Biosci. Biotech. Biochem., 60 (12) 2095-
2096, 1996) was known as an existing fact. However, these synthetic methods have low yields and use stoichiometric amount of expensive silver, so that it cannot be said to be industrial.

[0005]

DISCLOSURE OF THE INVENTION The present invention provides a method for producing a highly water-soluble hinokitiol glycoside industrially at low cost and a high yield, and hinokitiol acetyl which can be used for producing the hinokitiol glycoside. It is an object to provide a method for producing a glycoside.

[0006]

The summary of the present invention is as follows.
[1] A method for producing a hinokitiol acetyl glycoside, comprising a step of reacting hinokitiol and a polyacetylglycosyl halide in the presence of a chelating agent, a metal hydroxide and a phase transfer catalyst, [2] a metal salt of hinokitiol and polyacetyl A method for producing a hinokitiol acetyl glycoside, which has a step of reacting a glycosyl halide in the presence of a chelating agent and a phase transfer catalyst, and [3] a hinokitiol acetyl obtained by the production method according to the above [1] or [2]. The present invention relates to a method for producing a hinokitiol glycoside having a step of deacetylating a glycoside.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION As described above, the method for producing hinokitiol acetylglycoside of the present invention comprises a step of reacting hinokitiol and polyacetylglycosyl halide in the presence of a chelating agent, a metal hydroxide and a phase transfer catalyst. Have.

The hinokitiol may be a natural product extracted from an essential oil derived from Taiwan Hinoki, Hiba, Asunaro or the like, or may be a chemically synthesized product. Further, commercially available hinokitiol may be used as it is, or a salt of hinokitiol may be used. The hinokitiol salt is not particularly limited, and examples thereof include inorganic salts such as sodium salts, potassium salts, magnesium salts, calcium salts, copper salts, metal salts represented by zinc salts, ethanolamine salts, diethanolamine salts, propanol. Organic salts such as amine salts, piperazine salts, piperidine salts, arginine salts, lysine salts, histidine salts and the like can be mentioned. In the present invention, these hinokitiol and its salts may be used alone or in admixture of two or more.

The polyacetylglycosyl halide is
It refers to a halogenated O-acetylglucoside derivative, and examples thereof include formula (I):

[0010]

[Chemical 1]

Tetra-O-acetyl-α-D represented by
− Glucopyranosyl bromide (tetra-O-acetyl- α-D
-gulucopyranosyl bromide) and other monosaccharides, formula (II):

[0012]

[Chemical 2]

Hepta-O-acetyl-α-D represented by
− Maltosyl bromide (hepta-O-acetyl- α-D-malto
and disaccharides such as syl bromide).

The chelating agent is preferably pentamethyldiethylenetriamine, ethylenediaminetetraacetic acid, diethylenetriaminepentaacetic acid, tetraethyleneglycol or the like.

Examples of the metal hydroxide include hydroxides of alkali metals and alkaline earth metals. In addition, the form of the metal hydroxide is preferably a solution or an aqueous solution. Above all, a solution or aqueous solution of sodium hydroxide and potassium hydroxide is more preferable. By using such a metal hydroxide, hinokitiol is reacted as a metal salt of hinokitiol. Therefore, when using a metal salt of hinokitiol as a raw material, it is not necessary to add a metal hydroxide. Therefore, as another aspect of the present invention, there is provided a method for producing a hinokitiol acetyl glycoside, which comprises a step of reacting a metal salt of hinokitiol with a polyacetylglycosyl halide in the presence of a chelating agent and a phase transfer catalyst. In the present invention, the use of a metal hydroxide has an advantage that an acetyl glycoside can be obtained in good yield.

Examples of the phase transfer catalyst include tetra-n-butylammonium bromide, tetra-n-butylammonium chloride, tetra-n-butylammonium tribromide, tetra-n-butylammonium iodide, trioctylmethylammonium chloride (TOMAC), benzalkonium chloride. , Tetra-n-butylammonium hydrogen sulfate, acetamide,
N-cetylpyridinium chloride, tetraethylammonium ptoluenesulfonate, tetraethylammonium tetrafluoroborate, tetranormalpropylammonium hydroxide, benzonitrile, trimethylcetylammonium bromide, trimethyldodecylammonium chloride, trimethylbenzylammonium hydroxide, trinormalbutylbenzyl Ammonium chloride, trimethylbenzylammonium chloride aqueous solution, triethylbenzylammonium chloride aqueous solution,
Examples thereof include benzoyltributylammonium chloride. Among them, benzalkonium chloride and TOMAC are preferable from the viewpoint of reactivity and yield.

In the production method of the present invention, hinokitiol and polyacetylglycosyl halide are reacted in the presence of a chelating agent, a metal hydroxide and a phase transfer catalyst, for example, an aqueous solution in which a metal hydroxide is dissolved. A method in which hinokitiol, polyacetylglycosyl halide, a chelating agent and a phase transfer catalyst are added to a solvent for reaction, a reaction is performed by dissolving all of the above five components in a solvent, and an aqueous solution in which hinokitiol metal salt is dissolved is polyacetyl. Examples thereof include a method in which a glycosyl halide, a chelating agent, and a phase transfer catalyst are added to a solvent in which they are dissolved and the reaction is performed. Examples of the solvent include hydrophobic solvents such as toluene, xylene, hexane, benzene, ethyl acetate and ether, and hydrophilic solvents such as acetone, ethanol, methanol, 2-propanol, DMSO, dioxane and THF. Among them, toluene, ethyl acetate and ether are preferable from the viewpoint of reactivity and handling.

As the above-mentioned mixing conditions, for example, the temperature is preferably 20 to 120 ° C, more preferably 30 to 80 ° C.
Then, it is preferable to mix for about 30 to 60 minutes.

The content of hinokitiol in the mixture obtained as described above is 1 from the viewpoint of solubility and cost.
-10 wt% is preferable, and 3-5 wt% is more preferable. The content of the chelating agent is preferably 0.5 to 2.0 times the molar amount of hinokitiol, from the viewpoint of the amount necessary to form a chelate with hinokitiol, and 0.8 to
A 1.5 times mole is more preferable. The content of the metal hydroxide is 0.5 to 2.0 relative to hinokitiol, from the viewpoint of the amount of hinokitiol required to form a metal salt.
A double mole is preferable, and a 0.8 to 1.2 mole is more preferable. From the viewpoint of reactivity, the content of the phase transfer catalyst is preferably 0.01 to 2.0 times mol, and more preferably 0.05 to 0.20 times mol, relative to hinokitiol. The content of polyacetylglycosyl halide is 1.0 to 2.0 with respect to hinokitiol from the viewpoint of reactivity and cost.
A double mole is preferable, and a 1.2 to 1.5-fold mole is more preferable. When a metal salt of hinokitiol is used, the content of the metal salt of hinokitiol is preferably 1 to 10% by weight, more preferably 3 to 5% by weight from the viewpoint of solubility and cost.

As the reaction conditions, temperature conditions are 0 to 70.
C is preferable, and 30 to 60 C is more preferable. The reaction time is preferably about 3 to 20 hours. The reaction is terminated by, for example, LC analysis of a solvent layer such as a toluene layer [conditions: column: ODS-HG-5 (φ4.6 × 250 mm), mobile phase: acetonitrile / 10 mM KH ₂ PO ₄ buffer = 40 / 60, oven: 40 ℃, U
V: 210 nm, pump: 1.0 mL / min] and confirm the reaction yield.

By the above reaction, a hinokitiol acetyl glycoside is obtained. The hinokitiol acetyl glycoside cannot be unconditionally limited depending on the kind of the polyacetyl glycosyl halide as a raw material, but, for example, the formula (III) to
(VI):

[0022]

[Chemical 3]

Examples include compounds represented by: Formula (III)
The compound represented by 4-isopropyltropolone-2-
Tetra-O-acetyl-β-D-gluside (4-isopropyl
tropolone-2-tetra-O-acetyl-β-D-gulucide), formula (I
The compound represented by V) is 6-isopropyltropolone-
2-Tetra-O-acetyl-β-D-gluside (6-isopr
opyltropolone-2-tetra-O-acetyl-β-D-gulucide). The compound represented by the formula (V) is 4-isopropyltropolone-2-hepta-O-acetyl-β-D-maltoside (4-isopropyltropolone-2-hepta-O-acetyl-β-Dm
altocide), the compound represented by the formula (VI) is 6-isopropyltropolone-2-hepta-O-acetyl-β-D.
− Maltoside (6-isopropyltropolone-2-hepta-O-acety
l-β-D-maltocide). Here, the formula (III) or (I
V), or two kinds of hinokitiol acetyl glycosides as in formula (V) or (VI) can be obtained when hinokitiol is represented by the following formula (VII):

[0024]

[Chemical 4]

This is because it is a tautomer represented by

The structure of the hinokitiol acetyl glycoside can be confirmed by LCMASS.

The hinokitiol acetyl glycoside can be recovered by centrifuging, filtering, etc. the reaction solution after the reaction, but when used in the method for producing a hinokitiol glycoside described below, the reaction The liquid may be used as it is.

Next, the method for producing a hinokitiol glycoside of the present invention is obtained by a step of further deacetylating the hinokitiol acetylglycoside obtained as described above. 1 and 2 are schematic explanatory views of this method. Figure 1
Is a compound of formula (I) as a polyacetylglycosyl halide
The case of using tetra-O-acetyl-α-D-glucopyranosyl bromide represented by Also, in FIG.
The case where hepta-O-acetyl-α-D-maltosyl bromide represented by the formula (II) is used as the polyacetyl glycosyl halide is shown.

In this method, the formula (III) or (I
The method for obtaining the hinokitiol acetyl glycoside represented by V) is the same as the method for producing the hinokitiol acetyl glycoside.

In the present invention, the means for deacetylating the hinokitiol acetyl glycoside is not particularly limited as long as it is known, and for example, the hinokitiol acetyl glycoside is dissolved in methanol and potassium carbonate is added. A method of reacting with a catalyst and purifying by a conventional method is preferable. From the viewpoint of reactivity, the amount of methanol is 200 with respect to 100 parts by weight of hinokitiol acetyl glycoside.
˜1000 parts by weight is preferable, and 300 to 500 parts by weight is more preferable. Moreover, as the amount of potassium carbonate, from the viewpoint of reactivity, it is preferably 0.01 to 1.0 times mol, and 0.05 to 0.5 mol, relative to the hinokitiol acetyl glycoside.
A double mole is more preferable. As the reaction conditions, the reaction temperature is 0
-40 degreeC is preferable and 5-20 degreeC is more preferable. The reaction time is preferably 2 to 40 hours, more preferably 4 to 10 hours. The reaction was terminated by LC analysis of the reaction mixture [conditions: column: ODS-HG-5 (φ4.6 × 250 mm), oven: 40 ° C., U
V: 210 nm, pump: 1.0 mL / min, mobile phase: acetonitrile / 10 mM KH ₂ PO ₄ buffer solution = 40/60].

A hinokitiol glycoside is obtained by the above reaction. The hinokitiol glycoside cannot be unequivocally limited depending on the type of polyacetyl glycosyl halide, but for example, the formulas (VIII) to (XI):

[0032]

[Chemical 5]

Examples include compounds represented by: Formula (VII
The hinokitiol glycoside represented by I) is 4-isopropyltropolone-2-O-β-D-gluside (4-isopropyl).
tropolone-2-O-β-D-gulucide), the hinokitiol glycoside represented by the formula (IX) is 6-isopropyltropolone-2.
-O-β-D-Gluside (6-isopropyltropolone-2-O-β
-D-gulucide). The hinokitiol glycoside represented by the formula (X) is 4-isopropyltropolone-2-O-β-.
D-maltoside (4-isopropyltropolone-2-O-β-D-mal
The hinokitiol glycoside represented by the formula (XI) is 6-isopropyltropolone-2-O-β-D-maltoside (6-isopropyltropolone-2-O-β-D-maltocide).

The structure of the hinokitiol glycoside can be confirmed by LCMASS.

The method for purifying the resulting hinokitiol glycoside is not particularly limited as long as it is a conventional method.

The hinokitiol glycoside thus obtained has the characteristics of being highly water-soluble and having antibacterial activity.

According to the present invention, the effect that the above-mentioned hinokitiol glycoside can be obtained industrially at low cost and in high yield is exhibited.

[0038]

Example 1 3.5 g (21%) of hinokitiol was added to a 100 mL reactor.
mmol), tetra-O-acetyl-α-D-glucopyranosyl bromide 10.5 g (26 mmol), pentamethyldiethylenetriamine 3.7 g (21 mmo).
l), TOMAC 1.0 g (2 mmol) in toluene 5
It was dissolved in 2.5 mL. Sodium hydroxide 0.
An aqueous sodium hydroxide solution prepared by dissolving 84 g (21 mmol) in 35.0 mL of pure water was added, and the mixture was reacted at 40 ° C. for 5 hours and treated by an ordinary method to obtain 9.0 g of white crystals (yield. 86%). The obtained white crystals are LCMASS
As a result of analysis by the above, it was confirmed that it was a hinokitiol acetyl glycoside [formula (III) and (IV)] (FIG. 3).
The obtained hinokitiol acetyl glycoside 9.0 g (18
mmol) and 0.1 g (1 mmol) of potassium carbonate in 70.0 mL of methanol and reacted in a 100 mL reactor at 10 to 20 ° C. for 3 hours to carry out purification by a conventional method to obtain 4.3 g of white crystals. (Yield 73%). The obtained white crystals were analyzed by LCMASS, and as a result, it was confirmed that they were hinokitiol glycosides [formula (VIII) and (IX)] (FIG. 4). The experimental data of LCMASS is shown below. [LCMASS] Flow injection method (analytical instrument: M-1200 AP LC / MS system (manufactured by Hitachi, Ltd.), analytical conditions: pump: 1.0 mL / min, mobile phase: 100% methanol, MASS setting: positive Mode). m / z 495 [M ⁺ ] (hinokitiol acetyl glycoside) m / z 327 [M ⁺ ] (hinokitiol glycoside)

Example 2 8.1 g (49 g) of hinokitiol was added to a 500 mL reactor.
mmol), hepta-O-acetyl-α-D-maltosyl bromide 41.3 g (59 mmol), pentamethyldiethylenetriamine 8.5 g (49 mmol), T
2.0 g (4 mmol) of OMAC was dissolved in 195 L of toluene. 2.0g sodium hydroxide (50m
(mol) was added to 81 mL of purified water and reacted at 40 ° C. for 8 hours, the reaction proceeded quantitatively, and white crystals (38 g) were obtained by the conventional treatment. (V) and (VI)]. The reaction was terminated by LC analysis (conditions: column: Inertsil ODS-2, UV: 210 nm, column oven: 25 ° C., mobile phase: acetonitrile / 10 mM KH ₂
PO ₄ buffer solution = 50/50, pump: 1.0 mL / min). 38 g (48 mmol) of the obtained white crystals and 2.3 g (17 mmol) of potassium carbonate were added to 166 m of methanol.
Dissolve in L, 6 ~ 12 ℃ in a 500 mL reactor,
The reaction was carried out for 6 hours. The reaction was terminated by LC analysis (conditions: column: Inertsil ODS-2, UV: 210 nm, column oven:
25 ° C, mobile phase: acetonitrile / 10 mM KH ₂ PO ₄ buffer = 4
0/60, pump: 1.0 mL / min). Purification by a conventional method gave 16.8 g of white crystals (yield 70
%). The obtained white crystals were analyzed by LCMASS. As a result, hinokitiol glycoside [formula (X) and (XI)]
Was confirmed (FIG. 5). The analysis data of LCMASS is shown below. [LCMASS] Flow injection method (analytical instrument: M-1200 AP LC / MS system (manufactured by Hitachi, Ltd.), analytical conditions: pump: 1.0 mL / min, mobile phase: 100% methanol, MASS setting: positive Mode). m / z 489 [M ⁺ ]

Example 3 Hinokitiol (24.3 mmol), tetra-O-acetyl-α-D-glucopyranosyl bromide (2.4)
3 mmol), TOMAC (2.4 mmol), and pentamethyldiethylenetriamine (24.3 mmol) were dissolved in 60 mL of toluene. A sodium hydroxide solution prepared by dissolving sodium hydroxide (24.3 mmol) in 40 mL of purified water was added thereto, and the mixture was reacted at 40 to 45 ° C for 6 hours. After the reaction was completed, the toluene layer was analyzed by LC [conditions: column: ODS-HG-5 (φ4.6 x 250 mm), oven: 40 ° C, UV: 210 nm, pump: 1.0 mL / min, mobile phase: acetonitrile / The reaction yield of 10 mM KH ₂ PO ₄ buffer = 40/60, the same applies hereinafter) and hinokitiol acetyl glycoside [formula (III) and (IV)] was 83.5%.

Example 4 Hinokitiol (2.0 mmol), tetra-O-acetyl-α-D-glucopyranosyl bromide (2.4 m)
mol), TOMAC (0.2 mmol) and pentamethyldiethylenetriamine (2.0 mmol) were dissolved in 5 mL of toluene. Potassium hydroxide (2.0m
(mol) was dissolved in 5 mL of purified water, and a potassium hydroxide solution was added, and the mixture was reacted at 40 to 45 ° C. for 6 hours. After completion of the reaction, the toluene layer was analyzed by LC, and as a result, the reaction yield of hinokitiol acetyl glycoside [formula (III) and (IV)] was 8
It was 5.3%.

Example 5 Hinokitiol sodium salt (1.67 mmol), benzalkonium chloride (0.24 mmol) and pentamethyldiethylenetriamine (2.02 mmol) were dissolved in 5 mL of purified water. Tetra-O-acetyl-α
-D-glucopyranosyl bromide (2.43 mmo
1) was added to a solution of 5 mL of toluene, and 40 to 4
The reaction was carried out at 5 ° C for 4 hours. After the reaction is complete, the toluene layer is LC
As a result of analysis, the reaction yield of the hinokitiol acetyl glycoside [formula (III) and (IV)] was 82.3%.

Example 6 Hinokitiol sodium salt (1.67 mmol), T
OMAC (0.24 mmol) and pentamethyldiethylenetriamine (2.02 mmol) were dissolved in 5 mL of purified water. To this, tetra-O-acetyl-α-D-glucopyranosyl bromide (2.43 mmol) was added to a solution of toluene (5 mL), and the mixture was reacted at 40 to 45 ° C. for 4 hours. After completion of the reaction, the toluene layer was analyzed by LC. As a result, hinokitiol acetyl glycoside [formula (III) and (I
The reaction yield of V)] was 91.9%.

Example 7 Hinokitiol sodium salt (1.67 mmol), T
OMAC (0.24 mmol) and diethylenetriamine pentaacetic acid (2.02 mmol) were dissolved in 5 mL of purified water. Tetra-O-acetyl-α-D-glucopyranosyl bromide (2.43 mmol) was added to toluene 5 m.
It was added to the solution dissolved in L and reacted at 40 to 45 ° C. for 4 hours. After the reaction was completed, the toluene layer was analyzed by LC. As a result, the reaction yield of the hinokitiol acetylglycoside [formula (III) and (IV)] was 84.3%.

Comparative Example 1 Hinokitiol sodium salt (1.67 mmol), T
OMAC (0.24 mmol) was dissolved in 5 mL of purified water. Tetra-O-acetyl-α-D-glucopyranosyl bromide (2.43 mmol) was added to this with toluene 5
It was added to the solution dissolved in mL and reacted at 40 to 45 ° C for 4 hours. After the reaction was completed, the toluene layer was analyzed by LC,
Hinokitiol acetyl glycoside [Formulas (III) and (IV)]
The reaction yield was 49.8%.

Comparative Example 2 Hinokitiol sodium salt (1.67 mmol), pentamethyldiethylenetriamine (2.02 mmol)
Was dissolved in 5 mL of purified water. To this was added tetra-O-acetyl-α-D-glucopyranosyl bromide (2.43).
mmol) to a solution of 5 mL of toluene and add 4
The reaction was carried out at 0 to 45 ° C for 4 hours. After completion of the reaction, the toluene layer was analyzed by LC, and as a result, the reaction yield of the hinokitiol acetyl glycoside [formulas (III) and (IV)] was 46.5%.

Comparative Example 3 0.37 g (1.67 mm) of hinokitiol sodium salt
ol) was dissolved in 5 mL of purified water. Tetra-O
-Acetyl-α-D-glucopyranosyl bromide 1.
A solution prepared by dissolving 00 g (2.43 mmol) in 5 mL of toluene was added, and the mixture was reacted at 40 to 45 ° C for 4 hours. After completion of the reaction, the toluene layer was analyzed by LC. As a result, the reaction yield of the hinokitiol acetyl glycoside [formulas (III) and (IV)] was 22.9%.

Test Example 1 [Dissolution test of hinokitiol glycoside in water] 30 g of hinokitiol glycoside [formula (VIII and IX)] and 30 g of hinokitiol were precisely weighed in a 300 mL Erlenmeyer flask, and then 70 g of water was added. . After maintaining the temperature at 25 ° C and stirring for 30 minutes, dissolution in water was visually confirmed. As a result, all the hinokitiol glycosides were dissolved. In addition, hinokitiol was insoluble because it had a residual residue. From this,
It can be seen that the hinokitiol glycoside is superior in water solubility to hinokitiol.

Test Example 2 [Antibacterial activity test of hinokitiol glycosides] According to the MIC measurement method of the Japanese Society of Chemotherapy, hinokitiol glycosides [formula (VIII) and (IX)] were mixed on an agar plate medium. The presence or absence of growth of the test bacterium was observed. The agar plate medium was prepared as follows. A sample (hinokitiol glycoside) was diluted with ethyl alcohol in multiples, and the resulting diluted sample was added to an agar medium kept at 50 ° C to 1/1 of the medium.
00 amount was added so that the final concentration of the sample was 6 to 1600 ppm. Potato dextrose agar medium (pH 6) was used for the test, and the culture was performed at 24 ° C. for 10 days.
The results are shown in Table 1. The test strains used are shown below.

Test strain Pythium aphanidermatum IFO 32440 (cotton rot) Thanatephorus cucumeris IFO 30445 (Fruitling etc.) Fusarium solani IFO 9955 (Fruitling etc.) Botryotinia fuckeliana IFO 30915 (Gray mold) Phomopsis obscurans MAFFF 744018 ( Strawberry anthrax) Colletotrichum orbiculare MAFF 306518 (melon anthrax) Colletotrichum lagenarium (watermelon anthrax)

[0051]

[Table 1]

From the results in Table 1, it is understood that the hinokitiol glycoside has sufficient antibacterial activity because it suppressed the growth of various test bacteria even at the low concentration as described above.

[0053]

EFFECTS OF THE INVENTION The production method of the present invention has the effect that a highly water-soluble hinokitiol glycoside can be industrially obtained at low cost and in high yield.

[Brief description of drawings]

FIG. 1 is a schematic explanatory diagram of a method for producing a hinokitiol glycoside when tetra-O-acetyl-α-D-glucopyranosyl bromide is used as a polyacetylglycosyl halide.

FIG. 2 is a schematic explanatory diagram of a method for producing a hinokitiol glycoside in the case of using hepta-O-acetyl-α-D-maltosyl bromide as a polyacetyl glycosyl halide.

FIG. 3 shows the results of LCMASS analysis of the hinokitiol acetylglycosides evaluated by the formulas (III) and (IV). The peak of "495" in the figure corresponds to hinokitiol acetyl glycoside.

FIG. 4 shows the results of LCMASS analysis of hinokitiol glycosides represented by formulas (VIII) and (IX). The peak of "327" in the figure corresponds to the hinokitiol glycoside.

FIG. 5 shows results of LCMASS analysis of hinokitiol glycosides represented by formulas (X) and (XI). The peak of "489" in the figure corresponds to the hinokitiol glycoside.

Claims (3)

[Claims] 1. A method for producing a hinokitiol acetyl glycoside, comprising a step of reacting hinokitiol with a polyacetylglycosyl halide in the presence of a chelating agent, a metal hydroxide and a phase transfer catalyst. 2. A method for producing a hinokitiol acetyl glycoside, comprising a step of reacting a metal salt of hinokitiol with a polyacetyl glycosyl halide in the presence of a chelating agent and a phase transfer catalyst. 3. A method for producing a hinokitiol glycoside having a step of deacetylating the hinokitiol acetylglycoside obtained by the method according to claim 1.