JP3143269B2 - Hinokitiol glycoside and method for producing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel hinokitiol glycoside which is easy to handle and exhibits an excellent antibacterial action, and a method for producing the same.

[0002]

2. Description of the Related Art Hinokitiol is a natural tropolone isolated from the phenolic components of essential oils such as cypress plants and is widely used in various antibacterial agents, insect repellents, pharmaceuticals, etc. because of its excellent antibacterial properties. (See, for example, JP-A-2-40304 and JP-A-4-182408).

However, since hinokitiol is a sublimable crystal, when it is used in air, a phenomenon occurs in which the antibacterial effect is lost in a short period of time due to a volatilization phenomenon. On the other hand, long-term use as an aqueous solution has been attempted, but its water solubility is extremely low at about 0.2 g / l, so that it was difficult to prepare an aqueous solution exhibiting an effective antibacterial effect with a small amount. . As a result, although hinokitiol has excellent antibacterial properties, there is a problem in that it lacks storage stability, handleability, stability and the like.

[0004]

SUMMARY OF THE INVENTION The present invention solves the above-mentioned conventional problems, has almost no sublimation property, and can exhibit an antibacterial action for a long time even when used in air. It is also an object of the present invention to provide a hinokitiol glycoside capable of producing an aqueous solution having a high water solubility and exhibiting an antibacterial action effectively and exhibiting excellent preservability, handleability, stability and the like, and a method for producing the same. It was completed for the purpose.

[0005]

Means for Solving the Problems A first invention made to solve the above-mentioned problems is a hinokitiol glycoside characterized by glycating hinokitiol and linking a saccharide with the hinokitiol. Is a method for producing a hinokitiol glycoside, comprising dehydrating and condensing hinokitiol with a sugar to ether bond the sugar to a hydroxyl group of the hinokitiol.

Hereinafter, the present invention will be described in detail. Hinokitiol is a special substance having a 7-membered ring as shown in Chemical Formula 1 below, and has been known for a long time as a substance having a broad antibacterial spectrum. For example, extracted as an essential oil component of Aomori Hiba, various antibacterial agents and insect repellents It is used for medicines and food additives.

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The hinokitiol glycoside of the present invention is one wherein the hydroxyl group of the hinokitiol and the hydroxyl group of the saccharide are dehydrated and condensed by the action of an enzyme, and the saccharide is bound by an ether bond to bond the saccharide, as shown in Chemical formula 2. The hinokitiol glycoside synthesized as described above has a structure in which a sugar is bound to hinokitiol by a β-bond as shown in Chemical formula 3. Chemical formula 4 is an isomer of the hinokitiol glycoside shown in chemical formula 3, but has the same properties as those in chemical formula 3. As the glycosylation means, in addition to the above-mentioned enzymatic method, an organic chemical method, a method based on bioconversion, and the like can be used.

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The saccharides to be bound to hinokitiol are monosaccharides such as hexose such as glucose, fructose, mannose and galactose, pentosose such as xylose and arabinose, and disaccharides such as primeverose, gentiobiose, rutinose, strophantobiose and cellobiose. And other polysaccharides or their derivatives.

[0009]

The hinokitiol glycoside thus obtained has an extremely low sublimation property as compared with conventional hinokitiol, and can exhibit an antibacterial effect for a long time even when used in air. It is possible to prepare an aqueous solution that exhibits high antibacterial action effectively with excellent preservability,
It exhibits handleability and stability. And
Since the hinokitiol glycoside is easily hydrolyzed by enzymes such as β-glucosidase (for example, a microorganism contaminating food contaminants and microorganisms living in the intestine of termites) and cellulase widely existing in nature, it easily decomposes hinokitiol. It will have an excellent antibacterial effect. For example, when the hinokitiol glycoside of the present invention is applied as a pesticide for termites and ticks, hinokitiol is converted into the body by the hydrolysis of β-glucosidase held by intestinal microorganisms after the termites eat and drink the glycoside. And it can be reliably removed by antibacterial action.

[0010]

EXAMPLE A mixture of hinokitiol dissolved in acetonitrile at a concentration of 100 mg / ml and a 50% aqueous glucose solution were mixed in 5 cc portions, and the mixture was preheated at 40 ° C. for 30 minutes in a water bath to obtain 10,000 units of almond-derived β-glucosidase. By adding and reacting all day and night (40 ° C.), a hinokitiol glycoside was synthesized. 10 of the obtained reaction solution
The 100-fold dilution was subjected to HPLC (ODS column: 250 × 4.6 mm,
Mobile phase: 0.1% H ₃ PO ₄ /40% acetonitrile, flow rate: 1.0 ml,
(Detector conditions: absorption at 254 nm) to obtain a chart as shown in FIG. Next, a large amount of a peak considered to be a hinokitiol glycoside was collected and diluted 5-fold with water.
When subjected to C, it was confirmed that a large amount of hinokitiol was produced from the synthesized hinokitiol glycoside.

Next, the hinokitiol glycoside of the present invention is two-fold serially diluted using a solution obtained by adding 5 parts of sterile physiological saline and 2 parts of ethanol, and then the minimum inhibitory concentration (MIC) of the antibiotic is measured. Table 1 shows the results of measuring the antibacterial activity against various microorganisms according to the method. The medium used for intestinal bacteria and the like is Sensitive Disk Medium-N (manufactured by Nissui Co., Ltd.), fungi are potato dextrose agar medium (manufactured by Eiken Co., Ltd.), basidiomycetes are maltose agar medium, and lactic acid bacteria are lactic acid bacteria. A medium for detecting general lactic acid (manufactured by Nissui Co., Ltd.) and a CAM bouillon agar medium (manufactured by Nissui Co., Ltd.) were used for anaerobic bacteria. In addition, the result of similarly measuring the antibacterial activity of hinokitiol derived from Aomori Hiba was shown as a comparative example, and it was confirmed that the hinokitiol glycoside of the present invention exhibited the same antibacterial activity as conventional hinokitiol. Since the hinokitiol glycoside of the present invention is superior in water solubility as compared with conventional hinokitiol, an aqueous solution having an effective antibacterial effect can be easily prepared.

Next, the results of the measurement of the sublimability of the hinokitiol glycoside of the present invention are shown in FIG. The measurement method is
Thermogravimeter (manufactured by Shimadzu Corporation: TGA-5)
According to 0), a sample of 8.553 mg was sampled in an aluminum cell, nitrogen gas was flowed at 30 ml / min as an atmosphere, and heating measurement was performed at a heating rate of 10 ° C / min to 300 ° C to determine the weight loss of the sample. I asked. Further, the temperature of the tangent intersection point was determined from the obtained weight loss rate curve, and as a result, it was 235.66 ° C. On the other hand, for hinokitiol derived from Aomori Hiba, the weight loss rate was determined in the same manner, and the temperature at the tangent intersection point was determined to be 158.55 ° C. from the obtained weight loss rate curve, indicating that the hinokitiol glycoside of the present invention was a conventional hinokitiol. The temperature at the tangent intersection increased by about 80 ° C. as compared with, and it was confirmed that the sublimability was sufficiently suppressed.

[0013]

[Table 1]

[0014]

As is clear from the above description, the first
The invention has no sublimation and can exhibit an antibacterial effect for a long time even in use in the air, and it has high water solubility and can produce an aqueous solution that exhibits an effective antibacterial effect and has excellent storage. It can exhibit properties, handling properties, stability, etc. The second invention is capable of efficiently producing the above-mentioned hinokitiol glycoside using hinokitiol as a starting material. Therefore, the present invention greatly contributes to industrial development as a hinokitiol glycoside which has solved the conventional problems and a method for producing the same.

[Brief description of the drawings]

FIG. 1 is a chart showing the results of HPLC analysis in Examples of the present invention.

FIG. 2 is a graph showing an analysis result of thermogravimetry in an example of the present invention.

────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Yasuko Yoshida 3-1910-3 Otoro, Nakagawa-ku, Nagoya-shi, Aichi (56) References JP-A-4-183776 (JP, A) JP-A-2-2422692 ( JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) C07H 15/203 C12P 19/44 CA (STN) CAOLD (STN) CAPLUS (STN) REGISTRY (STN)

Claims (4)

(57) [Claims] 1. A hinokitiol glycoside, wherein hinokitiol is glycosylated and sugar is bound thereto. 2. The hinokitiol glycoside according to claim 1, wherein the sugar is linked to hinokitiol by a β-linkage. 3. The hinokitiol glycoside according to claim 1, wherein the saccharide is bound to hinokitiol by dehydration condensation. 4. A method for dehydrating and condensing hinokitiol and sugar to form hinokitiol.
It is characterized in that a sugar is ether-bonded to the hydroxyl group of chithiol.
A method for producing a hinokitiol glycoside as a feature.