JP2001261693A - New o-glycoside type glycolipid and method for producing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a new O-glycoside type glycolipid simply mass-producible from a readily obtainable naturally occurring substance as a raw material, useful as a functional material. SOLUTION: This O-glycoside type glycolipid comprises an aldose group as a glycosyl group and a group of the general formula (R1 is a hydrogen atom or a hydroxyl group; R2 is a hydrogen atom or a carboxyl group; R3 is an aliphatic saturated or unsaturated straight-chain hydrocarbon group) as an aglycone.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a novel O-glycoside type glycolipid using a long chain hydrocarbon group-substituted phenol residue as an aglycone, more specifically, to disperse it in water or a mixed solvent of water and alcohol. By forming organic thin films, closed vesicles (vesicles), fibrous aggregates, or thermotropic liquid crystals in the form of dry powder, new O-types can be used as functional materials in various industrial fields. It relates to glycoside-type glycolipids.

[0002]

BACKGROUND ART Glycosides are compounds widely distributed in the plant kingdom as plant pigments, plant dyes, natural medicines and the like. The hydrogen atom of the hemiacetal hydroxyl group of a sugar having a pyranose or furanose ring is an alkyl group or a hydrogen atom. It is substituted with an aryl group. This glycoside has a chemical structure in which a sugar residue and a non-sugar residue are bonded, and the sugar residue is generally called a glycosyl group, and the non-sugar residue is generally called an aglycone.

On the other hand, animal tissues contain 12 to 18 carbon atoms.
Glycosides containing an aliphatic linear hydrocarbon group of the general formula

Embedded image (Wherein R and R ′ in the formula are linear alkyl groups having 12 to 18 carbon atoms), and glycoside-type glycolipids having aglycone as a group, that is, sphingo-type glycolipids exist, which are hydrophilic. Since it has both hydrophobic saccharides and hydrophobic aliphatic hydrocarbon chains, it is expected to be used as a surfactant or functional amphiphile. It has not been put to practical use because of its complexity.

[0004] On the other hand, glyceroglycolipids having a glucose group as a hydrophilic group and a 1,2-O-dialkylglyceride group as a hydrophobic group are known as synthetic glycolipids ["Tetrahedron". L
Etters) ", Vol. 24, p. 1229 (198
3 years)], but it has a drawback that it cannot be carried out industrially because it requires the use of a method including a multi-step process requiring skill.

[0005]

The object of the present invention is to provide a novel O-glycoside type glycolipid useful as a functional material, which can be easily mass-produced from a readily available natural substance as a raw material. It was done.

[0006]

Means for Solving the Problems As a result of intensive studies on the O-glycoside type glycolipid, the present inventors have determined that a long chain hydrocarbon group-substituted phenol residue extracted from readily available cashew nuts is used as an aglycone. The glycolipid consisting of O-glycoside can be mass-produced by a simple method,
In addition, they have found that the material is a renewable functional material, and based on this finding, have accomplished the present invention.

That is, the present invention relates to an aldose residue as a glycosyl group and a general formula as an aglycone.

Embedded image Wherein R ¹ is a hydrogen atom or a hydroxyl group, R ² is a hydrogen atom or a carboxyl group, and R ³ is an aliphatic saturated or unsaturated linear hydrocarbon group. An object of the present invention is to provide an O-glycoside type glycolipid.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION The O-glycoside type glycolipid of the present invention contains an aldose residue as a glycosyl group and a long chain hydrocarbon group-substituted phenol residue represented by the above general formula (I) as an aglycone. And the general formula

Embedded image (Wherein R ¹ , R ² and R ³ have the same meaning as described above, and
Is an aldofuranose or aldopyranose residue in which the carbon atom at the reducing end is involved in an O-glycoside bond).

G in the general formula (II), that is, the glycosyl group includes, for example, aldopyranose such as glucopyranose, galactopyranose, mannopyranose, allopyranose, altopyranose, glopyranose, idpyranose and talopyranose; Residues obtained by removing a hydrogen atom from the hydroxyl group at the reducing end of the corresponding aldofuranose can be mentioned.

Next, R ³ in the general formula (II) is an aliphatic linear hydrocarbon group having 12 to 18 carbon atoms, preferably 15 carbon atoms, and this hydrocarbon group may be saturated or unsaturated.
When unsaturated, those containing 1 to 3 double bonds are preferred. Examples of such an aliphatic saturated linear hydrocarbon group include a dodecyl group, a tridecyl group, a tetradecyl group, a pentadecyl group, a hexadecyl group, a heptadecyl group, and an octadecyl group. A pentadecyl group is preferred in that respect. Further, as the aliphatic unsaturated linear hydrocarbon group, triene, diene or monoene residues of those corresponding to the above aliphatic saturated linear hydrocarbon groups can be mentioned, but the raw material is easily available. In that there are 8-pentadecenyl, 8,10-pentadecadienyl, 8,1
A 0,12-pentadecatrienyl group is preferred.

The O-glycoside type glycolipid represented by the general formula (II) is a novel compound which has not been described in any literature. According to the method of the present invention, the O-glucoside-type glycolipid has, for example, the general formula

Embedded image (Wherein R ¹ , R ² and R ³ have the same meanings as described above), the phenol substituted with a long-chain hydrocarbon group or a derivative thereof has aldopyranose or aldose in which all hydroxyl groups other than the reducing terminal hydroxyl group are protected. It can be produced by reacting a reactive functional derivative of a reducing terminal hydroxyl group of furanose (hereinafter simply referred to as protected aldose) to form an O-glucoside bond, and then removing the protecting group. As this protecting group, for example, an acetyl group,
A 1,2-methylene group, a 1,2-isopropylidene group and the like are used. Examples of the reactive functional derivative of the reducing terminal hydroxyl group include, for example, the corresponding aldose trichloroacetimidate, bromide (brom sugar), fluorinated compound (fluorinated sugar), thioglycoside, O-acylate and the like. . Of these, fluorinated compounds and trichloroacetimidate are preferable because they react in high yield.

Among the long-chain hydrocarbon group-substituted phenols represented by the general formula (III) and derivatives thereof, those having a saturated or unsaturated straight-chain hydrocarbon group having 15 carbon atoms include:
Cashew nuts can be easily obtained as a raw material.
That is, cashew varnish, cashew nut shell oil generally used as a raw material for mechanical and automotive brake pads and linings is vacuum-distilled to a boiling point of 220-2.
Collect fractions in the 35 ° C. range. In this case, the range of 250 to 700 Pa is appropriate as the degree of vacuum. This cashew nut shell oil is also called cashew nut oil, and is a cashew nut tree (Anacardium) belonging to the family Urushi.
is an oily liquid obtained by solvent extraction or heat fractionation of the oyster shells of Ocidentale). When the solvent is extracted, it is obtained as a mixture containing anacardic acid and cardol as main components, and when the solvent is fractionated by heating, it is obtained as a mixture mainly containing cardanol and cardol.

For use as a raw material of the present invention, the cashew nut shell liquid is subjected to an extraction operation using a solvent such as n-hexane, and the resulting cardanol, cardol and anacardic acid are dissolved in the solvent. By hydrogenation according to a conventional method, a phenol substituted with an aliphatic saturated hydrocarbon group or a derivative thereof is obtained. Usually, alcohols such as methyl alcohol and ethyl alcohol are used as reaction solvents in the hydrogenation reaction, and platinum / carbon-based catalysts, palladium / carbon-based catalysts and the like are used as hydrogenation catalysts.

On the other hand, the reactive functional derivative of protected aldose to be reacted with the long-chain hydrocarbon-substituted phenol or its derivative can be produced, for example, as follows. That is, a halide such as bromide or fluoride of the reducing terminal hydroxyl group of aldose, so-called bromosugar or fluorine sugar, is obtained by acetylating aldose in pyridine and then reacting hydrogen bromide or hydrogen fluoride in acetic acid. Obtained by:

The corresponding trichloroacetimidate is obtained by acetylating aldose in the same manner as described above, and then reacting the saccharide with a hydrazine acetate salt in dimethylformamide to selectively deacetylate only the reducing end. And then reacting with trichloroacetonitrile in the presence of a base catalyst. In this case, the reaction solvent is preferably a halogen compound such as methylene chloride or chloroform, and the base catalyst is preferably sodium hydride or cesium carbonate.

In the reaction for obtaining the aldose halide, the α-isomer can be selectively obtained. In the reaction for obtaining trichloroacetimidate, the reaction can be carried out at room temperature for 2 hours or more to obtain the α-isomer selectively. . This means that the ¹ H-NMR spectrum of these compounds (in deuterated chloroform at 25 ° C.) shows a doublet signal (spin-spin coupling constant of 3.4) at a δ value of 6.4 to 6.6 ppm.
〜4.0 Hz).

Next, the reaction for forming an O-glycosidic bond from the long-chain hydrocarbon group-substituted phenol represented by the general formula (III) or a derivative thereof and the reactive functional derivative of the protected aldose is as follows: It can be performed as follows. For example, when the protected reactive functional derivative of aldose is bromide, the reaction is carried out in the presence of a basic substance using tin trifluoromethanesulfonate as a catalyst. As a reaction solvent at this time, chloroform, toluene or the like is used, and a chloroform / toluene mixed solvent system is preferable from the viewpoint of solubility. As the basic substance, 2,4,6-trimethylpyridine or 1,1,3,3-tetramethylurea is used. The reaction temperature at this time is suitably from room temperature to 40 ° C. for 10 to 20 hours. In this reaction, even better results are obtained when molecular sieve 4A coexists.

Next, when the reactive functional derivative of the protected aldose is trichloroacetimidate,
The reaction is performed in the presence of a Lewis acid catalyst. As a reaction solvent at this time, a halogen-based solvent such as chloroform, methylene chloride and 1,2-dichloroethane, acetonitrile, nitromethane and the like are used, and methylene chloride is particularly preferable. As a Lewis acid catalyst for this reaction, trimethylsilyl trifluoromethanesulfonate or boron trifluoride / ether complex is used. The amount of the Lewis acid catalyst used is preferably 2 to 3 equivalents based on trichloroacetimidate. An appropriate reaction temperature at this time is -5 to 0C. The reaction time depends on the type of Lewis acid catalyst and the reaction temperature, but is usually 2 to 3 hours. This reaction is preferably performed in the presence of a molecular sieve with stirring. Using glucose as aldose,
With the use of boron trifluoride-ether complex, glucose is not converted to trichloroacetimidate in advance,
O-glycosides can be obtained in good yield even if all hydroxyl groups including the reducing terminal hydroxyl group are directly reacted with acetylated aldose. In particular, when glucose is used, this method is advantageous because the reaction is performed in high yield. When bromide or trichloroacetimidate is used, β-form O-glycoside can be selectively obtained. This means that the ¹ H-NMR spectrum (at 25 ° C. in deuterated dimethyl sulfoxide) of these compounds was 4.4 to δ.
This can be confirmed by showing a doublet signal (spin-spin coupling constant: 7.8 to 8.0 Hz) at 4.9 ppm.

In this manner, O having a protected sugar chain is
A glycoside is obtained, but it is necessary to finally remove the protecting group. Then, the elimination reaction of this protecting group, for example, an acetyl group, is performed by treating an O-glycoside having a protected sugar chain with an alkali metal alcoholate such as sodium methoxide or potassium methoxide, and then using a strongly acidic cation exchange resin. It can be performed by neutralization. Further, the reaction can be carried out more easily by mixing an aqueous solution of a trialkylamine such as trimethylamine with a several-fold volume of a reaction solvent and reacting with an O-glycoside having the protected sugar chain. At this time, the concentration of the aqueous trialkylamine solution is preferably 30 to 50% by weight. As a reaction solvent at this time, an alcohol solvent such as methyl alcohol or ethyl alcohol, or a mixed solvent of an ether solvent such as diethyl ether or tetrahydrofuran and an alcohol solvent is suitable. At this time, it is desirable to maintain the pH of the reaction solution at 8.0 to 8.5 in order to avoid side reactions such as an ester hydrolysis reaction. The reaction time depends on the reaction conditions, but is usually 12 to 2
4 hours is appropriate. After the completion of the reaction, the solvent is distilled off to obtain an O-glycoside type glycolipid having a long chain hydrocarbon group-substituted phenol residue represented by the general formula (I) as an aglycone as a white powder. The crude product thus obtained can be made highly pure by a separation and purification operation using a silica gel column.

In the compound of the present invention, the measured elemental analysis value agrees with the calculated value within an error range. Further, the compound whose sugar chain is protected by an acetyl group has a δ value of 2.03 to 2.08 pp in ¹ H-NMR (in deuterated chloroform at 25 ° C.).
m can be easily identified from the presence of a characteristic signal attributable to hydrogen of the methyl group of the acetyl group. on the other hand,
The compound from which the acetyl group has been removed has a δ value of 0.1 in ¹ H-NMR (in deuterated dimethyl sulfoxide at 25 ° C.).
88 ppm (hydrogen of a methyl group of a long-chain hydrocarbon group);
26 ppm (hydrogen of a methylene group of a long-chain hydrocarbon group),
1.58 ppm (hydrogen of the second methylene group counted from the aromatic portion in the long chain hydrocarbon group), 2.56 pp
m (hydrogen of a methylene group directly connected to an aromatic group), 3.1
3 to 3.69 ppm (C2, C3, C4, C5,
Hydrogen connected to C6 carbon), 4.82 ppm (C of sugar chain)
Anomer hydrogen linked to one carbon), 5.34-5.42
ppm (hydrogen linked to vinyl group), 6.79, 6.8
The product can be identified and confirmed from 0 to 6.89 ppm, 7.19 to 7.20 ppm (hydrogen linked to the aromatic ring) and the like.

[0021]

The O-glycoside type glycolipid having a long chain hydrocarbon group-substituted phenol residue as an aglycone according to the present invention is dissolved in a trace amount in a hydrophobic organic solvent such as chloroform, and Langmuir- An organic thin film having a thickness on the order of molecules is provided by developing by a jet jet method and transferring it onto a suitable substrate. Furthermore, a spherical vesicle (vesicle) can be obtained by heating a fibrous structure having a width of 100 nm to 1 μm by leaving it dispersed in water and an aqueous dispersion containing the fibrous structure. Also, a lyotropic liquid crystal can be formed by mixing a thermotropic liquid crystal in a bulk state with an appropriate solvent. Furthermore, since the O-glycoside type glycolipid of the present invention is a renewable plant resource, both the long-chain hydrocarbon group-substituted phenol forming the aglycone and the sugar residue forming the glycosyl group are treated as waste. There is also an advantage that it can be reused when it is used.

Since the O-glycoside type glycolipid having a long chain hydrocarbon group-substituted phenol residue as an aglycone according to the present invention has such properties, it can be used as a material for forming a vesicle film in the fields of medicine, cosmetics, etc. And microstructures, useful as microelectronic components in the electronics and information fields, and as emulsifiers, stabilizers, dispersants, and wetting agents in the food industry, agriculture, forestry, and textile industries. high.

[0023]

EXAMPLES Next, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples. In addition, R of thin layer chromatography
Hexane / ethyl acetate (volume ratio 6/4) as f value
The value when the mixed solvent as a developing solvent was Rf _1.

Example 1 Cashew nut oil was vacuum distilled twice at about 400 Pa, and components having a boiling point of 220 ° C. to 235 ° C. were collected to obtain cardanol. 1.52 g (5 mmol) of the cardanol was dissolved in anhydrous methylene chloride (10 ml),
In the presence of 2 g of molecular sieve 4A, 3.9 g (5 mmol) of β-D-glucose pentaacetate and 0.62 ml (5 mmol) of boron trifluoride diethyl ether were added. The reaction mixture was stirred at room temperature for 24 hours, and then poured into a 5% aqueous sodium hydrogen carbonate solution.
Then, the organic phase was separated, and aqueous sodium hydrogen carbonate solution was added.
Subsequently, after washing with water, it was dried over anhydrous sodium sulfate. The organic solvent was completely distilled off under reduced pressure, and the obtained crude product was recrystallized from ethanol. The resulting product solid was subjected to column chromatography using a mixed solvent of hexane / ethyl acetate (volume ratio: 7/3) as an eluent to obtain 2.36 g of 1- (O-β-D-glucopyranoside tetraacetate) cardanol as a white solid ( (75% yield).
Its physical properties are as follows. Rf value of thin layer chromatography: Rf ₁ = 0.47 Melting point: 60 ° C. Deuterochloroform of this product, ¹ at 25 ° C. H-N
FIG. 1 shows an MR spectrum chart.

Next, a 45% by weight aqueous solution of trimethylamine was mixed with 4 times the volume of methyl alcohol, and the obtained 1- (O-β-D-glucopyranoside tetraacetate) cardanol (1.26 g, 2 mmol) was mixed with 24%. Allowed to react for hours. After distilling off the solvent under reduced pressure, the syrupy residue obtained was crystallized from a mixed solvent of methyl alcohol / acetonitrile (volume ratio: 1/2) and further recrystallized from the same solvent to obtain the desired deacetylation. The obtained 1- (O-β-D-glucopyranoside) cardanol was almost quantitatively obtained as 0.88 g (95% yield) of a white solid. Its physical properties are as follows. Melting point: 135.2 ° C At 25 ° C. in deuterated dimethyl sulfoxide
FIG. 2 shows the ¹ H-NMR spectrum chart.

Example 2 Instead of cardanol in Example 1, 3'-n-
Example 1 except that pentadecylphenol was used.
By the same operation as in the above, the following compound was obtained. 3'-n-pentadecylphenyl-2,3,4,6-O
-Acetyl-β-D-glucopyranoside (white solid) Rf value of thin layer chromatography: Rf ₁ = 0.55 Melting point: 101 ° C. Deuterochloroform of this product, ¹ at 25 ° C. H-N
FIG. 3 shows the MR spectrum chart. 3'-n-pentadecylphenyl-β-D-glucopyranoside (white solid) Melting point: 143.5 ° C At 25 ° C. in deuterated dimethyl sulfoxide
FIG. 4 shows the ¹ H-NMR spectrum chart.

Example 3 The procedure of Example 1 was repeated, except that cardol was used instead of cardanol.
The following compound was obtained. 1- (O-β-D-glucopyranoside) cardol (white solid)

Example 4 The following compound was obtained in the same manner as in Example 1 except that anacardic acid was used instead of cardanol in Example 1. 1- (O-β-D-glucopyranoside) anacardic acid (white solid)

Example 5 In the same manner as in Example 1, cardanol and cardol were substituted for the crude long-chain hydrocarbon group-substituted phenol obtained by vacuum-distilling cashew nut oil once instead of cardanol in Example 1. Thus, an O-glycoside type glycolipid containing anacardic acid as a long-chain phenol component group was obtained. 1- (O-β-D-glucopyranoside) cardanol, 1- (O-β-D-glucopyranoside) cardol, and 1- (O-β-D-glucopyranoside) anacardic acid It was about 83: 14: 3 from the analysis.

Example 6 Distilled cardol (10 g), methyl alcohol (7
5 ml) and a platinum / carbon catalyst (0.5 g) in 250 m
The reaction mixture was placed in a 1 l shaker reaction vessel, and hydrogenated using a Pearl medium pressure hydrogenation reactor. The catalyst was removed from the reaction solution by filtration, and the filtrate was distilled under reduced pressure. 100-3
The fraction at 198 to 200 ° C. was collected at 00 Pa, and recrystallized twice from n-hexane. The following compound was obtained in the same manner as in Example 1 except that the obtained 3'-n-pentadecyl-5'-hydroxyphenol was used in place of cardanol in Example 1. 3'-n-pentadecyl-5'-hydroxyphenyl-
β-D-glucopyranoside (white solid)

Example 7 In place of cardol in Example 6, anacardic acid was used and hydrogenated in the same manner to obtain 2-carboxy-3-n-pentadecylphenol. This compound was used in place of cardanol in Example 1 to carry out the same operation to obtain the following compound. 2-carboxy-3-n-pentadecylphenyl-β-
D-glucopyranoside (white solid)

Example 8 Instead of cardanol in Example 6, a crude long-chain hydrocarbon group-substituted phenol obtained by subjecting cashew nut oil to vacuum distillation once was hydrogenated to obtain a saturated long-chain hydrocarbon group-substituted phenol compound group. Obtained. Using this group of compounds,
By the same operation as in Example 1, an O-glycoside type glycolipid containing the respective saturated long-chain phenol derivatives of cardanol, cardol and anacardic acid as a component group was obtained. 3'-n-pentadecylphenyl-β-D-glucopyranoside, 3'-n-pentadecyl-5'-hydroxyphenyl-β-D-glucopyranoside, and 2'-
Carboxy-3'-n-pentadecylphenyl-β-D
The composition ratio of each component of -glucopyranoside was about 81: 15: 4 by analysis using liquid chromatography.

[Brief description of the drawings]

FIG. 1 ¹ H-NM of 1- (O-β-D-glucopyranoside tetraacetate) cardanol obtained in Example 1
R spectrum chart (in deuterated chloroform, 25 ° C).

FIG. 2 is a ¹ H-NMR spectrum chart of 1- (O-β-D-glucopyranoside) cardanol obtained in Example 1 (in deuterated dimethyl sulfoxide at 25 ° C.).

FIG. 3 is a ¹ H-NMR spectrum chart of 3′-n-pentadecylphenyl-2,3,4,6-O-acetyl-β-D-glucopyranoside obtained in Example 2 (in deuterated chloroform at 25 ° C.) ).

FIG. 4 is a ¹ H-NMR spectrum chart of 3′-n-pentadecylphenyl-β-D-glucopyranoside obtained in Example 2 (in deuterated dimethyl sulfoxide at 25 ° C.).

Claims (8)

[Claims] An aldose residue as a glycosyl group,
General formula as aglycone Wherein R ¹ is a hydrogen atom or a hydroxyl group, R ² is a hydrogen atom or a carboxyl group, and R ³ is an aliphatic saturated or unsaturated linear hydrocarbon group. O-glycoside type glycolipid. 2. The glycolipid according to claim 1, wherein R ¹ and R ² in the general formula are hydrogen atoms. 3. The glycolipid according to claim 1, wherein R ¹ in the general formula is a hydroxyl group and R ² is a hydrogen atom. 4. The glycolipid according to claim 1, wherein R ³ in the general formula is an aliphatic saturated linear hydrocarbon group having 15 carbon atoms. 5. The glycolipid according to claim 1, wherein R ³ in the general formula is an aliphatically unsaturated linear hydrocarbon group having 15 carbon atoms. 6. The glycolipid according to claim 5, wherein R ³ in the general formula contains 1 to 3 double bonds. 7. The glycolipid according to claim 1, wherein the group represented by the general formula is a group derived from a cashew nut shell extract. 8. A compound of the general formula (Wherein R ¹ is a hydrogen atom or a hydroxyl group, R ² is a hydrogen atom or a carboxyl group, and R ³ is an aliphatic saturated or unsaturated linear hydrocarbon group). The derivative is reacted with a reactive functional derivative of the reducing terminal hydroxyl group of aldose in which all the hydroxyl groups other than the reducing terminal hydroxyl group are protected to form an O-glycoside bond, and then the protecting group is eliminated. The method for producing an O-glycoside type glycolipid according to claim 1, wherein