JPH1128096A - Production of saccharide derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To efficiently obtain saccharide derivative from the organic solvent and saccharide which are hardly miscrible with each other because of their marked viscosity difference by using an agitated reactor equipped with gate blades to allow an enzyme to react with the saccharide in the organic solvent. SOLUTION: In an organic solvent of an acrylate ester and/or a methacrylate ester, an enzyme as lipase or esterase from a microorganism is allowed to react with a saccharide as an alkyl-glucoside by using an agitated reactor that is equipped with a flat gate blade of a large agitation area. The gate blade is perforated to have a plurality of grid holes bored in a lattice structure and effects the agitation or stirring by its entrainment and scattering actions. Further, the reactor has the Max blend blade, a kind of gate blade equipped with a bottom paddle at the reactor bottom for swirling up the substances staying in the bottom, while the reactor is equipped with baffle plates on the tank wall. Since the reactor can effectively stir and mix the saccharide with the organic solvent, the objective saccharide derivative as an alkylglucosyl acrylate can be efficiently produced, even when they are hard to mix with each other because of their markedly different viscosity.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a saccharide derivative in which an enzyme is reacted with a saccharide which is difficult to mix with an organic solvent, and more particularly to a method for producing a saccharide derivative using a stirring reactor having a gate blade.

[0002]

2. Description of the Related Art Since sugar has various hydroxyl groups, it is a good raw material as a water-soluble chemical substance, and is considered to be a useful raw material as a raw material not using petroleum as a raw material in the future. It is also a material that is expected from the fact that it is easily susceptible to decomposition by living organisms and the environment, and has excellent compatibility when used for biomaterials. However, it is difficult to mix with organic solvents widely used industrially, and furthermore, saccharide derivatives such as alkylated saccharides and oligosaccharides may have high viscosity, so that they have been widely used as industrial raw materials. Not in. Further, since hydroxyl groups are present at various positions, it is difficult to carry out a selective reaction, which is a problem in producing a high-purity industrial chemical product.

[0003] Attempts have been made to regioselectively react hydroxyl groups at various positions by using enzymes in the reaction. Enzymatic reactions can selectively react with substrates having hydroxyl groups at various positions, such as sugars.
The selectivity for the substrate can also be controlled by a combination of the enzyme and the substrate. However, enzymes do not dissolve in organic solvents, and sugars and sugar derivatives also have low solubility in organic solvents. there were.

[0004] For this reason, the selection of an excellent stirring system that can disperse each well is the key to the reaction. For example, by stirring the immobilized microorganisms or enzymes with stirring blades in a draft tube, the non-aqueous phase is mixed. For a method of obtaining a product by mixing with an aqueous solution phase, see JP-B-7-106.
No. 154. In this method, the heterogeneous reaction between solutions having relatively low viscosity can be stirred without any problem, but sufficient consideration has not been given to solutions having high viscosity.

[0005] In particular, when saccharides, that is, monosaccharides, oligosaccharides and alkylated saccharides are reacted in an organic solvent, these are not only difficult to mix with the organic solvent, but also become a high-viscosity fluid, and are not only dissolved but dispersed. Not even that can be done easily. For this reason, it is known that the reaction becomes heterogeneous, the contact area between the substrates is small, the reaction hardly proceeds, and the saccharide precipitates and the heating is performed heterogeneously, so that carbonization and denaturation of the saccharide occur. .

[0006] Depending on the conditions, the hydrolysis of starch and the reaction for producing oligosaccharides are also heterogeneous, and the viscosity increases in the late stage of the reaction. In addition, when a sugar alkylation reaction is performed, the initial stage of the reaction starts heterogeneously. In such reactions, agitation is a major factor in determining the reaction rate. Conventionally, as a stirring reactor, a Fiddler blade, a turbine blade, a paddle blade, or the like has been used as a stirring blade to stir a low-viscosity liquid, and an anchor blade, to stir a high-viscosity solution. Screw wings, helical wings and the like are widely used for producing polymers and the like.

However, when a saccharide is reacted in an organic solvent, it is very difficult to uniformly stir a low-viscosity organic solvent and a high-viscosity saccharide or saccharide derivative. High-viscosity materials such as anchor wings, screw wings, and helical wings cannot be dispersed efficiently with low-viscosity stirring blades such as those for low-viscosity materials. And it was extremely difficult to stir uniformly.

The problem to be solved by the present invention is to mix and stir an organic solvent and a saccharide, which have significantly different viscosities and are difficult to mix, so that the enzyme can efficiently react with the saccharide. And a method for producing a sugar derivative.

[0008]

In recent years, stirring blades having a large stirring area such as a gate blade and having a small distribution of stirring speed in a stirring tank have been used. The advantage of this gate blade is that the stirring speed in the stirring tank is made uniform, and shearing due to high rotation of the stirring blade and stagnation in a low-speed portion can be prevented. The present invention uses a gate blade to satisfactorily stir an organic solvent and a saccharide with significantly different viscosities, which have been difficult in the past, and to perform an enzymatic reaction for heterogeneity more favorably. It has been found that the reaction can be performed efficiently, and the present invention has been completed.

That is, the present invention provides (1) a method for producing a sugar derivative in which a saccharide is reacted with an enzyme in an organic solvent using a stirring type reaction apparatus having a gate blade, and (2) a lipase or a lipase derived from a microorganism. The method for producing a sugar derivative according to (1), which is an esterase,

(3) The method for producing a saccharide derivative according to (1) or (2), wherein the saccharide is an alkyl glucoside, and (4) the organic solvent is an acrylate and / or methacrylate. A method for producing a sugar derivative according to any one of the above (1) to (3),

(5) The method for producing a sugar derivative according to any one of the above (1) to (4), wherein the gate blade is a max blend, and (6) a max blend blade. And a method for producing an alkylglucosyl acrylate in which an alkylglucoside is reacted with a lipase or an esterase derived from a microorganism in an acrylic ester and / or a methacrylic ester using a stirred reactor having the following formula.

[0012]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in detail. The gate blade referred to in the present invention is a general name of a special paddle blade that has a grid-like grid hole in a plate-like stirring blade having a large stirring area, and performs stirring by entrainment and dispersion. The gate wing is characterized by long grid holes that can disperse the substance in the tank.It is known that the shear stress required for liquid dispersion is small, and low shear mixing can be realized, so it is suitable for cell culture etc. in liquid medium. Applied.

Further, a gate blade provided with a paddle at the bottom of the tank for the purpose of winding up the substance that collects at the bottom of the tank is preferable for the purpose of preventing the sedimentation substance during the reaction. The blade diameter of the gate blade is preferably 0.5 to 0.8 of the diameter of the reaction tank, and the portion opened by the grid in the blade is preferably 0.2 to 0.8 of the blade diameter. The shape of the grid may be an arm parallel to the stirring axis, an arm perpendicular to the stirring axis, or a grid having both arms. It is preferable that the installation position of the gate blade in the reaction tank does not have a large gap so that there is no sediment at the tank bottom.

Furthermore, it is preferable to provide a baffle (baffle plate) on the tank wall or bottom of the reaction tank because the stirring efficiency can be increased. The shape of the baffle may be any of a flat plate, a round bar, a semicircle, an ellipse, and a semiellipse, and the flat plate may have an angle of 45 to 90 degrees with respect to the tangential direction of the flow. The size of the cross section of the baffle with respect to the tangential direction of the flow is preferably 5% to 15% of the tank diameter, and more preferably 5% to 10%. The number of baffles is preferably two to four. The installation position of the baffle may be in contact with the tank wall, or may be installed at a distance from the tank wall so as not to cause accumulation of a heterogeneous dispersion, and in the present invention, the baffle may be spaced from the tank wall. Is preferred.

The rotating shaft for transmitting power to the stirring blade may be either a shaft for transmitting power from the upper part of the reaction tank or a shaft for transmitting power from the upper part of the reaction tank. Power may be transmitted from both directions. The stirring blade may be supported by a bearing. Among these gate blades, a Max Blend stirrer manufactured by Sumitomo Heavy Industries, Ltd. is particularly preferable. Max Blend is known as a stirring blade capable of achieving both the advantages of the gate blade and the stirring and stirring up from the bottom of the tank. The Max Blend stirrer is described in detail in Japanese Patent Publication No. 1-37173. The stirring blade is composed of a central and upper grid part and a lower bottom paddle part, the bottom paddle part is in sliding contact with the bottom wall of the reaction tank, and the blade side is in sliding contact with a baffle installed with respect to the reaction tank wall. I have.

The saccharide of the present invention means a saccharide or a saccharide derivative. Examples of the saccharide include glucose, galactose, mannose, arabinose, xylose, fructose, glucosamine, galactosamine, acetylglucosamine, acetylglucosamine and sucrose. , Lactose, maltose, palatinose, disaccharides represented by cellobiose, maltotriose, dextran, oligosaccharides represented by dextrin, starch,
It includes polysaccharides represented by cellulose, chitosan and chitin, cyclic sugars represented by cyclodextrin, sorbitol, mannitol, lactitol, N-methylglucamine, and reduced sugars represented by reduced maltose.

Examples of the sugar derivative include esterified, acetylated, alkylated, (meth) acryloylated, arylated, and allylated saccharides. Is an alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, amyl, isoamyl, hexyl, heptyl, octyl, ethylhexyl, and nonyl. , Decyl group, undecyl group, dodecyl group, myristyl group,

The palmitoyl group and the octadecyl group are exemplified. The allyl group is an alkoxyphenyl group such as a phenyl group, a phenoxy group, a phenoxymethyl group, a phenoxyethyl group, a tolyl group, a dimethylphenyl group, a trimethylphenyl group, and an ethylphenyl group. Alkylphenyl group such as propylphenyl group, butylphenyl group, t-butylphenyl group, p-nitrophenyl group, o-nitrophenyl group, 3-chloro, 4-nitrophenyl group, hydroxyphenyl group, sulfophenyl group, carboxyphenyl Groups.

The bonding mode between the oxygen at the 1-position of the sugar and the alkyl group or the like may be either α or β, or a mixture thereof. In addition, those obtained by alkylating, arylating, or allylating the oxygen at the 1-position of the above-mentioned saccharide and further carboxylic esterifying the remaining hydroxyl group can also be mentioned.

The organic solvent used in the present invention includes (meth) acrylic acid and (meth) acrylic acid esters, which themselves serve as reaction substrates. Specifically, acrylic acid, methyl acrylate, ethyl acrylate, Propyl acrylate, isopropyl acrylate, butyl acrylate, isobutyl acrylate, tertiary butyl acrylate, methacrylic acid, methyl methacrylate, ethyl methacrylate, propyl methacrylate, isopropyl methacrylate, butyl methacrylate, isobutyl methacrylate, tertiary butyl methacrylate Is mentioned.

Further, as alcohols, methyl alcohol, ethyl alcohol, propyl alcohol, butyl alcohol, pentyl alcohol, hexyl alcohol,
Heptyl alcohol, octyl alcohol, ethylhexyl alcohol, nonyl alcohol, decyl alcohol, undecyl alcohol, dodecyl alcohol, tetradecyl alcohol, hexadecyl alcohol, octadecyl alcohol, aryl alcohol, phenol,
Methyl phenol, dimethyl phenol, trimethyl phenol, ethyl phenol, propyl phenol, butyl phenol, tertiary butyl phenol are exemplified.

Other examples include carboxylic acids, carboxylic anhydrides, and carboxylic esters which themselves serve as reaction substrates. Specific examples include acetic acid, acetic anhydride, methyl acetate, and the like.
Ethyl acetate, propyl acetate, butyl acetate, propanoic acid,
Propanoic anhydride, methyl propanoate, ethyl propanoate, butanoic acid, butanoic anhydride, methyl butanoate, ethyl butanoate, pentanoic acid, pentanoic anhydride, methyl pentanoate, ethyl pentanoate, hexanoic acid, hexanoic acid Anhydride, methyl hexanoate, ethyl hexanoate, heptanoic acid, heptanoic anhydride, methyl heptanoate, ethyl heptanoate,

Octanoic acid, octanoic anhydride, methyl octoate, ethyl octoate, nonanoic acid, nonanoic anhydride, methyl nonanoate, ethyl nonanoate, dodecanoic acid, methyl dodecanoate, ethyl dodecanoate, stearic acid, stearic acid Acid methyl, ethyl stearate, oleic acid,
Examples include methyl oleate and ethyl oleate.

In addition, ethylene glycol, glycerin, monoglyme, diglyme, acetonitrile, methyl nitrate, diethyl ether, DMSO, DMF, diethyl ether, diisopropyl ether, THF, dioxane, methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, Butyl acetate, isobutyl acetate, benzene, toluene, xylene, dichloromethane, chloroform, carbon tetrachloride,

Dichloroethane, trichloroethane, chlorobenzene, dichlorobenzene, trichlorobenzene,
Pyridine, pentane, hexane, heptane, octane,
Isooctane, cyclohexane and the like are preferred. The organic solvent used in the present invention may be a mixture of two or more of these. Further, the organic solvent used in the production method of the present invention is mainly composed of an organic solvent, and the present invention includes a reaction in which a small amount of water or a buffer solution or a salt aqueous solution is contained in these organic solvents.

The enzymes used in the present invention are not particularly limited, and may be any of oxidoreductases, transferases, hydrolases, elimination addition enzymes, and synthases. Esterases, lipases, phospholipases, and transferases are preferred, and more specifically, glucosidase, galactosidase, mannosidase, fructosidase, xylanase, lipase, phospholipase, cholesterol esterase, transaldolase, transketolase, pepsin, trypsin, chymotrypsin, Papain, renin and the like can be mentioned.

The method for producing the sugar derivative of the present invention is particularly suitable for the method for producing lucosyl acrylate, in which the organic solvent used in the present invention is used. That is, in the reaction of the present invention, particularly using (meth) acrylic acid or (meth) acrylic acid ester as a reaction substrate and a reaction solvent,
An alkylglucosyl acrylate can be obtained in good yield by carrying out an enzymatic reaction with another reaction substrate, an alkyl glycoside, at around these boiling points.

In this reaction system, by-product alcohol or water and (meth) acrylic acid or (meth) acrylic acid ester are coagulated and collected by a condenser, and then a by-product removal tank filled with a molecular sieve or the like is provided. By passing through, alcohol or water as a by-product is adsorbed and removed with a molecular sieve or the like, and (meth) acrylic acid or (meth) acrylic acid ester can be returned to the reaction tank as it is to continuously react.

The (meth) acrylic acid or (meth) acrylic ester recovered during the reaction can be continuously supplied to the reaction as it is. Unreacted saccharides, saccharide derivatives and enzymes can be recovered as precipitates by lowering the temperature of the reaction system after completion of the reaction, and can be used again for the next reaction without purification. For the purpose of improving the stirring efficiency of the reaction system and accelerating the dissolution of the substrate, another organic solvent or an aqueous solution may be added to the reaction system, if necessary, for the reaction.

The ratio of the solvent used in the production reaction of the alkylglucosyl acrylate is preferably 1 to 1000 parts by weight with respect to 10 parts by weight of the total of acrylic acid or acrylate, the alkyl glycoside and the enzyme. 5 to 500 parts by weight in consideration of the stirring to be performed, and 10 to 2 parts in consideration of the step of removing the solvent after the reaction.
It is preferably 00 parts by weight.

In consideration of enzyme activity, it is preferable to control the water content of the reaction system.
% (100,000 ppm), 10% for enzyme activity
It is preferable to add 1 ppm (10000 ppm) from 10 ppm to 1000 ppm in consideration of reaction equilibrium.
It is preferably set to ppm. These waters may be included in the enzyme to be added, or may be separately added to the reaction system,
A small amount of water may be sequentially added during the reaction.

It is preferable that the solvent or acrylic acid or acrylate is first heated to the reaction temperature, the alkyl glycoside is charged, and the mixture is sufficiently stirred and dispersed, and then the enzyme is charged. Further, in consideration of the fact that the alkyl glycoside is difficult to dissolve, it is also preferable to add the alkyl glycoside gradually and several times during the reaction.
It is also preferable to add the enzyme to the reaction system in several parts in consideration of the deactivation of the enzyme during the reaction.

The reaction temperature is preferably high in consideration of the solubility of the substrate and the reaction rate. On the other hand, the reaction temperature is preferably low in consideration of the deactivation of the enzyme due to heat. . The lipase or esterase obtained from the microorganism of the genus Alcaligenes used in the present invention generally has a heat resistance of 50 ° C. to 150 ° C., and preferably 50 to 100 ° C., because it has excellent heat resistance. Considering factors such as 5
0 to 80 ° C is more preferred.

[0034] Even when a lipase or esterase obtained from a microorganism of the genus Pseudomonas or Candida is used, in the present invention, the temperature is 50 ° C or higher, preferably 50 to 100 ° C.
When the heat resistance of the enzyme is taken into consideration, it is used at 50 to 80 ° C. The reaction temperature can be changed during the reaction, and there are a method of gradually increasing the temperature and a method of gradually decreasing the temperature, which are determined by the reaction system.

The reaction pressure is variable for the purpose of, for example, controlling the temperature by the boiling point.
The reaction can be carried out in the range of mHg, usually in the range of 10 mmHg to 1520 mmHg. The reaction time varies depending on the reaction system and is not specified unconditionally. However, considering the reaction efficiency and the yield, it is generally preferably from 3 hours to 48 hours, more preferably from 5 hours to 30 hours. Preferably, all unreacted raw materials are collected and used for re-reaction.

The reactor is provided with an aggregator for condensing and recovering acrylic acid or acrylates and solvent flowing out, and a by-product removal tank filled with a filler such as molecular sieves, and water or alcohol distilled from the reaction tank. Pass acrylics or acrylates containing
Next, these aggregates are passed through a by-product removal tank filled with a filler such as molecular sieves to adsorb and remove water or alcohols with the molecular sieves, and the acrylic acid or acrylic acid ester is continuously reacted as it is in the reaction tank. Preferred is a reactor that returns to.

As the filler to be filled in the by-product removal tank, it is preferable to select one that does not adsorb acrylic acid, methyl acrylate, or a solvent. Molecular sieves, silica gel, calcium chloride, potassium chloride, sodium chloride, oxide, Magnesium, magnesium sulfide, potassium carbonate, sodium sulfate and the like. Molecular sieves need to be appropriately changed depending on the type of by-product, but if the by-product is water or methanol, 3A type is used.
Of these or ethanol sugars, the 4A type is preferred. It is sufficient that the by-product removal tank has a volume of 1% to 100% of the reaction tank.

The molecular sieve is 30% of its weight
Although it is possible to adsorb a small amount of water or the like, it is preferable to fill an excessive amount from the viewpoint of reaction efficiency and the like. It is necessary to regenerate the filler during or after the reaction. Regeneration methods include washing, heating, and decompression. In general, heating and drying under reduced pressure are performed after washing with water and alcohol. The temperature is preferably 100 ° C. or higher, and 180 ° C. or higher enables fast regeneration.

To reduce the size of the by-product removal tank,
It is efficient to regenerate the filler during the reaction. For example, it is preferable to use two or more removal tanks in parallel and switch the tanks to be used for continuous operation. It is also preferable that the by-product removal tank has a structure like a Soxhlet extractor. In addition, it is also possible to put these fillers in the reaction tank directly for reaction without having a by-product removal tank and to remove them from the reaction product after the reaction.

Further, the method for producing the sugar derivative of the present invention comprises:
In particular, it is also suitable for a method for producing a long-chain carboxylic acid alkylglucosyl ester. In the reaction of the present invention, especially when using a long-chain carboxylic acid ester represented by octadecanoic acid from butanoic acid or octadecanoic acid ester from butanoic acid as a substrate, an excess amount of the reaction substrate is used as a reaction solvent, and the boiling point of these is reduced. By performing an enzymatic reaction in the vicinity, the by-product alcohol or water and the long-chain carboxylic acid ester are coagulated and collected by a condenser, and then passed through a by-product removal tank filled with molecular sieves, thereby forming a by-product. The alcohol or water to be formed is adsorbed and removed with a molecular sieve or the like, and the long-chain carboxylic acid ester can be returned to the reaction tank as it is to continuously react.

The long-chain carboxylic acid ester recovered during the reaction can be continuously supplied to the reaction as it is.
Unreacted saccharides, saccharide derivatives and enzymes can be recovered as precipitates by lowering the temperature of the reaction system after completion of the reaction, and can be used again for the next reaction without purification. The ratio of the solvent to be used is preferably from 1 to 1000 parts by weight with respect to a total of 10 parts by weight of the long-chain carboxylic acid and the long-chain carboxylic acid ester, the alkyl glycoside and the enzyme. 5
It is preferably 10 to 200 parts by weight in consideration of the solvent removal step after the reaction.

In consideration of enzyme activity, it is preferable to control the water content of the reaction system.
% (100,000 ppm), 10% for enzyme activity
It is preferable to add 1 ppm (10000 ppm) from 10 ppm to 1000 ppm in consideration of reaction equilibrium.
It is preferably set to ppm. These waters may be included in the enzyme to be added, or may be separately added to the reaction system,
A small amount of water may be sequentially added during the reaction.

Alkyl glycosides, solvents, long-chain carboxylic acids and long-chain carboxylic esters are difficult to mix.
The preparation procedure is important. That is, it is preferable to first heat the solvent or acrylic acid or acrylic acid ester to the reaction temperature, and then charge the alkyl glycoside, sufficiently stir and disperse the mixture, and then charge the enzyme. Further, in consideration of the fact that the alkyl glycoside is difficult to dissolve, it is also preferable to add the alkyl glycoside gradually and several times during the reaction. It is also preferable to add the enzyme to the reaction system in several parts in consideration of the deactivation of the enzyme during the reaction.

The reaction temperature is preferably a high temperature in consideration of the solubility of the substrate and the reaction rate, while a low temperature is preferable in consideration of the deactivation of the enzyme due to heat. . The reaction temperature in the present invention is 5
0 ° C to 150 ° C is preferred, and preferably 50 to 100 ° C.
C., 50 to 80.degree. C. is more preferable in consideration of the heat resistance of the enzyme. The reaction temperature can be changed during the reaction, and there are a method of gradually increasing the temperature and a method of gradually decreasing the temperature, which are determined by the reaction system.

The reaction pressure is variable for the purpose of, for example, controlling the temperature by the boiling point.
The reaction is possible in the range of mHg, usually 5 mmHg to 1
It is possible in the range of 520 mmHg. Preferably, the reaction is performed under reduced pressure and the pressure is in the range of 5 mmHg to 380 mmHg. During the reaction, the degree of reduced pressure can be adjusted. The reaction time varies depending on the reaction system and is not specified unconditionally. However, considering the reaction efficiency and the yield, it is generally preferably from 3 hours to 48 hours, more preferably from 5 hours to 30 hours. Preferably, all unreacted raw materials are collected and used for re-reaction.

The reaction apparatus used is the same as that used for the production reaction of the alkylglucosyl acrylate. The reaction apparatus is provided with a condenser and a by-product removal tank, adsorbs and removes water or alcohols with molecular sieves, and removes long-chain carboxylic acid and long-chain carboxylic acid. It is preferable that the carboxylic acid ester be continuously returned to the reaction tank as it is. The filling material to be filled in the by-product removal tank, the method for regenerating the filling material, and the filling device are the same as described above.

[0047]

The present invention will be specifically described below with reference to examples. (Reference Example 1) Synthesis of butyl glucoside Glucose 750 g (25 parts by weight), butanol 225
0 g (75 parts by weight) and 7 g (0.2 parts by weight) of p-toluenesulfonic acid as a catalyst were placed in a reactor, and the mixture was stirred and reacted at normal pressure under reflux for 4 hours. After the reaction, anion exchange resin W
30 g (1 part by weight) of A30 (manufactured by Mitsubishi Chemical) was added and left for 1 hour to remove the catalyst, which was separated by filtration. Then, excess butanol was removed under reduced pressure to obtain 954 g of the target butyl glucoside (97% yield, based on glucose). α /
The β anomer ratio was about 3/7. Hereinafter, amyl glucoside was synthesized in the same manner.

(Example 1) Synthesis of butyl glucosyl acrylate 1 part by weight of butyl glucoside, 95 parts by weight of methyl acrylate (methoxyphenol was used as a polymerization inhibitor in an amount of 0.03
% Included. Hereinafter, methyl acrylate containing a polymerization inhibitor is used unless otherwise specified. ), Lipase QLG (Alca
lingenes sp. Celite fixed, Meito Sangyo) Fill 1 part by weight of molecular sieve (4A type; use 4A unless otherwise noted) into the by-product removal tank, and do not contact the Max Blend blade and tank wall Using the apparatus shown in FIG. 1 equipped with two baffles as described above, the reaction was carried out with stirring at a reaction temperature of 80 ° C. for 24 hours.

During the reaction, butyl glucoside and the enzyme were
Every hour, 1 part by weight was added in four portions until the fourth hour, and both butylglucoside and the enzyme were added in a total of 5%. After the reaction, the desired 1-O-butylglucosyl-6-
O-acrylate was formed in a yield of 55%.

(Example 2) Synthesis of amyl glucosyl acrylate 5 parts by weight of amyl glucoside, 95 parts by weight of methyl acrylate, lipase QL (Alcalingenes sp., Manufactured by Meito Sangyo)
One part by weight of a by-product removal tank was filled with molecular sieves, and a max blend blade and two baffles equipped with two baffles so as not to be in contact with the tank wall were used.
The reaction was carried out with stirring at a reaction temperature of 70 ° C. for 18 hours. After the reaction, the target butylglucosyl acrylate has a yield of 68%.
Generated by

(Example 3) Synthesis of methyl glucosyl acrylate 5 parts by weight of α-methyl glucoside (manufactured by Sigma), 95 parts by weight of methyl acrylate, lipase PS (Psedomonas c)
1 part by weight of epacia (manufactured by Amano Pharmaceutical Co., Ltd.) was filled with a molecular sieve in a by-product removal tank, and the apparatus of FIG. The reaction was stirred at a reaction temperature of 60 ° C. for 40 hours. After the reaction, the total of the target methyl glucosyl acrylate and dimethyl glucosyl acrylate was 48% in yield.
Generated by The ratio of methyl glucosyl acrylate / methyl glucoside diacrylate was about 8/2.

After cooling the reaction solution, the enzyme and unreacted substrate were removed by filtration and unreacted methyl acrylate was removed under reduced pressure to obtain the desired methyl glucosyl acrylate and methyl glucoside diacrylate. The obtained methyl glucosyl acrylate / methyl glucoside diacrylate mixture was converted into an aqueous solution, packed in an activated carbon column, and then isolated using methanol as an eluent.

Example 4 Synthesis of methyl glucoside monoacrylate 5 parts by weight of α-methyl glucoside, 9 parts of methyl acrylate
5 parts by weight, Novozyme 435 (Novo Nordisk)
1 part by weight of a by-product removal tank was filled with molecular sieves, and the apparatus of FIG. 1 equipped with a max blend blade and two baffles so as not to contact the tank wall was used.
The reaction was stirred at 0 ° C. for 24 hours. During the reaction, methyl glucoside was added in 1 part by weight every one hour, divided into four portions until the fourth hour, and a total of 5% was added. After the reaction, only the target methyl glucoside monoacrylate was produced in a yield of 47%.

(Example 5) Synthesis of methyl glucoside monolaurate 45 parts by weight of α-methyl glucoside, 55 parts by weight of lauric acid, 1 part by weight of Novozyme 435 (manufactured by Novo Nordisk) in a reaction tank, and powdered molecular sieve 5
Using the device of Fig. 1 with two parts of baffle installed so that it does not contact the Max Blend wing and the tank wall,
The reaction was stirred at a reaction temperature of 65 ° C. for 14 hours. Only the desired methyl glucoside monolaurate was produced with a yield of 60%.

(Comparative Example) Synthesis of butyl glucosyl acrylate by full zone wing 1 part by weight of butyl glucoside, 95 parts by weight of methyl acrylate, and 1 part by weight of lipase QLG were filled with a molecular sieve in a by-product removal tank, and full zone wing (Shinko Pantech) A stirred reaction was started at a reaction temperature of 80 ° C. by using a device equipped with two baffles so as not to contact the tank wall and a modified paddle blade manufactured by the company. After 1.5 hours of reaction, sedimentation of butyl glucoside and the enzyme became severe, and after 2 hours, a viscous mixture of butyl glucoside and the enzyme hindered stirring, and the reaction could no longer be continued.

[0056]

According to the present invention, there is provided a method for producing a saccharide derivative, in which an organic solvent and a saccharide, which have significantly different viscosities and are difficult to mix, can be mixed and stirred satisfactorily, and the saccharide can efficiently react with an enzyme. Can be.

[Brief description of the drawings]

FIG. 1 is a diagram showing an example of a stirring type reaction apparatus having a gate blade according to the present invention.

Claims (6)

[Claims] 1. A method for producing a sugar derivative in which a saccharide is reacted with an enzyme in an organic solvent using a stirred reactor having a gate blade. 2. The method for producing a sugar derivative according to claim 1, wherein the enzyme is a lipase or an esterase derived from a microorganism. 3. The method for producing a saccharide derivative according to claim 1, wherein the saccharide is an alkyl glucoside. 4. The method for producing a sugar derivative according to claim 1, wherein the organic solvent is an acrylate and / or a methacrylate. 5. The method for producing a sugar derivative according to claim 1, wherein the gate blade is a max blend blade. 6. A method for producing alkyl glucosyl acrylate, comprising reacting a microbial lipase or esterase with an alkyl glucoside in an acrylic ester and / or a methacrylic ester using a stirred reactor having Max blend blades.