JPH0813844B2 - Alkyl-substituted phenylcarbamate derivatives of polysaccharides - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial field of application] The present invention relates to an alkyl-substituted phenylcarbamate derivative of a polysaccharide, which is a novel polymer which is extremely useful as a functional material of the present invention.

[Conventional technology]

It is already known that a packing material for liquid chromatography using cellulose trisphenylcarbamate as a stationary phase has an excellent optical resolution (Okamoto, Hatada et al., Journal of American Chemical Society, 106, 5357. P., (1984)).

[Means for solving problems]

As a result of earnest research on a polysaccharide carbamate derivative other than cellulose, the present inventors have found that an alkyl-substituted phenylcarbamate derivative of a polysaccharide other than cellulose can be easily produced and has excellent asymmetric discrimination ability. Came to complete.

That is, the present invention relates to an alkyl-substituted phenylcarbamate derivative of a polysaccharide (excluding cellulose) in which 80% to 100% of hydroxyl groups are substituted with a group represented by the following general formula (I).

(In the formula, R _{1 to} R ₅ are a hydrogen atom or an alkyl group having 1 to 8 carbon atoms, and at least one of them is a carbon atom having 1 carbon atom.
To 8 alkyl groups. The polysaccharide according to the present invention may be any one of synthetic polysaccharides, natural polysaccharides and modified natural polysaccharides as long as it is optically active, but preferably has high regularity of binding mode. For example, α-1,4-glucan (amylose, amylopectin), α-1,6-glucan (dextran), β-1,6-glucan (pustulan), β-
1,3-glucan (for example, curdlan, schizophyllan, etc.), α-1,3-glucan, β-1,2-glucan (Crown
Gall polysaccharide), β-1,4-galactan, β-1,4-mannan, α-1,6-mannan, β-1,2-fructan (inulin), β-2,6-fructan (levan), β-1,4-xylan, β-1,3-xylan, β-1,4-xylan, β-1,
4-N-acetylchitosan (chitin), pullulan, agarose, alginic acid, etc., and also starches containing amylose. Particularly preferred are amylose, β-1,4-chitosan, chitin, β-1,4-mannan, β-1,4-xylan from which a high-purity polysaccharide can be easily obtained.
Inulin, curdlan, etc.

The number average degree of polymerization of these polysaccharides (the average number of pyranose or furanose rings contained in one molecule) is 5 or more, preferably 10 or more, but there is no particular upper limit, but it is preferably 500 or less for easy handling. .

The carbamoyl group forming the carbamate derivative of the polysaccharide of the present invention is represented by the following general formula (II), and 80% to 100% of all the hydroxyl groups of the corresponding polysaccharide form a urethane bond with the carbamoyl group. The remaining 20% to 0% is generally hydrogen, but it may be partially substituted with other substituents.

R _{1 to} R _{5 in} the general formula (II) are a hydrogen atom or an alkyl group having 1 to 8 carbon atoms, preferably a hydrogen atom or a methyl group, at least one of which is an alkyl group having 1 to 8 carbon atoms, preferably Is a methyl group.

For the synthesis of the carbamate derivative according to the present invention, the usual reaction for producing urethane from alcohol and isocyanate can be applied as it is. For example, it can be obtained by reacting a corresponding isocyanate with a polysaccharide in a suitable solvent using a Lewis base such as a tertiary amine or a Lewis acid such as a tin compound as a catalyst. Further, the synthesis of the isocyanate can be easily obtained by, for example, reacting phosgene with the amino group of the corresponding aniline derivative.

To use the polysaccharide carbamate derivative of the present invention as a separating agent for the purpose of separating a compound or its optical isomer,
Generally, chromatographic methods such as gas chromatography, liquid chromatography, thin layer chromatography and the like are used, but other membrane separation can also be performed.

In order to apply the polysaccharide carbamate derivative of the present invention to a liquid chromatography method as a separating agent, a method of packing it in a column as a powder is generally used. As the method, it is preferable to grind or put on beads. Is more preferably porous. Further, in order to improve the pressure resistance of the separating agent, prevent swelling and contraction due to solvent substitution, and improve the theoretical plate number, it is preferable to support the polysaccharide carbamate derivative on a carrier.

When used as a powder, the particle size and carrier size vary depending on the size of the column used, but
m to 1 mm, preferably 1 to 300 μm. The carrier is preferably porous and has an average pore size of 10Å
˜100 μm, preferably 50 Å to 50,000 Å.
The amount of the polysaccharide carbamate derivative supported on the carrier is 1 to 100% by weight, preferably 5 to 50% by weight, based on the carrier.

The method of supporting the polysaccharide carbamate derivative on a carrier may be a chemical method or a physical method. As a physical method, the polysaccharide carbamate derivative is dissolved in a soluble solvent, mixed well with a carrier, and the material is distilled off by an air stream under reduced pressure or heating, or the polysaccharide carbamate derivative is dissolved in a soluble solvent. Another method is to disperse the soluble solvent by dispersing it in a solvent insoluble in the polysaccharide carbamate derivative after thoroughly mixing with the carrier. The separating ability of the separating agent thus obtained can be improved by performing appropriate treatments such as heating, addition of a solvent, and washing.

The carrier to be used may be a porous organic carrier or a porous inorganic carrier, preferably a porous inorganic carrier. Suitable examples of the porous organic carrier include polymeric substances such as polystyrene, polyacrylamide and polyacrylate. Suitable as the porous inorganic carrier are silica, alumina, magnesia, glass, kaolin, titanium oxide, silicate and the like, and these surfaces have good affinity with the polysaccharide carbamate derivative, or the carrier itself. You may use what was processed in order to modify the characteristic of the surface. Examples of the surface treatment method include silanization treatment with an organic silane compound and plasma polymerization.

The developing solvent for liquid chromatography or thin layer chromatography is not particularly limited, except for those which dissolve or react with the polysaccharide carbamate derivative. When the polysaccharide carbamate derivative is bound to a carrier by a chemical method or is insolubilized by crosslinking, there is no particular limitation except that it reacts with the carrier.

On the other hand, when performing thin layer chromatography, 0.1
A layer having a thickness of 0.1 mm to 100 mm consisting of the separating agent composed of particles of about μm to 0.1 mm and a small amount of a binder, if necessary, may be formed on the support plate.

When performing membrane separation, it is used as a hollow fiber or a film.

〔The invention's effect〕

INDUSTRIAL APPLICABILITY The polysaccharide carbamate derivative of the present invention is an extremely useful substance as a functional material, is particularly effective for separating various compounds, and is particularly useful as a filler for separating optical isomers, which has been difficult to separate in the past, that is, optical resolution. It is something.

〔Example〕

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

The definitions of terms used in the examples are as follows.

Example 1 Synthesis of amylose tris (3,5-dimethylphenylcarbamate) After drying 1.0 g of amylose (molecular weight about 16,000) in vacuum, 50 ml of dry pyridine was added and stirred. To this, add 4.0 ml of 3,5-dimethylphenyl isocyanate and add it in a nitrogen stream.
The mixture was heated and stirred at 100 ° C for 22 hours. Thereafter, the reaction product was transferred into methanol to cause precipitation, which was collected on a glass filter. The amount of amylose tris (3,5-dimethylphenylcarbamate) obtained was 2.465 g (yield 66.4%).

 The elemental analysis values of the obtained product are shown below.

CHN measured value (%): 65.20 6.17 6.93 Calculated value (%): 65.66 6.18 6.70 Application Example 1 Amylose tris (3,5-dimethylphenylcarbamate) obtained in Example 1 was treated with silica gel (E. Merck). The product is loaded onto a stainless steel column with a length of 25 cm and an inner diameter of 0.46 cm.
Optical resolution of various racemic compounds shown in Table 1 gave good results as shown in Table 1.

A 9: 1 mixed solvent of hexane and 2-propanol was used as the solvent. In the table K _'1 is a first-eluting retention capacity ratio of enantiomer, also in parentheses indicates the optical rotation, the α is the separation factor, Rs indicates the separation degree.

Example 2 A 3,5-dimethylphenylcarbamate derivative of starch was obtained in the same manner as in Example 1 except that starch was used instead of amylose. The yield of the pyridine-soluble portion was 14%, and the rest was insoluble material.

Optical resolution of various racemic compounds was performed on the obtained carbamate derivative in the same manner as in Application Example 1, and similarly good results were obtained.

Example 3 Synthesis of chitosan tris ((3,5-dimethylphenylcarbamate) 0.801 g chitosan, 50 ml pyridine, isocyanic acid-3,5
-5.5 ml of dimethylphenyl was heated and refluxed with stirring under a nitrogen stream and reacted for 43.5 hours. Pour all the reaction solution into methanol, collect the precipitate with a glass filter,
It was washed with methanol and dried under reduced pressure at 40 ° C. for 5 hours to obtain 3.418 g of a product {chitosan tris (3,5-dimethylphenylcarbamate)}.

The elemental analysis values of the obtained product {CHCl ₃ : CF ₃ CH ₂ OH (9: 1) soluble part} are shown below.

C H N actual value (%): 68.70 6.68 9.44 Calculated value (%): 68.77 6.35 9.30 Further, the infrared absorption spectrum of the obtained product was
FIG. 2 shows the infrared absorption spectrum of the CHCl ₃ : CF ₃ CH ₂ OH (9: 1) soluble part.

Application Example 2 The product obtained in Example 3 is insoluble in the solvent (chloroform, tetrahydrofuran, dimethylacetamide, etc.) usually used for loading. Therefore, about 0.625 g of the CHCl ₃ : CF ₃ CH ₂ OH (9: 1) soluble part of the obtained product was
It was dissolved in 12 ml of pyridine heated to 100 ° C., and loaded on 2.60 g of silica gel (treated with 3-aminotriethoxysilane, RI-CROSSI SI-1000 manufactured by E-Merck).

The filler thus prepared was 25 cm in length and 0.46 c in inner diameter.
Optical resolution of various racemic compounds shown in Table 2 was performed under the conditions of a column of m, hexane / 2-propanol (90/10) as an eluent and a flow rate of 0.5 ml / min and a temperature of 25 ° C. As a result, good results as shown in Table 2 were obtained.

Example 4 Amylose tris (4-methylphenyl carbamate)
Synthesis of amylose 0.800 g (4.93 mmol), p-toluyl isocyanate 5.07 g (38.1 mmol), pyridine 40 ml at 100 ° C
After heating and stirring for 24 hours, the mixture was poured into 400 ml of methanol. The generated precipitate was collected with a glass filter, washed with methanol, and dried under reduced pressure and constant temperature at 60 ° C. for 3 hours to obtain amylose tris (4-methylphenylcarbamate).

 The yield was 2.38 g (85.9%).

 The elemental analysis values of the obtained product are shown below.

CHN measured value (%): 62.79 5.46 7.39 Calculated value (%): 64.16 5.56 7.48 Example 5 Synthesis of dextran tris (3,5-dimethylphenylcarbamate) Dextran 1.00 g (6.17 mmol), N, N-dimethyl 30 ml of acetamide and 1.5 g of lithium chloride were stirred at 100 ° C. for 30 minutes to dissolve dextran. In addition, 8.63 g (58.7 mmol) of 3,5-dimethylphenyl isocyanate, pyridine 2.0
ml was added, and the mixture was heated and stirred at 100 ° C. for 27 hours, and then added to 1.5 l of methanol. The resulting precipitate was collected with a glass filter, washed with methanol and pyridine, and dried under reduced pressure and constant temperature at 40 ° C. for 2 hours to obtain dextran tris (3,5-dimethylphenylcarbamate).

 The yield was 2.49 g (66.6%).

 The elemental analysis values of the obtained product are shown below.

C H N actual value (%): 64.55 6.17 6.78 Calculated value (%): 65.66 6.18 6.70 Application example 3 Silica gel (E-Merck recross fur SI4000,10
Amylose tris (4) obtained in Example 4 was treated with 3-aminopropyltriethoxysilane.
-Methylphenylcarbamate) was loaded and packed in a stainless steel column having a length of 25 cm and an inner diameter of 0.46 cm (this is referred to as column 1).

Similarly, a column loaded with dextran tris (3,5-dimethylphenylcarbamate) obtained in Example 5 was packed in a column (this is referred to as column 2).

With these columns, hexane / 2-propanol (90/10) was used as the eluent, the flow rate was 0.5 ml / min, and the temperature was 25 ° C.
When the optical resolution of various racemic compounds shown in Table 3 was carried out under the conditions of, good results as shown in Table 3 were obtained.

Example 6 Xylan bis (3,5-dimethylphenyl carbamate)
Synthesis of Xylane was dried in an Abdehalden dryer for a whole day and night, and 1.00 g (6.40 mmol) of pyridine was added with 50 ml of pyridine and 3.3 ml (22 mmol) of 3,5-dimethylphenyl isocyanate, and the mixture was heated and stirred at about 100 ° C. for 26 hours under nitrogen. After confirming that isocyanate is present in the reaction solution,
The mixture was poured into 0 ml of methanol, and the resulting brown precipitate was collected with a glass filter, washed with methanol, dried under reduced pressure in a desiccator, and then dried at 50 ° C. for 6 hours under reduced pressure.

 The yield was 2.68 g (98.2%).

 The elemental analysis values of the obtained product are shown below.

CHN actual value (%): 63.95 6.09 6.60 Calculated value (%): 64.57 6.14 6.57 Application Example 4 Xylan bis (3,5-dimethylphenylcarbamate) 0.0675 g obtained in Example 6 was added to 12 ml of chloroform. Silica gel that has been dissolved and treated with 3-aminopropyltriethoxysilane (E. Merck, Inc.
0 μm) 2.70 g was loaded in four times. Particle size separation with hexane / 2-propanol (90/10), dispersion in hexane / liquid paraffin (2/1), packing by a slurry method into a column with a length of 25 cm and an inner diameter of 0.46 cm, and a column for optical resolution And

Using this column, hexane / 2-propanol (90/10) was used as an eluent, and the optical resolution of various racemic compounds shown in Table 4 was performed under the conditions of a flow rate of 0.5 ml / min. And a temperature of 25 ° C. However, the results shown in Table 4 were obtained.

[Brief description of drawings]

FIG. 1 is an infrared absorption spectrum of the product obtained in Example 3, and FIG. 2 is an infrared absorption spectrum of the CHCl ₃ : CF ₃ CH ₂ OH (9: 1) soluble part thereof.

Claims (1)

[Claims] 1. An alkyl-substituted phenylcarbamate derivative of a polysaccharide (excluding cellulose) in which 80% to 100% of hydroxyl groups are substituted with a group represented by the following general formula (I). (In the formula, R _{1 to} R ₅ are a hydrogen atom or an alkyl group having 1 to 8 carbon atoms, and at least one of them is a carbon atom having 1 carbon atom.
To 8 alkyl groups. )