JPS63178101A - Alkyl-substituted phenylcarbamate derivative of polysaccharide - Google Patents

Abstract

PURPOSE:To obtain an alkyl-substd. phenylcarbamate derivative of a polysaccharide with its hydroxyl groups substd. by specified groups, which is useful as functional materials, particularly as a packing for optical resolution. CONSTITUTION:The title product is an alkyl-substd. phenylcarbamate derivative of a polysaccharide (except cellulose) with 80-100% of its hydroxyl groups substd. by groups of formula 1, where R1-R5 are each H or a 1-8C alkyl group, at least one of which is a 1-8C alkyl group. The polysaccharides used may be any of synthetic or natural polysaccharides and those modified from natural substances, as far as it is optically active. They are preferably those which are highly regular in their bonding pattern, more preferably amylase, beta-1,4-chitosan, chitin, beta-1,4-mannan, inulin and curdlan. These polysaccharides should preferably have a number-average degree of polymerization of at least 10.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to alkyl-substituted phenyl carbamate derivatives of polysaccharides, which are novel polymers that are extremely useful as functional materials.

[Conventional technology]

It is already known that a packing material for liquid chromatography using cellulose trisphenyl-rubamate as a stationary phase has excellent optical resolution ability (Kaimoto, Hatada et al., Journal of the American Chemical Society,
Volume 106.

5357 True, (I984)).

[Means for solving problems]

As a result of extensive research into carbamate derivatives of polysaccharides other than cellulose, the present inventors discovered that alkyl-substituted phenyl carbamate derivatives of polysaccharides other than cellulose can be easily produced and have excellent asymmetric discrimination ability, and the present invention I have reached the point where I have completed the .

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

(In the formula, R1-R3 is a hydrogen atom or has 1 to 8 carbon atoms.
is an alkyl group, at least one of which is an alkyl group having 1 to 8 carbon atoms. ) The polysaccharide in the present invention may be any optically active polysaccharide, regardless of whether it is a synthetic polysaccharide, a natural polysaccharide, or a modified natural polysaccharide, but preferably one with a highly regular bonding pattern. Then, α-1,4-glucan (amylose, amylopectin), α-1,6-glucan (dextran), β-
1,6-glucan (pustulan), β-1,3-glucan (e.g. curdlan, schizophyllan, etc.), α-1,
3-glucan, β-1,2-glucan (Crown G
a1l 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-
These include 1,4-chitosan, β-1,4-N-acetylchitosan (chitin), pullulan, agarose, alginic acid, and starch containing amylose. Particularly preferred are amylose, β-1,4-chitosan, chitin, β-1,4-chitosan, and β-1,4-chitosan, from which highly pure polysaccharides can be easily obtained.
-mannan, β-1,4-xylan, inulin, curdlan, etc.

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

The carbamoyl group constituting the carbamate derivative of the polysaccharide of the present invention is represented by the following general formula (n), and 80% to 100% of the total hydroxyl groups of the corresponding polysaccharide form a urethane bond with the carbamoyl group. That's 20 left
% to 0% is generally hydrogen, but some other substituents can also be used.

RI-Rs in general formula (II) is a hydrogen atom or an alkyl group having 1 to 8 carbon atoms, preferably a hydrogen atom or a methyl group, of which at least one is an alkyl group having 1 to 8 carbon atoms, preferably is a methyl group.

For the synthesis of carbamate derivatives according to the present invention, the usual reaction that produces urethane from alcohol and isocyanate can be applied as is. For example, a Lewis base such as a tertiary amine or a Lewis acid such as a tin compound is catalyzed in an appropriate solvent. can be obtained by reacting the corresponding isocyanate with a polysaccharide. Furthermore, isocyanates can be easily synthesized by, for example, allowing phosgene to act on the amino groups of the corresponding aniline derivatives.

In order to use the polysaccharide carbamate derivative of the present invention as a separation agent for the purpose of separating compounds and their optical isomers, chromatography methods such as gas chromatography, liquid chromatography, and thin layer chromatography are generally used. However, membrane separation can also be used.

In order to apply the polysaccharide carbamate derivative of the present invention as a separation agent to liquid chromatography, it is common to fill it in a column as a powder. is more preferably porous. Further, it is preferable to support the polysaccharide carbamate derivative on a carrier in order to improve the pressure resistance of the separation agent, prevent swelling and shrinkage due to solvent substitution, and increase the number of theoretical plates.

When used as a powder, the particle size and carrier size vary depending on the column size used, but 1JI
Ia to 1 mm, preferably 1 to 300. The carrier is preferably porous, with an average pore size of 10 to 100 J! m, preferably 50 to 5
0000 people. 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 for supporting the polysaccharide carbamate derivative on a carrier may be a chemical method or a physical method.

Physical methods include dissolving the polysaccharide carbamate derivative in a soluble solvent, mixing well with the carrier, and distilling off the solvent with an air stream under reduced pressure or heating, and dissolving the polysaccharide carbamate derivative in a soluble solvent. Let it be, carrier and good (
There is also a method in which, after mixing, the polysaccharide carbamate g-conductor is dispersed in a solvent in which the polysaccharide carbamate g-conductor is insoluble, thereby diffusing the soluble solvent. It is also possible to improve the separation ability of the separation agent obtained in this way by subjecting it to appropriate treatments such as heating, addition of a solvent, and washing.

The carrier used may be a porous organic carrier or a porous inorganic carrier, preferably a porous inorganic carrier. Suitable porous organic carriers include polymeric substances such as polystyrene, polyacrylamide, and polyacrylate.

Suitable porous inorganic carriers include silica, alumina, magnesia, glass, kaolin, titanium oxide, and silicate. It may be used that has been treated to modify its surface properties.Surface treatment methods include silanization treatment using an organic silane compound and surface treatment method using plasma polymerization.

There are no particular restrictions on the developing solvent used in liquid chromatography or thin layer chromatography, as long as it dissolves or reacts with the polysaccharide carbamate derivative. When the polysaccharide carbamate derivative is bonded to a carrier by a chemical method or made insolubilized by crosslinking, there are no particular restrictions unless it reacts with the carrier.

On the other hand, when performing thin layer chromatography, 0.1
- The separation agent consisting of particles of about 0.1 tm- and, if necessary, a small amount of binder, having a thickness of 0.1-1 to 10
A layer of 0 tm- may be formed on the support plate.

In addition, when performing membrane separation, it is used as a hollow fiber or film.

〔Effect of the invention〕

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

〔Example〕

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

In addition, the definitions of terms expressed in the examples are as follows.

Total band width of both peaks Example 1 After drying 1.0 g of amylose (molecular weight approximately 16.000) in vacuo, dry pyridine 501 was added and stirred.

To this, 4.0-3,5-dimethylphenyl isocyanate
ml was added thereto, and the mixture was heated and stirred at 100° C. for 22 hours in a nitrogen stream. Thereafter, the reaction product was transferred into methanol and precipitated, which was collected on a glass filter.

The obtained amylose tris (3,5-dimethylphenyl carbamate) was 2.465 g (yield 66.4%)
Met.

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

CHN Actual value (χ'): 65.20 6.17 6
．． 93 calculated value (χ): 65.66 6.18
6.70 Application Example 1 The amylose tris (3,5-dimethylphenyl carbamate) obtained in Example 1 was mixed with silica gel (E, manufactured by Merck & Co., Ltd. -5I4000.101!Ia)
Supported by stainless steel, length 25cm, inner diameter 0.4
6c! When the various racemic compounds shown in Table 1 were optically resolved by filling a 1 liter column, good results as shown in Table 1 were obtained.

Incidentally, a 9:l mixed solvent of hexane and 2-propanol was used as the solvent. In the table, kl indicates the retention volume ratio of the first eluting enantiomer, the parentheses indicate its optical rotation, α indicates the separation coefficient, and Rs indicates the degree of separation.

Table 1 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%, with the remainder being insoluble material.

When the obtained carbamate derivative was subjected to optical resolution of various racemic compounds in the same manner as in Application Example 1, similarly good results were obtained.

Example 3 0.801 g of chitosan and 5.5 ml of pyridine 50n+L-3,5-dimethylphenyl isocyanate were heated under reflux and stirred under a nitrogen stream, and reacted for 43.5 hours.

The entire reaction solution was poured into methanol, the precipitate was collected with a glass filter, washed with methanol, and heated to 40°C.
The product (chitosantris (3,5
-dimethylphenylcarbamate) ) 3.418
I got g.

The obtained product (CHCh: CFsCHtOII
The elemental analysis values of (9: l) soluble part) are shown below.

CII N Actual value (χ) 7 68.70 6.68 9.
44t+Wノa(”1)!l;11177G96Q9n
In addition, the infrared absorption spectrum of the obtained product is shown in Figure 1.
That ClIC1+: CPICII! OH (9: 1
) Figure 2 shows the infrared absorption vector of the soluble part.

Application Example 2 The product obtained in Example 3 does not dissolve in solvents (chloroform, tetrahydrofuran, dimethylacetamide, etc.) commonly used for support. Therefore, the obtained product CHCl 3 :CF3Cl1□011(9
:1) Dissolve 0.625 g of the soluble portion in 12 ml of pyridine heated to about 100°C, and add silica gel (3-aminotriethoxysilane treated,
! -1000) was supported on 2.60 g.

The filler thus prepared was cut into a length of 25 cm.

Packed into an internal diameter 0.46 amO column, using hexane/2-propertool (90/10) as the eluent, flow rate 0.
．． When various racemic compounds shown in Table 2 were optically resolved under conditions of 5 ml/#Iin and a temperature of 25°C, good results as shown in Table 2 were obtained.

Table 2 Note) $IPh: Indicates phenyl group.

Try) represents a lythyl group ((Ph)ac).

acac Indicates niacetylacetone group.

"2 k'l+ α, Rs has the same meaning as Table-1.

Example 4 Amylose 0.800 g (4,93++v+ol)
, p-)ruyl isocyanate 5.07 g (38,
After heating and stirring 1 mmol) and pyridine 40a+1 at 100° C. for 24 hours, the mixture was poured into 400 ml of methanol. The resulting 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.

ON Actual measurement value (χ): 62,79 5,46 7.
39 calculated value (χ): 64.16 5.56
7.48 Example 5 Dextran 1.00 g (6.17 mmol), N
, N-dimethylacetamide 30 mL lithium chloride 1
．． 5 g was heated and stirred at 100° C. for 30 minutes to dissolve the dextran. Further, 8.63 g (58.7 ml 1 ol) of 3,5-dimethylphenylisocyanate and 2.0 ml of pyridine were added, and the mixture was heated and stirred at 100°C for 27 hours, and then poured into 1.52 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).

Revenue i! It was 2.49 g (66.6%).

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

CHN Actual value (χ”): 64.55 6.17 6
．． 78 calculated value (χ): 65.66 6.18
6.70 Application example 3 Silica gel (E, Merck & Co., Ltd. Lycrospher-5I400
The amylose tris (4-methylphenyl carbamate) obtained in Example 4 was supported on a stainless steel (0, 10 m) treated with 3-aminopropyltriethoxysilane, with a length of 25 cm and an inner diameter of 0.46 CN. It was packed into a column (this is referred to as column 1).

In addition, dextran tris (3
, 5-dimethylphenylcarbamate) was packed in a column (this will be referred to as column 2).

These columns allow hexane/2-
Using propatool (90/10), flow rate 0.5ml/
When the various racemic compounds shown in Table 3 were optically resolved under conditions of 25° C. and 25° C., good results as shown in Table 3 were obtained.

Table-3 Note> $1: Ph represents a phenyl group.

*2: α is the separation coefficient, and the number in parentheses indicates its optical rotation.

[Brief explanation of the drawing]

Figure 1 shows the infrared absorption spectrum of the product obtained in Example 3, and Figure 2 shows its ClIC1z:ChCIhOH
(9: 1) is the infrared absorption vector of the soluble part. Applicant's agent Kaoru Furuya Procedural Amendments (issued by Kaoru Furuya) June 5, 1986

Claims (1)

[Claims] Polysaccharides in which 80% to 100% of hydroxyl groups are substituted with groups represented by the following general formula (I) (excluding cellulose)
Alkyl-substituted phenyl carbamate derivatives of. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (I) (In the formula, R_1 to R_5 are hydrogen atoms or alkyl groups having 1 to 8 carbon atoms, and at least one of them is an alkyl group having 1 to 8 carbon atoms. be.)