JPH05239103A - New polysaccharide derivative and separating agent - Google Patents

Abstract

PURPOSE:To obtain a polysaccharide derivative useful as a separating agent having asymmetry discriminating ability capable of resolving racemic modification difficult to separate by using a polygalactosamine of polysaccharide to sterically control the main chain of the polygalactosamine. CONSTITUTION:Hydrogen atoms on hydroxyl group and amino group of an alpha-1,4-polygalactosamine of formula I ((n) is <=5) are partially or wholly replaced with atomic groups expressed by formula II to formula IV (R and R'' are 1-30C group and may contain hetero atom; R' is H or 1-30C group) to give the objective polysaccharide. The polygalactosamine has preferably <=500 number-average molecular weight (in terms of average number of pyranose rings contained in one molecule).

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel polysaccharide derivative which is extremely useful as a functional material for optical resolution, and a separating agent comprising this polysaccharide derivative.
The present invention relates to a novel polysaccharide derivative synthesized using 1,4-polygalactosamine and a separating agent composed of this polysaccharide derivative.

[0002]

2. Description of the Related Art Conventionally, the problems to be solved by the invention
Many derivatives of various polysaccharides are known, and it is also known that many racemic compounds can be optically resolved by using them. In particular, it is known that when a cellulose derivative or an amylose derivative substituted with an aromatic group is used as a packing material for a column for liquid chromatography, it has a large optical resolution (Japanese Patent Publication No.
60-142930, Japanese Patent Publication No. 60-108751, Chem. Lett., 198
7,1857, JP-A-2-289601). However, it is a fact that some compounds cannot be optically resolved even when these derivatives are used. Therefore, an object of the present invention is to provide a novel separating agent capable of resolving such a racemic compound which is difficult to resolve.

[0003]

Means for Solving the Problems As a result of intensive studies to solve the above problems, the present inventors have found that α-1,4 as a polysaccharide.
-The present invention has been completed by finding that a polysaccharide derivative having more excellent asymmetric discrimination ability can be obtained by sterically restricting the main chain of polygalactosamine. That is, the present invention uses the formula (1)

[0004]

[Chemical 3]

(Wherein n is a number of 5 or more), some or all of the hydrogen atoms on the hydroxyl group and amino group of α-1,4-polygalactosamine represented by the following formula (2) ,
The present invention provides a novel polysaccharide derivative obtained by substituting one or more of the atomic groups represented by (3) or (4), and a separating agent comprising this multilayer derivative.

[0006]

[Chemical 4]

(In the formulas (2), (3) and (4), R and R "are each a group having 1 to 30 carbon atoms and may contain a hetero atom. R'is a hydrogen atom or It is a group having 1 to 30 carbon atoms and may contain a hetero atom.) Hereinafter, the present invention will be described in detail.

<Polysaccharide> The polysaccharide in the present invention is α-1,4-polygalactosamine represented by the above formula (1), which is one of natural polysaccharides. The number average molecular weight (average number of pyranose rings contained in one molecule) is 5 or more, preferably
It is preferably 10 or more and 500 or less in terms of easy handling.

<Atomic group> The atomic group introduced on the hydroxyl group and amino group of α-1,4-polygalactosamine is
The above formula, which reacts with a hydroxyl group and an amino group of a polysaccharide to form an ester bond, a urethane bond or an ether bond.
It is an atomic group represented by (2), (3) or (4). Equations (2), (3)
In (4), the group constituting R and R "is a group having 1 to 30 carbon atoms, and the group constituting R'is a hydrogen atom or a group having 1 to 30 carbon atoms. Asymmetric center in the group of
It may contain a functional group such as an ether bond, a carbonyl bond or a halogen which does not participate in the actual reaction.

<Polysaccharide Derivatives> Typical polysaccharide derivatives of the present invention are shown below. (A) Ester bond

[0011]

[Chemical 5]

(In the formula, R is a group having 1 to 30 carbon atoms, preferably 1 to 14 carbon atoms, such as an aliphatic group and an aromatic group.

[0013]

[Chemical 6]

(B) Urethane bond

[0015]

[Chemical 7]

(In the formula, R'is a hydrogen atom or a carbon atom number 1 to
30, preferably 1 to 14 aliphatic groups, groups such as aromatic groups, specific examples include a hydrogen atom (-H),

[0017]

[Chemical 8]

(C) Ether bond

[0019]

[Chemical 9]

(In the formula, R "is a group having 1 to 30 carbon atoms, preferably 1 to 14 carbon atoms, such as an aliphatic group or an aromatic group.

[0021]

[Chemical 10]

<Synthesis Method> 1) Ester Bond The carbonyl group forming the ester derivative of the polysaccharide of the present invention is represented by the above formula (2), and among all hydroxyl groups and amino groups possessed by α-1,4-polygalactosamine. 30% to 100%, preferably 50% or more, more preferably 85% or more, form an ester bond with the carbonyl group. The ester derivative according to the present invention can be easily synthesized by converting the corresponding carboxylic acid to an acid chloride using thionyl chloride, oxalyl chloride, etc., and then reacting it with α-1,4-polygalactosamine in a pyridine solvent. can get.

2) Carbamate bond The carbamoyl group constituting the carbamate derivative of the polysaccharide of the present invention is represented by the above formula (3), and 30% to 100% of all hydroxyl groups and amino groups of α-1,4-polygalactosamine
%, Preferably 50% or more, and more preferably 85% or more are those forming a urethane bond with the carbamoyl 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 α-1,4-polygalactosamine 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.
Moreover, the synthesis of the isocyanate can be easily obtained by, for example, reacting phosgene with the amino group of the corresponding aniline derivative.

3) Ether Bond The group forming the ether derivative of the polysaccharide of the present invention is represented by the above formula (4).
The total hydroxyl groups and amino groups of α-1,4-polygalactosamine are 30% to 100%, preferably 50%.
% Or more, more preferably 85% or more, form an ether bond with the group. The synthesis of the ether derivative according to the present invention is carried out by reacting the corresponding halide with α-1,4-polygalactosamine, for example, in a solvent of dioxane or pyridine, using potassium hydroxide or potassium t-butoxide as a base. can get.

<Separator> The polysaccharide derivative of the present invention is an extremely useful substance as a functional material, and particularly useful as a filler for optical resolution, that is, a separator. When the polysaccharide derivative of the present invention is used as a separating agent for the purpose of separating a mixture of compounds or a mixture of optical isomers, gas chromatography, liquid chromatography, thin layer chromatography, etc. packed with the polysaccharide derivative of the present invention can be used. Generally, a chromatographic method is used, but in addition to this, a membrane containing the polysaccharide derivative of the present invention can be formed and the membrane separation can be performed using this.

In order to apply the polysaccharide derivative of the present invention as a separating agent to a liquid chromatography method, a method of packing the powder as a powder in a column is convenient. The polysaccharide derivative of the present invention is preferably ground or beaded, and the particles are more preferably porous. Further, it is also preferable to support the polysaccharide derivative on a carrier 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. When used as a powder, the size of the particles and the size of the carrier differ depending on the size of the column used,
The thickness is preferably 1 μm to 1 mm, more preferably 1 μm to 300 μm. The carrier is preferably porous, and its average pore diameter is preferably 10Å to 100 µm, more preferably 50Å to 50000Å. The amount of the polysaccharide derivative supported on the carrier is preferably 1 to 100% by weight, more preferably 5 to 50% by weight, based on the carrier.

The method of supporting the polysaccharide derivative on the carrier may be a chemical method or a physical method. As a physical method,
A method in which the polysaccharide derivative is dissolved in a soluble solvent and well mixed with the carrier, and the solvent is distilled off by an air stream under reduced pressure or heating, or after the polysaccharide derivative is dissolved in the soluble solvent and mixed well with the carrier, the polysaccharide There is also a method in which the soluble solvent is diffused by separating the derivative with an insoluble solvent. 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 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 polymer substances made of polystyrene, polyacrylamide, polyacrylate and the like. 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 derivative or the surface of the carrier itself. You may use what was processed in order to modify the characteristic of. 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 derivative. There is no particular limitation except for the case where the polysaccharide derivative is chemically bound to the carrier or is reacted with the carrier when it is insolubilized by crosslinking. On the other hand, when performing thin layer chromatography, a thickness of 0.1 mm consisting of the separating agent consisting of particles of about 0.1 μm to 0.1 mm and, if necessary, a small amount of binder.
A layer of ~ 100 mm may be formed on the support plate. When performing membrane separation, it is used as a hollow fiber or a film.

[0029]

The present invention will be described in detail below with reference to examples and application examples, but the present invention is not limited to these examples.

Example 1 α-1,4-polygalactosamine tris (3,5-dimethyl)
(1) Synthesis of α-1,4-polygalactosamine tris (3,5-dimethylphenylcarbamate) α-1,4-polygalactosamine (Higeta Shoyu Co., Ltd.),
Molecular weight 320,000) (1 g) was added to N, N-dimethylacetamide (40
ml) with stirring at 100 ° C. and with pyridine (7 ml).
3,5-Dimethylphenylisocyanate (6ml, 41mmo
l) was added and reacted at 100 ° C. for 24 hours, and then 3,5-dimethylphenyl isocyanate (5 ml, 34 mmol) was added,
The reaction was carried out at 00 ° C for 24 hours. This was poured into methanol and the precipitate formed was filtered to obtain the target product α
-1,4-polygalactosamine tris (3,5-dimethylphenylcarbamate) was obtained in an amount of 1.75 g with a yield of 81.5%.
The results of elemental analysis of the compound thus obtained are shown in Table 1.
Shown in.

[0031]

[Table 1]

From the results of elemental analysis, it was found that almost all hydrogen atoms on the hydroxyl group and amino group of α-1,4-polygalactosamine were reacted with 3,5-dimethylphenylisocyanate.

(2) Synthesis of a separating agent using α-1,4-polygalactosamine tris (3,5-dimethylphenylcarbamate) α-1,4-polygalactosamine tris (3,5) obtained in (1) 0.75 g of 5-dimethylphenylcarbamate) was dispersed in 20 ml of a mixture of chloroform and LiCl, and this was added dropwise to 3 g of silica gel (Nagel: particle size 1000Å, pore size 7 μm) surface-treated with 3-aminopropylethoxysilane, and the solvent was added. The target separating agent was obtained by distilling off.

Example 2 α-1,4-polygalactosamine tris (3,5-dichloro)
(1) Synthesis of α-1,4-polygalactosamine tris (3,5-dichlorophenylcarbamate) as a reaction reagent, instead of 3,5-dimethylphenylisocyanate Using dichlorophenylisocyanate (15 g, 79.8 mmol), 1.28 g of the target α-1,4-polygalactosamine tris (3,5-dichlorophenylcarbamate) was obtained in the same manner as in (1) of Example 1 in a yield. Obtained at 39.1%. The results of elemental analysis of the compound thus obtained are shown in Table 2.

[0035]

[Table 2]

(2) Synthesis of a separating agent using α-1,4-polygalactosamine tris (3,5-dichlorophenylcarbamate) α-1,4-polygalactosamine tris (3,5) obtained in (1) -Dichlorophenylcarbamate) (0.75 g) was used to obtain the desired separating agent in the same manner as in (2) of Example 1.

Example 3 α-1,4-polygalactosamine triphenylcarbame
Synthesis of separating agent using chromatography preparative (1) α-1,4 - Synthesis of polygalactosamine triphenyl carbamates alpha-l, 4 - polygalactosamine a (1 g) pyridine (7
ml), N, N-dimethylacetamide (15 ml), LiCl (1.
Phenylisocyanate (13 g, 109 mmol) in 5 g)
And reacted at 100 ° C for 67 hours. The reaction solution was poured into methanol, and the precipitate formed was filtered to obtain 1.21 g of the target α-1,4-polygalactosamine triphenylcarbamate in a yield of 37.4%.

(2) Synthesis of Separation Agent Using α-1,4-Polygalactosamine Triphenylcarbamate Using 0.75 g of α-1,4-polygalactosamine triphenylcarbamate obtained in (1), Example 1 The target separating agent was obtained in the same manner as in (2).

Application Example 1 The separating agents obtained in Examples 1 and 2 were mixed with liquid paraffin.
By a slurry method using a mixed solution of hexane (1: 2 / volume ratio), a stainless steel column having an inner diameter of 0.46 cm and a length of 25 cm was packed. Using this column, various racemic compounds shown in Table 4 were subjected to optical resolution under the following conditions. The results are shown in Table 4. <Separation conditions) Eluent: n-hexane / 2-propanol = 95/5 (v /
v) Flow rate: 0.5 ml / min The volume ratio (k '), separation coefficient (α) and separation degree (Rs) in the table are respectively defined by the following equations. Also, in the table
Ph represents a phenyl group, Me represents a methyl group, and the code in parentheses in the table is the code of the degree of illuminance of the eluate.

[0040]

[Equation 1]

[0041]

[Table 4]

Application Example 2 The separating agent obtained in Example 3 was packed in a column in the same manner as in Application Example 1. Using this column, the racemic compounds shown in Table 5 were subjected to optical resolution under the same conditions as in Application Example 1. The results are shown in Table 5.

[0043]

[Table 5]

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification code Internal reference number FI technical display location G01N 30/48 W 8506-2J

Claims (2)

[Claims] 1. Formula (1): (In the formula, n represents a number of 5 or more.) Α-1,4
-A novel one obtained by substituting a part or all of the hydrogen atoms on the hydroxyl group and amino group of polygalactosamine with one or more of the atomic groups represented by the following formula (2), (3) or (4) Polysaccharide derivative. [Chemical 2] (In the formulas (2), (3) and (4), R and R ″ are each a group having 1 to 30 carbon atoms and may contain a hetero atom.
R'is a hydrogen atom or a group having 1 to 30 carbon atoms and may contain a hetero atom. ) 2. A separating agent comprising the novel polysaccharide derivative according to claim 1.