JPS6230549A - Preparation of adsorbent - Google Patents

Abstract

PURPOSE:To efficiently separate and purify a mixture, by obtaining an adsorbent by converting the terminal ester of the acidic amino acid omega-ester constitutional unit of a crosslinked polymer containing specific synthetic polyamino acid to active ester before performing aminolysis. CONSTITUTION:A crosslinked polymer containing synthetic polyamino acid represented by formula (wherein n is an integer of 5 or more, R is an org. group having an ester group at the terminal thereof and R' is H or an alkyl group), which contains optically active acidic amino acid omega-ester as a main constitutional unit, as a constitutional component is swollen by 2-20-fold amount of a solvent. Subsequently, alcohol having an electron withdrawing group and an acidic catalyst are added to the swollen polymer and reaction is performed at 40-80 deg.C for 10-40hr to convert amino acid omega-ester to active ester. After the active esterified crosslinked polymer is swollen by 2-20-fold amount of a solvent, desired amine is added to the swollen polymer and reaction is performed at 20-80 deg.C for 10-40hr to introduce an amide group into the polymer to obtain an adsorbent.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides a novel adsorbent, particularly a polymer adsorbent comprising a crosslinked polymer containing an amino acid constituent unit having a specific amide group with a high degree of selectivity. Regarding the manufacturing method.

(o) Conventional optical resolution, that is, the separation of racemic mixtures into their optical antipodes, is a very important technology in the pharmaceutical, agricultural, food, and other industries. . The usual method is to convert a racemic mixture into a mixture of diastereomers, and then separate the diastereomer mixtures based on the differences in their physical properties, but the types of racemic mixtures that can be separated by this method are limited. It is being

In addition to these conventional methods, techniques for resolving racemic mixtures by chromatography have been actively researched in recent years.

However, all of the ones that have been put into practical use use porous silica gel as a carrier, and they are no more than a means for analysis and are not durable enough to withstand industrial use. Therefore, the location, durability, price,
No method has been found that is satisfactory in terms of ease of production, and therefore, it is industrially and technically difficult to apply the method to resolve racemates.

In order to provide a new polymer adsorbent to solve these problems, the present inventor conducted intensive research and discovered a cross-linked polymer containing an optically active synthetic polyamino acid as a constituent component. However, we were able to provide an adsorbent with unprecedented performance as an adsorbent for optical resolution, etc. Because of the unique steric structure of the polyamino acid component and the asymmetric environment it exposes, this adsorbent can preferentially adsorb one side of the racemic mixture and perform optical resolution with high efficiency.

Further, as a result of further studies, the present inventor found that among the various types of adsorbents, those having an amide group in the side chain of the polyamino acid component are particularly effective for hydrogen bonding between the amide group and the separation target. It has already been discovered that racemic mixtures can be effectively optically resolved by such interactions.

Based on these findings, the present inventors realized that in order to effectively perform optical resolution, it is necessary to introduce amide groups having various substituents suitable for the separation target into the side chains of polyamino acid components. It has arrived. One of the methods for introducing an amide group into the side chain of a polyamino acid is to introduce an amide group into the side chain or organic group of aspartic acid or glutamic acid constituting the polyamino acid. There are a few references regarding this method, but the most simple and practical method is to convert the benzyl ester of the side chain -COOH into 7 with an amine.
This is a method of minilysis.

Using this method, the present inventor succeeded in converting poly(acidic amino acid benzyl ester) supported on a crosslinked polymer carrier with benzylamine to benzylamide, and had previously proposed this method (Patent Application No. 44065
However, in this method, the reaction only progresses with amines that have an affinity for the crosslinked polymer, such as benzylamine1, and if diluted with a solvent etc. during the reaction, the reaction rate becomes extremely slow. It has the disadvantage that it is slow. Therefore, the above-mentioned method was not fully satisfactory because it was not possible to introduce amide groups having various substituents suitable for the separation target into the side chains of the polyamino acids in the crosslinked polymer.

In addition, in the conventional method, poly(γ-methyl-L-glutamate) obtained starting from industrially advantageous raw materials cannot be used as the poly(acidic amino acid ω-ester) in the crosslinked polymer. When considering actual industrialization, it was not completely satisfactory.

On the other hand, as a report on a method for converting poly(γ-methyl-L-glutamate) into a side chain methyl ester ml amide group, there is a literature on a method using a homogeneous solution of the uncrosslinked polyamino acid itself as a raw material [Shin Okawara, Japan] Journal of the Japanese Society of Chemistry, Volume 9, Page 1770 (1973)].

However, this method requires 1. As mentioned above, this is a reaction in a homogeneous solution of polyamino acids that are not crosslinked, and there is no description of polyamino acids in crosslinked polymers that are crosslinked and insolubilized in solvents.

As mentioned above, there have been no reports on the amitrilysis of polyamino acid esters in crosslinked polymers using conventionally known methods.
Moreover, there is no report on the ability to amidate side chain esters of amino acids in crosslinked polymers in good yields and the resulting polymer compounds are excellent as adsorbents.

An object of the present invention is to provide a novel method for producing an adsorbent that can solve the above-mentioned problems, and to obtain a novel adsorbent by the method.
Wow, □ tsu □ □ Wow 3. . A6.1 The inventor is:
As a result of intensive study, we found that the side chain structure of the poly(acidic amino acid ω-ester) in the crosslinked polymer,
By first substituting with an active ester and then performing amithrisis, amithrisis proceeds at a high reaction rate in the case of amines that have an affinity for crosslinked polymers, and also in the case of aliphatic amines that have no affinity for crosslinked polymers. ,
The inventors discovered that amithrisis could easily proceed and that an amide group could be introduced, leading to the present invention.

As a result, they discovered that it is possible to produce various adsorbents having an amide group attached to a substituent suitable for the separation target in the side chain of a polyamino acid.

The present invention was made based on the above findings, and consists of a general formula containing an optically active acidic amino acid ω-ester as a main structural unit, (wherein n is an integer of 5 or more, and R is an ester at the terminal The terminal ester in R of the acidic amino acid ω-ester constituent unit of the crosslinked polymer containing as a constituent a synthetic polyamino acid represented by an organic group (R' is H or an alkyl group) is first converted into an active ester. amidating the ester by converting and then amitrilysis;
The present invention relates to a method for producing an adsorbent characterized by introducing an amide group into R in the formula.

Examples of the optically active acidic amino acid ω-ester, which is the main structural unit of the synthetic polyamino acid that is a constituent of the adsorbent of the present invention, include β- or T-esters of aspartic acid or glutamic acid. Specific examples of esters include esters substituted with methyl groups, ethyl groups, propyl groups, butyl groups, benzyl groups, etc., but any ester can be used as long as it can be easily transesterified. good.

The adsorbent of the present invention can contain an amino acid other than the acidic amino acid ω-ester as a constituent unit. acidic amino acid ω-
The composition ratio of ester and other amino acids is 0.5 to 1.0
It is.

Synthetic polyamino acid constituent units other than the above-mentioned acidic amino acid ω-esters include optically active amino acids constituting proteins, such as D or L forms of protein-constituting amino acids such as alanine, valine, leucine, phenylalanine, and proline; Optical activity α- other than amino acids constituting
Aminocarboxylic acids (eg sarcosine) and their derivatives are used.

In the constituent components of the above general formula, n is 4 or more, and 10
It is generally 0 or less, but preferably 10 to 40.

As described below, the active ester in the present invention includes aliphatic or aromatic esters having an electron-withdrawing group such as halogen, nitrile, and nitro.

Since the excellent substrate selectivity of the adsorbent of the present invention is derived from its constituent optically active synthetic polyamino acids and/or derivatives thereof, the other constituents may be any polymer. Good too. However, the present adsorbent is required to swell in the solvent used in the adsorption operation. That is, when water is used as a solvent, it is preferable to use a hydrophilic polymer, and when an organic compound such as benzene or toluene is used as a solvent, a hydrophobic polymer is preferably used as a constituent other than the polyamino acid.

The synthetic polyamino acid component constituting the adsorbent of the present invention and other components may be bonded in any manner, as long as the bonded product is a crosslinked polymer. Examples include those in which a polyamino acid component is graft-bonded to a crosslinked polymer carrier, or those in which the polyamino acid component itself constitutes a crosslinking portion.

Regarding polyamino acid components linked at one end.

Preferable results may be obtained by protecting the other unbonded end with a protecting group.

In this case, a protective group that is chemically stable and difficult to eliminate is preferred.

The molecular weight, crosslinking density, etc. of the crosslinked polymer that is the adsorbent of the present invention can be selected as appropriate depending on the object to be adsorbed, and the ratio of the synthetic polyamino acid component in the adsorbent can also be selected as appropriate; %, preferably 10-60%
It is. The adsorption effect of the adsorbent of the present invention varies depending on the solvent system used as described above, but it also depends on the functional groups, stericity, etc. of the substance to be adsorbed. The type of amino acid, crosslinking density, etc. can be changed as appropriate.

The adsorption properties of the adsorbent of the present invention can be adjusted by crosslinking density or porosity, and the crosslinking density can be changed as appropriate depending on the substance to be adsorbed, but in general, the crosslinking density tends to decrease as the molecular weight of the substance to be adsorbed increases. There is.

Further, the adsorbent of the present invention can be made porous by using a diluent or the like as described later.

The crosslink density of the adsorbent of the present invention changes depending on whether it is made porous or not, but the crosslink density when it is not made porous is 0101 to 50.
%, preferably 0.5 to 10%, and the crosslinking density in the case of making it porous is 0.1 to 100%, preferably 5 to 30%.
%.

The crosslinked polymer containing as a constituent a synthetic polyamino acid whose main constituent unit is an optically active acidic amino acid ω-ester of the present invention can be produced, for example, by the following known method.

First, the general formula (In the formula, R is an organic group having an ester group at the end.

R' is H or an alkyl group) N-carboxy anhydride of an optically active acidic amino acid ω-ester or a mixture of the acidic amino acid ω-ester and another amino acid (hereinafter referred to as R').

NCA) is synthesized by known methods. Details of this method can be found, for example, in Murray Gutsman (M.

Goodman), Piobolimers (B i op
15, p. 1869 (1976
)It is described in.

Next, a crosslinked polymer carrier having a functional group convertible into an amino group or into which an amino group can be introduced is produced by a known method, and the functional group is converted into an amino group or an amino group is introduced.

The NCA is polymerized using the carrier having an amino group as an initiator to obtain a crosslinked polymer in which an optically active synthetic polyamino acid is supported on the carrier.

Examples of the crosslinked polymer carrier having a functional group convertible into an amino group or into which an amino group can be introduced include a chloromethylstyrene-styrene-divinylbenzene copolymer, an acrylamide-methylenebisacrylamide copolymer, etc. In short, monomers having a functional group convertible to an amino group such as chloromethylstyrene,
Alternatively, any crosslinked polymer polymerized using a monomer having a functional group capable of introducing an amino group such as glycidyl methacrylate as a monomer component may be used.

Suspension polymerization of these copolymers is carried out, for example, by the following method. First, the reaction raw material is an inert organic solvent, preferably an aromatic hydrocarbon such as benzene or toluene, or n-
It is dissolved in aliphatic hydrocarbons such as octane or alcohols such as cyclohexanol and lauryl alcohol. As for the amount of organic solvent, it is particularly advantageous to use 1 part by weight of the solvent per 1 part by weight of the reaction raw material, provided that the monomer can be completely dissolved, but in general, 0 to 3 parts by weight of the solvent is used. It will be done. This reaction solution is well mixed with an aqueous protective colloid solution, especially an aqueous polyvinyl alcohol solution, using an efficient stirrer, for example, using 2 to 25 parts by weight of the aqueous solution per 1 part by weight of this reaction solution. The stirred mixture is heated to about 40'C to 100C, preferably about 70C, under an atmosphere of non-reactive gas, particularly nitrogen. Polymerization time is about 4 hours to 72 hours, preferably about 10 hours.

In this case, a porous spherical gel can be obtained by adding a suitable diluent to the monomer phase.

As for the type of diluent, organic solvents that have low swelling properties for the resulting gel are suitable. For example, chloromethylstyrene
In the case of a styrene-divinylbenzene copolymer, octane, decane, dodecane, etc. are preferable, and instead of a diluent, linear polymers such as polystyrene, polymethylstyrene, polymethyl acrylate, etc. are co-present for polymerization, and then A porous spherical gel can also be obtained by extracting and removing the linear polymer from the produced spherical gel. Porous formation is applied to materials with low or high crosslinking density, but is generally applied to materials with high crosslinking density. This is preferable because it facilitates contact with the group.

Further, those having a high degree of crosslinking are very preferable because they have little swelling and shrinkage and high mechanical strength, and are particularly preferable in the case of chromatography.

Details of the conversion reaction of a functional group in a copolymer into an amino group and the reaction of introducing an amino group can be found in 5, for example, Merryfield (R
, B, Merriefield) Journal of the American Chemical Society (J
, A, C, S,) Volume 98, Page 7357 (1976)
It is described in etc.

After washing the obtained crosslinked polymer carrier having amino groups,
Completely dehydrate by Soxhlet extraction, etc., and thoroughly dry under reduced pressure and heat.

The types of amino groups that initiate polymerization of NCA are usually -
Although primary or secondary amino groups are used.

It is particularly preferable to use a -grade amino group as the initiator because it can support the polyamino acid quantitatively.

Next, convert the acidic amino acid side chain ester in the crosslinked polymer containing as a constituent component the synthetic polyamino acid whose main constituent unit is the optically active acidic amino acid ω-ester obtained by the method 5 above into an active ester. , then shows how to amylyse.

Conversion to an active ester is carried out by swelling the crosslinked polymer with 2 to 20 times the amount of solvent, then adding an alcohol having an electron-withdrawing group and an acidic catalyst, heating to 40 to 80°C, and 1
This can be done by reacting for 0 to 40 hours. In this case, the reaction can be promoted by reducing the pressure in one reaction system and distilling off the alcohol produced by the reaction together with the solvent.

Examples of the solvent include benzene, toluene, methylene chloride, chloroform, dichloroethane, dioxane, acetonitrile, benzonitrile, etc., and it is desirable to dehydrate and purify it before use.

Examples of alcohols having an electron-withdrawing group include 1, ethylene chlorohydrin, ethylene chloride, 2-
Examples include fluoroethanol, 2,2.2-trifluoroethanol, 2,2.2-trichloroethanol, and the like.

Generally, the higher the electron-withdrawing property of an active ester's substituent, the more likely it is to undergo amithrisis. That is, 2.2v2-trichloroethyl ester has much higher reactivity than monochloroethyl ester. However, the inventors have found that polyamino acid side chain esters in crosslinked polymers are more affected by steric effects than electronic effects.

Therefore, active esters that are not sterically bulky and have a substituent that has high electron-withdrawing properties to some extent are preferred.

Examples of the acidic solvent used in the transesterification reaction include concentrated sulfuric acid and p-toluenesulfonic acid.

The reaction product can be easily removed from the reaction system by filtration and purified by washing with a solvent. The progress of the reaction is indicated by the fact that the absorption of the ester shifts to the higher wavenumber side in the infrared absorption spectrum of the product, or in the case of cyanoethyl ester, the absorption of the ester shifts to the higher wavenumber side.
6 The reaction rate, which is confirmed from the observation of nitrile absorption at 50<-1>, can be determined from the nitrogen content or halogen content by elemental analysis.

The thus obtained active ester is converted into an amide group by undergoing amitrilysis with various amines in the following manner. First, the active esterified crosslinked polymer is swollen with 2 to 20 times the amount of solvent, then the desired amine is added, and 20 to 20 times the amount of solvent is added.
React at 80°C for 10 to 40 hours. In this case, the amine may be used as both a reaction reagent and a solvent. Particularly when the amine has an affinity for the crosslinked polymer, it is a preferable method to use the amine as a reaction reagent and solvent. .

The inventors of the present invention have found that in this reaction, the reactivity or the degree of occurrence of side reactions is completely different depending on the type of solvent. That is, the reaction does not proceed very well in solvents such as toluene, dioxane, acetonitrile, and dichloroethane.
On the contrary, it has been found that the reaction proceeds easily in aprotic polar solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and dimethylsulfoxide.

In particular, it has been found that a solvent that is difficult to decompose, such as N,N-dimethylacetamide, is one of the particularly preferred solvents in order to suppress the side reaction of cleavage of the main chain of the polyamino acid.

The amines that can be used include various -class or secondary amines, such as linear alkylamines such as ethylamine and n-butylamine, isopropylamine,
l-alkylamine such as t-butylamine, cyclic alkylamine such as cyclohexylamine, benzylamine,
Primary amines such as alkylamines having an aromatic ring such as p-hydroxybenzylamine and α-phenylethylamine; secondary amines such as diethylamine and diisopropylamine; polyamines such as ethylenediamine, hexamethylenediamine and diethylenetriamine;
A number of amines are used, including amines with functional groups such as monoethanolamine. As illustrated in the examples,
Even weakly basic or sterically bulky amines react easily. Furthermore, in the method of the present invention, since the amine can be diluted with a solvent, the reaction can easily proceed with aliphatic amines that have little affinity with the crosslinked polymer carrier.

The reaction temperature or reaction time is closely related to the basicity and steric bulk of the amine used, and as the basicity increases and the steric bulk decreases,
Preferred reaction temperatures are lower and reaction times are shorter. Reacting with a strongly basic amine at high temperature for a long period of time is not a preferable method because it only causes a side reaction of severing the main chain of the polyamino acid.

The amidated crosslinked polymer obtained as described above can be easily taken out of the reaction system by filtration and purified by washing with a solvent.

The progress of the reaction is indicated by the infrared absorption spectrum of the product at 1740 m.
-' absorption of ester decreases, and conversely 1650mm
The 0 reaction rate, which is confirmed by the increase in the absorption of the amide near -', cannot be accurately determined because the polyamino acid main chain is slightly cleaved, but it can be determined by the amount of decrease in the ester absorption in the infrared spectrum or the elemental Estimated based on nitrogen content determined by analysis.

The method of the present invention makes it possible to introduce various substituents into the amide groups of polyamino acid side chains in crosslinked polymers, which was difficult to do with conventional methods, and provides an adsorbent suitable for separation targets. It became possible to do so.

That is, the adsorbent obtained by the method of the present invention has hydrogen bonds between the polyamino acid side chain amide group in the crosslinked polymer and the object to be separated, and steric bonds between the substituents bonded to the amide and the object to be separated. Due to the combination of interactions such as obstacles,
Various mixtures can be efficiently separated and purified.

In particular, when performing advanced separation such as optical resolution of racemic mixtures, it is necessary to manufacture an adsorbent in which a substituent suitable for the separation target is bonded to the amide group of the polyamino acid side chain. This method is extremely useful in such cases.

Furthermore, by the method of the present invention, poly (
Poly(γ-methyl-L-glutamate) obtained starting from T-methyl-L-glutamate NCA, which is an industrially advantageous raw material (acidic amino acid ω-ester)
Therefore, the present invention can provide an industrially extremely advantageous method.

The present invention will be specifically explained with reference to the following production examples and examples, but the present invention is not limited only to these examples.

2 spots of chloromethylstyrene 2. Og, 55% divinylbenzene (crosslinking agent) 2.74g, styrene 95.26g, 75
A solution of 0.67 g of % dibenzoyl peroxide was added to a solution of 4.0 g of polyvinyl alcohol and 400 g of water, and the mixture was stirred at 1000 rpm for 10 hours at 70°C under nitrogen to form a solution of chloromethylstyrene-styrene. - A crosslinked polymer of divinylbenzene copolymer was produced. The crosslinked polymer was a translucent spherical gel.

85.8 g of this crosslinked polymer was mixed with 85 g of phthalimide potash.
．． 8 g, mixed with 686 ml DMF, 120°C
After stirring for 6 hours, the crosslinked polymer was taken out, washed and dried. Next, the crosslinked polymer was hydrated with hydrazine 68,6 m
After mixing with 686 ml of dioxane and stirring at 90° C. for 6 hours, the crosslinked polymer in which chloromethyl groups were converted to aminomethyl groups was taken, thoroughly washed, and completely dried.

The nitrogen content of this was 0.17%.

81 g of the obtained gel-like crosslinked polymer carrier was mixed with 32.4 g of β-benzyl-aspartate NCA and 6 g of dioxane.
The mixture was dispersed in 48 ml of solution and stirred at 35° C. under nitrogen for 72 hours to polymerize NCA. A portion of the crosslinked polymer was isolated and analyzed after purification, and the nitrogen content was 1.81%.
and poly (
The amount of supported β-benzyl-aspartate is 26.
1%, and its degree of polymerization was 12.4. After the polymerization reaction, 88.2 g of ethylene chlorohydrin and 3.5 g of 97% sulfuric acid were added to the polymer dispersion and stirred at 60°C for 10 hours to perform a transesterification reaction. The ethyl esterified crosslinked polymer was isolated, thoroughly washed, and then completely dried.

The elemental analysis values of this product were as follows.

C: 82.25% H: 7.30% N: 1.71% Cj! : 3.41% Reaction rate (conversion rate from benzyl ester to chloroethyl ester) calculated from elemental analysis value (chlorine 3.41%)
was 78.6%. Also, nitrogen content <1.71%
The degree of polymerization of the chloroethyl esterified polyaspartic acid calculated from ) is 11.7, indicating that cleavage of the polyamino acid main chain hardly occurs. 40g of this chloroethyl esterified crosslinked polymer was added to 320ml of dioxane.
Add 40g of cyclohexylamine and heat to 40°C.
After stirring for 24 hours, the mixture was isolated and purified. In the infrared absorption spectrum, the absorption peak of ester at 1740 aa-' decreased, and the absorption peak of amide at 1640-1660 cm-increased. The elemental analysis results were as follows: chlorine content decreased and nitrogen content increased.

Elemental analysis values C: 82.46% H: 7.38% N: 2.10% C1: 2.45% From the above results, part of the chloroethyl ester was partially converted to cyclohexylamide by amithurisis. I understand that. Conversion rate calculated from elemental analysis values is approximately 23%
Met. Thus, it can be seen that the method of the present invention makes it possible to produce an adsorbent having an amide group substituted with an alicyclic hydrocarbon in the side chain of the supported polyamino acid, which could not be obtained by conventional methods.

74 g of chloromethylstyrene, 58.54 g of 55% divinylbenzene (crosslinking agent), 294 g of styrene.
5g, 75% dibenzoyl peroxide 4.78g, n
- A solution of 304.12 g of octane (diluent) was added to a solution of 20.0 g of polyvinyl alcohol and 2000 g of water.

The mixture was stirred at 1000 rpm for 10 hours at 70° C. under nitrogen. The obtained crosslinked chloromethylstyrene-styrene-divinylbenzene copolymer was isolated in the same manner as in Production Example 1.

The crosslinked polymer was a porous white spherical gel.

A crosslinked polymer in which chloromethyl groups were converted to aminomethyl groups was obtained by the same method as in Production Example 1.

The nitrogen content of this was 0.12%. 223 g of the obtained porous crosslinked polymer carrier was mixed with 69 g of T-methyl-L-glutamate NCA and 223 g of 1,2-dichloroethane.
Dispersed in 0.007 ml of solution and incubated at 30°C under nitrogen for 40
The NCA was polymerized by stirring for an hour. When a part of the crosslinked polymer was isolated and analyzed after purification, the nitrogen content was found to be 2.0
3, and the poly in the crosslinked polymer calculated from this value
The content of (T-methyl-glutamate) is 19.7
%, and its degree of polymerization was 19.3.

After the polymerization reaction, 338 g of ethylene cyanohydrin, 223 g of dichloroethane, and 123 g of p-toluenesulfonic acid (monohydrate) as a catalyst were added to the catenary polymer dispersion, and the mixture was stirred at 60°C for 3 hours. The reaction mixture was further stirred for 6 hours under reduced pressure while methanol produced by the reaction was distilled off together with the solvent to carry out transesterification. After the reaction, the cyanoethyl esterified crosslinked polymer was isolated, thoroughly washed, and completely dried.

Since the yield after the reaction is slightly lower than the theoretical yield, during the reaction, the cleavage of the supported polyamino acid main chain, which is a side reaction, is approximately 10%.
It is estimated that this occurred to a certain degree. The elemental analysis values of this product were as follows.

C: 82.97%) (: 7.39% N: 3.10%) From the elemental analysis value (nitrogen 3.10%), the reaction rate (conversion rate from methyl ester to cyanoethyl ester>) is approximately 70%.
%It is estimated to be. FIG. 1 shows the infrared absorption spectrum of this product, and characteristic absorption of nitrile groups is observed at 2250 cm. Around 1650cm-' and 1550c
The absorption around m-' is due to the amide based on the supported polyamino acid.
and the characteristic absorption of amide ■.

This cyanoethyl esterified crosslinked polymer was reacted with various amines in the same manner as in Example 1 to produce various adsorbents. The results are shown in Table 1.

The progress of the reaction with the amine is indicated by the disappearance of the nitrile absorption at 2250 cm-' in the infrared absorption spectrum.
Decrease in ester absorption near 0 cm-', 1650 cm-
This is determined by the increase in amide absorption near '.

Figure 2 is an infrared absorption spectrum of the adsorbent obtained in Example 9, and it shows that nitrile absorption disappears, ester absorption decreases, amide absorption increases, and a wide range of hydroxyl absorption is observed around 3300 Cffl −'. It can be seen from the above that an amide group having a hydroxyethyl group as a substituent has indeed been introduced into the supported polyamino acid side chain.

As described above, according to the method of the present invention, it is possible to manufacture various adsorbents suitable for separation targets, and it can be seen that the wooden method is a useful method for manufacturing adsorbents.

A crosslinked polymer having an I content of 30.5% of the main poly(T-methyl-glutamate) and a degree of polymerization of 15.1 was produced in the same manner as in Example 2. did. Then, 18 g of the crosslinked polymer was dispersed in 180 ml of dichloroethane, and 30.5' 7 ethylene chlorohydrin was added.
g and 1.94 g of 97% sulfuric acid as a catalyst,
The mixture was stirred at 60° C. for 3 hours, and then stirred for an additional 4 hours while reducing the pressure of the reaction system and distilling methanol off to carry out a transesterification reaction. After the reaction, the chloroethyl esterified crosslinked polymer was isolated, thoroughly washed, and completely dried.

The elemental analysis values of this product were as follows.

C: 73.07% H: 6.94% N: 2.91% C1: 7.00% It is estimated that the transesterification proceeded almost quantitatively from the elemental analysis values (chlorine 7.00%).

Amitylysis was performed by dispersing 18 g of this chloroethyl esterified crosslinked polymer in 108 ml of benzylamine and stirring at 60° C. for 30 hours. After the reaction,
After isolation and purification and measurement of infrared absorption spectrum, it was found that 1
The absorption peak of 740an-1 ester disappeared, and 16
The absorption peak of the amide between 40 and 166°aI+1 increased. The results of elemental analysis of this product are as follows.

C: 80.34% H: 7.34% N: 5.15% (1: 0.3%) From the above results, the chloroethyl ester group was almost quantitatively converted to benzylamide group by amithrisis. Thus, it can be seen that the method of the present invention makes it possible to quantitatively introduce amide groups into side acids of supported polyamino acids, which was difficult to do using conventional methods.

Next, the obtained benzylamide crosslinked polymer Log was dispersed in a solution of 60 ml of dioxane and 2 ml of acetic anhydride, and stirred at 30'C for 24 hours to remove the unbonded polyamino acids. In order to evaluate the crosslinked polymer obtained by protecting the amine group at the end of the main chain with an acetyl group as an adsorbent for optical resolution,
．． It was packed into a stainless steel column with a length of 500 Wn. Next, using this packed column, the resolving power of the adsorbent was evaluated by chromatography. A Shimadzu LC-4A liquid chromatography device was used for liquid delivery and detection.

The chromatography conditions are as follows.

Eluent: 3:2 toluene-dioxane mixture flow rate:
0.5 ml/min Temperature: 10°C Detection: Differential refractometer and optical rotation detector As the evaluation target, a racemic mixture of isopropylhydantoin (sample amount 21% solution 200 μm) was divided into 5 parts. After 62 minutes, there is also an R-isomer with an optical rotation of 10.

After 73 minutes, 8 isomers with − optical rotation were eluted, making it clear that they could be completely separated into R isomer and 8 isomers.

Thus, it can be seen that the adsorbent of the present invention has an unprecedented optical resolution ability.

Comparative Example 1 In exactly the same manner as in Example 13, a crosslinked polymer having a supported amount of poly(γ-benzyl-L-glutamate) of 30.5% and a degree of polymerization of 15.1 was produced. Next, when the side chain benzyl □ ester was amicilyzed with benzylamine immediately without going through the active esterification reaction, the substitution rate was 70% after reacting at 60'C for 30 hours. - When the reaction temperature was raised to further increase the substitution rate, the main chain of the polyamino acid was cleaved and the amount of polyamino acid supported decreased. Therefore, it was impossible to increase the substitution rate with this method. The benzylamidated crosslinked polymer obtained by this method was treated in exactly the same manner as in Example 13 to acetylate the terminal amino group of the supported polyamino acid.

The adsorbent thus obtained was packed into a column in exactly the same manner as in Example 13, and the racemic mixture of isoprobylhydantoin was separated, giving a single elution curve with a peak top at 45 minutes.

Although the R isomer was eluted in the early stage and 8 isomers were eluted in the latter stage, complete resolution was not successful, and all of them were eluted as a mixture of R isomers and 8 isomers.

As mentioned above, it can be seen that the adsorbent of this comparative example obtained by the conventional method performs less efficient partitioning than the adsorbent of Example 13.

[Brief explanation of the drawing]

Figure 1 shows poly(γ-
Figure 2 shows an infrared absorption spectrum of a crosslinked polymer in which the side chain ω-ester of methyl-L-glutamate was transesterified to form a cyanoethyl ester. This is an infrared absorption spectrum of an adsorbent in which the ester is amidated by amitolysis with aminoethanol 5-nol and an amide group having a 2-hydroxyethyl group as a substituent is introduced.

Claims (1)

[Claims] (1) There are general formulas, ▲mathematical formulas, chemical formulas, tables, etc. that have an optically active acidic amino acid ω-ester as the main constituent unit▼ (In the formula, n is an integer of 5 or more, and R is an ester at the end. R of the acidic amino acid ω-ester structural unit of the crosslinked polymer containing as a constituent a synthetic polyamino acid represented by
first converting the terminal ester in the active ester, and then amidating the ester by aminolysis,
A method for producing an adsorbent, which comprises introducing an amide group into R in the formula.