JP2979143B1 - Amino acid polymer having carboxybetaine type structure in side chain and method for producing the same - Google Patents

Abstract

A carboxybetaine-type polymer electrolyte having biodegradability and a method for synthesizing the same are provided. SOLUTION: An amino acid polymer having a carboxybetaine type structure in a side chain. After reacting an amino acid polymer having a carboxyl group in the side chain with an alkylamine having a substituted amino group, the obtained product is reacted with an alkoxycarbonylalkyl halide, and then the obtained product is subjected to hydrolysis treatment. A method for producing the amino acid polymer as described above.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a novel amino acid polymer and a method for producing the same. Since the amino acid of the present invention has a carboxybetaine type structure having both positive and negative charged groups in the side chain, inorganic salts and organic salts can be incorporated in an aqueous solution. Therefore, it can be used as a water retention agent in deserts, a salt remover in salt-affected areas, sanitary products, drug sustained-release carriers, biocompatible materials, and the like. further,
Since the polymer of the present invention has a peptide bond and an amide bond in the main chain and the side chain, respectively, it is a biodegradable material suitable for environmental problems.

[0002]

2. Description of the Related Art A structure having both a quaternary ammonium group and a carboxyl group in one molecule is called a carboxybetaine type structure and has a property different from that of a normal electrolyte molecule. For example, a polymer electrolyte having such a charged group is
It is known that the molecular chain is expanded by adding a salt. For this reason, since this polymer can take in a salt in an aqueous solution, it is considered that it can be used as a new soil modifier, a sanitary product, and the like. Heretofore, such betaine-type polymer electrolytes having both charged groups have been poly [N- (3-sulfopropyl) -N-methacryloxyethyl-N, N-dimethylammonium betaine] and poly [4- (2 -Acrylamide-2-methylpropyldimethylammonio)
Butanates] are known, but all have a main chain of an alkyl chain. Therefore, there is no biodegradability, and there is a possibility that a new environmental problem such as garbage may occur. Therefore, development of a carboxybetaine-type polymer electrolyte having biodegradability is required.

[0003]

SUMMARY OF THE INVENTION An object of the present invention is to provide a carboxybetaine type polymer electrolyte having biodegradability and a method for synthesizing the same.

[0004]

Means for Solving the Problems The present inventors have made intensive studies to solve the above-mentioned problems, and as a result, have completed the present invention. That is, according to the present invention, the following general formula (1)
Carboxy solid on the side chain consisting of the repeating units shown
A glutamic acid polymer having an in-type structure is provided.

Embedded image (Wherein, R ¹ is an alkylene group having 1 to 12 carbon atoms, R ² and
And R ³ are an alkyl group having 1 to 6 carbon atoms, and R ⁴ is a carbon atom having 1 to 6 carbon atoms.
It represents an alkylene group of Formulas 1 to 6. Also, according to the present invention,
For example, an glutamic acid polymer may have an amino group having a substituted amino group.
After reacting the alkylamine, alcohol
Reaction with the oxycarbonylalkyl halide,
Wherein the hydrolyzed product is subjected to a hydrolysis treatment.
Glutamic acid having a carboxybetaine-type structure in the side chain
A method for making a polymer is provided.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION The amino acid polymer of the present invention includes a homopolymer and a copolymer, and can be produced using an amino acid represented by the following general formula (2) as a raw material.

Embedded image In the above formula, R ⁵ and R ⁶ represent hydrogen or a lower alkyl group.
You. In this case, the lower alkyl group preferably has 1 to 6 carbon atoms.
Or 1-3. The amide represented by the general formula (1)
Glutamic acid and its lower alkyl esters
And the like.

To produce the amino acid polymer of the present invention,
First, a homopolymer or a copolymer of the glutamic acid is synthesized. When synthesizing a copolymer, as the copolymer component, various amino acids, for example, glycine, alanine,
Monoaminomonocarboxylic acids such as valine, leucine and isoleucine; oxyamino acids such as serine and threonine; sulfur-containing amino acids such as cysteine, cystine and methionine; phenylalanine and proline; In this copolymer, the content of the amino acid component represented by the general formula (2) is 10 to 100 mol%, preferably 40 to 100 mol%, based on all amino acid components constituting the copolymer. is there. The glutamic acid polymer is conventionally known, and some of the glutamic acid polymers are already sold. In the present invention, those sold products can also be used.

Next, the amino acid polymer has the following general formula:
The alkylamine having a substituted amino group represented by (3) is reacted.

Embedded image In the above formula, R ¹ has 1 to 12 carbon atoms, preferably 2 to 2 carbon atoms.
5 represents an alkylene group, and R ² and R ³ represent a lower alkyl group having 1 to 6 carbon atoms, preferably 1 to ³ carbon atoms. In this reaction, a primary amino group (NH ₂ ) is bonded to a carboxyl group contained in the amino acid polymer to form an amide bond (CO 2
NH) is formed.

Next, a lower alkoxycarbonylalkyl halide represented by the following general formula (4) is used as a quaternizing agent in the amino acid polymer having a substituted amino group (dialkylamino group) in the side chain obtained by the above reaction. Is reacted.

Embedded image In the above formula, X represents a halogen such as chlorine or bromine, preferably bromine, and R ⁴ has 1 to 6, preferably 1 to 5 carbon atoms.
More preferably, it represents a 1-3 alkylene group, and R ⁷ represents a lower alkyl group having 1-6, preferably 1-3 carbon atoms. In this reaction, the lower alkoxycarbonylalkyl halide is bonded to the side chain amino group of the amino acid polymer by a dehydrohalogenation reaction to form a quaternary amino group (ammonium group).

Next, the alkoxycarbonyl group ( COOR ⁷ ) in the amino acid polymer having an ammonium group to which a lower alkoxycarbonylalkyl group obtained by the above reaction is hydrolyzed to form a carboxyl group (COO ⁷ ).
⁻ ). As described above, a glutamic acid polymer having a carboxyl betaine structure in the side chain (hereinafter, also referred to as amino acid polymer A) can be obtained.

The number average degree of polymerization n of the amino acid polymer A of the present invention is from 10 to 1,000, preferably from 100 to 1,000. Among the glutamic acid polymers of the present invention, preferred are those having a carboxybetaine-type structure represented by the following general formula (5) .

Embedded image (Wherein, R ¹ is an alkylene group having 1 to 12 carbon atoms, R ² and
And R ³ are an alkyl group having 1 to 6 carbon atoms, and R ⁴ is a carbon atom having 1 to 6 carbon atoms.
It represents an alkylene group of Formulas 1 to 6. )

[0011] In glutamic acid polymer of the present invention, glutamine and more preferred are represented by the following general formula (6)
It is an acid homopolymer.

Embedded image In the above formula, R ¹ , R ² , R ³ and R ⁴ have the same meaning as described above.
Have. n is a number average degree of polymerization of 10 to 1000, preferably
Is from 100 to 1,000.

[0012]

Next, the present invention will be described in more detail with reference to examples.

Example 1 As a sample, Compound 1 (poly (methyl-L-glutamate) molecular weight of 60,000) in 1,2-dichloroethane solution
Was air-dried on a glass plate, followed by vacuum drying to remove the solvent. The following reaction was performed on this sample. 1.8 g of Compound 1 is immersed in a mixed solution of 75 ml of 3-dimethylaminopropylamine and 10 ml of methanol, and
For 9 days. After filtration, the product was washed with a large amount of acetone. After dissolving in pure water, freeze-drying to give compound 2
I got Compound 1 and compound 2 were subjected to IR measurement. As for compound 1, the IR absorption peak was 154.
0, 1635, 1740 cm ^-1 , but compound 2
For a 1546 and 1652 ^-1, was observed in compounds 1, the peak of the ester bond 1740 cm ^-1 had disappeared completely in compound 2. ^{According to 1} HNMR measurement, the resonance peak was 1.68, 2.21, 2.3.
6, 3.19, and 4.17 ppm, indicating that Compound 2 was obtained. In addition, the result of elemental analysis
C: H: N = 54.96: 9.25: 18.96 (calculated value: 56.34: 8.92: 19.72). Regarding the quaternization reaction of the amino group from the compound 2 to the compound 3, an experiment was carried out by changing the amount of the solvent, the amount of the ethyl 4-bromobutyrate and the reaction time as shown in Table 1 below, and the reaction conditions were changed. investigated. The reaction rate is the backbone on protons and protons of the methyl groups attached to the quaternary ammonium group ¹
It was determined from the integrated value of the HNMR resonance peak. When acetonitrile was used as soot and reacted at 50 ° C. for 5 days,
The conversion reached 85-87%. Therefore, this sample was used as Compound 3. Specifically, 1.0 g of compound 2
And 12 g of ethyl 4-bromobutyrate in 135 ml of acetonitrile at 50 ° C. for 5 days to convert the amino group in the side chain into a quaternary ammonium salt. After the reaction, the product was precipitated using acetone, filtered, and washed with acetone. After dissolving in pure water, lyophilization was performed to obtain Compound 3. Compound 3 I
R absorption peaks are 1545, 1656, and 1727 cm.
^-1 . ^{The 1} H NMR resonance peak was 1. 27,
2.39, 2.53, 2.92, 3.13, 4.19,
4.38 ppm. The resonance peak at 2.92 ppm is the proton of the methyl group attached to the protonated amino group. Thus, this peak disappears upon ultrafiltration of compound 3 against pure water and reappears with the addition of acid. This polymer was mixed with a mixed solution of methanol, 2-propanol and 5 M NaOH (2/2/1 vol.
1 / vo1 / vo1) and hydrolyzed the side chain ester bond at room temperature for 3 days. After neutralization with HCl, ultrafiltration (fraction molecular weight 10,000) was performed. To this solution is added an ion exchange resin, which is then dialyzed (fraction molecular weight: 3,500)
Was carried out for 2 days and lyophilized to obtain Compound 4. The IR absorption peaks were 1576 and 1654 cm ⁻¹ , and the peak derived from the ester bond found in Compound 3 was 1727 cm 2.
^-1 completely disappeared in compound 4. The resonance peaks of ¹ HNMR were 1.76, 1.99, 2.25, and 2.3.
7, 3.09, 3.31, 4.31 ppm, and when DCI is added, 2.03, 2.05, 2.37,
2.52, 2.91, 3.12, 3.30, 3.35,
3.37, 3.40, and 4.35 ppm. Also,
The result of elemental analysis was C: H: N: 52.99: 9.2.
4: 13.78 (calculated: 56.20: 8.41: 14.
59 when the conversion was 87%).

[0014]

[Table 1]

The reactions performed in Example 1 including the chemical formulas are as follows.

[0016]

Embedded image

Example 2 The viscosity of an aqueous solution of Compound 4 was measured using an Ubbelohde viscometer while titrating HCl at 25 ° C. while changing the pH. As a result, a maximum of the viscosity occurred at a pH of around 3. Until the pH is around 3, the viscosity increases due to the increase in the repulsion by the positive charge of the quaternary ammonium group due to the decrease in the degree of dissociation of the carboxyl group accompanying the decrease in the pH. It is considered that the repulsion between charged groups was suppressed and the viscosity was reduced by the effect of the added salt.

[0018]

The amino acid polymer of the present invention is biodegradable, has a carboxybetaine type structure in the side chain, and is used as a salt removing agent, a sanitary product, a drug sustained release carrier, a biocompatible material and the like. Used.

──────────────────────────────────────────────────の Continued on the front page (58) Field surveyed (Int. Cl. ⁶ , DB name) C08G 69/00-69/50 CA (STN)

Claims (2)

(57) [Claims] 1. A repeating unit represented by the following general formula (1)
Having a carboxybetaine-type structure in the side chain
Rutamic acid polymer. Embedded image (Wherein, R ¹ is an alkylene group having 1 to 12 carbon atoms, R ² and
And R ³ are an alkyl group having 1 to 6 carbon atoms, and R ⁴ is a carbon atom having 1 to 6 carbon atoms.
It represents an alkylene group of Formulas 1 to 6. ) 2. A glutamic acid polymer having a substituted amino group.
After reacting the resulting alkylamine, the resulting product
Reacted with lower alkoxycarbonylalkyl halide
And then subjecting the resulting product to a hydrolysis treatment.
A method for producing a polymer according to claim 1, characterized in that: