JPS648007B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing a vinyl polymer having an N-methylated cyclic peptide in its side chain.

It is known that fat-soluble proteins exist in cell membranes, which have properties similar to those of organic solvents with low polarity, and are involved in the complexation, transport, and reaction of metal ions, and the expression of physiological activities. The present inventors have conducted extensive research with the aim of obtaining a substance that can utilize these characteristics of fat-soluble proteins industrially, and have further invented a method for producing a vinyl polymer having a cyclic peptide in its side chain ( (Special Application No. 104378, Showa 52).

The present inventors have continued their research to obtain a polymer having more significant properties than the polymer obtained by the above invention, and have completed the present invention.
That is, the gist of the present invention is that cyclo(N〓
-Acryloyl-N〓 ^, 〓-dimethyl-L-lysylsarcosine) or a mixed monomer containing this and a vinyl monomer having a substituent that is easily conjugated with a double bond is polymerized in the presence of a radical polymerization catalyst. The present invention relates to a method for producing a vinyl polymer having an N-methylated cyclic peptide in a side chain.

The present invention will be explained in detail below.

Cyclo(N〓-acryloyl-N〓 ^, 〓-dimethyl-L-lysylsarcosine), which is a monomer used in the method of the present invention, is synthesized, for example, as follows.

First, this synthesis reaction is expressed as follows.

The above compound () is synthesized according to the method disclosed in the specification of Japanese Patent Application No. 52-104378 (Japanese Unexamined Patent Publication No. 54-38394). Moreover, this compound () was synthesized for the first time by the present inventors.

This compound () 976 mg (4 mmol),
5.5 g (24 mmol) of Ag ₂ O and 3 ml of methyl iodide
(48 mmol) was dissolved or suspended in dimethylformamide (60 ml) immediately after distillation, and the light was blocked.
Attach a drying tube and stir at room temperature for 24 hours. The mixture was filtered and the liquid was evaporated to dryness to dry the resulting oily substance, and the same reaction procedure as above was repeated twice to obtain cyclo(N〓-acryloyl-N〓 ^, 〓-dimethyl-L-lysylsarcosine. ) [Compound ()] was obtained. The yield is 1.1g, and the yield is 100%. The resulting compound () is a pale yellow oil and is extremely hygroscopic. This product exhibits the following solubility in various solvents.

Easily soluble: water, dimethyl sulfoxide, dimethylformamide, methanol, acetone, chloroform, tetrahydrofuran, dioxane, benzene Virtually insoluble: n-hexane, diethyl ether i.e., water, alcohol, dipolar aprotic solvents, halogenated hydrocarbons It is characterized by its good solubility in a wide range of solvents, including aromatic hydrocarbons.

The polymerization catalyst used in the method of the present invention may be any catalyst normally used in radical polymerization reactions, and specifically, aliphatic azo compounds such as azobisisobutyronitrile (hereinafter referred to as AIBN), benzoyl peroxide, etc. Examples include organic peroxides such as potassium persulfate, inorganic peroxides such as hydrogen peroxide, and redox polymerization catalysts using these catalysts in combination with reducing compounds.

In the method of the present invention, cyclo(N〓-acryloyl-
Comonomers to be copolymerized with N〓 ^, 〓-dimethyl-L-lysylsarcosine) include styrene, nuclear-substituted styrene; acrylic acid, methacrylic acid, or alkyl esters of these acids (for example, methyl, ethyl, n-propyl, n -butyl ester), amides, alkylamides; acrylonitrile, methacrylonitrile; vinylpyridine, and the like.

Next, examples of homopolymerization of the above monomers will be described.

Example 1 Cyclo(N〓-acryloyl-N〓 ^, 〓-dimethyl-L-lysylsarcosine) was dissolved in dimethylformamide to make a 50% by weight solution, and 3% by weight of AIBN was added to the above monomer. After nitrogen gas is passed through this solution to remove oxygen, the tube is sealed under reduced pressure. Heat the solution in the sealed tube to 80℃
Polymerize for 40 hours. When the resulting solution is poured into 20 times the weight of diethyl ether, a pale yellow polymer precipitates. This polymer is dissolved in ethanol and the solution is poured into diethyl ether to reprecipitate the polymer and purify it. The unreacted monomer was soluble in a dimethylformamide-diethyl ether mixed solvent or an ethanol-diethyl ether mixed solvent. The yield of the polymer is 83%, and the repeating units of the polymer are estimated to be as follows.

The IR spectra of the obtained polymer and raw material monomer are shown in FIG. Figure 1A shows monomers, namely cyclo(N〓-acryloyl-N〓 ^, 〓-dimethyl-L-
Figure 1B is a diagram showing the IR spectrum of the polymer obtained by the KBr tablet method, as indicated by a and b in Figure 1A.
Absorption based on C=C double bonds observed near 970 cm ^-1 and 1620 cm ^-1 was not observed in FIG. 1B, which confirmed the formation of a polymer. Figure 2 shows a 100MHz solution of polymer in deuterated chloroform.
It shows an NMR spectrum, where δ=
The sharp singlet signal appearing at 2.99 ppm is attributed to the three N-CH ₃ protons present per repeating unit, indicating that a vinyl polymer having the N-methylated cyclic peptide of the present invention in its side chain was obtained. is clear.

The solubility of the produced polymer in various solvents is as follows.

Extremely soluble: water, methanol, ethanol, chloroform, methylene chloride, dimethylformamide Easily soluble: isopropanol, dioxane, benzene Partially soluble: acetone, tetrahydrofuran,
Almost insoluble in ethyl acetate: diethyl ether As mentioned above, the solubility of the homopolymer according to the present invention is extremely high, and it dissolves well in water and many types of organic solvents. This property is due to the vinyl polymer having the corresponding N-unsubstituted cyclic peftide in the side chain (the above-mentioned patent application
This is in contrast to the homopolymer according to the invention of No. 52-104378, which is soluble only in water or a mixed solvent of water and dimethylformamide or dimethyl sulfoxide. That is, by N-methylating all three amide bonds per repeating unit, the solubility of the polymer was significantly improved.

Dichloroethane solution of the obtained polymer, 25°C
The intrinsic viscosity measured was 0.074.

Next, an example will be shown in which a copolymer is produced from cyclo(N〓-acryloyl-N〓 ^, 〓-dimethyl-L-lysylsarcosine) and a monomer having a substituent that is easily conjugated with a double bond.

Example 2 50% by weight of cyclo(N〓-acryloyl-N〓 ^, 〓-
To a dimethylformamide solution (equimolar mixture of the two monomers) containing dimethyl-L-lysylsarcosine) and 20% by weight of styrene, 3% by weight of AIBN relative to the monomers was added, and nitrogen gas was passed through the solution to remove oxygen. Afterwards, seal the tube under reduced pressure. The solution in the sealed tube was heated to 80°C and polymerized for 40 hours.
When this solution was poured into 10 times the weight of water, a white copolymer precipitated. The copolymer is purified by dissolving it in tetrahydrofuran and pouring the solution into water to reprecipitate the copolymer. Copolymer yield is 74%
The intrinsic viscosity measured in dichloroethane solution at 25°C was 0.11. The proportion of monomer [compound ()] in the copolymer calculated based on the nitrogen content by elemental analysis is approximately 26 mol%
It was hot. This shows that the relative reactivity of compound () in radical polymerization is lower than that of styrene, and that the reactivity of a vinyl compound having a cyclic peptide in its side chain hardly changes even when the amide bond is N-methylated.

The solubility of the copolymer in various solvents is as follows.

Very easily soluble: acetone, tetrahydrofuran, chloroform, methylene chloride, dioxane, benzene, dimethylformamide Easily soluble: ethanol, ethyl acetate Partially soluble: methanol, isopropanol Barely soluble: water, diethyl ether Obtained by the above method The resulting copolymers are also highly soluble in a wide range of organic solvents. A copolymer of a vinyl compound having a corresponding N-unsubstituted cyclic peptide in its side chain [the above compound ()] and styrene (the above-mentioned patent application
When the copolymer according to the invention of No. 52-104378 contains about 25 mol% of the above compound (), it is considered that it does not dissolve very well in dioxane, methylene chloride, benzene, etc., so it is recommended to use a monomer with N-methylated amide bonds. The increase in solubility of the copolymer by the method of the invention is evident. Comparing the solubility of the homopolymer and copolymer according to the present invention, the copolymer has low solubility in water, alcohol, etc., but is easily soluble in acetone, tetrahydrofuran, dioxane, benzene, etc. This solubility is thought to be due to the presence of copolymerized styrene units in the copolymer.

The IR spectrum (KBr tablet method) of the copolymer obtained in this example is shown in FIG. In this figure, the absorption near 1670 cm ^-1 (C in the figure) is assigned to the amide bond of cyclo(N〓-acryloyl-N〓 ^, 〓-dimethyl-L-lysylsarcosine), and at 700 cm
The absorptions near ^-1 and 750 cm ^-1 (d and e in the figure) are attributed to the phenyl group of styrene. In other words, the characteristic absorption of each comonomer is as shown in Figure 3.
Considering the observations in the IR spectrum and the solubility of the copolymer, it is clear that a true copolymer was obtained. That is, polystyrene is insoluble in alcohols, but the one obtained in this example is soluble.

The repeating units of this copolymer are estimated to be as follows.

The homopolymers and copolymers obtained by the method of the present invention are utilized in the following fields due to the N-methylated cyclic peptides in their side chains. For example, it is used for the removal of various metal ions (light metal ions, heavy metal ions), halogen molecules such as iodine, homopolymers are used in aqueous solutions and organic solvents, and copolymers are used for the removal of substances that can form complexes in organic solvents. can. In addition, homopolymers and copolymers with copper ions coordinated serve as catalysts for oxidation reactions (e.g., epoxide production by oxidation of olefins, aldehyde production by alcohol oxidation, etc.), and those with rhodium ions coordinated can be used for reduction. Reactions (e.g. production of alkanes by reduction of olefins, production of alcohols by reduction of ketones, etc.)
It can be used as a catalyst. In this case, as a catalyst supported on an asymmetric polymer, it can be expected to serve as a catalyst for asymmetric, substrate-selective oxidation and reduction reactions.

Homopolymers and copolymers of the above-mentioned compound () having a non-N-methylated cyclic peptide in the side chain obtained by the method of the present invention (according to the invention of Japanese Patent Application No. 104378/1982) Distinguishing features of the resulting polymers are that they have a significantly high coordination power for metal ions and that the metal salt complex has a high solubility in organic solvents.

What has been explained above and shown in the examples is related to typical examples to help the understanding of the present invention, and the present invention is not limited to these examples, and other modifications may be made within the gist of the invention. It is something that can be taken.

[Brief explanation of drawings]

Figures 1A and 1B are cyclo(N〓-acryloyl-N〓 ^, 〓dimethyl-L-lysylsarcosine), respectively.
and IR spectrum diagram of its homopolymer, 2nd
The figure shows the 100MHz NMR spectrum of the above homopolymer, and Figure 3 shows the cyclo(N〓-acryloyl-
FIG. 2 is an IR spectrum diagram of a copolymer of N〓 ^, 〓-dimethyl-L-lysylsarcosine) and styrene. In Figure 1 A, B and Figure 3, the vertical axis shows transmittance (%) and absorbance, the horizontal axis shows wavelength (10 ^-6 m) and wavenumber (cm ^-1 ), and in Figure 2, the vertical axis shows transmittance (%) and absorbance. Relative intensity, horizontal axis shows chemical shift (ppm).

Claims (1)

[Claims] 1 A mixed monomer containing cyclo(N〓-acryloyl-N〓 ^, 〓-dimethyl-L-lysylsarcosine) or a vinyl monomer having a substituent that is easily conjugated with a double bond is used as a radical polymerization catalyst. 1. A method for producing a vinyl polymer having an N-methylated cyclic peptide in its side chain, the method comprising polymerizing in the presence of an N-methylated cyclic peptide.