JP2003040932A - Optically active polyacrylamide macromonomer and polymer thereof, and separating agent and separation method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a new optically-active monomer, capable of expecting an excellent optical property, and a polymer thereof, and to provide a separating agent composed of this polymer and a separation method of an optically active material using this separating agent. SOLUTION: The new optically-active polyacrylamide macromonomer by general formula (1) (In the formula, R1 is a methyl group or an alkoxycarbonyl group, R2 is a phenyl group, a naphthyl group or a benzyl group, m is a number of 2-5,000, and the mark of * is an optically active carbon), the polymer thereof, the separating agent, composed of this polymer, of the optically active material, and the separation method of the optically active material using this separating agent, are provided.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an optically active polyacrylamide macromonomer, a polymer thereof, a separating agent comprising the polymer, and a separating method using the separating agent.

[0002]

2. Description of the Related Art Many optically active synthetic polymer substances used as functional materials such as separating agents for optical resolution, liquid crystals and nonlinear optical materials have been known. For example,
Optically active triphenylmethyl methacrylate polymer (JP-A-56-106907, JP-A-56-142216), optically active acrylic acid amide polymer (JP-A-56-167708), diphenyl methacrylate -2-pyridylmethyl (JP-A-57-209908), poly (meth) acrylamide compound having an optically active substituent on the side chain chemically bonded to the surface of silica gel (JP-A-63-001446), optically active Composition using various synthetic polymer compounds (Patent Document 1)
79230), optically active methacrylic acid ester polymers (JP 08-208749 A, JP 2001-114832 A) and the like are known.

[0003]

However, although each of these optically active polymers has unique properties, its application range is naturally narrow. For example, when the above-mentioned optically active polymer is used as a separating agent for an optically active substance, the separable racemic compound and usable solvent are limited. Therefore, in order to expand such application range, it is necessary to increase the kinds of novel optically active polymers.

The present invention has been made in view of the above circumstances, and is a novel optically active monomer, a polymer thereof, a separating agent comprising the polymer, and an optical using the separating agent, which are expected to have excellent optical properties. It is an object to provide a method for separating an active substance.

[0005]

[Means for Solving the Problems] In order to achieve the above-mentioned object, the present inventor has conducted extensive studies and, as a result, found a novel optically active polyacrylamide macromonomer, and further, a polymer thereof as an optical resolving agent. The inventors have found that they exhibit excellent performance and completed the present invention.

That is, the optically active polyacrylamide macromonomer of the present invention is a novel optically active monomer represented by the following general formula (1), and the polymer of the present invention is represented by the following general formula (2). Which is a polymer of the optically active monomer, the separating agent of the present invention is a separating agent of the optically active substance consisting of the polymer, and the separating method of the present invention is a method of separating an optically active substance using the separating agent. Is the way to do it.

[0007]

[Chemical 3]

(In the formula, R ₁ represents a methyl group or an alkoxycarbonyl group, R ₂ represents a phenyl group, a naphthyl group, or a benzyl group, m is a number in the range of 2 to 5000, and * indicates optical. Represents activated carbon.)

[0009]

[Chemical 4]

(In the formula, R ₁ represents a methyl group or an alkoxycarbonyl group, R ₂ represents a phenyl group, a naphthyl group, or a benzyl group, m and n are numbers in the range of 2 to 5000, and * marks Represents optically active carbon.)

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION The optically active acrylamide macromonomer of the present invention is a compound represented by the above general formula (1), and the production method thereof is not particularly limited to the present invention. It can be prepared by reacting the optically active polyacrylamide represented by the general formula (3) with 2-methacryloyloxyethyl isocyanate.

[0012]

[Chemical 5]

(In the formula, R ₁ represents a methyl group or an alkoxycarbonyl group, R ₂ represents a phenyl group, a naphthyl group, or a benzyl group, m is a number in the range of 2 to 5000, and * indicates an optical Represents activated carbon.)

The polymer of the optically active acrylamide macromonomer of the present invention is a compound represented by the above general formula (2), and the production method thereof is not particularly limited, but for example, the present invention is used. The macromonomer of the above general formula (1) can be prepared by radical polymerization in the presence of a radical initiator (reaction initiator).

The method of generating radicals is not limited to the method of adding the above-mentioned radical initiator, and for example, a method of irradiating with light, radiation or the like can be used.

The radical initiator is not particularly limited, but for example, azobisisobutyronitrile,
Azo compounds such as 2,2′-azobisisobutyrate and 4,4′-azobis (4-cyanovaleric acid), benzoyl peroxide, di-t-butyl peroxide, benzoyl peroxide, lauroyl peroxide, etc. And a redox system such as potassium persulfate and cerium ammonium nitrate, etc., and the amount used is preferably 0.01 to 10 mol% with respect to the raw material to be used in the reaction.

As the solvent used for the polymerization, any solvent can be used as long as it is an inert solvent for the reaction. Usually, a solvent that can sufficiently dissolve the raw materials and the reaction initiator used for the reaction is used. . Specific examples thereof include tetrahydrofuran (hereinafter abbreviated as THF), N, N-dimethylformamide (hereinafter abbreviated as DMF), dichloromethane, chloroform, benzene, toluene, xylene, and the like. 1 to 10 by weight of raw material
It is preferable to use about 0 times.

The reaction temperature varies depending on the types of raw materials and reaction initiators used in the reaction and is not particularly limited,
Usually, the range of 50 to 150 ° C is suitable.

The reaction time varies depending on the types of raw materials and reaction initiators and is not particularly limited, but usually the reaction is completed within a range of 1 hour to 240 hours.

After completion of the reaction, the polymer of the optically active polyacrylamide macromonomer of the present invention is obtained as a powder by dropping and crystallization of the reaction solution in a solvent having a low solubility of products such as hexane, heptane, methanol and ethanol. it can. In order to improve the purity, it may be dissolved in a solvent such as THF or DMF and then re-crystallized by adding it again to a solvent having a low solubility such as methanol. Incidentally, these solvents are
They may be used alone or as a mixture of two or more kinds of solvents.

The polymer of the optically active polyacrylamide macromonomer of the present invention can be used as a separating agent for an optically active substance.

The method of separating an optically active substance using the polymer of the optically active polyacrylamide macromonomer of the present invention is not particularly limited, but is represented by, for example, the above-mentioned general formula (2) as a raw material. The optically active polyacrylamide macromonomer is polymerized in the presence of a porous carrier having a vinyl group on the surface to chemically bond the polymer of the optically active polyacrylamide macromonomer of the present invention to the porous carrier. The optically active substance can be easily separated by high performance liquid chromatography using a column packed with the prepared separating agent.

The carrier for supporting the polymer of the optically active polyacrylamide macromonomer of the present invention is not particularly limited, and examples thereof include silica gel, alumina, crosslinked styrene, polysiloxane and the like. The carrier particles are 1 μm to 200 μm, and the average pore size is 10Å to 300Å
Those described above are preferable as the separating agent in high performance liquid chromatography.

The method for preparing the porous carrier having a vinyl group on the surface is not particularly limited. For example, silica gel is surface-treated with 3-aminopropyltriethoxysilane, and then 2-methacryloyloxyethylisocyanate is used. One that has been reacted with nato.

The supporting method is not particularly limited, but the polymer of the optically active polyacrylamide macromonomer of the present invention may be chemically bonded to a porous carrier, or the optically active polyacrylamide of the present invention may be used. A polymer of acrylamide macromonomer may be brought into contact with a porous carrier to be physically supported.

The amount of the optically active polyacrylamide macromonomer polymer supported on the carrier varies depending on the type and physical properties of the carrier used and is not particularly limited, but is usually 1 to 50% by weight with respect to the weight of the filler. It can be supported in the range of%.

The separating agent in which the polymer of the optically active polyacrylamide macromonomer of the present invention is supported on a porous carrier is applicable to the separation of optically active substances capable of hydrogen bonding, π-π interaction and the like. . For example, when used as a packing material for a column for high performance liquid chromatography, a normal phase system using hexane-isopropanol as an eluent,
It can be widely applied to any reversed phase system using alcohol-water or the like.

According to the embodiment described in detail above,
The present invention provides excellent optical properties, a novel optically active monomer, a polymer and a separating agent comprising the polymer, and a method for separating an optically active substance using the separating agent, (1) Easy to manufacture because it can be prepared by radical polymerization, (2) both a chemical bond and a physical bond are possible with a carrier, and (3) when a chemical bond type separating agent is used, the eluent is not limited. In addition, it can be used in both normal phase and reverse phase systems.

[0029]

EXAMPLES The present invention will be specifically described below with reference to examples, but it goes without saying that the present invention is not limited to these examples.

In the following examples, the average molecular weight was determined by gel permeation chromatography (SPD-10 manufactured by Shimadzu Corporation).
Calculated in terms of polystyrene according to A) and the optical rotation is made by JASCO
It is measured by DIP-140. Liquid chromatography LC-10AT manufactured by Shimadzu, UVD detector SPD-10A, and Chromatopack C-R8A were used to measure the separability of the prepared polymer of optically active acrylamide macromonomer.

Example 1 (S) -methylbenzylacrylamide (hereinafter
MBZAA) 1 g, 4,4′-azobis (4-cyanovaleric acid) (hereinafter abbreviated as ACPA) 80 mg and THF 5 mL were charged, and polymerization was carried out for 24 hours while shaking at 60 ° C. under a nitrogen atmosphere.

After completion of the reaction, the reaction solution was poured into 100 mL of methanol / water (2/1 _volume ) and the precipitate was collected by filtration.
It was dried at room temperature under reduced pressure. After drying, use the minimum amount of product
Dissolve in THF and again 100 mL of methanol / water (2/1
_volume ) and recrystallized. After recrystallization by the same method, it is dried at room temperature under reduced pressure to give poly (MBZA with a carbonyl group at the terminal.
A) (hereinafter referred to as PreMB-1) 0.95 g was obtained (yield 95
%).

Optical rotation [α] ₄₃₅ ²⁵ = -125.3 ° (C
= 1.0 g / dL, DMF) Molecular weight Mn = 11700 Polydispersity Mw / Mn =
1.62

Example 2 Using the same apparatus as in Example 1, 1 g of MBZAA, 5 mg of azobisisobutyronitrile (hereinafter abbreviated as AIBN), 18 mg of 2-mercaptoethanol and 5 mL of THF were charged and shaken at 60 ° C. for 24 hours. Polymerization was carried out, and after the same post-treatment operation as in Example 1, poly (MBZA
1 g of A) (hereinafter abbreviated as PreMB-2) was obtained (yield 100%).

Optical rotation [α] ₄₃₅ ²⁵ = -129.4 ° (C
= 1.0 g / dL, DMF) Molecular weight Mn = 3000 Polydispersity Mw / Mn =
1.62

Example 3 Using the same apparatus as in Example 1, (S) -phenylalanine ethyl ester acrylamide (hereinafter abbreviated as PAEAA) 1
g, ACPA 12 mg and THF 5 mL were charged, polymerization was carried out for 24 hours while shaking at 60 ° C., and after the same post-treatment operation as in Example 1, poly (PAEAA) having a carbonyl group at the terminal (hereinafter abbreviated as PrePAE-1). ) 0.98 g was obtained (yield 98%).

Optical rotation [α] ₄₃₅ ²⁵ = + 62.0 ° (C =
1.0 g / dL, DMF) Molecular weight Mn = 9100 Polydispersity Mw / Mn =
1.35

Example 4 Using the same apparatus as in Example 1, 1 g of PAEAA, 4 mg of AIBN,
13 mg of 2-mercaptoethanol and 5 mL of THF were charged, polymerization was carried out for 24 hours while shaking at 60 ° C., and after the same post-treatment operation as in Example 1, poly (PAEAA) having a hydroxyl group at the terminal (hereinafter referred to as PrePAE-2 Abbreviated) 0.95 g was obtained (yield 95%).

Optical rotation [α] ₄₃₅ ²⁵ = + 61.5 ° (C =
1.0 g / dL, DMF) Molecular weight Mn = 3100 Polydispersity Mw / Mn =
1.34

Example 5 In a 100 mL round-bottomed flask, 5 g of PreMB-1, 0.2 g of 2-methacryloyloxyethyl isocyanate, di-n-
Charge 20 mg of butyltin dilaurate and 50 mL of THF, and add 5
The reaction was carried out at 0 ° C for 24 hours.

After completion of the reaction, the reaction solution was concentrated under reduced pressure,
It was placed in a 100mL of methanol / water _{(2/1 v} olume). The precipitate was collected by filtration and dried under reduced pressure at room temperature. After drying, the product was dissolved in a minimum amount of THF and re-crystallized by adding it again to 100 mL of methanol / water (2/1 _volume ). Further, recrystallization was performed again by the same method and then dried at room temperature under reduced pressure to obtain a high molecular weight poly (MBZAA) macromonomer (hereinafter abbreviated as PMB-1) (conversion rate 100%).

Optical rotation [α] ₄₃₅ ²⁵ = -118.9 ° (C
= 1.0 g / dL, DMF) Molecular weight Mn = 12700 Polydispersity Mw / Mn =
1.40 Reduced viscosity η _red = 0.097 (DMF, 30 ° C)

Example 6 Using the same apparatus as in Example 5, 5 g of PreMB-2, 0.2 g of 2-methacryloyloxyethyl isocyanate, di-n
-Butyltin dilaurate (20 mg) and THF (50 mL) were charged and reacted at 50 ° C for 24 hours, and after the same post-treatment operation as in Example 5, a low molecular weight poly (MBZAA) macromonomer (hereinafter abbreviated as PMB-2) was obtained. (Conversion rate 90%).

Optical rotation [α] ₄₃₅ ²⁵ = -120.8 ° (C
= 1.0 g / dL, DMF) Molecular weight Mn = 3400 Polydispersity Mw / Mn =
1.50 Reduced viscosity η _red = 0.092 (DMF, 30 ° C)

Example 7 Using the same apparatus as in Example 5, 5 g of PrePAE-1, 0.2 g of 2-methacryloyloxyethyl isocyanate, di-n
-Butyltin dilaurate (20 mg) and THF (50 mL) were charged and reacted at 50 ° C for 24 hours, and after the same post-treatment operation as in Example 5, a high molecular weight poly (PAEAA) macromonomer (hereinafter abbreviated as PPAE-1) was obtained. (Conversion rate 100%).

Optical rotation [α] ₄₃₅ ²⁵ = + 60.8 ° (C =
1.0 g / dL, DMF) Molecular weight Mn = 12900 Polydispersity Mw / Mn =
1.21 Reduced viscosity η _red = 0.058 (DMF, 30 ° C)

Example 8 Using the same apparatus as in Example 5, 5 g of PrePAE-2, 0.2 g of 2-methacryloyloxyethyl isocyanate, di-n
-Butyltin dilaurate (20 mg) and THF (50 mL) were charged, the reaction was carried out at 50 ° C for 24 hours, and after the same post-treatment operation as in Example 5, a low molecular weight poly (PAEAA) macromonomer (hereinafter abbreviated as PPAE-2) was obtained. (Conversion rate 95%).

Optical rotation [α] ₄₃₅ ²⁵ = + 59.9 ° (C =
1.0 g / dL, DMF) Molecular weight Mn = 3900 Polydispersity Mw / Mn =
1.22 Reduced viscosity η _red = 0.032 (DMF, 30 ° C)

Example 9 Into a polymerization tube, 5 of the macromonomer PMB-1 prepared in Example 5 was added.
00 mg, AIBN 0.2 mol% and THF 1 mL were charged, and polymerization was carried out for 24 hours while shaking at 60 ° C. in a nitrogen atmosphere.

After completion of the polymerization, the reaction solution was poured into 100 mL of THF, the precipitate was collected by filtration, washed with THF and dried under reduced pressure. After drying, the precipitate was dissolved in 2 mL of DMF, and 100 mL of
The mixture was poured into a THF / methanol (8/2 _volume ) mixed solution for recrystallization. Further, recrystallization was performed again by the same method, and then dried at room temperature under reduced pressure to obtain 350 mg of the target poly (PMB-1) (yield 70%).

Optical rotation [α] ₄₃₅ ²⁵ = -119.0 ° (C
= 1.0 g / dL, DMF) Reduced viscosity η _red = 0.141 (DMF, 30 ° C)

Example 10 Using the same apparatus as in Example 9, 500 mg of macromonomer PMB-2 prepared in Example 6, 0.2 mol% of AIBN and 1 mL of THF were used.
Was charged and polymerized for 24 hours while shaking at 60 ° C. in a nitrogen atmosphere, and after the same post-treatment operation as in Example 9, 425 mg of the target poly (PMB-2) was obtained (yield 85%). .

Optical rotation [α] ₄₃₅ ²⁵ = -135.3 ° (C
= 1.0 g / dL, DMF) Reduced viscosity η _red = 0.146 (DMF, 30 ° C)

Example 11 Using the same apparatus as in Example 9, 500 mg of macromonomer PPAE-1 prepared in Example 7, 0.2 mol% of AIBN and 1 m of THF were used.
Charge L and shake under nitrogen atmosphere at 60 ° C for 24
After time-polymerization and the same post-treatment as in Example 9, 400 mg of the target poly (PPAE-1) was obtained (yield 80%).

Optical rotation [α] ₄₃₅ ²⁵ = + 71.8 ° (C =
1.0 g / dL, DMF) Reduced viscosity η _red = 0.137 (DMF, 30 ° C)

Example 12 Using the same apparatus as in Example 9, 500 mg of macromonomer PPAE-2 prepared in Example 8, 0.2 mol% of AIBN and 1 m of THF were used.
Charge L and shake under nitrogen atmosphere at 60 ° C for 24
After time-polymerization and the same post-treatment operation as in Example 9, 425 mg of the target poly (PPAE-2) was obtained (yield 85%).

Optical rotation [α] ₄₃₅ ²⁵ = + 82.4 ° (C =
1.0 g / dL, DMF) Reduced viscosity η _red = 0.135 (DMF, 30 ° C)

Reference Example 1: Preparation of silica gel having vinyl group on the surface Silica gel (TSK-GEL SI100 manufactured by Tosoh Corp., average particle size 5 μm) was placed in a 100 mL eggplant flask equipped with a reflux condenser.
m, average pore size 100 Å) 10 g, charged with 3-aminopropyltriethoxysilane 14 mL and toluene 80 mL, 24
Refluxed for hours. After cooling the reaction product, it was filtered, washed with toluene, acetone, and methanol in this order, and dried to obtain 3-aminopropyltriethoxysilane-treated silica gel.

Then, in a 100 mL eggplant-shaped flask, 8 g of silica gel treated with 3-aminopropyltriethoxysilane,
2-methacryloyloxyethyl isocyanate 16mL
And 80 mL of dichloromethane were charged and reacted at 35 ° C. for 36 hours. After completion of the reaction, filtration, followed by washing with dichloromethane, acetone and methanol in this order and drying,
A silica gel having a vinyl group on the surface was obtained.

Examples 13 to 16: Preparation of silica gel chemically bound to polymacromonomer and its column packing In a Schlenk tube of 50 mL, 1 g of silica gel having a vinyl group on the surface prepared in Reference Example 1, Example 5 Macromonomers (PMB-1, PMB-2, PPAE-1, PPAE-2) prepared in ~ 8.
5 g, AIBN 10 mg and THF 10 mL were charged, and the reaction was carried out under nitrogen atmosphere while shaking at 60 ° C. for 24 hours. After completion of the reaction, the reaction product was filtered, washed with THF, acetone, and methanol in this order and dried. In this way, silica gel to which the desired polymacromonomer was chemically bound was obtained.

The weight of the polymacromonomer chemically bonded to silica gel was calculated by the following operation.
The polymacromonomer prepared in Examples 9 to 12 and the silica gel having a vinyl group on the surface prepared in Reference Example 1 were mixed in an appropriate weight ratio, and the infrared spectroscopic spectrum was measured.
A calibration curve was prepared from the absorption intensity ratio of the absorption due to the phenyl group in the polymacromonomer at 0 cm ⁻¹ and the absorption due to the silica gel at 800 cm ⁻¹ . Then Examples 13-1
The infrared spectroscopic spectrum of the silica gel chemically bound to the polymacromonomer prepared in 6 was measured, and the supported amount of the polymacromonomer chemically bound to the silica gel was calculated using the calibration curve prepared above.

After dispersing the prepared silica gel chemically bound to the polymacromonomer in methanol, a stainless steel column of 2 mm (ID) × 150 mm (L) was used with a high-pressure pump and a flow rate of 1.0 to 2.0 mL / min, maximum pressure 20
It was filled with 0 kg / cm ² .

The theoretical plate number of the obtained column was measured by using methanol as an eluent and eluting with toluene. The theoretical plate number was calculated by the following formula.

Theoretical plate number (N) = 5.54 × [Tr / (W
_1/2 )] ² Tr = holding time (sec) W _1/2 = full width at half maximum (mm)

Table 1 shows the amount (supported amount) of the polymacromonomer chemically bound to Silyaker and the theoretical plate number of the prepared column.

[0066]

[Table 1]

Comparative Example 1 A 50 mL Schlenk tube was charged with 1 g of silica gel having vinyl groups on the surface prepared in Reference Example 1, 0.5 g of PAEAA as a raw material for preparing a macromonomer, 10 mg of AIBN and 10 mL of THF, and the mixture was kept at 60 ° C. under a nitrogen atmosphere. The reaction was carried out while shaking for 24 hours. After completion of the reaction, the reaction product is filtered, then THF,
Acetone and methanol were washed in this order and dried. Thus, silica gel chemically bound to poly (PAEAA) was obtained. The loading amount of poly (PAEAA) on silica gel is 11.
It was 8%.

After dispersing the prepared silica gel chemically bound to poly (PAEAA) in methanol, a stainless steel column of 2 mm (ID) × 150 mm (L) was used with a high-pressure pump and a flow rate of 1.0 to 2.0 mL. / Min, maximum pressure 200k
It was filled with g / cm ² . The theoretical plate number of the obtained column is 460.
Met.

Examples 17 to 20 Using the columns prepared in Examples 13 to 16, various racemates were separated under the conditions shown in Table 2. The results are shown in Table 2.
Shown together.

[0070]

[Table 2] Remarks 1 Racemate (1): Menthol racemate (2): Mandelic acid Remarks 2 Mobile phase 50/50: Methanol / water (vol / v)
mobile phase 95/5: n-hexane / 2-propanol (vol)
/ Vol)

The chromatograms of Examples 19 and 20 were analyzed by using the column prepared in Comparative Example 1, and the eluent was n-
Hexane / 2-propanol (95/5), flow rate 0.1 mL /
It is shown in FIG. 1 together with a chromatogram obtained by analyzing mandelic acid at min.

From these results, the separating agent composed of the polymer of the optically active polyacrylamide macromonomer obtained according to the present invention has a higher chiral recognition ability than the conventional separating agents composed of the optically active polyacrylamide. It is clear that it has a wide range of applications.

[0073]

INDUSTRIAL APPLICABILITY The present invention provides a novel optically active monomer having excellent optical properties, a polymer thereof, a separating agent comprising the polymer, and a method for separating an optically active substance using the separating agent. In addition, since it can be prepared by radical polymerization, it is easy to produce. Both a carrier and a chemical bond or a physical bond are possible. It has the effect that it can be used with both phase systems.

[Brief description of drawings]

FIG. 1 is a trihedral view showing chromatograms of Examples 19 and 20 in comparison with a chromatogram of a conventional technique in which mandelic acid was analyzed by using the column prepared in Comparative Example 1. (A) is a chromatogram of Example 19 of the present invention, (B) is a chromatogram of Example 20 of the present invention,
(C) is a conventional chromatogram.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) G01N 30/48 G01N 30/48 SW 30/88 30/88 W // G01N 27/447 27/26 315F F-term (reference) 4D017 BA03 CA13 CA14 CB01 DA03 EA05 4J027 AA08 AJ01 AJ02 CD00 4J100 AM21P BA20 BC43 BD11 JA15

Claims (7)

[Claims] 1. An optically active polyacrylamide macromonomer represented by the following general formula (1). [Chemical 1] (In the formula, R ₁ represents a methyl group or an alkoxycarbonyl group, R ₂ represents a phenyl group, a naphthyl group, or a benzyl group, m is a number in the range of 2 to 5000, and * represents an optically active carbon. Represents.) 2. A polymer of an optically active polyacrylamide macromonomer represented by the following general formula (2). [Chemical 2] (In the formula, R ₁ represents a methyl group or an alkoxycarbonyl group, R ₂ represents a phenyl group, a naphthyl group, or a benzyl group, m and n are numbers in the range of 2 to 5000, and * indicates an optically active group. Represents carbon.) 3. A separating agent comprising the polymer of the optically active polyacrylamide macromonomer according to claim 2. 4. A separating agent comprising the carrier of the polymer of the optically active polyacrylamide macromonomer according to claim 2. 5. A method for separating an optically active substance by using the separating agent according to claim 3 or 4. 6. A high performance liquid chromatography column packed with the separating agent according to claim 3 or 4. 7. A method for separating an optically active substance by high performance liquid chromatography using the high performance liquid chromatography column according to claim 6.