JPH07101885A - Optically resolving membrane - Google Patents

Abstract

PURPOSE:To obtain an optically resolving membrane effective for optically resolving medicines and organic compounds having complicated structure to which an optically resolving membrane have not, heretofore been much applied, capable of optically resolving various compounds. CONSTITUTION:This optically resolving membrane is obtained by forming a membrane from a carbamate derivative of an azobenzene residue-containing polysaccharide such as a carbamate derivative of a cellulose containing an azobenzene group only at the 6-position of the cellulose.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a novel optical division film. More specifically, it relates to an optical resolution film having an optically active polysaccharide having a photoresponsive aromatic azo group as a chiral selector.

[0002]

BACKGROUND OF THE INVENTION Optical isomers refer to optical isomers that have the same physical and chemical properties but different optical properties, and they usually have different effects on living organisms. It is known. Therefore, in the fields of medicine, agrochemicals, biochemistry-related industries, etc., it is extremely important to prepare an optically pure compound in order to improve drug efficacy per unit, side effects, prevention of drug damage, etc. ing.

To date, numerous resolving means have been investigated for the separation, ie optical resolution, of mixtures of optical isomers. However, there are merits and demerits in any means, and they cannot be decisive means. In particular, optical resolution by a film has been actively researched in recent years, and is one of the fields that are expected in the future. However, most of the target compounds of the optical resolution film to date are mainly amino acids and amino acid derivatives, and there are no films that can be expected to be versatile (JP-A-62-180701, JP-A-4-110026, Japanese Patent Laid-Open No. 5-25060, Desalina
tion, 90 (1993) 127).

[0004]

As a result of intensive studies to solve the above problems, the inventors of the present invention have found that a carbamate derivative of a polysaccharide having an azobenzene residue, particularly an azobenzene residue only at the 6-position of cellulose. The inventors have found that a film having a carbamate derivative of cellulose as a chiral selector has excellent asymmetric discrimination ability, and completed the present invention. That is, the present invention provides an optical resolution film comprising a film of a carbamate derivative of a polysaccharide having an azobenzene residue.

The carbamate derivative of a polysaccharide having an azobenzene residue used in the present invention is a polysaccharide aromatic compound in which the hydroxyl group of the polysaccharide is substituted with a group represented by the following general formula (I) having a photoresponsive azobenzene residue. A carbamate derivative is preferable, and a carbamate derivative of cellulose having an azobenzene residue only at the 6-position of cellulose is particularly preferable.

[0006]

[Chemical 1]

(However, it may have a substituent on the benzene ring in the above formula.) As the carbamate derivative of cellulose used in the present invention, especially the number average polymerization degree of cellulose (included in one molecule The average number of glucose units) is preferably 5 or more, more preferably 10 or more. There is no particular upper limit to the number average degree of polymerization, but those having a number average degree of polymerization of 500 or less are preferred from the viewpoint of easy handling.

Examples of the carbamoyl group constituting the carbamate derivative of the polysaccharide of the present invention include those represented by the above general formula (I). However, 50% or more of the 6-position hydroxyl group possessed by cellulose is the carbamoyl group and urethane. Those which form a bond and the remaining hydroxyl groups are partially or wholly substituted with other substituents are particularly preferable. In addition, the other substituents referred to herein include a substituted phenyl carbamate, a substituted benzoate,
It is a substituted benzyl ether or the like, and by using these substituents, the asymmetric discrimination ability of the cellulose derivative can be made different from that when substituted by a single substituent. In the above general formula (I), the benzene ring may have substituents (alkyl, halogen, alkoxy, aryl, etc.), and the presence of these substituents can change the asymmetric discrimination ability of the polysaccharide derivative. . A typical example of the polysaccharide carbamate derivative used in the present invention is a cellulose carbamate derivative having a repeating unit represented by the following formula (II).

[0009]

[Chemical 2]

For the synthesis of the polysaccharide 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 the corresponding isocyanate with a polysaccharide 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. Further, the isocyanate can be easily synthesized, for example, by causing phosgene to act on the amino group of the corresponding aniline derivative.

The optical resolution film in the present invention is obtained by forming the above-mentioned polysaccharide carbamate derivative into a film. The film forming method may be a known method or a known method. For example, a method of evaporating a good solvent after spreading a dope solution obtained by dissolving a polysaccharide carbamate derivative in a good solvent on a Teflon plate, a metal plate, a glass plate, or a porous support, for example,
There is a method in which a PTFE (polytetrafluoroethylene) film or the like is dipped in a dope solution and then pulled up and dried, or a method in which the dope solution is applied on a support so that the film thickness becomes uniform. Also, by controlling the substitution reaction with a film having a functional group such as a hydroxyl group (for example, polyvinyl alcohol),
It is also possible to bind the polysaccharide carbamate derivative having the remaining hydroxyl group with a bifunctional crosslinking agent.

In the film of the polysaccharide carbamate derivative of the present invention thus obtained, the azobenzene residue is light (h
ν) or heat (Δ), as shown in the following equation, −N =
Cis-trans isomerization occurs reversibly with respect to the N-double bond. Therefore, the optical resolution film of the present invention can control the chiral discrimination ability by light or heat.

[0013]

[Chemical 3]

[0014]

EFFECTS OF THE INVENTION By utilizing the film material of the present invention, various compounds can be optically resolved, and in particular, drugs and organic compounds having a complicated structure, which have not been targeted so far for optical resolution films, can be used. It is effective for optical division.

[0015]

EXAMPLES The present invention will now be described in detail with reference to Examples, but the present invention is not limited thereto.

Example 1 (1) Cellulose 2,3-bis (3,5-dimethylphenylcarboxyl )
Lubamate) -6- (4-phenylazophenylcarba
Mate) (1-CPAPC) (a) Synthesis of 6-O-tritylcellulose 5 g (30.5 mmol) of microcrystalline cellulose (Merk), 20
80 ml of g (71.7 mmol) trityl chloride (Tokyo Kasei)
After heating and stirring in dry pyridine at 80 ° C for 24 hours, the temperature was returned to room temperature, the yellow homogeneous reaction solution was added to 400 ml of methanol, and the formed precipitate was collected by filtration to obtain 6.20.
g, yield 50.0%. The elemental analysis values are shown below.

C: 57.73%, H: 8.05% (b) Synthesis of cellulose 2,3-bis (3,5-dimethylphenylcarbamate) -6- (4-phenylazophenylcarbamate) (1-CPAPC) Dry pyridine (115 ml) in 6-O-trityl cellulose
(5.5 g) was reacted with excess 3,5-dimethylphenylisocyanate (8.8 g) at 95 ° C for 26 hours to quantitatively give cellulose 6-O-trityl-2,3-bis (3,5-dimethylphenylcarbamate). Got Next, the trityl group was removed in methanol containing 1% hydrochloric acid to give cellulose 6-hydroxy-2,3-bis (3,5-dimethylphenylcarbamate).
Was quantitatively obtained. Take 1.5 g of this, and in 30 ml of dry pyridine, add excess 4-phenylazophenyl isocyanate.
(1.6 g) was reacted at 90 ° C. for 18 hours. Then, the mixture was poured into methanol, filtered and dried, and then the solvent was separated with ethyl acetate to remove by-product urea. The soluble portion was poured into excess methanol, filtered and dried to give 1.5 g of the title compound,
Obtained in 63% yield. As a result of elemental analysis, it was found that 70% of the 6-position was substituted with a 4-phenylazophenylcarbamate group and 30% was substituted with a 3,5-dimethylphenylcarbamate group. Purification was carried out by dissolving 1.5 g of the obtained polymer in 60 ml of tetrahydrofuran and reprecipitating it in 800 ml of methanol. The elemental analysis values are shown below.

C: 65.52%, H: 5.74%, N: 7.97
% (2) Preparation of trans membrane 1 ml of a tetrahydrofuran solution (50 mg / ml) of trans 1-CPAPC obtained by the above method was added to a commercially available Teflon membrane filter (25 mmφ; 0.10 μm pore; ADVANTEC).
Was irradiated with ultrasonic waves, the film was taken out and dried under a nitrogen stream. The polymer weight on the membrane was 15 mg.

(3) Asymmetric Adsorption Racemic 1- (9-anthryl) -2,2,2-trifluoroethanol and oxprenolol hexane and 2
-The above trans membrane was immersed in 4 ml of a 9: 1 mixed solution of propanol (1 mg / ml) at 15 ° C for 90 minutes, then the membrane was taken out and the surface of the membrane was quickly washed with hexane: 2-propanol = 9: 1. , Hexane: 2-propanol = 7 /
The membrane was immersed in 3.3 ml for 30 minutes at 30 ° C. to desorb the compound adsorbed on the membrane. This solution is used as an HPLC column for separation of optically active substances CHIRALCEL OD (Daicel Chemical Industries: 0.46 cmφ × 25 cm)
Was used to determine the optical purity (% ee) and the adsorption amount (% by weight). The results are shown in Table 1, which shows the optical purity of the adsorbate, and Table 2, which shows the amount of the adsorbate with respect to the polymer on the film.

Example 2 (1) Conversion of trans 1-CPA PC into cis form Trans 1-CPA obtained in Example 1 was irradiated with light using a 400 W high pressure mercury lamp equipped with a filter manufactured by Toshiba Glass Co.
PC was isomerized to cis form. For trans-cis to cis-isomerization, stack two UV-D36C and UV-35 filters,
It was performed by irradiating with light of 400 nm. Regarding this isomerization by light, the absorption spectrum accompanying the photoisomerization and
When the change in the CD spectrum was investigated, the absorption spectrum showed that the π-
π ^* transition, absorption at 440 nm, which is considered to be derived from cis n-π ^* transition, is observed, and clear isosbestic points are 299 nm and 413 nm.
present in nm. In the CD spectrum, a peak derived from a trans-azobenzene residue was found at around 370 nm, the intensity became smaller as the cis formation proceeded, and no peak was found in this region in the cis form. These spectra changed reversibly with isomerization.

(2) Preparation of cis membrane cis 1 obtained by cis isomerization by the above method
A cis membrane was prepared by casting a tetrahydrofuran solution (10 mg / ml) of -CPAPC (cis content of 65%) on a Teflon membrane filter placed on a glass plate and drying under nitrogen. Polymer weight on the membrane is 6-11 mg
Met.

(3) Asymmetric Adsorption According to Example 1, using the above cis membrane, racemic 1-
Asymmetric adsorption of (9-anthryl) -2,2,2-trifluoroethanol and oxprenolol was performed. Result is,
Table 1 shows the optical purity of the adsorbate, and Table 2 shows the amount of the adsorbate with respect to the polymer on the film.

Example 3 The cis 1-CPAPC film obtained in Example 2 was treated with heat and Y-47.
It was converted to a trans form again by irradiating light of 470 nm or more using a filter (conversion rate 100%). Similar asymmetric adsorption was performed using this membrane. The results are shown in Table 1, which shows the optical purity of the adsorbate, and Table 2, which shows the amount of the adsorbate with respect to the polymer on the film.

[0024]

[Table 1]

[0025]

[Table 2]

Claims (2)

[Claims] 1. An optical resolution film formed by forming a film of a carbamate derivative of a polysaccharide having an azobenzene residue. 2. The optical resolution film according to claim 1, wherein the carbamate derivative of a polysaccharide having an azobenzene residue is a carbamate derivative of cellulose having an azobenzene residue only at the 6-position of cellulose.