Claims
- 1. A separating agent which comprises particles having a particle size of 1 micron to 10 mm and essentially consisting of a polysaccharide derivative having 30-100% of the hydroxyl groups thereof substituted with a substituent selected from the group consisting of an acyl group of the formula (1): ##STR80## wherein R represents an atomic group having a nucleus comprising a conjugated pi-bond system in which the number of bonds interposed between (1) a first atom contained in said atomic group and bonded with the carbonyl and (2) a second atom contained in the pi-bond system and most distant from said first atom is at least 5 by the shortest route, wherein said polysaccharide derivative is cellulose tri-.beta.-naphthoate.
- 2. A separating agent which comprises a carrier having a particle size of 1 micron to 10 mm and a pore size of 10 A to 100 microns and a polysaccharide derivative having 30-100% of the hydroxyl groups thereof substituted with a substituent selected from the group consisting of an acyl group of the formula (1): ##STR81## wherein R represents an atomic group having a nucleus comprising a conjugated pi-bond system in which the number of bonds interposed between (1) a first atom contained in said atomic group and bonded with the carbonyl and (2) a second atom contained in the pi-bond system and most distant from said first atom is at least 5 by the shortest route, wherein said polysaccharide derivative is cellulose tri-.beta.-naphthoate.
Priority Claims (1)
| Number |
Date |
Country |
Kind |
| 59-59365 |
Mar 1984 |
JPX |
|
(Effects of the invention)
This application is a divisional application of U.S. Ser. No. 07/246,449, filed Sept. 19, 1988, now U.S. Pat. No. 4,879,038, which is a continuation-in-part of U.S. Ser. No. 716,791, filed Mar. 27, 1985, now abandoned.
The invention relates to a separation agent which comprises a polysaccharide derivative having an acyl or a carbamoyl group as a substituent for a hydroxyl group. It has a conjugated .pi.-bond system. The separation agent of the invention is useful for separation of various chemical substances, especially optical resolution of optical isomers. In addition, it serves for separation of geometrical isomers and polymers having different molecular weight ranges from each other. They have not easily been separated in the state of the prior art.
The resolving agent of the present invention can be used for separation of all sorts of chemical substances, particularly for optical resolution of them.
It has been well known that optical isomers of a chemical compound have effects different from each other in vivo generally. Therefore, it is an important problem to obtain chemically pure compounds for the purposes of improving medicinal effects per unit dose of the compounds or removing adverse reactions thereof and damage from them in medical, agricultural and biochemical fields. A mixture of optical isomers has been optically resolved by preferential crystallization process or diastereomer process. However, varieties of the compounds capable of being optically resolved by these processes are limited and these processes require a long time and much labor. Under these circumstances, development of a technique of conducting the optical resolution by an easy chromatographic process has eagerly been demanded.
Chromatographic optical resolution has been investigated from old times. However, resolving agents developed heretofore have problems that they have only an unsatisfactory resolution efficiency, compounds to be resolved should have a specific functional group or their stability is only poor. Thus, it has been difficult to optically resolve all sorts of compounds with satisfactory results.
An object of the present invention is to provide a resolving agent having a chemical structure different from those of known resolving agents and, therefore, resolving characteristics different from those of the known ones or a higher faculty of discriminating and identifying the optical isomers.
Particularly, the asymmetric structure of the polysaccharide is amplified by modifying it with a substituent having a sufficient length so as to obtain a higher faculty of identifying optical isomers.
The above-mentioned object of the present invention is attained by an agent for separation which contains as an effective component a polysaccharide derivative having as a substituent an acyl group of the following formula (1) or a carbamoyl group of the following formula (2): ##STR2## wherein R represents an atomic group having a nucleus comprising a conjugated .pi.-bond system in which the number of bonds interposed between an atom contained therein and bonded with the carbonyl or amino group and an atom contained in the .pi.-bond system and most distant from said atom is at least 5 even in the shortest route.
The resolving agent of the invention exhibits preferably different powers of adsorbing different optical isomers of a given compound.
In the identification of the asymmetric structure of a cellulose derivative such as cellulose tribenzoate or cellulose trisphenylcarbamate, an asymmetric space formed by adjacent substituents on C.sub.2 and C.sub.3 of the cellulose may contribute most greatly to the identification. Therefore, the inventors thought that the enlargement of said space would increase the faculty of identifying optical isomers. After intensive investigations, the inventors have found surprisingly that the polysaccharide derivatives having the above-mentioned substituents have quite excellent faculty of identifying optical isomers. The present invention has been completed on the basis of this finding.
The term "polysaccharide" herein involves any optically active polysaccharide selected from the group consisting of synthetic, natural and modified natural polysaccharides. Among them, those having highly regular bonds are preferred. Examples of them include .beta.-1, 4-glucans (celluloses), .alpha.-1, 4-glucans (amylose and amylopectin), .alpha.-1, 6-glucan (dextran), .beta.-1, 6-glucan (pustulan), .beta.-1, 3-glucans (such as curdlan and schizophyllan), .alpha.-1, 3-glucan, .beta.-1, 2-glucan (Crown gall polysaccharide), .beta.-1, 4-galactan, .beta.-1, 4-mannan, .alpha.-1, 6-mannan, .beta.-1, 2-fructan (inulin), .beta.-2, 6-fructan (levan), .beta.-1, 4-xylan, .beta.-1, 3-xylan, .beta.-1, 4-chitosan, .beta.-1, 4-N-acetylchitosan (chitin), pullulan, agarose and alginic acid. Still preferred ones are those capable of easily yielding highly pure polysaccharides, such as cellulose, amylose, .beta.-1, 4-chitosan, chitin, .beta.-1, 4-mannan, .beta.-1, 4-xylan, inulin and curdlan.
These polysaccharides have a number-average degree of polymerization (average number of pyranose or furanose rings in the molecule) of at least 5, preferably at least 10. Though there is provided no upper limit of the degree of polymerization, it is preferably 500 or less from the viewpoint of easiness of the handling.
In the substituents of the polysaccharide derivatives of the following formulae according to the present invention: ##STR3## R represents an atomic group comprising a conjugated .pi.-bond system having at least a given length and capable of conjugation with the carbonyl or carboxyamino group. The term "at least a given length" herein means that the number of bonds interposed between an atom bonded the carbonyl or carboxyamino group and an atom contained in the conjugated .pi.-bond system and most distant from said atom is at least 5 in even the shortest route. The term ".pi.-bond system" refers to not only usual double and triple bonds, but also lone electron pairs and vacant orbitals capable of conjugation with them. For example, in a p-methoxybenzoate group of the following formula: ##STR4## the conjugated .pi.-bond system corresponding to R is conjugated with the carbonyl group. However, in this structure, the number of bonds interposed between an atom bonded with the carbonyl group, i.e., C.sub.1, and an atom contained in the conjugated .pi.-bond system and most distant from said atom (C.sub.1), i.e., an oxygen atom of the methoxy group, is 4. Therefore, this structure is not included in the present invention. Examples of R included in the invention are as follows:
(1) substituted phenyl group such as those shown below: ##STR5##
(2) phenylethenyl and phenylethynyl groups: ##STR6##
(3) condensed aromatic ring and condensed hetero aromatic ring groups such as those shown below: ##STR7##
(4) condensed quinones such as those shown below: ##STR8## as well as substituted derivatives of them. The number, position and variety of the substituents are not particularly limited.
30 to 100%, preferably 85 to 100%, of the hvdroxyl groups of the polysaccharides forming the derivatives should be acylated or carbamoylated in the present invention. The balance of the hydroxyl groups may be present in the form of free hydroxyl groups or they may be esterified, etherified or carbamoylated so far as the resolving capacity of the resolving agent is not damaged.
When a styryl or phenyl group is introduced into a cellulose or amylose triphenylcarbamate derivative, a high liquid-crystallizability or crystallizability is expectable, since the side chains are arranged regularly and the rigidity of the main chain is increased. Therefore, it was believed that these triphenyl derivatives might have an interesting optical resolution power.
Since an interesting change in the optical resolution power was observed when chloroform was added to the eluent, the effect of using chloroform with these polysaccharide derivatives was also investigated.
It also was believed that when ##STR9## is introduced into position 4 of a cellulose triphenylcarbamate derivative, the conjugated system of the phenyl group would become larger and the characteristics of the side chain as the mesogenic group would become more remarkable. On the basis of this idea, cellulose tris[4-(2-phenylethynyl)phenylcarbamate] was examined with respect to its optical resolution power.
The optical resolution powers of triphenylcarbamates having an phenoxy group as a substituent also were investigated.
To synthesize the polysaccharide derivative used in the present invention, a corresponding polysaccharide is pretreated suitably, if necessary, and then reacted with an acylating agent or carbamoylating agent. The acylating agents include usually corresponding acid halides, acid anhydrides and mixed anhydrides with other strong acids. Usually, the reaction is conducted in the presence of a catalyst comprising a tertiary amine, particularly pyridine or an acidic substance. The carbamoylating agents include usually corresponding isocyanates. The reaction proceeds easily in the presence of a catalyst comprising a tertiary amine or a Lewis acid. In producing mixed derivatives, the substituted polysaccharide is reacted with these reagents or, alternatively, the polysaccharide is reacted with these reagents and then with other esterifying, etherifying or carbamoylating agent (see, for example, "Dai-Yuki Kagaku", 'Tennen Kobunshi Kagaku I and II", published by Asakura Book Store, and R. L. Whistler "Methods in Carbohydrate Chemistry" III, IV and V, published by Academic Press).
The resolving agent of the present invention is used for the purpose of resolving compounds and optical isomers thereof generally according to a chromatographic method such as gas, liquid or thin layer chromatographic method. Further, the resolving agent may be used in membrane resolution method.
In using the resolving agent of the present invention in liquid chromatography, there may be employed a method wherein the powdered resolving agent is packed in a column, a method wherein a capillary column is coated with the resolving agent, a method wherein a capillary is made from the resolving agent to use the inner wall thereof and a method wherein the resolving agent is spun and bundled up to form a column. Among them, the method wherein the powdered resolving agent is employed is most general.
The resolving agent is powdered preferably by crushing or by forming beads. The particle size which varies depending on the size of a column or plate used is 1 .mu.m to 10 .mu.m, preferably 1 to 300 .mu.m. The particles are preferably porous.
It is preferred to support the resolving agent on a carrier so as to improve the durability thereof to pressure, to prevent swelling or shrinkage thereof due to solvent exchange or to reduce the number of theoretical plates. The suitable size of the carrier which varies depending on the size of the column or plate used is generally 1 .mu.m to 10 .mu.m, preferably 1 to 300 .mu.m. The carrier is preferably porous and has an average pore diameter of 10 .ANG. to 100 .mu.m, preferably 50 to 50,000 .ANG.. The amount of the resolving agent to be supported is 1 to 100 wt. %, preferably 5 to 50 wt.%, based on the carrier.
The resolving agent may be supported on the carrier by either chemical or physical means. The physical means includes one wherein the resolving agent is dissolved in a suitable solvent, the resulting solution is mixed with a carrier homogeneously and the solvent is distilled off by means of a gaseous stream under reduced pressure or heating and one wherein the resolving agent is dissolved in a suitable solvent, the resulting solution is mixed homogeneously with a carrier and the mixture is dispersed in a liquid incompatible with said solvent by stirring to diffuse the solvent. The resolving agent thus supported on the carrier may be crystallized, if necessary, by heat treatment or the like. Further, the state of the supported resolving agent and accordingly its resolving power can be modified by adding a small amount of a solvent thereto to temporarily swell or dissolve it and then distilling the solvent off.
Both porous organic and inorganic carriers may be used, though the latter is preferred. The suitable porous organic carriers are those comprising a high molecular substance such as polystyrene, polyacrylamide or polyacrylate. The suitable porous inorganic carriers are synthetic or natural products such as silica, alumina, magnesia, titanium oxide, glass, silicate or kaolin. They may be surface-treated so as to improve their affinity for the resolving agent. The surface treatment may be effected with an organosilane compound or by plasma polymerization.
In liquid or thin layer chromatography, any developer may be used except those in which the resolving agent is soluble or which are reactive with the resolving agent. In case the resolving agent has been bound to the carrier by the chemical process or it has been insolubilized by crosslinking, any solvent other than a reactive liquid may be used. As a matter of course, it is preferred to select the developer after examination of various developers since the resolving characteristics of chemical substances or optical isomers vary depending on the developer used.
In the thin layer chromatography, a layer having a thickness of 0.1 to 100 mm and comprising the resolving agent in the form of particles of about 0.1 .mu.m to 0.1 mm and, if necessary, a small amount of a binder is formed on a supporting plate.
In the membrane resolution process, the resolving agent is used in the form of a hollow filament or film.
The resolving agent of the present invention containing the polysaccharide having an acyl or carbamoyl substituent as the effective component is effective for the resolution of various compounds. Particularly, it is quite effective for the resolution of optical isomers which are quite difficult to resolve. Either one of the optical isomers to be resolved is selectively adsorbed on the resolving agent.
US Referenced Citations (14)
Non-Patent Literature Citations (2)
| Entry |
| The Merck Index, Eighth Edition, Merck & Co., 1968, p. 135. |
| Optical Resolution on Polymers by Yoshio Okamoto, A publication presented at the 49th Spring Annual Meeting of the Chemical Society of Japan, Mar. 10, 1984, pp. 1-4. |
Divisions (1)
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Number |
Date |
Country |
| Parent |
246449 |
Sep 1988 |
|
Continuation in Parts (1)
|
Number |
Date |
Country |
| Parent |
716791 |
Mar 1985 |
|
Patent Grant
4966694
