JPH053860B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Application Field] The present invention relates to a method for obtaining each enantiomer of an optically active dihydric alcohol by optically resolving it. Although the optically resolved alcohol can be used as it is for its physiological activity, it is also used as an intermediate in organic synthesis to obtain a number of optically active compounds. Optical isomers of compounds with chirality usually have different physiological actions, and this is the main reason why optically active compounds are required. Recently, the use of optically active compounds in optical materials such as liquid crystals has been considered, and there is also a great demand for them as reagents for research. As an example of using an optically active dihydric alcohol as it is, it is known that 1,3-butanediol is expensive for diabetes treatment, but it is known that the L-form is effective (Seijinbyo Kenkyu).
5 , 91 (1976). Optically active dihydric alcohols have extremely wide applicability as optically active intermediates in organic synthesis due to their difunctional properties. For example, optically active 1,2-propanediol is used in the synthesis of optically active amino acids (Ann. Quim. 75 , 958 (1979)) and in the synthesis of amino acids by asymmetric reduction. ₂ PCH ₂
-CHCH ₃ PPh ₂ ) (J.Amer.
Chem.Soc., 100 , 5491 (1978), and is also used in various organic syntheses via optically active methyloxirane (propylene oxide). Optically active 1,3-butanediol is used as a raw material for the same asymmetric reduction catalyst as above (J.Amer.Chem.
Soc., 100 , 5491 (1978). Compounds derived from this may be used as a fragrance, but it has been reported that the D and L forms have different scents (West German Patent Publication No. 2455975). The S form of 1,4-pentanediol is brefeldin A.
It is used as a partial skeleton in synthesis (Tetrahedron Letters (1979) 3021), and optically active 1,5-hexanediol can be used as a partial skeleton of macrolide compounds, diplodialide, etc. In addition, optically active substances such as 2,3-butanediol, 2,4-pentanediol, trans-1,2-cycloalkanediol, and trans-1,2-cycloalkanedimethanol are raw materials for the synthesis of asymmetric reaction catalysts, respectively. (J.Amer.
Chem.Soc., 103 , 2280 (1981). These are only some of the examples that have already been used in actual synthesis, but they demonstrate the usefulness of these optically active dihydric alcohols, and furthermore, various useful optical compounds can be derived from them. Partial skeletons can be found. [Prior Art] As mentioned above, each enantiomer of an asymmetric compound often has different effects on living organisms, and for this reason optical resolution and asymmetric synthesis methods are the biggest challenge in current organic chemistry. It has become one of the Conventional methods for obtaining optically active substances include asymmetric synthesis, optical resolution after induction into diastereomers, and chemical production methods using enzymes or microorganisms. Asymmetric synthesis methods have the problem of not being able to obtain compounds with high optical purity of the target compound, and diastereomer derivatization cannot be easily achieved using the method of deriving diastereomers. However, there was a problem in that equimolar amounts of different types of optically active compounds were required. Biochemical methods have the disadvantage that it is difficult to identify appropriate enzymes and microorganisms. [Problems to be solved by the invention] The situation is the same with dihydric alcohols, which are the object of the present invention, and there are many attempts to obtain them from the corresponding carbonyl compounds by asymmetric hydrogenation. The optical yield is still not satisfactory.
By converting optically active substances that exist in large quantities in nature,
One method is to obtain such compounds; for example, lactic acid, glutamic acid, malic acid, etc. can be used as raw materials for these dihydric alcohols. However, starting from these natural products does not always have suitable starting materials for both enantiomers, and requires multi-step chemical transformations and cumbersome reagents, making them unsuitable for industrial production. There were many cases. On the other hand, 2,4-pentanediol,
Compounds with a _C2 axis of symmetry, such as 1,2-cyclohexanediol and 1,2-cyclopentanediol, have good crystallinity, so they can sometimes be resolved by the diastereomer method, but this is an easy method for industrialization. It wasn't. Since racemic forms of these dihydric alcohols are easily available, if they can be separated by chromatography either as they are or after a simple chemical conversion, they can be used as chromatographic fixatives. As long as the phase is sufficiently stable and inexpensive, industrialization is easy;
The contribution it makes is extremely large. [Means for Solving the Problems] As a result of extensive studies, the present inventors found that when a separation agent containing an optically active polysaccharide derivative as an active ingredient uses these dihydric alcohols as ester derivatives or aralkyl derivatives, It was discovered that this method is extremely effective in optical resolution, leading to the present invention. The polysaccharide separating agent used here has an abundance of raw materials and can be prepared relatively easily. It also has excellent optical stability and has properties suitable for industrial chromatographic separation. That is, the present invention relates to a method for optically resolving dihydric alcohols, which comprises derivatizing an enantiomeric mixture of dihydric alcohols and then optically resolving the derivatized mixture using a separating agent containing a polysaccharide derivative as an active ingredient. The dihydric alcohol used in the present invention has 15 carbon atoms.
A compound consisting of the following, preferably having 2 to 6 carbon atoms, each having two alcoholic hydroxyl groups bonded to different carbon atoms (a hydroxyl group bonded to a carbon atom having 4 σ bonds): In addition to this hydroxyl group, there are also heteroatoms such as halogen, sulfur, oxygen, and nitrogen, aryl groups, and unsaturated bonds (double,
(triple bond), etc., but compounds that do not have any functional groups other than hydroxyl groups are generally more difficult to divide than compounds that do have them.
In such cases, the dividing method according to the invention is of greater importance. An example of such a dihydric alcohol is etc. In the above formula, R represents a lower alkyl group such as methyl, ethyl, isopropyl or propyl. According to the present invention, optical resolution of these dihydric alcohols is carried out with one or both of the two hydroxyl groups modified with an acyl group, aralkyl group, aryl group, or sulfonyl group. Modification here specifically means replacing hydrogen in the alcoholic hydroxyl group with the above atomic group, and two hydrogen atoms may each be replaced with different atomic groups. Examples of the atomic groups are shown below.
HCO, CH ₃ (CH ₂ ) _o CO (n=0, 1, 2, 3,
4, 5, 6, 7, 8) (CH ₃ ) ₂ CHCO, (CH ₃ ) ₃
CCO，Cl ₃ CCO，

[Table] When preparing an ester by modifying a dihydric alcohol with an acyl group, it is common to treat it with the corresponding acid halide or acid anhydride, but carbamate esters can be prepared by treating with the corresponding isocyanate. It will be done. Benzyl ethers are obtained by reacting benzyl halides with bases. Phenyl ether is produced by treating a halide, sulfonate, or epoxide corresponding to the desired dihydric alcohol with a phenolate anion, but care must be taken as the stereochemistry is often reversed at this time. The divided derivative may be directly subjected to the next chemical conversion, but if you want to regenerate the dihydric alcohol, ester derivatives can be decomposed with water or alcohol in the presence of an acid or alkali, and ether derivatives can be decomposed with water or alcohol in the presence of an acid or alkali. should be reduced by contact. The separating agent used in the present invention contains polysaccharides and derivatives thereof as active ingredients. The polysaccharide referred to here may be any optically active polysaccharide, including synthetic polysaccharides, natural polysaccharides, and modified natural polysaccharides, but it is preferably a highly regular homoglycan with a constant bonding pattern. It is something. More preferably, cellulose, amylose, β-1,4-chitosan, chitin, β-1,4-mannan, β-1,
These include 4-xylan, inulin, α-1,3-glucan, β-1,3-glucan, and the like. A polysaccharide derivative is one in which some or all, preferably 85% or more, of the hydrogen atoms on the hydroxyl groups of the polysaccharide are replaced with other atomic groups. The atomic group here is

【formula】 【formula】 [Effect]

The reason why optical resolution of dihydric alcohol derivatives is effectively achieved by the method of the present invention is not clear, but the reason is that the aromatic ring or ester group on the ether group effectively interacts with the polysaccharide derivative, and It is thought that optical resolution is achieved by reflecting chirality. However, the reason why dihydric alcohol derivatives exhibit especially superior resolution compared to monohydric alcohols is that two such interacting groups work cooperatively, making it possible to recognize chiraity more effectively. It shows what will happen. [Effects of the Invention] The present invention realizes the acquisition of optically active forms of various dihydric alcohols, which are important industrial raw materials, using inexpensive raw materials, simple chemical conversion, and simple chromatography technology. It is expected that this method will make a significant contribution to the synthesis of many optically active compounds using . [Examples] Hereinafter, the present invention will be specifically explained with reference to Examples, but it goes without saying that the present invention is not limited to these. In addition, as a column for liquid chromatography, silica gel obtained by treating a cellulose derivative with diphenylsilane (Lichrospher Si manufactured by MERCK) is used.
1000) with approximately 22% weight-loaded filler on the length 25
cm, packed in a stainless steel column with an inner diameter of 0.46 cm. In addition, the detection of the eluting optical isomer was performed using an ultraviolet detector (Shimadzu SPD-) and a differential refractometer (Showa Denko Shodex).
RI SE 31) and a photometer equipped with a flow cell (JASCO Corporation DIP 181). The parameter α used in the examples is defined as follows. k' (capacity ratio) = retention time of a certain optical isomer - dead time / dead time α (separation coefficient) = k' of the more strongly adsorbed optical isomer / k' of the weaker adsorbed optical isomer. The graphical conditions are as follows unless otherwise noted. Eluent: hexane-2-propanol (9:1),
Temperature: 20°C Flow rate: 0.5 ml/min or less: The compound, the polysaccharide derivative that is the active ingredient of the separation agent, the obtained α, and if it is clear, the optical isomer that elutes earlier is in the eluent. The positive and negative numbers shown in the bracket are shown in the box.

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Claims (1)

[Claims] 1 An enantiomeric mixture of an optically active dihydric alcohol is combined with an optically inactive acyl group, an aralkyl group,
1. A method for optical resolution of dihydric alcohols, which is characterized in that the optical resolution is carried out using a separating agent modified with an aryl group or a sulfonyl group and containing a polysaccharide derivative as an active ingredient.