JP2001220392A - How to determine the absolute configuration of a chiral compound - Google Patents

Abstract

(57) [Summary] [Problem] To provide a general-purpose, absolute configuration of a new chiral compound in which the kinds of basic groups to be bound can accurately and easily determine the absolute configuration of a chiral compound. Provide a decision method. The present invention has a structure of a porphyrin dimer cross-linked by a carbon chain, and extends from the carbon at a cross-linking position of one porphyrin ring of the dimer structure along the outer periphery of the porphyrin ring. Metal porphyrins with a bulky substituent on at least one of the second carbons more than an ethyl group,
A chiral compound having an asymmetric carbon to which a basic group capable of coordinating to a metal of the other porphyrin ring in the dimer structure of the metal porphyrin or an asymmetric carbon at a position adjacent to the carbon atom to which the basic group is bonded And determining the absolute configuration of the chiral compound from the sign of the Cotton effect by circular dichroism spectrophotometric analysis.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a method for determining the absolute configuration of a chiral compound.

[0002]

2. Description of the Related Art Heretofore, attempts have been made to determine the absolute configuration of an external ligand by the induced cotton effect as determined by circular dichroism (CD) spectrophotometry. For example, the following reports have been made.

(1) J.I. Am Chem. Soc. , 1
997, 119, 6345-6359; Yashima,
T. Matsushima and Y. Okamoto found that for macromolecules that take a helical structure in the presence of a chiral compound, there is a good correlation between the sign of the circular dichroism-induced Cotton effect induced by the ligand (chiral compound) and the absolute configuration of the ligand. I have found it.

However, since the induction of the helical structure results from the formation of an ion pair between the carboxylate group of the polymer side chain and the ammonium group of the ligand, this method is applicable to general monoamines and amino alcohols, Is not applicable.

(2) J. J. Am Chem. Soc. , 1
998,120,6185-6186, X. Huan
g, B.C. H. Rickmann, B .; Borhan,
N. Berova, K .; Nakanishi reports the induction of circular dichroism by chiral ligands in porphyrin dimers peeled by long cross-linked chains. There is a correlation between the sign of the Cotton effect and the absolute configuration of the ligand, but this system is applicable because circular dichroism is induced only when one molecule of ligand is coordinated to two porphyrin units at the same time. Compounds are limited to bifunctional compounds such as diamines and amino alcohols.

(3) Bull. Chem. Soc. , J
pn. , 1998, 71, 1117-1123, M.P. Takeuchi, T .; Imada, S.M. Shinkai reports that a porphyrin dimer having a phenylboronic acid unit exhibits circular dichroism in the presence of various sugars.

This method is applicable only to a polyol (polyhydric alcohol) which forms a bond with a boronic acid,
Moreover, it is not a method that can directly determine the absolute configuration around a specific (one) chiral center.

(4) J.I. Chem. Soc. , Dalt
on Trans. , 1999, 11-12, H .; Tsukube, M .; Hosokubo. M. Wada, S.M. Shinoda, H.S. In Tamiaki, we have shown that tris (β-diketonato) complexes of lanthanides show circular dichroism in the presence of chiral amino alcohols. However, in this system, monoamines and monoalcohols do not induce chirality.

(5) Org. Lett. , 1999,
1, 861-864, S.M. Zahn, J .; W. Cana
ry revealed that the absolute configuration of amino acids and amino alcohols could be determined by the circular dichroism of the copper complex.

However, this method is applicable only to amino acids and amino alcohols capable of bidentate coordination with copper, and not to monoamines and mono alcohols.

As described above, there has been no report on a method for determining the absolute configuration of a chiral compound having a wide range of basic groups including a monoalcohol.

An X-ray diffraction method is known as a method for determining the absolute configuration of a chiral compound, but this method is limited to a crystalline one.

[0013]

DISCLOSURE OF THE INVENTION The present invention overcomes the limitations and problems of the prior art described above, and can accurately determine the absolute configuration of a chiral compound having a wide variety of basic groups bonded thereto,
Moreover, it is a main object of the present invention to provide a general-purpose method for determining the absolute configuration of a new chiral compound that can be easily determined.

[0014]

In view of these problems of the prior art, the present inventors have made intensive studies and as a result found that the above object can be achieved by adopting a specific method, and finally completed the present invention. Reached.

That is, the present invention relates to the following method for determining the absolute configuration of a chiral compound.

1. A porphyrin dimer structure cross-linked with a carbon chain, wherein at least one of the second carbons along the outer periphery of the porphyrin ring from the carbon at the cross-linking position of one of the porphyrin rings in the dimer structure An asymmetric carbon or a basic group in which a basic group capable of coordinating to a metal of the other porphyrin ring of the dimeric structure of the metal porphyrin is bonded to a metal porphyrin having a bulky substituent at least at the ethyl group. Coordinating a chiral compound having an asymmetric carbon at a position adjacent to the bonded carbon atom, and determining the absolute configuration of the asymmetric carbon of the chiral compound from the sign of the Cotton effect by circular dichroism spectrophotometric analysis. Method for determining the absolute configuration of a chiral compound.

2. Bulk substituents more than ethyl group,
1) a hydrocarbon group having 2 or more carbon atoms, 2) an oxygen-containing substituent,
3) The method according to the above-mentioned item 1, which is a nitrogen-containing substituent, 4) a halogen atom or 5) a halogenated hydrocarbon group.

3. Chiral compounds include 1) primary amines,
2) Secondary amines, 3) primary diamines, 4) secondary diamines, 5) monoalcohols or 6) amino alcohols.

4. The metalloporphyrin has the following formula (I)

[0020]

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The method according to any one of the above items 1 to 3, wherein

[0022]

DETAILED DESCRIPTION OF THE INVENTION In the present invention, the above-described circular dichroism (CD) spectrophotometric analysis method is applied. In this analysis, the sign of the induced cotton effect is the same as that of the external ligand. It will depend on the absolute configuration of the asymmetric carbon. CD exciton chirality method (Harada,
N. : Nakanishi, K .; Circular
Dichroic Spectroscopy-Exc
ition coupling in 0rganic
Stereochemistry; University
y Science Books; Mill Ball
ey, 1983. , Nakanishi, K .; Ber;
ova, N .; In Circular Dichroi
sm; Principles and Applica
Woods, R. Tions; , Ed; VCH Pub
lishers; New York, 1994; pp3
According to 61-398), when two interacting electron transition moments are arranged clockwise, positive chirality is created, and when they are arranged counterclockwise, negative chirality is obtained.

The present invention is based on the finding that there is a certain correspondence between the absolute configuration of the asymmetric carbon (R-form or S-form) of the chiral compound as a ligand and the sign of the Cotton effect. Was completed.

In principle, the determination of the absolute configuration is expressed by the following equation (I).

[0025]

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The case of zinc porphyrin represented by the following formula will be described as an example.

This zinc porphyrin has an ethylene bridged chain (—CH ₂ —CH ₂₎ of one porphyrin ring of a dimer structure.
-) are those having both the ethyl group of the second carbon atom of (b) (b) (-CH 2 CH 3) carbon atoms of the crosslinked position (a) along the outer periphery of the porphyrin ring by.

Of course, in the present invention, the ethylene cross-linked chain has a carbon chain (preferably a carbon chain having 2 to 3 carbon atoms) such as an alkylene chain having various carbon atoms, and is bonded to a porphyrin ring. Metal porphyrins having a bulky substituent on at least one of the ethyl group sites (b) and (b) can also be used as appropriate.

The present inventors have proposed that the above-mentioned zinc octaethylporphyrin dimer (ZnD) is, for example, an alcohol or an amine represented by the following formula:

[0030]

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It has been found that the coordination changes the conformation from syn type to anti type.

Further, it has been found that when a new chiral alcohol or amine is coordinated, asymmetry is induced in the anti-type conformer, and a circular dichroism as shown in FIG. 1 is obtained. The mechanism of asymmetry induction is explained as shown in FIG. That is, the largest substituent (X) bonded to the α carbon of the ligand and the ethyl group (E
It can be understood that the steric hindrance during t) causes a twist in the orientation of the porphyrin, resulting in the appearance of circular dichroism based on the exciton interaction between the porphyrins.

The relationship between the absolute configuration of the ligand (R or S) and the sign of the Cotton effect can be shown in Table 1, for example. From Table 1, it can be seen that there is a certain correspondence between the configuration around the α-carbon of the amino group or the hydroxy group and the sign of the Cotton effect. As shown in FIG. 1, a shorter wavelength peak indicates the second Cotton effect, and a longer wavelength peak indicates the first Cotton effect. The sign of each peak may be positive or negative. For example, in the case of 1-phenylethylamine in FIG. 1, if the absolute configuration is (R), the sign of the second Cotton effect is positive, the sign of the first Cotton effect is negative, and the absolute configuration is (S). If so, these signs are reversed. That is, when the sign of the first Cotton effect is positive, the absolute configuration of the chiral compound is (S). On the other hand, when the sign of the first Cotton effect is negative, the result is (R). Table 1 shows that this correspondence holds for many chiral compounds. This proves that the above-mentioned putative mechanism for the induction of chirality is correct,
The absolute configuration of a compound whose absolute configuration is unknown can be determined.

[0034]

[Table 1]

In Table 1, the B‖ transition is a transition in the case where the moments of two porphyrin rings whose absorption band is a B band are both in the direction of binding the porphyrin ring. This is a transition when the moments are both in the direction perpendicular to the direction in which the porphyrin rings are bound (see the solid line in FIG. 3). In a chiral porphyrin dimer, the direction of the moment of one ring is slightly shifted from the direction of the other moment in both the B‖ transition and the B⊥ transition as compared to the achiral case ( (See the dotted line in FIG. 3).

In the present invention, it is possible to determine the absolute configuration of the asymmetric carbon of a chiral compound, as seen in the above example of zinc porphyrin.

The metal porphyrin has a structure of a porphyrin dimer cross-linked by a carbon chain in the method of the present invention, and the carbon at the cross-linking position of one porphyrin ring of this dimer structure by the carbon chain ( In other words, at least one of the second carbons along the outer periphery of the porphyrin ring from the carbon atom on the porphyrin ring bonded to the crosslinked carbon chain has a bulky substituent at least as high as an ethyl group.

A substituent which is more bulky than an ethyl group means a substituent which is as bulky as or more than an ethyl group. Examples of such a bulkier substituent than an ethyl group include 1) a hydrocarbon group having 2 or more carbon atoms such as an ethyl group, a propyl group and a butyl group, and 2) an ester group (a methyl ester group, an ethyl ester group, etc.). ), An oxygen-containing substituent such as a carboxylmethyl group, 3) an amino group,
Nitrogen-containing substituents such as amide group and 2-aminoethyl group, 4)
Halogen atoms such as —Cl, —Br, and —F; and 5) halogenated hydrocarbon groups such as an ethyl chloride group. The substituents bonded to the metalloporphyrin may be the same or different from each other.

As the metalloporphyrin, various metal compounds of porphyrin are considered. In this case, any metal may be used as long as it is a six-coordinate metal. For example, in addition to zinc, Fe, Mn, Ru and the like are exemplified. The two metals of the dimeric structure may be the same or different from each other.

The metalloporphyrin used in the present invention is
It can be synthesized according to a known production method (for example, JP-A-11-255790). In the present invention, particularly, the above-mentioned zinc porphyrin can be suitably used.

On the other hand, the chiral compound whose absolute configuration is determined by the method of the present invention is basically one porphyrin ring having a bulky substituent more than an ethyl group in the dimer structure of the metalloporphyrin. An asymmetric carbon to which a basic group capable of coordinating to the metal of the other porphyrin ring bonded to the metal or an asymmetric carbon adjacent to the carbon atom to which the basic group is bonded (that is, the carbon to which the basic group is bonded) (Asymmetric carbon bonded to an atom).

In this case, typical examples of the basic group include an amino group and a hydroxyl group. More specifically, the chiral compound whose absolute configuration can be determined by the method of the present invention is a chiral compound which forms a ligand with a metalloporphyrin, and typically includes, for example, 1) primary amines, 2) secondary amines Amines, 3) primary diamines,
4) Secondary diamines, 5) monoalcohols, 6) amino alcohols and the like.

Here, for example, the compounds up to N-methyl-1-phenylethylamine of 2-butanol or less shown in Table 1 are used for the asymmetric carbon to which a basic group capable of coordinating to the metal of the porphyrin ring is bonded. Corresponds to a chiral compound having Further, 2-methyl-1-butylamine corresponds to a chiral compound having an asymmetric carbon at a position adjacent to a carbon atom to which a basic group capable of coordination is bonded. In compounds having two or more asymmetric carbon atoms, such as bornylamine and diamine, also shown in Table 1, the absolute configuration of the asymmetric carbon atom to which the amino group coordinated to the metal of the metalloporphyrin is determined. .

In the present invention, the coordination of the metal porphyrin and the chiral compound capable of forming a ligand for the metal porphyrin is preferably carried out in a non-ligand forming solvent, and the coordination is carried out. In the state
CD spectrophotometric analysis is performed.

That is, the novel method of the present invention for determining the absolute configuration of various chiral compounds capable of forming a ligand with a metal porphyrin is described below. Are analyzed together in a non-ligand forming solvent. According to this method, it is possible to directly observe the absolute configuration without deriving a chiral compound into a special modified compound, and to obtain a carbon atom directly linked to a ligand-forming group or a carbon atom adjacent thereto. Chirality can be determined.

Examples of the non-ligand-forming solvent include chloroform (CHCl ₃ ) and methane dichloride (CH ₂ Cl).
₂ ), ethane dichloride (CH ₂ ClCH ₂ Cl), ethane tetrachloride (CHCl ₂ CHCl ₂ ), carbon tetrachloride (CCl ₄ )
And the like, and aliphatic hydrocarbons such as hexane and heptane.

In the method of the present invention, sample preparation for CD spectrophotometric analysis can be performed, for example, as follows.

That is, the chiral compound and the metalloporphyrin are dissolved in the solvent. The concentrations of the chiral compound and the metalloporphyrin are not critical. The concentration of the chiral compound may be usually at least 10 ^-4 mol / l. In addition, the concentration of the metalloporphyrin may be usually at least 10 ^-6 mol / l. What is necessary is just to set suitably according to the kind of solvent used in these ranges.

The minimum concentration required for observing a sufficient Cotton effect is, in the case of the metalloporphyrin of the above formula (I), about 10 ^-3 mol / l of a primary acyclic monoamine,
About ^10-4 moles aromatic cyclic monoamines / l, about 10 ^-4 mol / l at secondary amines, about ^10-3 mol / l at diamines, about ^10-3 mol aminoalcohols / The minimum concentration of a monoalcohol which exhibits a sufficient cotton effect is about 10 ^-1 mol / l and the temperature is-
Preferably, the temperature is 80 ° C.

More specifically, the following cases 1 to 5 can be exemplified.

<Case 1> The absolute chirality of primary monoamines is about 10 ^{-4 to} 10 in chloroform, methane dichloride, carbon tetrachloride, ethane tetrachloride, hexane or heptane. ^-3 mol / l,
When the concentration of the metalloporphyrin of the above formula (I) is about 10 ^-6 mol / l, it can be clarified preferably. The primary monoamines in this case include, for example, 2-butylamine, 1-phenylethylamine, 1- (1-naphthyl)
Ethylamine, 1-cyclohexylethylamine, 2-
Methyl-1-butylamine, [endo- (1R) -1,
7,7-trimethylbicyclo [2,2,1] heptane-
2-amine] and the like.

<Case 2> The absolute chirality of the secondary monoamine is adjusted to a minimum concentration of about 10 ^-4 mol / l in chloroform, methane dichloride, carbon tetrachloride, ethane tetrachloride, hexane or heptane. It can be preferably elucidated when the concentration of the prepared metal porphyrin of the formula (I) is about 10 ^-6 mol / l. In this case, examples of the secondary monoamines include N-methyl-1-phenylethylamine.

<Case 3> The absolute chirality of the diamine is adjusted to a minimum concentration of about 10 ^-3 mol / l in chloroform, methane dichloride, carbon tetrachloride, ethane tetrachloride, hexane or heptane. It can be preferably clarified when the concentration of the metalloporphyrin of the formula (I) is about 10 ^-6 mol / l. As the diamine in this case, for example, 1,2-diphenylethylenediamine, 1,2-diamine
Diaminocyclohexane and the like.

<Case 4> The absolute chirality of amino alcohols was adjusted to a minimum concentration of about 10 ^-3 mol / l in chloroform, methane dichloride, carbon tetrachloride, ethane tetrachloride, hexane or heptane. This can be preferably solved when the concentration of the metalloporphyrin of the formula (I) is about 10 ⁻⁶ mol / l. Examples of the amino alcohol in this case include 1-amino-2-propanol and 2-amino-4-methyl-1-pentanol.

<Case 5> The absolute chirality of the monoalcohol is adjusted to a minimum concentration of about 10 ^-1 mol / l in methane dichloride or hexane, and the metal porphyrin of the above formula (I) is prepared. Is about 10 ^-6 at -80 ° C
It can be clarified preferably in the case of mol / l. Monoalcohols in this case include, for example, 2-butanol, 1-butanol
Phenylethanol and the like.

According to the present invention, the absolute configuration of a chiral compound having a wide variety of basic groups bonded thereto, that is, an asymmetric carbon to which a coordinable basic group is bonded or a carbon atom to which the basic group is bonded It is possible to accurately and easily determine the absolute configuration of a chiral compound having an asymmetric carbon at an adjacent position. More specifically, for example, the following excellent effects can be obtained.

The absolute chirality of various optically active compounds can be directly observed.

A very small amount of a sample is required for a metal porphyrin, μg for a chiral compound, μg for an amine, and mg for an alcohol.

Because no chemical changes occur, the specimens can be easily collected as needed.

The measurement of absolute chirality is very fast. Sample preparation and CD spectrum measurement are completed within 10 minutes.

The detection of the Cotton effect is 400-450
Usually, the absorption of most chiral compounds is 4 nm.
Since it is up to 00 nm, a very wide range of compounds can be analyzed.

No derivatization of the chiral compound to a special modified compound is required.

The absolute chirality of an amorphous compound can be measured.

[0064]

According to the present invention, the following effects can be obtained. (1) The aluminum alloy powder of the present invention is particularly suitable for Gd and S
m is contained in a specific amount,
A highly reliable neutron shielding material can be provided. That is, since there is almost no non-uniformity (dispersion non-uniformity of the shielding element), the problem as in the related art can be solved. (2) The neutron shielding material of the present invention, in addition to being capable of efficiently shielding neutrons, has excellent strength, workability, high thermal conductivity,
It has uniformity and the like. For this reason, it can be advantageously used particularly in applications where a neutron shielding effect and heat resistance are simultaneously required. (3) According to the production method of the present invention, the aluminum alloy powder of the present invention, which is a raw material of a neutron shielding material, can be efficiently produced at a relatively low cost, so that it is suitable for production on an industrial scale.

[0065]

The following examples are provided to further clarify the features of the present invention. However, the scope of the present invention is not limited to these examples.

Example 1 In a 3 ml cell, about 10 ^-6 mol / l of the zinc porphyrin of the above formula (I) and about 10 ^-4 mol / l of (R)-(-)
A CH ₂ Cl ₂ solution of -1-cyclohexylamine was prepared, and a circular dichroism spectrum at 350 to 500 nm was observed at room temperature. FIG. 4 shows the results.

The absolute configuration of the chiral compound will be determined by the sign of the first Cotton effect on the longer wavelength side. That is, as is clear from FIG. 4, since the sign of the first Cotton effect was negative, it was confirmed that the absolute configuration was (R).

Similarly, about 10 ^-6 mol / l of zinc porphyrin and about 10 ^-1 mol / l of (R)-
A CH ₂ Cl ₂ solution of (−)-1-phenylethanol was prepared, and a circular dichroism spectrum of 350 to 500 nm was observed at −80 ° C. The result is shown in FIG.

Also in this case, since the sign of the first Cotton effect was negative, it was confirmed that the absolute configuration was (R).

The effectiveness of the method of the present invention for determining the absolute configuration of a chiral compound as described above was confirmed as the assignment of the absolute configuration of various chiral amines and alcohols as shown in Table 1 above.

[Brief description of the drawings]

FIG. 1 illustrates the circular dichroism of a zinc porphyrin dimer induced by a chiral amine.

FIG. 2 is a schematic diagram showing the mechanism of asymmetric induction in a zinc porphyrin dimer.

FIG. 3 is a diagram illustrating the direction of the moment for the maximum absorption band of the porphyrin dimer.

FIG. 4 is a view showing a CD spectrum when (R)-(−)-1-cyclohexylethylamine is used in Examples.

FIG. 5 is a view showing a CD spectrum when (R)-(−)-phenylethanol is used in Examples.

Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat II (reference) // C07M 7:00 C07M 7:00

Claims (4)

[Claims] 1. A porphyrin dimer structure cross-linked by a carbon chain, wherein a second porphyrin ring is formed along a periphery of the porphyrin ring from a carbon at a cross-linking position of one porphyrin ring of the dimer structure by the carbon chain. An asymmetric carbon in which a basic group capable of coordinating to a metal of the other porphyrin ring of the dimeric structure of the metal porphyrin is bonded to a metal porphyrin having a bulky substituent at least on one side of an ethyl group or more of carbon; A chiral compound having an asymmetric carbon is coordinated at a position adjacent to the carbon atom to which the basic group is bonded, and the absolute configuration of the asymmetric carbon of the chiral compound is determined from the sign of the Cotton effect by circular dichroism spectrophotometry. A method for determining the absolute configuration of a chiral compound. 2. A substituent which is more bulky than an ethyl group is 1)
The method according to claim 1, which is a hydrocarbon group having 2 or more carbon atoms, 2) an oxygen-containing substituent, 3) a nitrogen-containing substituent, 4) a halogen atom or 5) a halogenated hydrocarbon group. 3. The chiral compound includes 1) primary amines, 2)
The method according to claim 1, which is a secondary amine, 3) a primary diamine, 4) a secondary diamine, 5) a monoalcohol or 6) an amino alcohol. 4. The metalloporphyrin is represented by the following formula (I): The method according to any one of claims 1 to 3, wherein: