JPH08245552A - Diaminocarboxylic acid derivative and its production - Google Patents

Abstract

PURPOSE: To obtain a diaminocarboxylic acid derivative useful as an intermediate for producing an enzyme inhibitor. CONSTITUTION: A compound is shown by formula I [R1 is a (substituted) 1-20C alkyl, alkenyl, (substituted) cycloalkyl or (substituted) phenyl; R2 is a 1-6C lower alkyl, a (substituted) phenyl or benzyl; R3 is H, a 1-4C lower alkyl, phenyl or benzyl; R4 is a 1-6C lower alkyl or benzyl; R5 is H or an acyl] such as 1-(benzoyl)amino-2-(p-tolylsulfonyl)amino-2-phenylpropionic acid methyl ester. The compound of formula I is obtained by hydrolyzing a racemic or an optically active imidazolinecarboxylic acid derivative of formula II.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel racemic or optically active diaminocarboxylic acid derivative which is useful for pharmaceuticals or agricultural chemicals and a method for producing the same.

[0002]

2. Description of the Related Art The diaminocarboxylic acid derivative of the present invention and its intermediate, an imidazolinecarboxylic acid derivative, are novel compounds synthesized for the first time by the present inventor and have not been known at all.

[0003]

The present invention provides such a novel and useful diaminocarboxylic acid derivative and an efficient method for producing the same, and particularly provides a stereoselective synthetic method thereof.

[0004]

That is, the present invention is based on the general formula 1 (In the formula, R ₁ has a carbon number of 1 to 1 which may have a substituent.
20 alkyl or alkenyl group, optionally substituted cycloalkyl group or optionally substituted phenyl group, R ₂ is a lower alkyl group having 1 to 6 carbon atoms, or a substituted group. A phenyl group or a benzyl group, R ₃ is a hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, a phenyl group or a benzyl group, and R ₄ is a carbon atom of 1
To 6 are lower alkyl groups or benzyl groups, and R ₅ is a hydrogen atom or an acyl group. ) The racemic or optically active diaminocarboxylic acid derivative represented by

In the racemic or optically active diaminocarboxylic acid derivative represented by the general formula 1 of the present invention, the general formula 2 in which the substituent R ₅ is a hydrogen atom. In the case of producing the racemic or optically active diaminocarboxylic acid represented by (In the formula, R ₁ , R ₂ , R ₃ and R ₄ have the same meanings as described above), which is easily obtained by hydrolyzing the racemic or optically active imidazoline carboxylic acid derivative, In the racemic or optically active diaminocarboxylic acid derivative represented by 1, the general formula 3 in which the substituent R ₅ is an acyl group (Wherein R ₁ , R ₂ , R ₃ and R ₄ have the same meanings as described above, and R is an acyl group), and when the racemic or optically active diaminocarboxylic acid is It can be easily produced by acylating the racemic or optically active diaminocarboxylic acid represented by the formula 2.

The racemic or optically active imidazolinecarboxylic acid derivative represented by the above-mentioned general formula 4 which is a raw material for such a reaction is also a novel compound which has been found by the present inventors and which has not been described in the literature. General formula 5 R ₁ CH = NSO ₂ R ₂ (In the formula, R ₁ and R ₂ have the same meanings as described above.)
And a sulfonylimine derivative represented by the general formula 6 CNCH (R ₃ ) COOR ₄ (wherein R ₃ and R ₄ have the same meanings as described above).
It can be produced by reacting an isocyano derivative represented by the following in the presence of a catalyst.

The sulfonylimine derivative represented by the general formula 5 and the isocyano derivative represented by the general formula 6, which are the raw materials in this reaction, are both known and should be synthesized by the method described in the literature, or commercially available products should be used as they are. You can

In each of the compounds represented by the above general formulas 1 to 6, the alkyl or alkenyl group having 1 to 20 carbon atoms of the substituent R ₁ is methyl, ethyl, propyl, isopropyl, butyl, sec- Butyl, t-
Butyl, dodecanyl, octadecanyl, vinyl, propenyl, butenyl, geranyl and the like, cycloalkyl groups are exemplified by cyclopentyl, cyclohexyl, etc., these are halogen atoms, alkyl groups, substituents such as alkoxyl groups and halogen atoms, alkyl groups, It may have a phenyl group substituted with an alkoxyl group, a methylenedioxy group, an ethylenedioxy group, a dibenzyloxy group or the like as a substituent. When R ₁ is a phenyl group, the phenyl group is a halogen atom, an alkyl group, an alkoxyl group, a methylenedioxy group, an ethylenedioxy group,
It may be substituted with a hydroxy group or the like. Substituent R ₂
The lower alkyl group having 1 to 6 carbon atoms is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, t-
Butyl, amyl, hexyl, etc. are exemplified respectively, and R
_{When 2} is a phenyl group or a benzyl group, these may be substituted with a halogen atom, an alkyl group, an alkoxyl group, a methylenedioxy group, an ethylenedioxy group or the like. Examples of the lower alkyl group having 1 to ₄ carbon atoms of the substituent R ₄ include methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, t-butyl and the like. In addition, examples of the lower alkyl group having 1 to 6 carbon atoms of the substituent R ₂ include methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, t-butyl, amyl, hexyl and the like.

A catalyst is used in the reaction with the sulfonylimine derivative represented by the general formula 5 and the isocyano derivative represented by the general formula 6, and the catalyst is represented by the general formula 7 Or general formula 8 (In the above formulas, R ₆ represents a cycloalkyl group or a phenyl group which may have a substituent, R ₇ represents a lower alkyl group having 1 to 4 carbon atoms, and R ₈ represents a substituted amino group, n is an integer of 1 to 5), and an asymmetric complex catalyst prepared from an optically active ferrocenylbisphosphine having a ferrocene planar asymmetry and a Group 1B metal compound is preferably used, and such an asymmetric complex is used. The catalyst may be prepared in advance, or may be used while being prepared in the reaction system.

Here, the 1B group metal compound is 1B
Any compound derived from a group metal can be used without particular limitation, and gold or silver bis (cyclohexylisocyanide) tetrafluoroborate, a halide, a halogenated cyclohexylisocyanide complex,
Trifluoromethane sulfonate and the like are preferably used.

The optically active ferrocenyl bisphosphine having ferrocene plane asymmetry is represented by the above formulas. The substituent R ₆ in the formula is cyclopentyl group, cycloalkyl group such as cyclohexyl group or halogen atom,
Examples thereof include a phenyl group which may be substituted with an alkoxyl group, an alkyl group, a trifluoromethyl group, and R ₇
Examples of the lower alkyl group having 1 to 4 carbon atoms such as a methyl group, an ethyl group, a propyl group, an isopropyl group, and a butyl group, and examples of the substituted amino group of the substituent R ₈ include a dimethylamino group, a diethylamino group, Examples thereof include a morpholino group, a piperidino group, and an N-methylpiperazino group.

The optically active ferrocenyl bisphosphine having such ferrocene asymmetry is an optically active N
-Methyl-N- [2- (disubstituted amino) ethyl or 3- (disubstituted amino) propyl] -1- [1 ', 2-bis (diphenylphosphino) ferrocenyl] -ethylamine, and specifically, Optically active (R) -N-methyl-N- [2- (disubstituted amino) ethyl or 3- (disubstituted amino) propyl] -1-[(S) -1 ', 2
-Bis (diphenylphosphino) ferrocenyl] -ethylamine or optically active (S) -N-methyl-N- [2
Examples include-(disubstituted amino) ethyl or 3- (disubstituted amino) propyl] -1-[(R) -1 ', 2-bis (diphenylphosphino) ferrocenyl] -ethylamine.

In the above-mentioned optically active ferrocenylbisphosphine, the steric coordination of the imidazolinecarboxylic acid derivative represented by the general formula 4 can be freely created by properly using the optically active steric coordination. Alternatively, among the Group 1B metal compounds, a silver-based metal compound is used to make a trans-coordinated imidazoline carboxylic acid derivative, and a gold-based metal compound is used to make a cis-coordinated imidazoline carboxylic acid derivative. Can
The optically active imidazoline carboxylic acid derivatives thus produced are maintained in the same conformation as in the general formula 1
To a diaminocarboxylic acid derivative represented by

In the reaction of the sulfonylimine derivative represented by the general formula 5 with the isocyano derivative represented by the general formula 6, as described above, the optically active ferrocenylbisphosphine represented by the general formula 7 or 8 and the group 1B group are used. An asymmetric complex catalyst prepared from a metal compound is used,
As such a catalyst, a commercially available product may be used as it is, or by a known method described in literature, for example, Gazz.Chim.Ital. 1
03, p. 373, according to the method described in 1973. 1
A typical example of a group B metal compound is bis (cyclohexylisocyanide) gold tetrafluoroborate,
hem. Soc. Jpn. 53, p. 1138, 1980. Optically active (R) -N-methyl-N- [2-] which is a typical example of optically active ferrocenyl bisphosphine.
(Di-substituted amino) ethyl or 3- (di-substituted amino) propyl] -1-[(S) -1 ′, 2-bis (diphenylphosphino) ferrocenyl] -ethylamine was prepared respectively and prepared in advance. It may be used as an asymmetric complex catalyst, or both may be added to the reaction system to be used while preparing the asymmetric complex catalyst in the reaction system. The amount of such a catalyst used as an asymmetric complex catalyst is usually 0.0001 mol or more, preferably 0.001 mol or more, based on the reaction substrate.

In the reaction of the sulfonylimine derivative represented by the general formula 5 with the isocyano derivative represented by the general formula 6, the amount of the isocyano derivative used is not particularly limited as long as it is equimolar or more to the sulfonylimine derivative. Usually, it is in the range of 1.02 to 2 mole times. This reaction is usually carried out in the presence of a solvent, and examples of such a solvent include halogenated hydrocarbons such as chloroform, dichloromethane, dichloroethane, chlorobenzene and dichlorobenzene, and ethers such as tetrahydrofuran and diethyl ether.
Examples of the solvent include solvents which are inert to the reaction of aliphatic or aromatic hydrocarbons such as hexane, cyclohexane, petroleum ether, ligroin, benzene and toluene, and esters such as ethyl acetate. The reaction temperature is generally -78 to 70 ° C, preferably -50 to 50 ° C.
The reaction time is not particularly limited.

After the completion of the reaction, water is added to the reaction mixture in the usual manner, for example, water is added to the reaction mixture as it is, or water and an organic solvent are added to the residue obtained by concentrating the reaction mixture, and the mixture is separated into an organic layer and an aqueous layer. By drying and then distilling off the organic solvent, the imidazolinecarboxylic acid derivative represented by the general formula 4 can be isolated, and if necessary, can be purified by column chromatography or the like.

The obtained imidazolinecarboxylic acid derivative represented by the general formula 4 has the general formula 9 And a trans body represented by the general formula 10 Among the 1B group metal compounds, a trans-coordinated imidazoline carboxylic acid derivative is used, and a gold-based metal compound is used in the cis-coordinated imidazoline. Each of the carboxylic acid derivatives can be produced predominantly. In addition, such a mixture of trans isomer and cis isomer can be easily separated by, for example, column chromatography.

The optically active imidazolinecarboxylic acid derivative thus obtained is hydrolyzed to give an optically active diamino compound represented by the general formula 2 in which the substituent R ₅ in the general formula 1 is a hydrogen atom. The carboxylic acid can be converted to an optically active diaminocarboxylic acid represented by the general formula 3 in which the substituent R ₅ in the general formula 1 is an acyl group by acylating the carboxylic acid. . In this case, the configuration of the optically active imidazoline carboxylic acid derivative of the raw material is maintained as it is,
An optically active diaminocarboxylic acid derivative having a configuration corresponding to this can be obtained.

Hydrolysis can be carried out, for example, by Agric.Biol.Chem.
42, page 1565, according to the method described in 1978, imidazoline carboxylic acid derivatives were treated with hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, toluenesulfonic acid, benzenesulfonic acid, trifluoroacetic acid, trichloroacetic acid, hydroiodic acid, bromide. It is easily carried out by treating in the presence of an acidic catalyst such as an inorganic acid such as a hydroacid, a strongly acidic resin or an organic acid. The amount of the acidic catalyst used in the hydrolysis reaction is usually 0.1 with respect to the imidazolinecarboxylic acid derivative.
It is 01 to 30 times by mole. Such a reaction is usually carried out in a solvent, and examples of the solvent include water, methanol, ethanol, propanol, tetrahydrofuran, dioxane, alcohols such as dimethyl sulfoxide and polar solvents. The reaction temperature is generally -10 to 150 ° C, preferably 0 to 100 ° C.

The diaminocarboxylic acid represented by the general formula 3, which is an acylated product of the diaminocarboxylic acid represented by the general formula 2, is obtained by converting the diaminocarboxylic acid represented by the general formula 2 obtained by the above-mentioned hydrolysis reaction into the general formula 11 R ₉ COR ′ (in the formula, R ₉ is a lower alkyl group having 1 to 6 carbon atoms, a phenyl group which may have a substituent, R ′ is a hydroxyl group, OC
Indicates OR ₉ or a halogen atom. It can be easily produced by reacting with a carboxylic acid represented by).

In the carboxylic acids represented by the general formula 11 used herein, the substituent R ₉ is methyl group, ethyl group, propyl group, isopropyl group, butyl group, se
lower alkyl group having 1 to 6 carbon atoms such as c-butyl group, t-butyl group, amyl group, hexyl group or halogen atom,
Examples thereof include a phenyl group which may have a substituent such as an alkoxy group, an alkyl group and a nitro group. Examples of such carboxylic acids include acetic acid, propionic acid, valeric acid,
Examples thereof include benzoic acid, toluic acid, dinitrobenzoic acid, chlorobenzoic acid, acid anhydrides thereof, and acid halides (eg chloride, bromide). In the acylation reaction, when a solvent is used, examples of the solvent include tetrahydrofuran, ethyl ether, acetone, methyl ethyl ketone, toluene, benzene, chlorobenzene, dichloromethane, dichloroethane, and chloroform.
Carbon tetrachloride, dimethylformamide, hexane, etc.
Solvents such as tellurium, ketones, aliphatic or aromatic carbons, hydrogen halides, aprotic polar solvents and the like which are inert to the reaction may be used alone or as a mixture, and the amount thereof is not particularly limited.

In the above reaction, the amount of the carboxylic acid to be used needs to be 1 equivalent times or more with respect to the diaminocarboxylic acid derivative, and the upper limit is not particularly limited, but it is preferably 1.1 to 10 equivalent times. . Further, in this reaction, when an acid anhydride or an acid halide is used as the carboxylic acid, a catalyst is usually used, and examples of such a catalyst include dimethylaminopyridine, 4-pyrrolidinopyridine, triethylamine and tri-n-. Examples thereof include organic or inorganic basic substances such as butylamine, pyridine, collidine, imidazole sodium carbonate, sodium micitrate, potassium hydrogencarbonate, and the amount thereof is 1 equivalent times or more with respect to the acid halide. When a carboxylic acid is used, it is usually carried out in the presence of a condensing agent by dehydration condensation using 1 to 2 equivalents of the carboxylic acid. As the condensing agent used at this time,
Carbodiimides such as N, N'-dicyclohexylcarbodiimide and N-cyclohexyl-N '-(4-diethylamino) cyclohexylcarbodiimide are preferably used, and if necessary, 4-dimethylaminopyridine, 4-pyrrolidinopyridine, pyridine, triethylamine An organic base is used together. The amount of the condensing agent used is usually 1 to 1.5 equivalent times the carboxylic acid, and when the organic base is used in combination, the amount of the condensing agent used is 0.1 to 5 equivalent times. .

The reaction temperature is usually -30 to 100 ° C, preferably 0 to 80 ° C. The reaction time is not particularly limited, and the time point when the raw materials disappear can be used as the end point of the reaction. After completion of the reaction, the acylated diaminocarboxylic acid can be obtained in good yield by a usual separation means such as extraction, separation, concentration, etc., and if necessary, column chromatography can be performed again. It can also be purified by crystals or the like.

The diaminocarboxylic acid derivative represented by the general formula 1 of the present invention is useful as an intermediate for agricultural chemicals, pharmaceuticals and the like, and can be led to a compound represented by the following formula which is useful as an enzyme inhibitor.

[0025]

INDUSTRIAL APPLICABILITY The racemic or optically active diaminocarboxylic acid derivative of the present invention is useful as an intermediate for pharmaceutical applications such as enzyme inhibitors.
It can be easily produced using a sulfonylimine derivative and an isocyano derivative as starting materials.

[0026]

The present invention will be described in detail below with reference to examples, but the present invention is not limited thereto.

Example 1 N- (benzylidene) -toluene-4-sulfonamide 259.3 mg (1 mmol), silver (I) trifluoromethanesulfonate 2.6 mg (10 μmol) and (S) -N-methyl- N- [2- (piperidino) ethyl] -1-[(R) -1 ', 2-bis (diphenylphosphino) ferrocenyl] ethylamine 8.0 mg (11
μmol) was placed in a Schlenk tube, and after purging with nitrogen, 2 ml of methylene chloride was added to dissolve it, and the mixture was stirred in a nitrogen stream for 5 minutes. Next, it cooled at -30 degreeC, 0.1 ml (1.1 mmol) of methyl isocyanoacetates was dripped, and it stirred at the same temperature. After 99 hours, disappearance of the raw materials was confirmed, the reaction mixture was returned to room temperature, and the solvent was further distilled off to obtain a crude product. The obtained crude product was purified by silica gel chromatography (solvent: ethyl acetate), and white solid of 3- (p-tolylsulfonyl) -4-phenyl-5-methoxycarbonylimidazoline 409.6 mg (yield 99% or more) ) Got. ^{From the 1} H-NMR measurement results, the cis form and trans
The body ratio was 24:76. This imidazoline can be separated into a trans form by chromatography, and the NMR measurement was carried out for this, and the following results were obtained. In addition, ¹ H-NMR was measured using JEOL-JMN-EX-270, and tetramethylsilane was used as an internal standard.
It was measured as = 0 ppm. p-tol-Ph (trans) ¹ H-NMR (270 MHz, CDCl ₃ ) δ 2.39 (s, 3H, Ts-CH ₃ ), 3.69 (s, 3H, CO ₂ -CH ₃ ), 4.66 (dd,
1H, J = 7.3Hz, 2.3Hz, C2-H), 5.09 (d, 1H, J = 7.3Hz, C3-H),
7.13 ~ 7.26 (m, 7H, aromatic), 7.65 (d, 1H, J = 2.3Hz, C5-
H) 157.8 mg (0.44 mm) of imidazoline obtained above
ol) is dissolved in 7 ml of methanol, and concentrated hydrochloric acid is 1.4 ml.
(17 mmol) was added and the mixture was heated with stirring at 55 ° C. for 2 hours. After the reaction was completed, the reaction solution was concentrated under reduced pressure to give 1-amino-2.
-(P-Tolylsulfonyl) amino-2-phenylpropionic acid methyl ester hydrochloride 166 mg (yield 98
%) Was obtained. 82 mg of this methyl ester hydrochloride (0.
21 mmol) to 5 ml of methylene chloride, 0.4 ml of triethylamine and 8 of 3,5-dinitrobenzoyl chloride.
6 mg (0.37 mmol) was added, and the mixture was stirred at room temperature for 2 hours. After completion of the reaction, the reaction solution was concentrated under reduced pressure, water was added to the residue, and the mixture was extracted with methylene chloride. The crude product obtained by concentrating the organic layer was purified by preparative thin layer chromatography (solvent: ethyl acetate: hexane = 1: 1) to give white 1- (3,5-dinitrobenzoyl) amino-2. -(P
85 mg (74% yield) of -tolylsulfonyl) amino-2-phenylpropionic acid methyl ester were obtained. This is an optically active column (SUMIPAX OA-4500,
High Performance Liquid Chromatography-Analysis (hexane: dichloroethane: ethanol =)
10: 5: 1), the enantiomer excess of the cis isomer was 6% ee. Separately, 82 mg (0.21 mmol) of the above methyl ester hydrochloride was added to 5 ml of methylene chloride,
0.3 ml of triethylamine and 0.1 of benzoyl chloride.
04 ml (0, 3 mmol) was added, and the mixture was stirred at room temperature for 2 hours. After completion of the reaction, the reaction solution was concentrated under reduced pressure, water was added to the residue, and the mixture was extracted with methylene chloride. The crude product obtained by concentrating the organic layer was purified by preparative thin-layer chromatography (solvent: ethyl acetate: hexane = 1: 1) to give white 1- (benzoyl) amino-2- (p-tolyl). Sulfonyl) amino-2-phenylpropionic acid methyl ester 26 mg (yield 27%) was obtained. This was analyzed by high performance liquid chromatography using an optically active column (SUMIPAX OA-4500) (hexane: dichloroethane:
When ethanol = 50: 15: 1), trans
The enantiomeric excess of the body was 73% ee.

Example 2 N- (2-fluorobenzylidene) -benzenesulfonamide 263.3 mg (1 mmol), gold (I) chloride cyclohexyl isocyanide complex 3.4 mg (10 μmo)
1) and (S) -N-methyl-N- [2- (piperidino) ethyl] -1-[(R) -1 ', 2-bis (diphenylphosphino) ferrocenyl] ethylamine 8.0 m.
g (11 μmol) was put into a Schlenk tube, and after substituting with nitrogen, 2 ml of methylene chloride was added to dissolve it, and the mixture was stirred in a nitrogen stream for 5 minutes. Next, it cooled at -30 degreeC, 0.1 ml (1.1 mmol) of methyl isocyanoacetates was dripped, and it stirred at the same temperature. After 326 hours, the disappearance of the raw materials was confirmed, the reaction mixture was returned to room temperature, and the solvent was further distilled off to obtain a crude product. The obtained crude product was purified by silica gel chromatography (solvent: ethyl acetate) to give a white solid, 3-
(Benzenesulfonyl) -4- (2-fluorophenyl) -5-methoxycarbonylimidazoline 361.8
mg (yield 99% or more) was obtained. ¹ H-NMR to ci
The ratio of the s form and the trans form was 80:20. This imidazoline can be separated into a cis form and a trans form by chromatography, and NMR measurement was performed on each of them in the same manner as in Example 1, and the following results were obtained. Ph-oC ₆ H ₄ (trans) ¹ H-NMR (270MHz, CDCl ₃ ) δ3.70 (s, 3H, CO ₂ -CH ₃ ), 4.75 (dd, 1H, J = 7.3Hz, 2.0Hz, C2-
H), 5.32 (d, 1H, J = 7.3Hz, C3-H), 6.84 to 7.62 (m, 9H, arom
atic), 7.65 (d, 1H, J = 2.0Hz, C5-H) Ph-oC ₆ H ₄ (cis) ¹ H-NMR (270MHz, CDCl ₃ ) δ3.19 (s, 3H, CO ₂ -CH ₃ ), 5.24 (d, 1H, J = 11.6Hz, 2.0Hz, C2-
H), 5.45 (d, 1H, J = 11.6Hz, C3-H), 6.80 ~ 7.73 (m, 9H, arom
atic), 7.78 (s, 1H, C5-H) 95 mg (0.24 mmol) of the imidazoline obtained above
Was dissolved in 7 ml of methanol and 1.4 ml of concentrated hydrochloric acid (17
mmol) was added and the mixture was heated with stirring at 55 ° C. for 2 hours. After completion of the reaction, the reaction solution was concentrated under reduced pressure to obtain 167 mg (yield 98%) of 1-amino-2- (benzenesulfonyl) amino-2- (2-fluorophenyl) propionic acid methyl ester hydrochloride. 95 mg of this methyl ester hydrochloride
(0.24 mmol) in 5 ml of methylene chloride, 0.4 ml of triethylamine and 0.1 ml of benzoyl chloride
(0.9 mmol) was added, and the mixture was stirred at room temperature for 2 hours. After completion of the reaction, water was added to the residue obtained by concentrating the reaction solution under reduced pressure, and the mixture was extracted with methylene chloride. The crude product obtained by concentrating the organic layer was purified by preparative thin layer chromatography (solvent: ethyl acetate: hexane = 1: 1) to give white 1-benzoylamino-2- (benzenesulfonyl) amino-. 2-
84 mg (yield 76%) of methyl ester of (2-fluorophenyl) propionic acid was obtained. This was analyzed by high performance liquid chromatography using an optically active column (SUMIPAX, OA-1100) (hexane: dichloroethane:
Ethanol = 200: 40: 1), the enantiomer excess of the cis isomer was 83% ee. Further, high performance liquid chromatography-analysis (hexane: dichloroethane: ethanol = 50: 15: 1) using an optically active column (SUMIPAX, OA-4500) revealed that
The enantiomer excess of the trans isomer was 33% ee.

Example 3 3.4 mg of gold (I) cyclohexyl isocyanide complex in place of silver (I) trifluoromethanesulfonate
3- (p-tolylsulfonyl) -4-was reacted and worked up according to Example 1 except that (10 μmol) was used.
Phenyl-5-methoxycarbonylimidazoline was obtained. This product was confirmed to be cis and tran by ¹ H-NMR.
The ratio of the s isomer was 75:25. The cis-form of this imidazoline can be separated by chromatography, and the NMR measurement was performed on this imidazole in the same manner as in Example 1. The following results were obtained. p-tol-Ph (cis) ¹ H-NMR (270 MHz, CDCl ₃ ) δ2.38 (s, 3H, Ts-CH ₃ ), 3.13 (s, 3H, CO ₂ -CH ₃ ), 5.15 (d, 1
H, J = 11.6Hz, C3-H), 5.22 (dd, 1H, J = 11.6Hz, 2.0Hz, C2-H)
, 6.99 (d, 2H, J = 8.6Hz, Ts-C3,5-H), 7.10 ~ 7.24 (m, 5H, a
romatic), 7.41 (d, 2H, J = 8.3Hz, Ts-C2,6-H), 7.77 (d, 1
H, J = 2.0Hz, C5-H) 1-amino-2- (benzenesulfonyl) was prepared by treating the imidazoline obtained above with concentrated hydrochloric acid in methanol in the same manner.
Amino-2- (2-fluorophenyl) propionic acid methyl ester hydrochloride was obtained. This was further acidified with 3,5-dinitrobenzoyl chloride, and the product was subjected to high performance liquid chromatography analysis (hexane: dichloroethane: ethanol = 10: 5: 1) using an optically active column (SUMIPAX OA-4500). The enantiomeric excess of the cis form was 56% ee.

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Claims (11)

[Claims] 1. A general formula 1 (In the formula, R ₁ has a carbon number of 1 to 1 which may have a substituent.
20 alkyl or alkenyl group, optionally substituted cycloalkyl group or optionally substituted phenyl group, R ₂ is a lower alkyl group having 1 to 6 carbon atoms, or a substituted group. A phenyl group or a benzyl group, R ₃ is a hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, a phenyl group or a benzyl group, and R ₄ is a carbon atom of 1
To 6 are lower alkyl groups or benzyl groups, and R ₅ is a hydrogen atom or an acyl group. ) A racemic or optically active diaminocarboxylic acid derivative represented by 2. A general formula 4 (Wherein R ₁ , R ₂ , R ₃ and R ₄ have the same meanings as described above), and the racemic or optically active imidazoline carboxylic acid derivative is hydrolyzed. (In the formula, R ₁ , R ₂ , R ₃ and R ₄ have the same meanings as described above.) A process for producing a racemic or optically active diaminocarboxylic acid. 3. A racemic or optically active diaminocarboxylic acid represented by the general formula 2 according to claim 2, which is acylated. (In the formula, R ₁ , R ₂ , R ₃ and R ₄ have the same meanings as described above, and R ₅ represents an acyl group.) A process for producing a racemic or optically active diaminocarboxylic acid. 4. The method for producing an optically active diaminocarboxylic acid according to claim 2, wherein both the imidazolinecarboxylic acid derivative and the diaminocarboxylic acid are optically active substances. 5. The method for producing an optically active diaminocarboxylic acid according to claim 3, wherein both the imidazolinecarboxylic acid derivative and the diaminocarboxylic acid are optically active substances. 6. A racemic or optically active imidazolinecarboxylic acid derivative represented by the general formula 4. 7. General formula 5 R ₁ CH = NSO ₂ R ₂ (wherein R ₁ and R ₂ have the same meanings as described above).
And a sulfonylimine derivative represented by the general formula 6 CNCH (R ₃ ) COOR ₄ (wherein R ₃ and R ₄ have the same meanings as described above).
The method for producing a racemic or optically active imidazolinecarboxylic acid derivative according to claim 6, wherein the isocyano derivative represented by the formula (1) is reacted in the presence of a catalyst. 8. A catalyst of the general formula 7 Or general formula 8 (In each formula, R ₆ represents a cycloalkyl group or a phenyl group which may have a substituent, R ₇ represents a lower alkyl group having 1 to 4 carbon atoms, R ₈ represents a substituted amino group, and n
Is an integer of 1 to 5. ) An optically active ferrocenyl bisphosphine having a ferrocene plane asymmetry and 1
The method for producing a racemic or optically active imidazoline carboxylic acid derivative according to claim 7, which is a Group B metal compound. 9. The racemic compound according to claim 8, wherein the Group 1B metal compound is bis (cyclohexylisocyanide) tetrafluoroborate of gold or silver, a halide, a halogenated cyclohexylisocyanide complex or trifluoromethanesulfonate. Alternatively, a method for producing an optically active imidazoline carboxylic acid derivative. 10. An optically active ferrocenyl bisphosphine is an optically active N-methyl-N- [2- (disubstituted amino) ethyl or 3- (disubstituted amino) propyl] -1-.
[1 ', 2-bis (diphenylphosphino) ferrocenyl] -ethylamine, The method for producing a racemic or optically active imidazolinecarboxylic acid derivative according to claim 8. 11. An optically active N-methyl-N- [2- (disubstituted amino) ethyl or 3- (disubstituted amino) propyl] -1- [1 ', 2-bis (diphenylphosphino).
Ferrocenyl] -ethylamine is RN-methyl-N
-[2- (disubstituted amino) ethyl or 3- (disubstituted amino) propyl] -1-[(S) -1 ', 2-bis (diphenylphosphino) ferrocenyl] -ethylamine or (S) -N- Methyl-N- [2- (disubstituted amino) ethyl or 3- (disubstituted amino) propyl]-
The method for producing a racemic or optically active imidazoline carboxylic acid derivative according to claim 10, which is 1-[(R) -1 ', 2-bis (diphenylphosphino) ferrocenyl] -ethylamine.