JPH0249758A - Production of (1r,2s)-cis-2-aminocyclopentanecarboxylic acid - Google Patents

Abstract

NEW MATERIAL:(1R,2S)-cis-2-Aminocyclopentanecarboxylic acid. USE:An antimicrobial agent. PREPARATION:A cis-2-aminocyclopentanecarboxylic acid derivative expressed by formula I (R is protected carboxy) or a racemic modification at the amino group thereof is reacted with an amino acid having protected amino group or a reactive derivative at the carboxyl group thereof (e.g., acid halide or anhy dride) to separate the L-isomer of the compound expressed by formula I in which the amino group thereof is protected with a residue after removing hydroxy group from the carboxy group of the above-mentioned amino acid. The amino-protecting group and carboxy-protecting groups are then eliminated from the separated compound to afford the objective compound expressed by formula II.

Description

Detailed Description of the Invention [Industrial Field of Application] This invention provides (IR, 2S)-cis-2, which is useful as an antibacterial agent, by optically resolving the racemic form of cis-2-aminocyclopentanecarboxylic acid. - A method for producing aminocyclopentanecarboxylic acid.

[Prior Art] (IR, 23)-cis-2-aminocyclopentanecarboxylic acid is a new compound, and the method for producing it has not been known.

[Object of the invention] This invention provides a novel compound (IR,2S)-cis-
The object of the present invention is to provide a method for producing 2-aminocyclopentanecarboxylic acid.

[Structure of the Invention] The method of the present invention provides a method for preparing a cis-2-aminocyclopentanecarboxylic acid derivative represented by the general formula (wherein R means a protected carboxy group) or a reactive derivative in its amino group. Compound (
After separating five compounds of compound (11) in which the amino group of 11) is protected with a residue obtained by removing the hydroxy group from the carboxy group of the amino acid, the amino protecting group and the carboxy protecting group of the conjugate are separated. The key point lies in the elimination, whereby (IR,2S)-cis-2-aminocyclopentanecarboxylic acid represented by formula (I) is obtained.

[Detailed Description of the Invention] The racemic form of the cis-2-aminocyclopentanecarboxylic acid derivative represented by the general formula (II), which is the starting material of this invention, is a known compound. - Examples of the protected carboxy group represented by R in the compound represented by formula (II) include esterified carboxy groups, and examples of the ester include methyl ester, ethyl ester, propyl ester, and isopropyl ester. ester,
Butyl ester, isobutyl ester, tertiary butyl ester, pentyl ester, tertiary pentyl ester,
Lower alkyl esters such as hexyl ester and 1-cyclopropylethyl ester; acetoxymethyl ester, propionyloxymethyl ester, butyryloxymethyl ester, valeryloxymethyl ester, 2-
Alkanoyloxy (lower) alkyl esters such as acetoxyethyl ester, 2-propionyloxyethyl ester, and pivaloyloxymethyl ester; alkanesulfonyl alkyl esters such as mesylmethyl ester and ethanesulfonyl ethyl ester; 2-iodoethyl ester; 2. 2. Lower alkyl esters having one or more suitable substituents such as mono (or di or tri) haloalkyl esters such as 2-trichloroethyl ester; alkenyl esters such as vinyl esters and allyl esters; ethynyl esters, propynyl esters, etc. Alkynyl ester; benzyl ester, 4-methoxybenzyl ester, 4-nitrobenzyl ester, phenethyl ester, trityl ester, benzhydryl ester, bis(4-methoxyphenyl)methyl ester, 3,4-dimethoxybenzyl ester, 4-hydroxy Al (lower) alkyl esters which may have one or more suitable substituents such as -3,5-ditertiary butyl benzyl esters; phenyl esters, tolyl esters,
Aryl esters which may have one or more suitable substituents such as tertiary butyl phenyl ester, xylyl ester, mesityl ester, cumenyl ester, etc. are mentioned. In addition, when synthesizing the known compound represented by formula (If), for example, DL-cis-2-
Synthesis of cyclopentanecarboxylic acid, Israeli Journal of Chemistry, Vol. 10. P55
~58.1972), for example, methanol, ethanol, propatool, in the presence of thionyl chloride, etc.
Isopropyl alcohol, butanol.

When a lower alkanol such as isobutyl alcohol or tertiary butyl alcohol is reacted, general formula (II) in which R is carboxy esterified with a lower alkyl ester
can be obtained.

In the present invention, the general formula (
Using the compound of II) or its reactive derivative at the amino group as a starting material, this is reacted with an amino acid with a protected amino group or a reactive derivative at its carboxyl group, so that the amino group in general formula (11) is converted to the amino group of the amino acid. D-compounds and L-compounds protected with a residue obtained by removing a hydroxy group from a carboxy group (hereinafter referred to as an amino acid residue; therefore, when we refer to an amino acid residue, we mean one in which the amino group in the amino acid is protected) A mixture of (racemate) is obtained. Since these D-form compounds and L-form compounds have different solubility in solvents, they can be effectively separated by selecting an appropriate solvent. For example, when ethyl acetate or methylene chloride is used as a solvent, the L-form compound dissolves in the solvent, but the D-form compound precipitates out of the solvent, so the D-form compound can be removed by filtration.

Here, as the reactive derivative at the amino group of the compound represented by the above formula (11), for example, the compound (11
) and a carbonyl compound, Schiff's base type imino or its enamine type tautomer; Compound (II) and bis(trimethylsilyl)acetamide,
Silyl derivatives produced by reaction with silyl compounds such as trimethylsilylacetamide; compound (11)
) and phosphorus trichloride or phosgene.

In addition, the amino acids among the amino acid residues with protected amino groups include glycine and alanine.

Monoamino monocarboxylic acids such as valine, leucine, and isoleucine; oxyamino acids such as serine and threonine; sulfur-containing amino acids such as cysteine, cystine, and methionine; monoamino dicarboxylic acids such as aspartic acid and glutamic acid; lysine.

Examples include diaminomonocarboxylic acids such as arginine; amino acids having an aromatic nucleus such as phenylalanine and tyrosine; and amino acids having a heterocycle such as histidine, tryptophan, proline, and oxyproline. Preferred amino-protecting groups for these amino acid residues include those commonly used in peptide synthesis chemistry. Preferred examples of such amino-protecting groups include alkoxycarbonyl or cycloalkoxycarbonyl (e.g. tertiary
-class butoxycarbonyl, tertiary pentoxycarbonyl,
cyclohexylcarbonyl, etc.), aralkoxycarbonyl such as ff1ttA or unsubstituted phenyl lower alkoxycarbonyl (e.g. benzyloxycarbonyl, 2-chlorobenzyloxycarbonyl, etc.), substituted or unsubstituted arylsulfonyl (e.g. benzenesulfonyl, p-toluenesulfonyl, etc.).

Examples of reactive derivatives at the carboxy group of amino acids with protected amino groups include acid halides, acid anhydrides,
Examples include activated amides and active esters. Suitable examples thereof include acid chlorides; acid azides such as dialkyl phosphoric acid, phenyl phosphoric acid, diphenylic acid, dibenzilic acid,
Substituted phosphoric acids such as halogenated phosphoric acids, dialkyl phosphorous acids, sulfurous acids such as methanesulfonic acid, ethanesulfonic acid, alkanesulfonic acids, thiosulfuric acids, alkyl carbonates such as pivalic acid, pentanoic acid, isopentanoic acid, 2-ethylbutyric acid, Mixed acid anhydrides with acids such as aliphatic carboxylic acids such as acetic acid or trichloroacetic acid or aromatic carboxylic acids such as benzoic acid; activated amides with symmetric acid anhydrides - imidazole, dimethylpyrazole, triazole or tetrazole; or activated esters such as cyanomethyl ester, methoxymethyl ester, dimethyliminomethyl [(CH3)2N"=CH-] ester, vinyl ester, propargyl ester, p-nitrophenyl ester, 2,4-dinitrophenyl ester, trichlorophenyl ester, pentachlorophenyl ester, mesylphenyl ester, phenylazophenyl ester, phenylthioester, p-nitrophenylthioester, p-talesylthioester, carboxymethylthioester, pyranyl ester, pyridyl ester, piperidyl ester, 8-quinolylthioester, or N,N-dimethylhydroxylamine, 1-hydroxy-2-(IH)-pyridone, N-hydroxysuccinimide, N-hydroxyphthalimide or 1-
Examples include esters with hydroxy-6-chloro-IH-benzotriazole. These reactive derivatives can be arbitrarily selected from among them depending on the type of amino acid to be used.

When the thus separated L-compound whose amino group is protected by a protected amino acid residue is subjected to an elimination reaction of the amino-protecting group and the carboxy-protecting group, the target compound (IR,2S)-cis- 2-Aminocyclopentanecarboxylic acid can be obtained.

The elimination reaction of the above amino protecting group and carboxy protecting group can be carried out by conventional methods such as hydrolysis and reduction. Acids and bases for hydrolysis.

Methods using hydrazine and the like are included, and these methods are appropriately selected depending on the type of protecting group to be removed.

Examples of acids used in hydrolysis using acids include organic and inorganic acids such as formic acid, trifluoroacetic acid, benzenesulfonic acid, p-toluenesulfonic acid, and hydrochloric acid. Among these, particularly preferred are , formic acid, trifluoroacetic acid, hydrochloric acid, etc., are low melting point solvents that can be easily removed from the reaction mixture by conventional means such as vacuum distillation.

These acids are appropriately selected depending on the type of amino protecting group to be removed, and the reaction can be carried out either in the absence of a solvent or in the presence of a solvent. Suitable solvents include water, hydrophilic organic solvents, and mixed solvents thereof. Note that the elimination reaction using trifluoroacetic acid may be performed in the presence of anisole.

Bases used in hydrolysis using a base include, for example, alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; alkaline earth metal hydroxides such as magnesium hydroxide and calcium hydroxide; sodium carbonate, potassium carbonate, etc. alkali metal carbonates; alkaline earth metal carbonates such as magnesium carbonate and calcium carbonate; sodium hydrogen carbonate;
Alkali metal hydrogen carbonates such as potassium hydrogen carbonate; alkali metal acetates such as sodium acetate and potassium acetate; alkaline earth metal phosphates such as calcium phosphate and magnesium phosphate;
In addition to inorganic bases such as alkali metal hydrogen phosphates such as disodium hydrogen phosphate and dipotassium hydrogen phosphate, trialkylamines such as trimethylamine and triethylamine, picoline, N-methylpyrrolidine, N-methylmorpholine, 1.
5-diazabicyclo[4,3,0]nonan-5-ene,
1.4-diazabicyclo[2,2,2]octane, 1,
Examples include organic bases such as 5-diazabicyclo[5,4,0oundecan-5-ene. Hydrolysis using a base is carried out in a tofu, water, a wood-loving organic solvent, or a mixed solvent thereof.

Reductive elimination methods include, for example, elimination of protective groups such as haloalkoxycarbonyl groups such as trichloroethoxycarbonyl, substituted or unsubstituted aralkoxycarbonyl groups such as hensyloxycarbonyl, 2-pyridylmethoxycarbonyl, etc. It is effectively applied when Suitable reduction methods include, for example, reduction with an alkali metal hydride such as sodium borohydride; metals such as tin, zinc, iron or metal salt compounds of these metals (e.g. chromous chloride). , chromous acetate, etc.) in combination with an organic or inorganic acid such as acetic acid, propionic acid, or hydrochloric acid; and catalytic reduction. Suitable catalysts for use in the catalytic reduction process include conventional catalysts such as Raney nickel, platinum oxide, palladium/carbon, and the like.

The reaction temperature is not particularly limited and is appropriately selected depending on, for example, the type of amino protecting group mentioned above, the type of elimination method, etc., but the reaction can be carried out under mild conditions such as cooling, room temperature or slightly heating. is preferred.

By the way, in the above explanation, the L-compound in which the amino group in general formula (11) is protected with the amino acid residue is directly subjected to the elimination reaction of the amine protecting group and the carboxy protecting group, but in this elimination reaction, the amino acid The amino protecting group on the residue may be removed from the amino acid residue as the elimination reaction progresses, and in this case, the amino acid is liberated and the target compound FJ (when the target compound is dissolved in the solvent) is mixed into the solution).

This makes the operation for separating the target compound (the operation for removing the free amino acid) complicated and may also lead to a decrease in yield.

Therefore, an L-form compound in which the amino group in the formula , the amine group of the free amino acid residue from which the protecting group has been removed is converted into a highly stable N-phenylthiocarbanyl group by the action of phenylthiocyanate, etc., and then the amino protecting group and the carboxy protecting group are simultaneously removed. It may also be configured to undergo a separation reaction (for example, Nidoman decomposition).

This can avoid decomposition of the amino protecting group in the amino acid residue, and can prevent free amino acids from being mixed into the target compound layer.

As a method for removing the amine protecting group that protects the amine group in the above amino acid residue, an appropriate method depending on the type of protecting group may be adopted from among the conventional methods such as hydrolysis and reduction described above. Preferably, hydrolysis with formic acid, hydrochloric acid, trifluoroacetic acid, etc. is recommended, and the reaction can be carried out in a solvent such as water, acetone, chloroform, methylene chloride, tetrahydrofuran, etc. under mild conditions at room temperature or heating. good.

Production Example 1 Thionyl chloride (13 ml) was added dropwise into methanol (50 ml) at -15 to -5°C. The mixture was stirred at the same temperature for 10 minutes, and cis-2-aminocyclopentanecarboxylic acid was added to the hydrochloric acid solution. Salt (5 g) was added and the mixture was stirred at room temperature for 1.
After stirring for 5 hours and removing the organic solvent under reduced pressure, cis-2-
The hydrochloride of the methyl ester of aminocyclopentanecarboxylic acid (5.05 g) was obtained.

mp: 120-123℃ IR (Nujol): 1715.15951555
cm-'NMR (C20, δ): 1.68-2.32 (
8Lm), 3.11 to 3.33 (LH, a+), 3.
78 (31-1, S), 3.82-4.02 (tH
,m) C,H,,CI N O.

C:46.80. Nia, 85. Nia, 80. C1:
19.73G:46.39. Nia, 84. Nia, 7
8 C1: 19.32 Elemental analysis subvalue; Analysis value; Production example 2 Hydrochloride of methyl ester of cis-2-aminocyclopentanecarboxylic acid (15 g) was added to ethyl acetate (200 ml)
and methylene chloride (1 oomt), and to the resulting suspension were added N-tert-butoxycarbonyl-phenylalanine (22.15 g) and 1-hydroxybenzotriazole eternity (11.28 g) at room temperature. Added below. 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (14.26 g") was added to the mixture under water cooling, and the mixture was stirred at the same temperature for 30 minutes. Water was added to the resulting reaction mixture, and the mixture was fractionated. Add more water to the organic layer, then IN
The pH was adjusted to 2 with hydrochloric acid. The organic layer was separated, washed with water, a 5% aqueous sodium bicarbonate solution, and a saturated aqueous sodium chloride solution, and then dried over magnesium sulfate. The residue obtained by distilling off the organic solvent under reduced pressure was dissolved in ethyl acetate (90 ml) at a temperature of 50 to 60°C, and then left at room temperature for 15 hours.

When the precipitate that precipitated during standing was collected by filtration, (IS.

2R) -N-(N-tertiary butoxycarbonyl-cyclophenylalanyl)-cis-2-aminocyclopentanecarboxylic acid methyl ester (9.8 g) was obtained. The crystal was the raw material of Reference Example 1. The filtrate was used as the raw material of Example 1.

mp: 132 to 134 ℃ [α co-+ 45.6' (C= 1
, C2+(50H)IR(Nujol):3330
,3310,1715.1680.1640 cm-'
NMR (CD(: 13, δ): 1.28-2.0
3 (61-19m), 1.41 (9H.

s), 2.78-3.14 (IH, m), 3.01[2
H, d, J-8Hz), 3.58 (3)1. s)4
．． 12-4.55 (28, m), 5.11 (IHd, J
-8Hz), 6.21 (IH, d, J-8Hz) 7.2
7 (5H, s) Elemental analysis Cx□HsoN20s Calculated value, C: 64.60. )I+7.74. Nia,
17 analysis value, C: 84.38. Nia, 58. N:3
．． 13 Example 1 The filtrate collected in the final step of Production Example 2 was dried under reduced pressure, and the residue was dissolved in ether at 30 to 35°C and incubated at room temperature for 15 minutes.
I left it for a while. When the obtained precipitate is collected by filtration, (IR,
2S)-N-(N-tertiary butoxycarbonyl-cyclophenylalanyl)-cis-2-aminocyclopentanecarboxylic acid methyl ester (9.8 g) was obtained.

m9: 112 to 115 °C [α]20=-δ3.0' (C=1, (:z
HsOH)IR (NuJol): 3350, 3330,
1730, 1690, 1650 crn-'NMR (
CDC13, δ): 1.41 (9H, s), 1.48
〜2.18(6)1゜m), 2.78〜3.03(I
H, m), 3.04 (2H, d, J-81 (Z),
3.60 (3)1. s).

4.18-4.58 (2H, m), 4.97 (IH.

d, J-8H2), 6.84 (IH, d, J-8Hz)
7.24 (5H, s) Elemental analysis C21H3ON205 Calculated value, C: 64.60. H Near, 74. N near, 1
7 analysis value, C: 64.38. H Near, 58. Nia,
13 Example 2 Methyl ester of (I R,2S)-N-(N-tertiary butoxycarbonyl-L-phenylalanyl)-cis-2-aminocyclopentanecarboxylic acid (0.5 g),
The mixture was added to a solution of 4N hydrochloric acid in 1,4-dioxane (2.5 ml) at room temperature, and stirred at the same temperature for 15 minutes. Ethyl acetate and water were added to the residue obtained by distilling off the organic solvent under reduced pressure to give a 5%
The pH was adjusted to 7 with an aqueous sodium hydrogen carbonate solution. The organic layer was separated, washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain (IR,2S)-N-(L-phenylalanyl)-
Methyl ester of cis-2-aminocyclopentanecarboxylic acid (0,283 g) was obtained.

mp: 96-101℃ [α Koni'= 119.5'' (C
= 1, Ct[1+)IR(Nujol
): 3310, 1730, 1850.1530 cm
-'NMR (D'MSOda, δ): 1.30-2.0
3(6)1. [11), 2.76 ~ 3.20 (3)
! , m), 3.25 to 3.47 (IH.

m), 3.52 (3H, s), 4. lO~4.52(I
H, m), 7.22 (5H, s), 7.78 (IHd,
J-8Hz) Example 3 Methyl ester of (IR,2S)-N-(L-phenylalanyl)-cis-2-aminocyclopentanecarboxylic acid (3.7 g) was dissolved in ethanol (8.2 ml). Then, phenyl thiocyanate (2.3 ml) was added thereto, and the mixture was stirred at room temperature for 10 minutes. After the reaction is complete, ether is added to the mixture and the resulting precipitate is collected by filtration, resulting in (I
R,2S)-N-(N-phenylthiocarbamyl-
Methyl ester of (phenylalanyl)-cis-2-aminocyclopentanecarboxylic acid (3,11 g') was obtained.

mp: 171 to 172°C [α]:'--66,8° (C=1.CHCl3
) IR (Nujol): 3320, 1715, 1645
．． 1830 co+-'NMR (CDC13, δ)+
1.35 ~ 2.11 (61 (, m), 2.61 ~
3.2B (3)1, turtle), 3.56 (3)1.
s), 4.15-4.52 (l)I, l11),
4.95 to 5.29 (IH, m), 6.95 to 7.
43 (IOH, m).

7.52 (IH, d, J-8Hz), 8.09 (IH.

d, J-8Hz), 9.66 (IH, br, S) Elemental analysis C23H27N s Os 5 calculated value, C:
64.92. H:6.39. N:9.87. S near, 5
3 analysis value, C: 65.00]: 6.55. N:9.8
3. S Near, 56 Example 4 (I R,2S) -N-(N-phenylthiocarbamyl-phenylalanyl)-cis-2-aminocyclopentanecarboxylic acid methyl ester (2,47 g) was Dissolved in fluoroacetic acid (25 ml) and stirred at room temperature for 10 minutes.
After stirring for a minute, the organic solvent was distilled off under reduced pressure. Methylene chloride (20 ml) and water (10 ml) were added to the residue, and the aqueous layer was separated. Concentrated hydrochloric acid (15 ml) was added to the aqueous layer, heated to 70-80°C, and held for 30 minutes. After the solvent was distilled off from the mixture under reduced pressure, acetone (15 ml) was added. When the obtained precipitate was collected by filtration, (IR,2S)-cis-2-aminocyclopentanecarboxylic acid hydrochloride (0
, 48g) was obtained.

01+1: 156-157℃ [α]; 0=-5.6° (C=1.H,0)IR(N
ujol): 3350, 3250, 1710, 1640
．． 15901500 cm” NMR (D, O5δ): 1.48-2.43 (6) 1.
m), 2.90 ~ 3.33 (it(, m), 3.67
~4.03(1)1. m) Example 5 (IR,2S)-cis-2-aminocyclopentanecarboxylic acid hydrochloride (200 mg) was added to water (10 ml) at room temperature.
), and the pH was adjusted to 5.7 by adding Diaion 5AIOA (OH-type: manufactured by Mitsubishi Chemical Corporation). When the solvent was distilled off under reduced pressure from the aqueous layer obtained by filtering off the residue, (IR
,2S)-cis-2-aminocyclopentanecarboxylic acid (110 ml) was obtained.

mp: 199-200°C (decomposition) [α]: 0 = -8.9° (C = 1.H, 0) IR (N
ujol) :3300~3400,2200.164
0 cm-'NMR (D, O, δ): 1.52-2.
30(6)1. a+), 2.67-3.05 (IH,
m), 3.47 to 3.87 (IH, m) Elemental analysis C
3) 111NO2 Calculated value: (::55.80.)I:8.58. N:1
0.84 analysis value, C: 55.52. H:8.44. N
:10.65 The above data for this compound is based on the reference sample (W
S7562).

Reference Example 1 Using methyl ester (5 g) of (IS, 2R)-N-(N-tert-butoxycarbonyl-cyclophenylalanyl)-cis-2-aminocyclopentanecarboxylic acid as a raw material, the same procedure as Example 2 was carried out. When processed in the same way, (I S, 2R) -
Methyl ester of N-(L-phenylalanyl)-cis-2-aminocyclopentanecarboxylic acid (3,01 g
)was gotten.

mp Near 2-74℃ [α]2'= +75.0' (C=1, C
2C2H50H)IR(Fi1+3400.3310,
1730, 1640, 1505 crn-'NMR (C
DC13, δ): 1.31-2.19 (68, s), 2
．． 73-3.06. (3H,s), 3.22-3.
48 (2M.

m), 3.54 (3H, s), 7.21 (5H, s).

7.70 (IH, d, J-8Hz) Elemental analysis C181 (22N203 calculated value; C: 86.19.l near, 64.N: 9.8
5 analysis value, C: 66.26. )lnia, 52. N:9
．． 58 Reference Example 2 When methyl ester (2.5 g) of (IS, 2R)-N-(L-phenylalanyl)-cis-2-aminocyclopentanecarboxylic acid was used as a raw material and treated in the same manner as in Example 3, Methyl ester of (IS,2R)-N-(N-phenylthiocarbamyl-L-phenylalanyl)-cis-2-aminocyclopentanecarboxylic acid (3,58 g
)was gotten.

mp: 12s ~ 127 °C [α co:' = + 16.5 ° (C = 1
．． CHCl3) IR (Nujol): 32
90,1735,1710,1675.1660 c
m'''NMR (DMSO-da, δ): 1.27-2.
07 (6H, m), 2.78 - 3.18 (3H, m)
, 3.58(3)1. s).

4.08-4.47 (IH, m), 4.93-5
．． 25 (IH, m), 6.91 ~ 7.59 (lot (
, +n), 7.60 (IH, d, J-8Hz), 8.
02 (IH, d, J-8Hz) 9.79 (IH, br
, s) Reference Example 3 Using methyl ester (2,56 g) of (IS, 2R)-N-(N-phenylthiocarbamyl-cyclophenylalanyl)-cis-2-aminocyclopentanecarboxylic acid as a raw material , when processed in the same manner as in Example 4, (Is, 2
R)-cis-2-aminocyclopentanecarboxylic acid hydrochloride (359 mg) was obtained.

mp: 156-157°C [α]2'=+4.6° (C=1.H20)IR(N
ujol) :33B0.3230,1715,165
0 cl'NMR (C20, δ): 1.52-2.33
(6M, m), 2.81-3.33 (IH, m), 3.
72-4.01 (LH, +n) Reference Example 4 When (IS, 2R)-cis-2-aminocyclopentanecarboxylic acid hydrochloride (300 mg) was treated in the same manner as in Example 5 as a raw material, (IS.

2R)-cis-2-aminocyclopentanecarboxylic acid (
112 mg) was obtained.

Claims (1)

[Claims] A cis-2-aminocyclopentanecarboxylic acid derivative represented by the general formula ▲ Numerical formula, chemical formula, table, etc. ▼ (II) (in the formula, R means a protected carboxy group) or The racemic form of the reactive derivative at the amino group is reacted with an amino acid with a protected amino group or a reactive derivative at the carboxyl group, and the compound (
After separating the L-form of compound (II) in which the amino group of II) is protected with a residue obtained by removing the hydroxy group from the carboxy group of the amino acid, the amino-protecting group and the carboxy-protecting group of the L-form compound are removed. (1R, 2S)
-Production method of cis-2-aminocyclopentanecarboxylic acid.