Method for optical resolution of DL-cysteine and (R,S)-1-(1-naphthyl) ethylamine

Method for optical resolution of DL-cysteine by (1) reacting DL-cysteine with formaldehyde to prepare DL-thiazolidine-4-carboxylic acid (DL-TCA), (2) forming diastereomer salts of D-TCA and of L-TCA by reacting DL-TCA with an optically active 1-(1-naphthyl)ethylamine, (3) separating said diastereomer salts by difference of the solubilities thereof in a solvent, (4) recovering D-TCA from said diastereomer salt of D-TCA and finally obtain D-cysteine, and recovering L-TCA from said diastereomer salt of L-TCA and finally obtain L-cysteine. Method for optical resolution of (R,S)-1-(1-naphthyl)ethylamine (R,S)-NEA by (1) reacting an optically active cysteine with formaldehyde to prepare an optically active thiazolidine-4-carboxylic acid, (2) forming diastereomer salts of (R)-NEA and of (S)-NEA by reacting (R,S)-NEA with optically active thiazolidine-4-carboxylic acid, (3) separating said diastereomer salts of (R)-NEA and of (S)-NEA by difference of the solubilities thereof in a solvent, (4) recovering (R)-NEA from said diastereomer salt of (R)-NEA, and recovering (S)-NEA from said diastereomer salt of (S)-NEA.

FIELD OF THE INVENTION 
The present invention relates to a method for optical resolution of 
DL-cysteine and (R,S)-1-(1-naphthyl)ethylamine. 
Both L-cysteine and D-cysteine are important compounds, since they are used 
widely for various pharmaceutical products, cosmetics and for food 
additives. Recently, L-cysteine is produced mainly from the natural 
resources through extraction method. However, availability of the natural 
resources is limited, increasing demand of L-cysteine cannot be satisfied. 
Similar to the above, a large quantity of demand of D-cysteine is expected 
as for intermediates of synthesizing various antibiotics, however 
D-cysteine is produced only by method of optical resolution of 
DL-cysteine, any suitable method for producing D-cysteine in an industrial 
scale have not been developed yet. 
Under the circumstances, optical resolution method for DL-cysteine which 
can be suitable for industrial scale application is greatly desired, since 
DL-cysteine can be produced in a large scale with less expensive 
production cost through synthetic methods. [Japanese Patent Publication 
No. 58-5194 (1983), Japanese Patent Publication No. 57-16099 (1982) and 
Angew. Chem., (1981), Vol. 93, page 45]. 
On the other hand, (R,S)-1-(1-naphthyl)ethylamine is widely used for 
optical resolving agent, similar to natural basic optical resolving 
agents, such as ephedrine, quinine and the like, again optical resolution 
method for (R,S)-1-(1-naphthyl)ethylamine is greatly desired. 
PRIOR ART 
1. There are known some methods for optical resolution of DL-cysteine in 
prior art literatures as follows: 
(1) Methods using enzymes: 
(1) Method of treating S-benzyl-N-acetyl-DL-cysteine with aminoacylase. 
[Arch. Biochem. Biophys., Vol., 39, page 108 (1952)]. 
(2) Method of treating S-benzyl-DL-cysteine with amides. [J. Bio. Chem., 
Vol. 184, page 55, (1950)]. 
(3) Method of treating S-alkylmercapto-N-acetyl-DL-cysteine. [Japanese 
Patent Publication No. 57-21985 (1982)]. 
(2) Methods for converting DL-cysteine into diasteromers by using optical 
resolving agent having optical activity: 
(1) Method of treating S-benzyl-N-formyl-DL-cysteine with brucine. [J. Bio. 
Chem., Vol. 130, page 109, (1939)]. 
(2) Method of treating DL-cysteine with mandelic acid. [Japanese Patent 
Application Kokai (Laid-open) No. 57-193448 (1982)]. 
(3) Method for optical resolution of 
2-substituted-thiazolidine-4-carboxylic acid prepared by reacting 
DL-cysteine with an optically active sugar. [Japanese Patent Publication 
No. 60-33824 (1985)]. 
(3) Methods of preferential crystallization: 
(1) Method of preferential crystallization of DL-cysteine hydrochloride. 
[Japanese Patent Publication No. 60-55063 (1985)]. 
(2) Method of preferential crystallization of DL-thiazolidine-4-carboxylic 
acid. [Japanese Patent Application Kokai (Laid-open) No. 60-142952 
(1985)]. 
These methods known in the prior art literatures, however are not 
considered as satisfactory methods for optical resolution of DL-cysteine 
which can be applied for industrial scale production, for the reasons that 
these methods involve several difficulties, such as lower yield of the 
desired products, complexity in the process steps, difficulties on 
controlling the optical resolution conditions and others. 
2. On the other hand, methods for optical resolution of 
(R,S)-1-(1-naphthyl)ethylamine are reported in the prior art literatures 
as follows: 
(1) Method by using (+)-tartaric acid. [U.S. Pat. No. 2,996,545 (1961) by 
R. R. Bottoms]. 
(2) Method by using (-)-menthylphthalate. [U.S. Pat. No. 3,000,947 (1961) 
by R. R. Bottoms]. 
(3) Method by using (-)-di-O-isopropylidene-2-keto-L-gulonic acid. [U.S. 
Pat. No. 3,904,632 (1975) by C. William]. 
(4) Method of using cis-1,2-cyclohexanedicarboxylic acid. [Japanese Patent 
Application Kokai (Laid-open) No. 57-146743 (1982)]. 
(5) Method by using cis-2-benzamidocyclohexanecarboxylic acid. [Japanese 
Patent Application Kokai (Laid-open) No. 58-24545 (1983)]. 
These methods known in the prior art literatures, however are not 
considered as satisfactory methods for optical resolution of 
(R,S)-1-(1-naphthyl)ethylamine which can be applied for industrial scale 
production, for the reasons that these methods require a large quantity of 
organic solvents, and can only be obtained the desired optically active 
products having high purity in lower yield since several steps of 
recrystallization are required. 
SUMMARY OF THE INVENTION 
An object of the present invention is to provide a method for optical 
resolution of DL-cysteine so as to obtain D-cysteine and L-cysteine having 
high optical purity in high yields. 
Another object of the present invention is to provide a method for optical 
resolution of (R,S)-1-(1-naphthyl)ethylamine so as to obtain 
(R)-1-(1-naphthyl)ethylamine and (S)-1-(1-naphthyl)ethylamine, both of 
which having high optical purity, in high yields. 
DETAILED EXPLANATION OF THE INVENTION 
The present inventors have conducted extensive studies for overcoming 
several drawbacks involved in the methods known in the prior art 
literatures, and finally succeeded to establish the present invention by 
using thiazolidine-4-carboxylic acid (hereinafter referred to as "TCA", 
thus optically inactive isomer is referred to as "DL-TCA", and optically 
active isomers are referred to as "D-TCA" and "L-TCA", respectively) 
having the formula: 
##STR1## 
for optical resolution of DL-cysteine to obtain D-cysteine and L-cysteine, 
as well as for optical resolution of (R,S)-1-(1-naphthyl)ethylamine 
[hereinafter referred to as "(R,S)-NEA", and optically active isomers are 
referred to as "(R)-NEA" and "(S)-NEA", respectively]. 
Generally, the mercapto group in cysteine is a functional group having 
highly reactivity which is susceptible to oxidation, for this reason when 
optical resolution of cysteine is conducted without protecting the 
mercapto group, the resultant optically active isomers can only be 
obtained in lower yields and with lower optical purities. Furthermore, 
cysteine in which the mercapto group is protected, can hardly form a 
NEA-salt thereof in a solvent, if the amino group therein is also 
protected, similar to in the case of neutral amino acids. 
The TCA used in the present invention has the structural formula in which 
the mercapto group and the amino group in the cysteine are protected at 
the same time, thus optically inactive isomer and optically active isomers 
can be obtained in higher yield when each of the corresponding optical 
isomers of cysteine is reacted with formaldehyde in water [J. Amer. Chem. 
Soc., Vol. 59, page 200 (1937)]. 
This TCA can easily be formed a salt with NEA in a solvent. Also TCA opens 
its ring structure to forms cystine which is a dimer of cysteine when it 
is treated with an oxidizing agent such as hydrogen peroxide, iodine or 
the like, in an aqueous medium [J. Amer. Chem. Soc., Vol. 59, page 200, 
(1937)]. 
Cystine can be converted into cysteine by a common reducing method, for 
example electrolytic reduction [Japanese Patent Application Kokai 
(Laid-open) No. 51-136620 (1976)]. Thus, optically active isomers of TCA 
obtained from optical resolution of DL-TCA can easily be converted into 
the corresponding optically active isomers of cysteines. 
The present invention is characterized by treating DL-TCA with an optically 
active NEA isomer [(R)-NEA or (S)-NEA] to form a corresponding diasteromer 
salt, then separating said diasteromer salt by the difference of 
solubility in the solvent, or by treating (R,S)-NEA with an optically 
active TCA isomer (D-TCA or L-TCA) to form a corresponding diasteromer 
salt, then separating said diasteromer salt by the difference of 
solubility in the solvent. 
In conducting an optical resolution according to the present invention, any 
one of the optically resolving agent, i.e., (R)-NEA, (S)-NEA, or D-TCA, 
L-TCA is dissolved in a suitable solvent, by warming, with DL-TCA or 
(R,S)-NEA, respectively, then the thus prepared solution is cooled slowly 
to a predetermined temperature, and allowed to stand for a certain hours, 
so as to preferentially crystallize any one of the two diasteromers formed 
in the solution. The crystals thus precipitated in the solution is 
collected by means of, for example, filtration, and the mother liquor is 
further cooled to a certain temperature and allowed to stand for a certain 
length of time, then another diasteromer salt is crystallized. 
As to the solvent to be used in the present method, water or any organic 
solvents, such as methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 
2-butanol and acetone and the like can be used in single form or a mixture 
thereof, and from an industrial purpose, water is used preferably. 
The amount of the solvent to be used in the present method, there are some 
differences between the type of the solvents, and generally a certain 
times of the solvent to the amount of the salt formed can be used, and 
there is not any restriction to the amount of the solvent. Preferably, 
when water is used, which is advantageous from an industrial standpoint, 
generally 1.0 to 5.0 times of water is preferably used. 
The cooling temperature for crystallizing the hardly soluble salts is 
different depend on the type of the solvent and the amount of the solvent 
used, and generally a temperature in the range of from 10.degree. C. to 
50.degree. C. can be applied, and in view of the easiness in practical 
operation, room temperature is the most preferable. In addition to the 
above, the temperature for crystallizing another salt of diasteromer, a 
temperature in the range of from 0.degree. C. to -20.degree. C. is 
preferable. 
The time for stand the solution to crystallize the salt is not specifically 
restricted, and can be selected from a wide range, and generally, 10 to 24 
hours is preferable for crystallize the salt sufficiently with make the 
operation efficiently. 
The molar ratio of the optical resolving agent to the optically inactive 
isomer to be optically resolved is not specifically restricted, and can be 
selected from a wide range, and generally an equimolar quantity of both 
optical resolving agent and optically inactive isomer can be used 
preferably. 
Next, an aqueous solution of sodium hydroxide or of potassium hydroxide is 
added to the salt, the salt is decomposed and NEA is separated as an oily 
substance. Then, said oily substance is extracted with an organic solvent, 
the TCA is separated in the aqueous layer, and the NEA is separated in the 
organic layer. 
As to the organic solvent used for the extraction, any organic solvent 
which will not miscible with water, and can be able to dissolve the NEA 
can be used. In view of to make the extraction efficiently, diethyl ether, 
diisopropyl ether and ethyl acetate and the like may preferably be used. 
According to method of the present invention, in the case of optical 
resolution of DL-TCA by using (R)-NEA, after the treatment of firstly 
crystallized salt, to the aqueous solution being separated is added 
hydrochloric acid so as to adjust the pH to about 4.0, then the solution 
is concentrated and cooled to obtain D-TCA having high optical purity can 
be obtained as crystals. On the other hand, another salt obtained by 
cooling further lower temperature, there can be obtained L-TCA having high 
optical purity can be obtained by treating similarly to that in the case 
of the salt firstly obtained. In this case, to the filtrate obtained after 
separation of the first salt, is added a predetermined amount of an 
aqueous solution of sodium hydroxide or of potassium hydroxide so as to 
separate (R)-NEA as in the form of an oily substance, and after said oily 
substance is removed by extraction with an organic solvent, hydrochloric 
acid is added to the aqueous solution to adjust the pH to about 4.0, then 
the solution is concentrated and cooled to obtain L TCA having high 
optical purity can also be obtained. The (R)-NEA being extracted with the 
organic solvent can be recovered in higher yield by removing the organic 
solvent. 
In the case of conducting optical resolution of DL-TCA by using (S)-NEA as 
the optical resolving agent, L-TCA can be obtained from the firstly 
crystallized salt on one hand, and D-TCA can be obtained from the filtrate 
after separation of the firstly formed salt, or can be obtained the salt 
precipitated at lower cooled temperature on the other hand. 
While, in accordance with the present invention, in the case of conducting 
optical resolution of (R,S)-NEA by using L-TCA as the optical resolving 
agent, the salt firstly crystallized is treated by a procedure similar to 
the above, then the organic solvent layer is dehydrated with anhydrous 
sodium sulfate, then the dehydrating agent is removed by filtration, the 
organic solvent is removed by evaporation under reduced pressure, if 
necessary the desired product can be obtained by distillation, so that 
(S)-NEA having high optical purity can be obtained, on one hand. The 
crystals precipitated lower temperature are treated by a method similar to 
that used in the firstly obtained salt, then (R)-NEA can be obtained. In 
this case, to the filtrate being separated the firstly crystallized salt 
by filteration is made alkaline, then removed NEA containing much amount 
of (R)-isomer, and further conducting optical resolution by using D-TCA, 
there is obtained (R)-NEA in a high yield. 
In the case of conducting optical resolution of (R,S)-NEA by using D-TCA, 
similar to the above, (R)-NEA can be obtained from the firstly 
crystallized salt on one hand, and (S)-NEA can be obtained from the salt 
crystallized at lower temperature on the other hand. 
The present invention relates to optical resolution of (R,S)-NEA by using 
optically active TCA, or to optical resolution of DL-TCA by using 
optically active NEA. However, when the method is conducting practically, 
it is preferable to carry out optical resolution of (R,S)-NEA by using 
L-TCA which is the only obtainable optical isomer prepared from L-cysteine 
exists in the natural resource. 
Thus, in the case of optically resolving (R,S)-NEA by using L-TCA, there 
can be obtained (S)-NEA and (R)-NEA. Then DL-TCA is optically resolved by 
using (R)-NEA or (S)-NEA, then L-TCA and D-TCA can be obtained. As 
explained above, the optically active isomers once obtained according to 
the present invention, they can be recovered in high yield, and thus said 
optically active isomers can be used repeatedly for obtaining the desired 
optical isomers.

The present invention can be explained by way of illustrating the following 
examples, however, the present invention is not restricted only to these 
examples. 
EXAMPLE 1 
To 500 ml of water, there ,was added 171.2 g (1 mol) of (R,S)-NEA and 133.3 
g (1 mol) of L-TCA, then the whole mixture was heated to 
80.degree.-90.degree. C. with stirring on a water-bath so as to dissolve 
the solid matters. Heating was stopped when the solid matters were 
completely dissolved, (S)-NEA.L-TCA was added as the crystal nucleus, and 
the solution was cooled to 20.degree. C. and allowed to stand for 24 
hours. The crystals precipitated were collected by filtration and dried, 
there was obtained 125 g of (S)-NEA.L-TCA salt. 
To 125 g of the above-mentioned crystals, there was added 500 ml of 
1N-sodium hydroxide aqueous solution, then the oily substance separated 
therefrom was extracted twice with 500 ml of diethyl ether. The ether 
layer was dehydrated with anhydrous sodium sulfate, and diethyl ether was 
removed by evaporation under reduced pressure, there was obtained 70 g of 
(S)-NEA (yield: 40.9%). ].alpha.].sub.D.sup.20 =-60.1.degree. (c=2 
methanol). Optical purity=96.9%. 
To the filtrate after separation of the salt which is hardly soluble in 
water, there was added (R)-NEA.L-TCA as the crystal nucleus, then was 
cooled to -5.degree. C., and allowed to stand for 24 hours. Then the 
crystals precipitated were collected by filtration and dried, there was 
obtained 86 g of salt of (R)-NEA.L-TCA. 
To 86 g of the crystals, there was added 300 ml of 1N-sodium hydroxide 
aqueous solution, then the oily substance separated therefrom was 
extracted twice with 300 ml of diethyl ether. The ether layer was 
dehydrated with anhydrous sodium sulfate, and diethyl ether was removed by 
evaporation under reduced pressure, there was obtained 44.5 g of (R)-NEA 
(yield=26%). [.alpha.].sub.D.sup.20 =+60.9.degree., (c=2 methanol). 
Optical purity 98.2%. 
EXAMPLE 2 
To 500 ml of water, there were added 171.2 g (1 mol) of (R.S)-NEA and 133.3 
g (1 mol) of L-TCA, then the whole mixture was heated to 
80.degree.-90.degree. C. with stirring on a water-bath so as to dissolve 
the solid matters. Heating was stopped when the solid matters were 
completely dissolved, (S)-NEA.L-TCA was added as the crystal nucleus, and 
the solution was cooled to 20.degree. C. and allowed to stand for 24 
hours. The crystals precipitated were collected by filtration, and dried, 
there was obtained 128 g of (S)-NEA.L-TCA. 
To 128 g of the crystals, there was added 500 ml of 1N-sodium hydroxide 
aqueous solution, then the oily substance separated therefrom was 
extracted twice with 500 ml of diethyl ether. The ether layer was dried 
with anhydrous sodium sulfate, and diethyl ether was removed by 
evaporation under reduced pressure, there was obtained 71 g of (S)-NEA 
(yield: 41.5%), [.alpha.].sub.D.sup.20 =-59.9.degree. C. (c=2 methanol), 
Optical purity: 96.9%. 
To the filtrate after separation of the salt which is hardly soluble in 
water, there was added 130 ml of 5N-sodium hydroxide aqueous solution, 
then the oily substance separated thereform was extracted twice with 200 
ml of diethyl ether. The ether layer was dehydrated with anhydrous sodium 
sulfate, and diethyl ether was removed by evaporation under reduced 
pressure, there was obtained 98 g (yield=57.8%) of NEA containing 
(R)-isomer in much amount. [.alpha.].sub.D.sup.20 =+40.9.degree. (c=2 
methanol) 
Two of aqueous layers after extraction of NEA were combined, then 98 ml of 
concentrated hydrochloric acid was added thereto so as to adjust the pH to 
about 4, then this mixture was concentrated under pressure so as to the 
volume of about 400 ml. The resultant concentrate was allowed to stand in 
a refrigerator for 24 hours. The crystals thus formed were collected by 
filtration, and dried. There was obtained 125 g of L-TCA (recovery rate: 
93.8%) [.alpha.].sub.D.sup.20 =-206.3.degree. (c=4 1N-NaOH). 
EXAMPLE 3 
To 25 ml of water, there were added 6.66 g (5.times.10.sup.-2 mol) of 
DL-TCA and 8.56 g (5.times.10.sup.-2 mol) of (S)-NEA obtained in Example 
1, then the mixture was heated to 80.degree.-90.degree. C. with stirring 
on a water-bath. Heating was stopped when the solid matters were 
completely dissolved, the mixture was cooled slowly to 20.degree. C., then 
allowed to stand as it was for 24 hours. The crystals precipitated were 
collected by filtration, and dried to obtain 6.4 g of L-TCA-(S)-NEA salt. 
50 Milliliters of 0.5N-sodium hydroxide aqueous solution was added to the 
above-mentioned crystals, then the oily substance separated therefrom was 
extracted twice with 50 ml of diethyl ether. To the aqueous layer was 
added hydrochloric acid so as to adjust the pH of the solution to about pH 
4, then was concentrated the aqueous layer under reduced pressure to 
dryness, then 20 ml of water was added to the residue. Then the resultant 
solution was allowed to stand in a refrigerator for about 24 hours. The 
crystals precipitated were collected by filtration and dried. There was 
obtained 2.4 g of L-TCA (yield=36%). [.alpha.].sub.D.sup.20 
=-207.1.degree. (c=4 1N-NaOH). 
To the filtrate after separation of the salt which is hardly soluble in 
water, there was added D-TCA.(S)-NEA as the crystal nucleus, then the 
mixture was cooled to -5.degree. C., and allowed to stand as it was for 24 
hours. The crystals thus precipitated were collected by filtration to 
obtain 4.5 g of D-TCA-(S)-NEA salt. 
40 Milliliters of 0.5N-sodium hydroxide aqueous solution was added to 4.5 g 
of D-TCA.(S)-NEA salt, then the oily substance separated therefrom was 
extracted twice with 40 ml of diethyl ether. To the aqueous layer was 
added hydrochloric acid so as to adjust the pH to about 4, then water was 
removed by evaporation to remove about 15 ml of water. Thus obtained 
concentrate was allowed to stand in a refrigerators for 24 hours. The 
crystals precipitated were collected by filtration and dried, there was 
obtained 1.5 g (yield=22.5%) of D-TCA. [.alpha.].sub.D.sup.20 
=+206.3.degree. (c=4 1N-NaOH). 
EXAMPLE 4 
340 Milliliters of water was added to 98 g (5.72.times.10.sup.-1 mol) of 
NEA containing much amount of (R)-isomer prepared in the above-mentioned 
Example 2 and 76.3 g (5.72.times.10.sup.-1 mol) of D-TCA prepared in the 
above-mentioned Example 3, the mixture was heated with stirring on a water 
bath so as to dissolve the solid matters. Heating was stopped when the 
solid matters were dissolved completely. The solution was cooled slowly to 
20.degree. C., and allowed to stand as it was for 24 hours. The crystals 
precipitated were collected by filtration to obtain 125 g of (R)-NEA.D-TCA 
salt. 
To this crystals was added 500 ml of 1N-sodium hydroxide aqueous solution, 
then the oily substance separated therefrom was extracted twice with 500 
ml of diethyl ether. The ether layer was dried with anhydrous sodium 
sulfate, then this drying agent was removed by filtration, and diethyl 
ether was removed by evaporation under pressure. There was obtained 68 g 
(yield=39.7%) OF (R)-NEA. [.alpha.].sub.D.sup.20 =+61.4.degree. (c=2 
methanol). Optical purity=99.0%. 
EXAMPLE 5 
To 25 ml of water was added 8.56 g (5.times.10.sup.-2 mol) of (R,S)-NEA and 
6.66 g (5.times.10.sup.-2 mol) of D-TCA, then the mixture was heated to 
80.degree.-90.degree. C. with stirring on a water-bath so as to dissolve 
the solid matters. Heating was stopped when the solid matters were 
completedly dissolved. The solution was cooled slowly to 20.degree. C., 
and allowed to stand as it was for 24 hours. The crystals precipitated 
were collected by filtration and dried, there was obtained 6.1 g of 
(R)-NEA.D-TCA salt. 
The crystals were recrystallized from 20 ml of water to obtain 5.4 g of 
(R)-NEA.D-TCA salt. 
To the said crystals was added 50 ml of 0.5N-sodium hydroxide aqueous 
solution, then the oily substance separated therefrom was extracted twice 
with 50 ml of diethyl ether. The ether layer was dried with anhydrous 
sodium sulfate, and the drying agent was removed by filtration, then 
diethyl ether was removed by evaporation under reduced pressure to obtain 
3.0 g of (R)-NEA (yield 35%). [.alpha.].sub.D.sup.20 =-62.0.degree. (c=2 
methanol). Optical purity 100%. 
EXAMPLE 6 
To 30 ml of water was added 6.66 g (5.times.10.sup.-2 mol) of DL-TCA and 
8.56 g (5.times.10.sup.-2 mol of (R)-NEA, and the mixture was heated with 
stirring to 80.degree.-90.degree. C. on a water-bath so as to dissolve the 
solid matters. Heating was stopped when the solid matters were completely 
dissolved. The solution was cooled slowly to 10.degree. C., and allowed to 
stand as it was for 24 hours. The crystals precipitated were collected by 
filtration and dried, there was obtained 6.5 g of D-TCA.(R)-NEA salt. 
The above-mentioned crystals were dissolved in 50 ml of 0.5N-sodium 
hydroxide aqueous solution, then the oily substance separated therefrom 
was extracted twice with 50 ml of diethyl ether. To the aqueous layer was 
added concentrated hydrochloric acid so as to adjust the pH of the 
solution to about 4, and was concentrated under reduced pressure, to 
dryness, then 20 ml of water was added to the resultant residue and this 
solution was allowed to stand in a refrigerator for overnight. The 
crystals precipitated were collected by filtration, and dried to obtain 
2.5 g (yield=37.9%) of D-TCA. [.alpha.].sub.D.sup.20 =+207.2.degree. (c=4 
1N-NaOH). 
1.33 g of D-TCA was dissolved in 90 ml of water, then 0.5 ml of 35% 
hydrogen peroxide was added, and the mixture was allowed to stand in a 
refrigerator overnight. The crystals precipitated were collected by 
filtration, and dried to obtain 1.0 g of D-cystine (yield=83.3%). 
[.alpha.].sub.D.sup.20 =+223.5.degree.. (c=2 1N-HCl). 
To the filtrate after separation of the hardly soluble D-TCA.(R)-NEA salt 
was added 15 ml of 2N-sodium hydroxide aqueous solution, then the oily 
substance separated therefrom was extracted twice with 50 ml of diethyl 
ether. To the aqueous layer was added concentrated hydrochloric acid to 
adjust the pH of the solution to about pH 4, then the aqueous solution was 
concentrated under reduced pressure to remove dryness, then 20 ml of water 
was added to the residue. The resultant solution was allowed to stand in a 
refregirator overnight. The crystals precipitated were collected by 
filtration, and dried to obtain 2.5 g of L-TCA (yield=37.9%). 
[.alpha.].sub.D.sup.20 =-206.9.degree. (c=4 1N-NaOH). 
1.33 of L-TCA was dissolved in 90 ml of water, and 0.51 ml of 35% hydrogen 
peroxide was added, then the mixture was allowed to stand in a 
refrigerator overnight. The crystals precipitated were collected by 
filtration and dried. There was obtained 1.0 g of L-cystine (yield=83.3%). 
[.alpha.].sub.D.sup.20 =-222.1.degree. (c=1 1N-HCl). 
EXAMPLE 7 
To 120 g of D-cystine, obtained by a method similar to that described in 
Example 6, added 120 ml of concentrated hydrochloric acid and 300 ml of 
water. This solution was used as the negative electrode solution. On the 
other hand, an aqueous solution prepared by diluting 7.5 ml of 
concentrated sulfuric acid with 75 ml of water, was used as the positive 
electrode solution. As to the diaphragm, Selemion CMV cationic 
ion-exchange membrane (manufactured by Asahi Glass Co., Ltd.) was used, 
further a silver plate was used as the negative electrode and platinum 
plate was used as the positive electrode. Electrolytic reduction was 
conducted at 7-8 A of current, and 4.5-5 volts for 15 hours. After the 
electrolytic reduction was completed, the negative electrode solution was 
taken out, and decolored by adding 3 g of activated carbon with stirring. 
Then the activated carbon was removed by filtration and the resulting 
filtrate was concentrated under pressure and the crystals were 
precipitated. The crystals were collected by filtration and dried to 
obtain 165.5 g of D cysteine hydrochloride monohydrate. (yield: 94%). 
[.alpha.].sub.D.sup.20 =-6.31.degree. (c=8 1N-HCl). 
EXAMPLE 8 
By a method similar to that described in Example 7, there was obtained 158 
g (yield=89.5%) of L-cysteine hydrochloride monohydrate was obtained from 
120 g of L-cystine prepared by a method similar to that described in 
Example 6. [.alpha.].sub.D.sup.20 =+6.28.degree. (c=8 1N-HCl).