JPH049486A - High-yield method for electrochemical preparation of cysteine and its analogue - Google Patents

Abstract

PURPOSE: To directly and electrochemically synthesize cysteine and its analog at a high yield of ≥90% by subjecting a basic nitrogenous electrolytic soln. contg. a disulfide compd. to electrolytic reduction at a prescribed cathode current density.

CONSTITUTION: The basic nitrogenous electrolytic soln. contg. the disulfide compd. is introduced into an electrolytic cell having an anode and a cathode of a large surface area. Next, a DC voltage is impressed between both electrodes described above and the disulfide compd. is reduced at the cathode to form an amino acid free base. The product yield (current efficiency) of ≥90 is attained at the cathode current density of ≥50 mA/cm².

COPYRIGHT: (C)1992,JPO

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Field of Application) The present invention provides for direct electrochemistry of cysteine and its sulfhydryl analogues as salt-free amino acids, i.e., bases, without forming acid salts as intermediates. This relates to an improved method for synthetic synthesis.

(Conventional Technique?#) Cysteine is a sulfhydryl-containing amino acid that has become increasingly important in recent years and is used in hair-waving formulations, nutritional supplements, and as an intermediate in the synthesis of some pharmaceutical products. It’s happening!-Shimata nine?!-
a? It is derived from naturally occurring E-cystine, which is produced by hydrolysis of animal products from Hatun HICJ Yiyun. However, mixtures of d-cysteine and the optically inactive racemic d12~ are also derived in various ways. It is known that cysteine is unstable in neutral or alkaline media and is easily oxidized to cystine in the air.

Cysteine has the following formula: (-5-CHzC)I(NHz)COJ)z”
2tl" + 2e -2H5CHzctl (N
tl□) CO□H can be prepared by reduction of cystine or disulfide. This reduction is carried out chemically in aqueous +1 (J) with reactants such as Na/liquid ammonia, Zn, Af or Sn, or NaBHn
? G liquid is used. However, these methods yield impure cysteine contaminated with inorganic by-products.

The by-products are often difficult or expensive to separate. Also, small and trace amounts of such impurities are unacceptable for some applications, such as nutritional supplements.

Hitherto, electrochemical reduction of cystine to cysteine has generally been carried out in aqueous acid solutions, where cystine is dissolved in aqueous 11CN or 112SO.

Rambachny (Rambachcr) is U.S. Patent No. 2,
No. 907,703 (1959), 2N aqueous 11
describes the electrochemical reduction of an aqueous suspension of cystine hydrochloride in Sn, Cu, Ag, N
An electrochemical cell containing an ionic or carbon cathode is used, in which the anode chamber is separated from the cathode chamber by a porous diaphragm. If the cathode is a Cu sheet or carbon rod, 5nCf2 is added to the catholyte, and if the cathode is made of Ag or Ni, metallic Sn is added to the catholyte. Cystine as 11C1 salt is obtained after long electrolysis. Additional steps are required to obtain pure cysteine as the free base of this amino acid. Thus, in order to electrochemically prepare cysteine free base by Lambatigny's method, the acid salt had to first be made.

Similarly, Wong and -ang are J.

Chir+ese Chem, Soc, 1977,
Group, p. 149, describes the electrochemical reduction of cystine in an aqueous 11C7' solution using stainless steel electrodes in an electrochemical cell equipped with an anion exchange membrane.

The purpose of using this anion exchange membrane is to allow it to pass anions, such as chloride ions, but not cations or starting materials or products. The electrolytic product after evaporation of the aqueous electrolyte solution was +1 (1!) cysteine as a salt. Therefore, the free amino acid cysteine was obtained by dissolving the cysteine hydrochloride in ethanol and pl
It was prepared by carefully adding an aqueous N II,OH solution to +6.2, filtering and drying the resulting free cysteine.

On the other hand, this electrochemical process gave the cysteine+1 product in 92% yield, and the neutralization step gave free cystine in only 80% yield. Cystine is an expensive product. Since the cost is generally about $50/kg, the loss of cysteine during the precipitation process etc. will lead to a cost increase.The Wong & Wang method described above is not practical from the viewpoint of long production times. Under these conditions, the stainless steel anode will be immediately corroded as CI!2 is generated at the anode, and the resulting Cβ2 or +10C1 will be removed by the use of this type of anion exchange membrane [Asahi Glass (^5ahiGlass)].
s) Company: Selemion AMν] may be attacked or destroyed.

Mizuguchi et al. used a porous porcelain diaphragm for separation of the anode and cathode chambers in the first electrolytic cell to separate an aqueous acid medium (HCl or ozso4) and an aqueous alkaline medium (NaOI+, N
Electrolysis of cystine was carried out in a2CO3 and NH,011) (Bull, Tokyo, In5t, Te
chnol, 1965, 64, pp. 1-6).

It was demonstrated that when the aqueous acid solution was further electrolyzed in a second electrolytic cell containing an ion exchange resin diaphragm, deoxidation to free cysteine occurred in high yield. in alkaline medium,
Mizuguchi has shown that significant cystine and cysteine loss occurs through the porous porcelain diaphragm. Mizuguchi's results on aqueous N Ha Off m fluids are particularly relevant to the present invention. Cystine (12,1g)
The electrolysis of 3 M NH,OH(NH4) 2C(h
NH,O (about 10% by weight) at the pb cathode. After a long period of electrolysis, the catholyte is evaporated to dryness and
9 containing 7.0 g cystine and 2.0 g cystine
．． It gave 0g of crude product. According to the author, no pb was detected in the product. Mizuguchi et al., page 6, concluded that alkaline electrolysis provides pure cysteine or its salts in lower yields than acid electrolysis. Based on actual results, Mizuguchi et al. calculated a yield of cysteine of about 58%, with perhaps a loss of about 25% of valuable product and/or valuable starting material to the anode chamber via the separator. And so. Under these conditions approximately 12
The low current efficiency of % indicates that most of the cathode current is wasted for H2 generation.

Japanese Patent Publication No. 58-23450 (Hasaka)
(Published June 7, 1962) discloses a method for the electrochemical reduction of cystine to cysteine in an aqueous alkaline solution of ammonia, ammonium carbonate, ammonium chloride, pyridine hydrochloride or piperidine hydrochloride. Hasaka performed this reaction using the cathode as a low surface area two-dimensional plate. Reduce the current density to only 10-30mA/cm
'Met.

Similar to Mizuguchi et al., the product yield of Hasaka using alkaline electrolyte was as low as 75%.

Although Hasakah's published patents emphasize that low-cost metals can be used with alkaline anolytes that cannot be used with acidic solutions, the use of a lead cathode similar to Hasakah's does not allow the use of lead in cystine concentrations that are dangerous. introduced in
It has also been found that this makes the product unacceptable as an intermediate for the synthesis of food grade materials, especially for additives, nutritional supplements and pharmaceuticals and other products, especially for internal and external use.

Thus, the loss of expensive disulfide raw materials and sulfhydryl products is minimized, the use of ancillary conductive salts is not required, and the separation of the product as one amino acid from the electrolyte is simplified and the second Cystine and its counterparts using a single improved electrolyzer that does not require the use of deoxidizing electrolyzers and provides the product at high current densities, high yields, high current efficiencies and conversions. It would be desirable to develop a more economical, high-fidelity, and highly efficient method for electrochemically producing highly purified cysteine and its analogs from analogs that contain cysteine and its analogs.

The present invention provides such an improved electrochemical method for producing cysteine and its sulfhydryl analogs.

(Problems to be Solved by the Invention and Means for Solving the Problems) The main object of the present invention is to provide a method for electrochemically preparing amino acid free bases directly without preparing acid salts as intermediates. The object of the present invention is to provide a high-yield, economical process that includes the step of equipping an electrochemical cell with an anode and a high surface area, non-contaminating cathode. A basic nitrogen-containing electrolyte solution containing a disulfide compound is introduced into the acid bath as a catholyte. The product is formed by applying a voltage between the anode and the cathode of a value sufficient to reduce the disulfide compound at the cathode.

This amino acid free base is obtained in high yield when the basic nitrogen-containing electrolyte is removed. The concentration of the disulfide compound in the electrolyte and the high surface area of the cathode result in a current density of at least 50 mA/cm" and a current density of at least 90%
is sufficient to give a product yield of 100%, the product being free of any potentially harmful trace metals and other impurities from the acid bath electrodes. This amino acid free base material is characterized as being largely free of impurities and is amenable to use as food grade additives or materials or intermediates for the synthesis of food grade additives or materials as well as pharmaceuticals.

Another object of the present invention is to provide a method containing especially aqueous ammonia, anhydrous liquid ammonia (containing a sufficient concentration of disulfide reactant) to provide at least 90% of a given amount without loss of valuable disulfide reactant. The object of the present invention is to provide a basic nitrogen-containing electrolyte that maintains a high product yield. Yet another object is to carry out the reaction in an electrochemical cell with a high-yield partition and, in particular, a membrane of the ion-exchange type for separating the catholyte from the anolyte without loss of reactants. There is a particular thing.

Another object of the present invention is to carry out the above electrochemical reactions consistently with high current efficiencies of at least 90% using improved high surface area electrodes, which electrodes are made of carbonaceous materials in amorphous or crystalline form. , for example only partially graphitized amorphous carbon, glassy or glassy carbon and fluorinated carbon, and in particular the cathode consists of a high surface area three-dimensional carbonaceous cathode with a length, width and depth. .

The method of the invention comprises purifying the free base material in an aqueous medium;
removing any insoluble residue, including unreacted disulfide compounds, from the aqueous mixture and recovering the amino acid free base material by excluding the aqueous medium. This method also allows recovery of any unreacted disulfide reactant. The invention also includes the step of converting the amino acid free base, if necessary, to a salt of an inorganic acid.

These and other features and advantages will become more apparent from the following detailed description of the invention.

The method of the invention converts an amino acid, eg, its d, l- or djl! - Primarily concerned with preparation in molds.

The term disulfide analog includes cysteine and related compounds containing a reducible disulfide bond, at least one basic nitrogen group, and a carboxyl group of the following general formula (1): where R1 and R2 are H1 Lower aliphatic (01~C&)
R1 and R2 may together form a nitrogen-containing heterocyclic group having 3 to 7 atoms in which nitrogen is basic.

Thus, the disulfide compound of structure I has α-β-1γ
- or ω-amino acids. Examples of disulfide amino acid analogs of Structure I include:

(-3CII□C82CH(NHK)CO2H) 2
: Homocystine (tlzNcHz-CIICO□11)
2-1: Isocystine ((CI+3) 2CCH(NHK)CO,H)! :
Benicillamine disuride (-3C1lzC1l□NIIC)12cOZH)2
; (-5(Jig-C1l(NHK)CIIZC
O□■)2(-S-(C1h) 3-C(C1h) (
NFlz) COzll) z ;(-S-(C11□)
2-CHCO□II)2(CHz)6 NR+Rz Similarly, examples of mercaptoamino acids of structure (II) are cysteine, homocystine, isocystine, penicillamine, 2-mercap1-nicotinic acid, and 2-amino-3
- Contains mercaptobenzoic acid. Other examples of mercaptoamino acids will be apparent to those skilled in the art from the amino acid analogs described above.

Basic nitrogen-containing catholytes for the electrochemical production of cysteine and its analogues (H) according to the invention include aqueous ammonia, anhydrous liquid ammonia and aqueous amine solutions.

The amine is a lower aliphatic amine, preferably has a boiling point below the boiling point of water at atmospheric pressure, and has a boiling point of about 13
It has a boiling point below 0°C, making it easy to separate it from the desired product. An important feature in the selection of the amine-containing nitrogenous catholyte is that it is completely released from solution upon distillation or evaporation and is free of salt-free disulfide materials and/or salts.
or leave a sulfhydryl product and that does not undergo any or substantially all racemization or undesired reactions.

Nitrogen-containing catholytes also contain volatile auxiliary solvents,
It can help dissolve some otherwise insoluble disulfide substrates. These volatile co-solvents include solvents such as lower alcohols such as methanol, ethanol and imebrobanol, as well as acetonitrile, tetrahydrofuran, dioxane and other volatile solvents or mixtures of nitrogenous catholytes such as NH1 in water and/or alcohols. and (C113)J. Suitable amines are of the general formula R3N, where R is H, methyl, ethyl, propyl,
Isopropyl, butyl, isobutyl, 5ec-butyl,
It is t-butyl or a mixture of alkyl groups. Other amines are also useful, such as pyrrolidine, isoamylamine, n-amylamine, piperidine, ethylenediamine, and morpholine. Among the above nitrogen-containing solutions, a 2 volume solution of aqueous or anhydrous ammonia is preferred. This is because they have a high solubilizing capacity for substrates and products;
This is because it has a low boiling point, exhibits good ionic conductivity in combination with dissolved substrates and/or products, is easy to separate, and is low cost.

The nitrogen-containing solution component may be present in the electrolyte at a concentration that partially or completely neutralizes the disulfide, or may be in slight or large excess.

Thus, a preferred concentration of the nitrogen-containing component is such that its solution with the disulfide reactant has satisfactory electrolyte conductivity and sufficient solubility of the disulfide so that at high current densities, the mercaptan product The value is such that it gives a high yield and current efficiency.

When using an aqueous solution of ammonia, the ammonia is preferably present in an amount greater than about 5% by weight, more preferably greater than about 10%, optimally greater than about 20% by weight, and the substrate
1) It is possible to obtain a highly concentrated solution. 30% by weight
Commercially available ammonia solutions with higher effective concentrations can also be prepared by slurrying a saturated mixture of disulfide substrate and 30% aqueous ammonia while bubbling NH gas until the substrate solution reaches the desired concentration. . This high disulfide substrate? Agricultural efficiency makes it possible to carry out electrolysis at high current densities, often at low electrolytic sliding voltages, and with higher product current efficiencies and higher yields than hitherto achievable. As a result, the expense required for distillation or evaporation for solvent removal is saved.

The starting concentration of the disulfide substrate (1) in the nitrogenous catholyte should be about 0.001M or higher, preferably about 0.1M, most preferably about 0.2-1.0M.
Or it should be more.

Although conductive salts of the nitrogen-containing component, such as carbonates and bicarbonates, can be added to increase the concentration of the effective nitrogen-containing component and decompose these salts during the preparation process, the addition of these salts is usually unnecessary; and often undesirable. These salts add additional complexity to the process and make it uneconomical.

When an ion exchange membrane is used as an element of the electrolytic cell, this exchange membrane prevents the migration and loss of the negatively charged carboxylate anions and/or products of the disulfide substrate through the acid membrane and into the anode chamber. In order to minimize this, it should preferably be a cation exchange membrane. In a membrane-separated electrolytic cell, the anolyte may preferably be a suitable electrically conductive solution that generates protons at the anode during electrolysis. Such an anolyte is dissolved in an aqueous medium. Various ammonium salts such as (N114)2SO4, (N1
4): +f'On, (N)IdzC(h and can be ammonium 1. salts of organic acids such as acetate, polumate, oxalate. Other suitable anolytes are aqueous +l2S
o4 or aqueous H3P0. It can be. Halogen-containing anolyte, for example aqueous Nt141! and aqueous H(l) can also be used, but are not preferred, since precautions must be taken against the generation of C7!2 and possible undesirable and dangerous chlorinated nitrogen by-products, such as nitrogen trichloride. It is.

The anode may be a carbonaceous material, such as carbon, graphite, vitreous carbon, or particularly fluorinated carbon, graphite or vitreous carbon. The specifically fluorinated carbon is manufactured by The Electrosynthesis Company, Inc.
thesis Company Inc,) P, 0
゜Box 430, Ys 1- Unburst (Eas
It is a soft fluorinated carbon manufactured and sold by tA+++herst) N, Y, 14051, and has the trademark “
It is readily available as "SFC" carbon.

SFC materials tend to increase the corrosion stability of these carbons and impart useful catalytic properties. The anode is also T
PL supported on i, Pt/Ir supported on Ti
, PbO□ supported on Pb, PbO supported on Ti
It can be a metal such as ff1 or a catalyzed or uncatalyzed ceramic, for example an Ebonex anode (Ti407). When not catalyzed with PT or other noble metals, Evonex anodes have been found to have higher overpotentials for the oxidation of sulfhydryl products to the corresponding disulfides compared to the oxidation of nitrogen-containing electrolyte solutions. Although some reoxidation of the product to disulfide substrates occurs at the anode, the use of Evonesox anodes allows the removal of ion exchange membranes from the electrolyzer design, resulting in significant capital and operating costs. Save money.

Careful selection of cathode materials is critical to high yield reduction of cystine and its disulfide analogs. Known metal cathodes, particularly those composed of +1111, tag, and their alloys, introduce traces to significant amounts of potentially harmful metals into the final product, rendering the product unsuitable for some applications. There is a risk that it may become inappropriate. Generally, the object of the present invention is to provide a "non-contaminating cathode".
ting cathode)” does not introduce potentially harmful substances into the product, yet renders the product as a food, pharmaceutical, or cosmetic grade material, free from heavy metals and other contaminants present in these. The concentration of the substance is U,
S, Hood, Drug & Cosmetics Act (Uni
ted 5tates Food.

Druy and Goametic Act, ) shall mean such cathode materials as shall be within the limits set by the Druy and Goametic Act, ). Toxic heavy metals, such as lead, are not tolerated in pharmaceutical products, while for some topical applications the use of trace amounts of heavy metals may violate adulterant regulations. It is acceptable to some extent.

High surface area carbon materials are preferred. This is because the amount of contaminants in the final product is usually minimal or almost absent. The most preferred carbonaceous cathode materials are of the porous and multidimensional type, examples of which include amorphous and graphitic carbons, vitreous carbons, fluorinated carbons and especially soft fluorinated carbons. Particularly high product yields, conversion rates and current efficiencies are found for these carbonaceous cathodes compared to metal cathodes. However, granular beds, porous carbon, felt, cloth or reticulated vitreous carbon (ERG)
Carbonaceous cathodes, such as those manufactured by Co., Ltd. (California), provide better properties. For example, carbon felts give almost quantitative yields, conversions and current efficiencies in the electrolysis of cystine in ammonia solution by passing a stoichiometric amount of current. For the purposes of the present invention,
All expressions such as “carbon felt” and “carbon cloth” encompass high surface area amorphous carbon, graphitic carbon and partially graphitized amorphous carbon. Representative examples of such materials are 8 inch and 1!4 inch thick materials are available from The Electrosynthesis Company under the names GFS5 and CF-86.
rosynthesis Company Inc.)
, East Unburst N, Y. Thin, high surface area, carbonaceous materials represented by carbon fabrics include fabrics with a flat jersey construction. The carbon cloth also includes carbon fiber fabric. Also included in the expression "carbon felt" are so-called "graphite felts", which in many instances are primarily amorphous carbon, which has been carbonized and only a portion of which has been converted to graphite. In many cases, the porous high surface area carbonaceous cathodes of the present invention include these so-called "graphite" materials. To obtain larger electrode geometries, these high surface area felts, cloths and reticulated vitreous carbons can be treated with inert, more conductive current carriers, e.g. by suitable conductive epoxies.
For example, in combination with graphite, Evonex or Ti, the current density distribution can be improved by making the current density uniform over the entire available electrode surface.

Solid polymer electrolyte technology can be advantageously used in these electrolysis. A suitable cation exchange membrane may be used, such as Nafion (Nafion, manufactured by DuPont, USA).
The anode side of the ion (2) 117 is coated with a layer of PT or Au, for example by electroless plating, and then a Ti-supported Pt anode screen is mechanically pressed onto this plating layer. Therefore, the anolyte supply is water and no additional conductive ions are required. This is because the polymeric ionomer membrane itself provides the ionic conductivity necessary for electrolysis. The use of solid polymer electrolyte technology has other advantages of low layer voltage and simple cell design.

Electrolysis of disulfide substrates is preferably carried out at low temperatures, usually -10
It should be carried out at ~+50°C to avoid racemization of the optically active substrate, product and other undesired reactions, but in cases where racemization or side reactions are not involved and other undesired reactions such as polymerization or decomposition. If there is little or no possibility of this occurring, it can be carried out at temperatures as high as approximately the boiling point of the nitrogen-containing electrolyte. Since the reoxidation of sulfhydrin products to the disulfide form can occur in the presence of oxygen or air, especially in alkaline media, −
C. Electrolysis is carried out in an inert atmosphere, usually under a nitrogen atmosphere.

The cell design should provide sufficient turbulent circulation of the nitrogen-containing electrolyte solution containing the disulfide substrate to minimize mass transfer limitations. Electrocell System
A plate frame like the one made in Sweden
df frame) vessels are suitable for this purpose, with sufficient tolerance in stage weight and allowing the use of solid electrodes, especially bed electrodes, and other porous electrodes, such as carbonaceous felt and cloth as well as reticulated vitreous carbon. do.

Other suitable tank designs, including monopolar and bipolar designs, can be found in various books, such as Chapman and Hall.
d flail, published in 1982, and Industrial Electrochemistry, written by Pletcher.
Electrochemistry).

The electrolysis is carried out to 80-150% of the theoretical Crohn's value required to convert disulfide to sulfuryl product, but more preferably to 100-110% of the theoretical value to ensure high conversion and Minimize hydrogen generation. The cathode current density for these electrolysis is usually 50-50
0 mA/cm'', higher effective cathode current densities are more suitable near the beginning of electrolysis, and decreasing the density as the electrolysis moves toward complete conversion. One advantage of the high surface area carbonaceous cathode is that at least 50 mA /cm'
, more preferably from 75 to about 250 m/cm2, without significant deterioration in current efficiency.
It can be maintained throughout the entire electrolysis until almost all of the disulfide substrate is converted.

Once this electrolysis is complete, the desired product is isolated, usually by removing the nitrogenous liquid by distillation or evaporation under reduced pressure. As for cysteine, this solid product can be used for numerous applications. I mean,
Although it is 98% pure or more, it can be further easily purified, primarily for cystine, by placing the product in enough cold water to electrolyze most of the initial product and removing any undesired cystine and This is because it is carried out by filtering out insoluble substances.

The recovered cystine can be recycled and used as starting material.

The filtrate is then evaporated to obtain cysteine with a purity of 99.5% or more. Purification can also be carried out by recrystallization from cold water or water-alcohol.

If necessary, the amino acid free base can be converted to an inorganic salt by known means. Typical examples are hydrochlorides, sulfates and phosphates.

EXAMPLES Although the following specific examples demonstrate various aspects of the invention, they are given solely to illustrate the purpose of the invention and are intended to illustrate the terms and scope thereof. It is not prescriptive at all.

Example 1 A two-compartment electrochemical fluidized bath system was used. Here, Electrocell System (ElectrocellSys)
telIls) A B (Sweden) MP flow tank (Fliw Ce1l), storage tanks for anolyte and catholyte, magnetically driven pump, Sorensen model (Sorenso
n Model) OCR-45B Power Supply (P
5 apply) and an ESC model 640 digital coulometer. This MP flow tank has a polypropylene frame, EPDM gasket, Pt/I
Titanium anode with r coating (1,00cm”)
, various cathode materials, and DuPont ([)uPon
t) It consisted of a Nafior+ 423 cation exchange membrane. The volumes of the catholyte and anolyte are initially about 11, and the catholyte is 0.42M in 30% aqueous ammonia solution! - Contains cystine and the anolyte contains 3
M aqueous sulfuric acid solution. The catholyte was circulated at a rate of 4.7 A/min and its temperature was maintained below 40 f, while being kept under a nitrogen gas atmosphere to prevent air oxidation. Table 1 shows comparative results of electrochemical reduction of l-cystine on silver, graphite and carbon felt cathodes. This carbon felt cup (・ is carbon felt (100c)
rn”) (Electrossynthesis, Inc.)
Synthesis Co, Inc.) Catalog Yang GF
-36) was bonded to a graphite plate using an epoxy resin rated by Grapheye I.

The cathode current density was 60n+A/ throughout this experiment.
Cm", and electrolysis was carried out to about 100% of the theoretical charge passed for the conversion of l-cystine to p-cystine. After electrolysis, the ammonia solvent was evaporated to dryness, and the product was converted to iodine. Analyzed by titration method.

The anolyte was 3M aqueous 11□SO.

1 Silver plate 4.2-6.1 75.6
2 Graphite plate 4.4-6.0 82.8
3 Carbon felt, 4.4-4.8 96.6
*Yield and current efficiency are the same here.

The yields shown in Table 1 demonstrate that high surface area carbon fer 1- is superior to low surface area silver or graphite plate electrodes in reducing disulfide bonds.

The experimental flow tank apparatus described in Example 1 was used.
It included a carbon felt cathode and conducted electrolysis over a range of current densities.

Table 2 shows the results of electrolyzing β-cystine (0.42M) to form E-cystine with the theoretically required number of clones. Except as stated, 1■ of l-cystine true ILII? iJ, LT: Kanegishi (Engineering) 1 proverb 1u [b 几 ke 11 tank 11 Lα) 60 4.4~4.8 100 5.2~6,5100
6.2～8,4150 6.4
~7.8200 6.6~9.8250
6.2-8.4* Anolyte is 1M aqueous (NHm) □S04゜** Yield and current efficiency are the same here 96.6 99.2 95.6 96.5 90.6 94.6 Table 2 show that carbon felt cathodes can be used very effectively to reduce disulfide bonds with yields of over 90% even at much higher and more practical current densities than previously reported.

To illustrate the relative frugality of product isolation and purification using a nitrogen-containing catholyte, the product of electrolysis experiment number 3 of Example 1 was purified. 750++ of the crude product after evaporation of ammonia
+I! of distilled water, the resulting mixture was filtered, and the solid was washed with a small amount of cold distilled water. Filter the filtrate under vacuum
The purified material was obtained by evaporation to dryness at 0°C. Iodometric analysis showed that this material contained 99.6% by weight l-cysteine. 1M aqueous 1 (C1 solution 10
The specific rotation of a sample of 5.02 g of the material dissolved at 0 mf was +6.255. This is 99.4% p
- Corresponds to the test for cysteine. Elemental analysis (%)
was as follows.

Actual value: C29,69: H5,84; N 11
．． 51; S 26.41 calculated value: C29,74;
H5,82; N 11.56: S 26.46 Example 4 Using an aqueous NlI4011 solution containing (N114)zcO:+,
The l-cysteine road base was prepared according to the method outlined in aka)).

The two compartments were separated using a cation exchange membrane (Nafion).
n■) 324). The cathode was a lead sheet. After electrolysis, the catholyte was evaporated to dryness and the product was dried under vacuum. The product contained 8941% by weight p-cysteine and was found to contain 43 ppm lead by atomic absorption spectrometry.

For many applications, especially food and pharmaceutical applications, this high lead concentration would be unacceptable in the product.

Although the invention has been described in connection with specific embodiments thereof, this is done by way of example only. Therefore,
Many alternatives, modifications and variations will be apparent to those skilled in the art in light of the above description, and all such alternatives, which fall within the scope of the above broad claims and spirit of the invention. It should be understood that improvements and changes are included.

Procedural amendment (formality) %formula% 1. Display of incident 1999 Patent Application No. 339899 2. Name of the invention Electricity of cysteine and its analogs High yield method for chemical preparation 3. Person who makes corrections Relationship with qr items

Claims (1)

[Claims] (1) A basic nitrogen-containing electrolyte solution containing a disulfide compound is introduced into an electrochemical cell equipped with an anode and a high surface area cathode, and the disulfide compound is reduced at the cathode. applying a sufficient voltage between the anode and the cathode to remove the basic nitrogen-containing electrolyte solution to produce an amino acid free base; an amino acid having a surface area sufficient to provide a cathodic current density of at least 50 mA/cm^2 and a value sufficient to achieve a product yield and current efficiency of at least 90%. High-yield method for electrochemical preparation of free bases. 2. The method of claim 1, wherein the high surface area cathode is a non-fouling cathode. (3) A compound in which the amino acid free base is represented by the following formula: ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ and compounds in which the disulfide is represented by the following formula: ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼, and in the above formula, R_1 and R_2 are a hydrogen atom, a lower aliphatic group, an aryl group, or an aralkyl group, or R_1 and R_2 together are nitrogen atoms having 3 to 7 atoms, where the nitrogen is basic. Claim 2 representing a containing heterocyclic group
Method described. 4. The method of claim 3, wherein the high surface area cathode comprises a carbonaceous material. 5. The method of claim 3, wherein the high surface area cathode comprises carbon felt or cloth. (6) The method of claim 4, wherein the electrochemical cell includes an ion exchange membrane. (7) The method according to claim 6, wherein the disulfide compound is cystine, the amino acid free base is cysteine, and the basic nitrogen-containing electrolyte solution is aqueous ammonia or anhydrous liquid ammonia. (8) The method according to claim 7, wherein the basic nitrogen-containing electrolyte solution contains a volatile organic co-solvent. (9) The initial concentration of the disulfide compound in the basic nitrogen-containing electrolyte solution is at least 0.1 mol.
Method described. 10. The method of claim 6, wherein the electrochemical reaction is conducted with a current efficiency of at least 90%. 11. The method of claim 6, wherein the electrochemical cell comprises a solid polymer electrolyte. (12) introducing a basic nitrogen-containing electrolyte solution into an electrochemical cell containing cystine and having an anode and a cathode; a solution sufficient to reduce cystine at the cathode; reducing cystine in the electrochemical cell, comprising applying a voltage; removing the basic nitrogen-containing electrolyte solution to produce cysteine as a free base;
In the electrochemical preparation of cysteine free base, the reaction is carried out in an electrochemical cell containing a high surface area, non-fouling cathode, and the cathode is at least 50 mA/cm^.
provides a cathode current density of 2 and at least 90%
The above process is characterized in that it has a surface area sufficient to give a product yield as well as a current efficiency of . (13) The method according to claim 12, wherein the step of removing the basic nitrogen-containing electrolyte solution is performed by evaporation or distillation. (14) The high surface area cathode is carbon felt, carbon cloth,
13. The method of claim 12, comprising a carbonaceous material selected from the group consisting of specifically fluorinated carbon and reticulated vitreous carbon. (15) The method according to claim 14, wherein the electrochemical cell is equipped with an ion exchange membrane. (16) The basic nitrogen-containing electrolyte solution is aqueous ammonia,
16. The method of claim 15, which is anhydrous liquid ammonia, an aqueous amine solution, or a mixture thereof. (17) producing the cysteine free base material by mixing the cysteine free base material with water, removing any residual insoluble residue from the aqueous mixture containing unreacted cystine, and recovering the purified cysteine free base material by removing the water; 17. The method of claim 16, comprising purifying the free base material. 18. The method of claim 17, comprising the step of: (18) converting the cysteine free base material to a salt of an inorganic acid. (19) The preparation of the amino acid free base was performed using Ti_4O_7
2. The method of claim 1, wherein the method is carried out in an electrochemical cell having an anode comprising: (20) The preparation of the amino acid free base was performed using Ti_4O_7
2. The method of claim 1, wherein the method is carried out in an electrochemical cell having an anode comprising: