JPH08119932A - Production of s-hydroxypropyl-l-cysteine - Google Patents
Production of s-hydroxypropyl-l-cysteineInfo
- Publication number
- JPH08119932A JPH08119932A JP25318694A JP25318694A JPH08119932A JP H08119932 A JPH08119932 A JP H08119932A JP 25318694 A JP25318694 A JP 25318694A JP 25318694 A JP25318694 A JP 25318694A JP H08119932 A JPH08119932 A JP H08119932A
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- Prior art keywords
- cysteine
- hydroxypropyl
- reaction
- producing
- component
- Prior art date
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、Ｓ−ヒドロキシプロピ
ル−Ｌ−システインの工業的に有利な製造法に関する。FIELD OF THE INVENTION The present invention relates to an industrially advantageous method for producing S-hydroxypropyl-L-cysteine.
【０００２】[0002]
【従来の技術及び発明が解決しようとする課題】従来、
Ｓ−ヒドロキシプロピル−Ｌ−システインの製造法とし
ては、システインと３−ハロゲノ−１−プロパノールと
をアルカリ（縮合剤）の存在下反応させる方法〔Ｂｉｏ
ｃｈｅｍ．Ｊ．１００，３２６（１９６２）；Ｊｏｕｒ
ｎａｌｏｆ Ｐｈａｒｍａｃｅｕｔｉｃａｌ Ｓｃｉｅ
ｎｃｅｓ ５０，３１２（１９６１）〕及びチオール誘
導体とβ−クロロアラニンをpH１０〜１３の水性溶液中
で反応させる方法（特開昭６０−２５８１５９号）が知
られている。2. Description of the Related Art Conventionally, the problems to be solved by the invention
As a method for producing S-hydroxypropyl-L-cysteine, a method of reacting cysteine and 3-halogeno-1-propanol in the presence of an alkali (condensing agent) [Bio
chem. J. 100 , 326 (1962); Jour.
nalf Pharmaceutical Scié
50 , 312 (1961)] and a method of reacting a thiol derivative with β-chloroalanine in an aqueous solution having a pH of 10 to 13 (JP-A-60-258159).
【０００３】しかしながら、前者の方法では、シスチン
が副生してしまい、純度の低下をまぬがれなかった。一
方、後者の方法では反応時間が長く、原料が高価である
等の欠点があり、工業的に有利な方法とは言い難いもの
であった。However, in the former method, cystine was produced as a by-product and the purity could not be reduced. On the other hand, the latter method has drawbacks such as a long reaction time and expensive raw materials, and it is difficult to say that the method is industrially advantageous.
【０００４】従って本発明の目的は、Ｓ−ヒドロキシプ
ロピル−Ｌ−システインの工業的に有利な製造方法を提
供することにある。Accordingly, it is an object of the present invention to provide an industrially advantageous method for producing S-hydroxypropyl-L-cysteine.
【０００５】[0005]
【課題を解決するための手段】斯かる実情に鑑み本発明
者らは鋭意研究を行った結果、下記の原料と反応条件に
よれば、Ｓ−ヒドロキシプロピル−Ｌ−システインを工
業的に有利に製造し得ることを見出し本発明を完成し
た。In view of such circumstances, the present inventors have conducted diligent research and as a result, according to the following raw materials and reaction conditions, S-hydroxypropyl-L-cysteine was industrially advantageous. The inventors have found that they can be manufactured and have completed the present invention.
【０００６】すなわち本発明は、次の６種のＳ−ヒドロ
キシプロピル−Ｌ−システインの製造法を提供するもの
である。 （１）システイン又はシステイン塩酸塩とアリルアルコ
ールとをラジカル開始剤の存在下反応させることを特徴
とするＳ−ヒドロキシプロピル−Ｌ−システインの製造
法。 （２）システイン又はシステイン塩酸塩とアリルアルコ
ールとをラジカル開始剤及び還元剤の存在下反応させる
ことを特徴とするＳ−ヒドロキシプロピル−Ｌ−システ
インの製造法。 （３）システイン又はシステイン塩酸塩とアリルアルコ
ールとを光照射下に反応させることを特徴とするＳ−ヒ
ドロキシプロピル−Ｌ−システインの製造法。 （４）２，２−ジメチルチアゾリジン−４−カルボン酸
に３−ハロゲノ−１−プロパノールをpH８〜１０で反応
させることを特徴とするＳ−ヒドロキシプロピル−Ｌ−
システインの製造法。 （５）システイン又はシステイン塩酸塩と３−ハロゲノ
−１−プロパノールをpH８〜１０で反応させ、得られた
反応混合物に還元剤を反応させることを特徴とするＳ−
ヒドロキシプロピル−Ｌ−システインの製造法。 （６）システイン又はシステイン塩酸塩と３−ハロゲノ
プロピル−１−アセテートとをアルカリ存在下で反応さ
せることを特徴とするＳ−ヒドロキシプロピル−Ｌ−シ
ステインの製造法。 なお、本発明においてシステイン塩酸塩は水和物であっ
てもよい。That is, the present invention provides the following six types of S-hydroxypropyl-L-cysteine production methods. (1) A method for producing S-hydroxypropyl-L-cysteine, which comprises reacting cysteine or cysteine hydrochloride with allyl alcohol in the presence of a radical initiator. (2) A method for producing S-hydroxypropyl-L-cysteine, which comprises reacting cysteine or cysteine hydrochloride with allyl alcohol in the presence of a radical initiator and a reducing agent. (3) A method for producing S-hydroxypropyl-L-cysteine, which comprises reacting cysteine or cysteine hydrochloride with allyl alcohol under light irradiation. (4) S-Hydroxypropyl-L-characterized in that 2,2-dimethylthiazolidine-4-carboxylic acid is reacted with 3-halogeno-1-propanol at pH 8-10.
Method for producing cysteine. (5) S- characterized by reacting cysteine or cysteine hydrochloride with 3-halogeno-1-propanol at pH 8 to 10 and reacting the resulting reaction mixture with a reducing agent.
Process for producing hydroxypropyl-L-cysteine. (6) A method for producing S-hydroxypropyl-L-cysteine, which comprises reacting cysteine or cysteine hydrochloride with 3-halogenopropyl-1-acetate in the presence of an alkali. In the present invention, cysteine hydrochloride may be a hydrate.
【０００７】本発明方法（１）において、アリルアルコ
ールの使用量はシステイン又はシステイン塩酸塩（以下
「システイン等」という）に対して、モル比で１〜３
倍、好ましくは１．５〜２．５倍程度、特に２倍程度と
することが好ましい。またここで用いるラジカル開始剤
としては、システインのチオール基をラジカルとするも
のであれば特に制限されないが、過硫酸塩、例えば過硫
酸ナトリウム、過硫酸カリウム、過硫酸アンモニウム等
が挙げられる。ラジカル開始剤の使用量はシステイン等
に対して１０重量％程度とすることが好ましい。反応溶
媒としては、水、アルコール、又はこれらの混合物等の
水性のものが好ましい。反応時間は温度により異なるが
通常５〜６０分とすることが好ましい。また反応温度は
０℃〜室温とすることが好ましい。In the method (1) of the present invention, the amount of allyl alcohol used is 1 to 3 in molar ratio with respect to cysteine or cysteine hydrochloride (hereinafter referred to as "cysteine etc.").
It is preferable to set it to twice, preferably about 1.5 to 2.5 times, especially about twice. The radical initiator used here is not particularly limited as long as it uses the thiol group of cysteine as a radical, and examples thereof include persulfates such as sodium persulfate, potassium persulfate, and ammonium persulfate. The amount of the radical initiator used is preferably about 10% by weight with respect to cysteine and the like. The reaction solvent is preferably an aqueous solvent such as water, alcohol, or a mixture thereof. Although the reaction time varies depending on the temperature, it is usually preferably 5 to 60 minutes. The reaction temperature is preferably 0 ° C to room temperature.
【０００８】本発明方法（２）の条件は、更に還元剤を
添加して反応せしめること以外は（１）と同様である。
ここで用いる還元剤としては塩化第一鉄、メタ重亜硫酸
ナトリウム等が挙げられ、使用量はシステイン等に対し
て５〜１０重量％程度とすることが好ましい。The conditions of the method (2) of the present invention are the same as those of (1) except that a reducing agent is further added and reacted.
Examples of the reducing agent used here include ferrous chloride and sodium metabisulfite, and the amount used is preferably about 5 to 10% by weight with respect to cysteine and the like.
【０００９】本発明方法（３）においては、光を照射し
反応を開始させる。光照射は波長２５０〜２６０nmの光
を、１０〜６０分間程度行うことが好ましい。好ましい
光照射ランプとしては、低圧銀ランプが挙げられる。こ
のような光照射以外の使用原料モル比、反応温度、反応
時間、反応溶媒は前記方法（１）と同様が好ましい。In the method (3) of the present invention, light is irradiated to start the reaction. The light irradiation is preferably performed with light having a wavelength of 250 to 260 nm for about 10 to 60 minutes. A low-pressure silver lamp is mentioned as a preferable light irradiation lamp. Except for such light irradiation, the molar ratio of raw materials used, reaction temperature, reaction time, and reaction solvent are preferably the same as those in the above method (1).
【００１０】本発明方法（４）は２，２−ジメチルチア
ジアゾリジン−４−カルボン酸を同モル程度の３−ハロ
ゲノ−１−プロパノールと反応せしめることが好まし
い。３−ハロゲノ−１−プロパノールのハロゲン原子と
してはフッ素原子、臭素原子、塩素原子、ヨウ素原子が
挙げられる。反応時のpHは８〜１０であるが、９程度が
好ましい。pHを調整するには、水酸化ナトリウム、水酸
化カリウム、炭酸ナトリウム、炭酸カリウム等のアルカ
リを用いることが好ましい。反応は０℃〜室温で行うこ
とができ、攪拌しながら１時間〜１日程度行うことが好
ましい。In the method (4) of the present invention, it is preferable that 2,2-dimethylthiadiazolidine-4-carboxylic acid is reacted with approximately the same molar amount of 3-halogeno-1-propanol. Examples of the halogen atom of 3-halogeno-1-propanol include a fluorine atom, a bromine atom, a chlorine atom and an iodine atom. The pH during the reaction is 8 to 10, but about 9 is preferable. To adjust the pH, it is preferable to use an alkali such as sodium hydroxide, potassium hydroxide, sodium carbonate or potassium carbonate. The reaction can be carried out at 0 ° C to room temperature, and is preferably carried out for about 1 hour to 1 day while stirring.
【００１１】本発明方法（５）は、システイン等と方法
（４）で例示した如き３−ハロゲノ−１−プロパノール
を反応させた後、更に還元剤を反応させる。ここで用い
る還元剤としては、硫化ナトリウム、ハイドロサルファ
イド等が挙げられ、この使用量はシステイン等に対し１
〜５重量％程度とすることが好ましい。また、これら反
応においてはpHを８〜１０、特に９程度とすることが好
ましく、反応温度は４０〜７０℃程度とすることが好ま
しい。反応時間は最初の反応では３０〜６０分、還元剤
添加後の反応では４〜８時間程度が好ましい。In the method (5) of the present invention, cysteine or the like is reacted with 3-halogeno-1-propanol as exemplified in the method (4), and then a reducing agent is further reacted. Examples of the reducing agent used here include sodium sulfide, hydrosulfide, etc., and the amount used is 1 with respect to cysteine etc.
It is preferably about 5% by weight. In these reactions, the pH is preferably set to 8 to 10, particularly about 9, and the reaction temperature is preferably set to about 40 to 70 ° C. The reaction time is preferably 30 to 60 minutes in the first reaction and about 4 to 8 hours in the reaction after addition of the reducing agent.
【００１２】本発明方法（６）は３−ハロゲノプロピル
−１−アセテートとシステイン等とをアルカリ存在下で
反応させる方法であるが、ここで用いる３−ハロゲノプ
ロピル−１−アセテートとしては、３−フルオロプロピ
ル−１−アセテート、３−クロロプロピル−１−アセテ
ート、３−ブロモプロピル−１−アセテート、３−アイ
オドプロピル−１−アセテートが例示される。３−ハロ
ゲノ−１−アセテートは安価なジハロゲノプロパンに無
水酢酸等を反応せしめれば得ることができる。３−ハロ
ゲノ−１−アセテートは、システイン等に対し１〜２モ
ル程度使用することが好ましい。また、用いるアルカリ
は水酸化ナトリウム、水酸化カリウム、炭酸ナトリウ
ム、炭酸カリウム等が例示される。このアルカリにより
反応時のpHを１０〜１２程度好ましくは１１程度とする
のが好ましい。また反応温度は４０〜７０℃とすること
が好ましい。上記の如くして得られた粗生成物は、常法
により洗浄、精製すれば、純度の高いＳ−ヒドロキシプ
ロピル−Ｌ−システインとすることができる。The method (6) of the present invention is a method in which 3-halogenopropyl-1-acetate is reacted with cysteine or the like in the presence of an alkali, and 3-halogenopropyl-1-acetate used here is 3- Examples include fluoropropyl-1-acetate, 3-chloropropyl-1-acetate, 3-bromopropyl-1-acetate, and 3-iodopropyl-1-acetate. 3-halogeno-1-acetate can be obtained by reacting inexpensive dihalogenopropane with acetic anhydride or the like. It is preferable to use 3-halogeno-1-acetate in an amount of about 1 to 2 mol based on cysteine or the like. Examples of the alkali used include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate and the like. It is preferable to adjust the pH during the reaction to about 10 to 12, preferably about 11, with this alkali. The reaction temperature is preferably 40 to 70 ° C. The crude product obtained as described above can be converted into highly pure S-hydroxypropyl-L-cysteine by washing and purifying by a conventional method.
【００１３】[0013]
【発明の効果】本発明によれば、工業的に有利にＳ−ヒ
ドロキシプロピル−Ｌ−システインを製造することがで
きる。INDUSTRIAL APPLICABILITY According to the present invention, S-hydroxypropyl-L-cysteine can be industrially produced advantageously.
【００１４】[0014]
【実施例】次に実施例を挙げて本発明を更に詳細に説明
するが、本発明はこれらに限定されるものではない。The present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.
【００１５】実施例１ システイン２．０ｇ（１６．５ミリモル）を水２０mlに
溶かし、次いでアリルアルコール１．９５ｇ（３３ミリ
モル）を加え、室温攪拌下過硫酸カリウム２００mgを添
加し１５分反応を行った。反応終了後、溶媒を減圧下留
去し、残留物に２５％エタノールを加え不溶物を濾去し
た。濾液を濃縮し残留物を水−エタノールにて再結晶
し、無色結晶のＳ−（３−ヒドロキシプロピル）−Ｌ−
システイン２．５１ｇ（収率：８５％）を得た。Example 1 2.0 g (16.5 mmol) of cysteine was dissolved in 20 ml of water, 1.95 g (33 mmol) of allyl alcohol was added, and 200 mg of potassium persulfate was added with stirring at room temperature to carry out a reaction for 15 minutes. It was After completion of the reaction, the solvent was distilled off under reduced pressure, 25% ethanol was added to the residue, and the insoluble material was filtered off. The filtrate was concentrated and the residue was recrystallized from water-ethanol to give colorless crystals of S- (3-hydroxypropyl) -L-.
2.51 g (yield: 85%) of cysteine was obtained.
【００１６】実施例２ システイン２．０ｇ（１６．５ミリモル）を水２０mlに
溶かし、次いでアリルアルコール１．９５ｇ（３３ミリ
モル）を加え、室温攪拌下塩化第一鉄２００mg及び過硫
酸アンモニウム２００mgを添加し、１５分反応を行っ
た。反応終了後、溶媒を減圧下留去し、残留物に２５％
エタノールを加え、不溶物を濾去した。濾液を濃縮し残
留物を水−エタノールにて再結晶し、無色結晶のＳ−
（３−ヒドロキシプロピル）−Ｌ−システイン ２．３
６ｇ（収率：８０％）を得た。Example 2 2.0 g (16.5 mmol) of cysteine was dissolved in 20 ml of water, 1.95 g (33 mmol) of allyl alcohol was added, and 200 mg of ferrous chloride and 200 mg of ammonium persulfate were added with stirring at room temperature. The reaction was performed for 15 minutes. After the reaction was completed, the solvent was distilled off under reduced pressure, and the residue was 25%.
Ethanol was added and the insoluble material was filtered off. The filtrate was concentrated and the residue was recrystallized from water-ethanol to give colorless crystals of S-
(3-Hydroxypropyl) -L-cysteine 2.3
6 g (yield: 80%) was obtained.
【００１７】実施例３ システイン２．０ｇ（１６．５ミリモル）を水２０mlに
溶かし、次いでアリルアルコール１．９５ｇ（３３ミリ
モル）を加え、室温攪拌下低圧水銀ランプ（２５０〜３
１０nm，１０Ｗ）を３０分間照射した。反応終了後、反
応混合物を酢酸エチルで洗浄し水層を減圧下留去した。
残留物を水−エタノールにて再結晶し無色結晶のＳ−
（３−ヒドロキシプロピル）−Ｌ−システイン ２．７
８ｇ（収率：９４％）を得た。Example 3 2.0 g (16.5 mmol) of cysteine was dissolved in 20 ml of water, and then 1.95 g (33 mmol) of allyl alcohol was added, and the mixture was stirred at room temperature under a low pressure mercury lamp (250-3).
Irradiation with 10 nm, 10 W) for 30 minutes. After completion of the reaction, the reaction mixture was washed with ethyl acetate and the aqueous layer was evaporated under reduced pressure.
The residue was recrystallized from water-ethanol to give colorless crystals of S-.
(3-Hydroxypropyl) -L-cysteine 2.7
8 g (yield: 94%) was obtained.
【００１８】実施例４ ２，２−ジメチルチアゾリジン−４−カルボン酸１．６
１ｇ（１０ミリモル）を水１０mlに溶かし、氷冷攪拌下
５％水酸化ナトリウム水溶液６mlを加えpH９とした。こ
れに３−ブロモ−１−プロパノール１．５３ｇ（１１ミ
リモル）を加え、室温にて一昼夜攪拌した。反応終了
後、２Ｎ塩酸にて中和し溶媒を減圧下留去した。残留物
をイオン交換クロマトグラフィー（Ｄｏｗｅｘ−５０
Ｗ）に付し、２Ｎアンモニア水で流出する画分を集め減
圧濃縮した。残留物を水−エタノールにて再結晶し、無
色結晶のＳ−（３−ヒドロキシプロピル）−Ｌ−システ
イン１．３６ｇ（収率：７６％）を得た。Example 4 2,2-Dimethylthiazolidine-4-carboxylic acid 1.6
1 g (10 mmol) was dissolved in 10 ml of water, and the mixture was adjusted to pH 9 by adding 6 ml of 5% sodium hydroxide aqueous solution while stirring with ice cooling. 1.53 g (11 mmol) of 3-bromo-1-propanol was added to this, and it stirred at room temperature all day and night. After completion of the reaction, the mixture was neutralized with 2N hydrochloric acid and the solvent was distilled off under reduced pressure. The residue was subjected to ion exchange chromatography (Dowex-50).
Then, the fractions flowing out with 2N aqueous ammonia were collected and concentrated under reduced pressure. The residue was recrystallized from water-ethanol to obtain 1.36 g (yield: 76%) of colorless crystals of S- (3-hydroxypropyl) -L-cysteine.
【００１９】実施例５ システイン塩酸塩−水和物８．７ｇ（４９．５ミリモ
ル）、水酸化ナトリウム４．２ｇ、炭酸ナトリウム（無
水）２ｇ及び３−クロロ−１−プロパノール５ｇに水１
５mlを加えpH９で６０℃１時間攪拌した。次いで反応混
合物に硫化ナトリウム９０mgを加え、２Ｎ水酸化ナトリ
ウム水溶液にてpHを９に調整しながら同温度で４時間攪
拌した。反応終了後、１０％塩酸にてpH４とし反応混液
をイオン交換クロマトグラフィー（Ｄｏｗｅｘ−５０
Ｗ）に付し、２Ｎアンモニア水で流出する画分を集め減
圧濃縮した。残留物を水−エタノールにて再結晶し無色
結晶のＳ−（３−ヒドロキシプロピル）−Ｌ−システイ
ン ７．９７ｇ（収率：９０％）を得た。Example 5 Cysteine hydrochloride monohydrate 8.7 g (49.5 mmol), sodium hydroxide 4.2 g, sodium carbonate (anhydrous) 2 g and 3-chloro-1-propanol 5 g and water 1.
5 ml was added and the mixture was stirred at pH 9 for 1 hour at 60 ° C. Next, 90 mg of sodium sulfide was added to the reaction mixture, and the mixture was stirred at the same temperature for 4 hours while adjusting the pH to 9 with a 2N sodium hydroxide aqueous solution. After completion of the reaction, the reaction mixture was adjusted to pH 4 with 10% hydrochloric acid and the reaction mixture was subjected to ion exchange chromatography (Dowex-50).
Then, the fractions flowing out with 2N aqueous ammonia were collected and concentrated under reduced pressure. The residue was recrystallized from water-ethanol to obtain 7.97 g (yield: 90%) of colorless crystals of S- (3-hydroxypropyl) -L-cysteine.
【００２０】実施例６ １−ブロモ−３−クロロプロパン４０ｇ（２５４ミリモ
ル）、酢酸カリウム３０ｇ（３０６ミリモル）、トリエ
チルアミン０．２５６ｇ及び無水酢酸３mlの混合物を７
５℃で９時間反応した。反応後、水４５mlを加え下層
（水層）を除き、上層より３−クロロプロピルアセテー
ト２９．８４ｇ（収率：８６％）を得た。次いで、Ｌ−
システイン９．６８ｇ（８０ミリモル）を水６０mlに懸
濁し、２Ｎ水酸化ナトリウム水溶液を加えpH１１に調整
した。これに得られた３−クロロプロピルアセテート１
２ｇ（８８ミリモル）を加え、２Ｎ水酸化ナトリウム水
溶液にてpHを１１に保ちながら６０℃で５時間攪拌し
た。反応終了後、１０％塩酸にてpH４とし溶媒を減圧下
留去した。残留物をイオン交換クロマトグラフィー（Ｄ
ｏｗｅｘ−５０Ｗ）に付し、２Ｎアンモニア水で流出す
る画分を集め減圧濃縮した。残留物を水−エタノールに
て再結晶し、無色結晶のＳ−（３−ヒドロキシプロピ
ル）−Ｌ−システイン １０．２ｇ（収率：７１％）を
得た。Example 6 A mixture of 40 g (254 mmol) of 1-bromo-3-chloropropane, 30 g (306 mmol) of potassium acetate, 0.256 g of triethylamine and 3 ml of acetic anhydride was added.
The reaction was carried out at 5 ° C for 9 hours. After the reaction, 45 ml of water was added to remove the lower layer (aqueous layer), and 29.84 g (yield: 86%) of 3-chloropropyl acetate was obtained from the upper layer. Then L-
9.68 g (80 mmol) of cysteine was suspended in 60 ml of water, and 2N aqueous sodium hydroxide solution was added to adjust the pH to 11. 3-chloropropyl acetate 1 obtained in this
2 g (88 mmol) was added, and the mixture was stirred at 60 ° C. for 5 hours while maintaining the pH at 11 with a 2N sodium hydroxide aqueous solution. After the reaction was completed, the pH was adjusted to 4 with 10% hydrochloric acid, and the solvent was distilled off under reduced pressure. The residue was subjected to ion exchange chromatography (D
owex-50W), and the fractions flowing out with 2N aqueous ammonia were collected and concentrated under reduced pressure. The residue was recrystallized from water-ethanol to obtain 10.2 g (yield: 71%) of colorless crystals of S- (3-hydroxypropyl) -L-cysteine.
─────────────────────────────────────────────────────
─────────────────────────────────────────────────── ───
【手続補正書】[Procedure amendment]
【提出日】平成６年１０月２６日[Submission date] October 26, 1994
【手続補正１】[Procedure Amendment 1]
【補正対象書類名】明細書[Document name to be amended] Statement
【補正対象項目名】０００２[Name of item to be corrected] 0002
【補正方法】変更[Correction method] Change
【補正内容】[Correction content]
【０００２】[0002]
【従来の技術及び発明が解決しようとする課題】従来、
Ｓ−ヒドロキシプロピル−Ｌ−システインの製造法とし
ては、システインと３−ハロゲノ−１−プロパノールと
をアルカリ（縮合剤）の存在下反応させる方法〔Ｂｉｏ
ｃｈｅｍ．Ｊ．１００，３６２（１９６６）；Ｊｏｕｒ
ｎａｌｏｆ Ｐｈａｒｍａｃｅｕｔｉｃａｌ Ｓｃｉｅ
ｎｃｅｓ ５０，３１２（１９６１）〕及びチオール誘
導体とβ−クロロアラニンをｐＨ１０〜１３の水性溶液
中で反応させる方法（特開昭６０−２５８１５９号）が
知られている。2. Description of the Related Art Conventionally, the problems to be solved by the invention
As a method for producing S-hydroxypropyl-L-cysteine, a method of reacting cysteine and 3-halogeno-1-propanol in the presence of an alkali (condensing agent) [Bio
chem. J. 100 , 362 (1966); Jour
nalf Pharmaceutical Scié
50,312 (1961)] and a method of reacting a thiol derivative with β-chloroalanine in an aqueous solution having a pH of 10 to 13 (JP-A-60-258159).
Claims (6)
ルアルコールとをラジカル開始剤の存在下反応させるこ
とを特徴とするＳ−ヒドロキシプロピル−Ｌ−システイ
ンの製造法。1. A method for producing S-hydroxypropyl-L-cysteine, which comprises reacting cysteine or cysteine hydrochloride with allyl alcohol in the presence of a radical initiator.
ルアルコールとをラジカル開始剤及び還元剤の存在下反
応させることを特徴とするＳ−ヒドロキシプロピル−Ｌ
−システインの製造法。2. S-hydroxypropyl-L, which comprises reacting cysteine or cysteine hydrochloride with allyl alcohol in the presence of a radical initiator and a reducing agent.
-Method for producing cysteine.
ルアルコールとを光照射下に反応させることを特徴とす
るＳ−ヒドロキシプロピル−Ｌ−システインの製造法。3. A method for producing S-hydroxypropyl-L-cysteine, which comprises reacting cysteine or cysteine hydrochloride with allyl alcohol under light irradiation.
ルボン酸に３−ハロゲノ−１−プロパノールをpH８〜１
０で反応させることを特徴とするＳ−ヒドロキシプロピ
ル−Ｌ−システインの製造法。4. A 2,2-dimethylthiazolidine-4-carboxylic acid containing 3-halogeno-1-propanol at a pH of 8 to 1
A method for producing S-hydroxypropyl-L-cysteine, which comprises reacting at 0.
ハロゲノ−１−プロパノールをpH８〜１０で反応させ、
得られた反応混合物に還元剤を反応させることを特徴と
するＳ−ヒドロキシプロピル−Ｌ−システインの製造
法。5. Cysteine or cysteine hydrochloride and 3-
Reacting halogeno-1-propanol at pH 8-10,
A method for producing S-hydroxypropyl-L-cysteine, which comprises reacting the obtained reaction mixture with a reducing agent.
ハロゲノプロピル−１−アセテートとをアルカリ存在下
で反応させることを特徴とするＳ−ヒドロキシプロピル
−Ｌ−システインの製造法。6. Cysteine or cysteine hydrochloride and 3-
A method for producing S-hydroxypropyl-L-cysteine, which comprises reacting with halogenopropyl-1-acetate in the presence of an alkali.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP25318694A JP3223052B2 (en) | 1994-10-19 | 1994-10-19 | Method for producing S-hydroxypropyl-L-cysteine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP25318694A JP3223052B2 (en) | 1994-10-19 | 1994-10-19 | Method for producing S-hydroxypropyl-L-cysteine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH08119932A true JPH08119932A (en) | 1996-05-14 |
| JP3223052B2 JP3223052B2 (en) | 2001-10-29 |
Family
ID=17247751
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP25318694A Expired - Lifetime JP3223052B2 (en) | 1994-10-19 | 1994-10-19 | Method for producing S-hydroxypropyl-L-cysteine |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3223052B2 (en) |
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|---|---|---|---|---|
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1994
- 1994-10-19 JP JP25318694A patent/JP3223052B2/en not_active Expired - Lifetime
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102180820A (en) * | 2011-03-16 | 2011-09-14 | 四川科伦药物研究有限公司 | Purification method for preparing high-purity fudosteine |
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| CN103382171A (en) * | 2013-07-22 | 2013-11-06 | 江苏万特制药有限公司 | Preparing method of Fudosteine oxidation impurities |
| JP2017019735A (en) * | 2015-07-08 | 2017-01-26 | 株式会社日本触媒 | Manufacturing method of primary or secondary amine compound having (poly)alkylene glycol chain and composition containing primary or secondary amine compound having (poly)alkylene glycol chain |
| CN105622474A (en) * | 2016-01-12 | 2016-06-01 | 安徽悦康凯悦制药有限公司 | Production technique of fudosteine |
| CN105777595A (en) * | 2016-04-23 | 2016-07-20 | 威海迪素制药有限公司 | Preparation method of fodor stanozolol suitable for industrialized production |
| CN108358820A (en) * | 2018-01-17 | 2018-08-03 | 威海迪素制药有限公司 | A kind of preparation method of high-quality Fudosteine bulk pharmaceutical chemicals |
| CN108358820B (en) * | 2018-01-17 | 2021-09-03 | 迪嘉药业集团有限公司 | Preparation method of high-quality fudosteine raw material medicine |
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