JPH0717989A - Production of l-ascorbic acid-2-phosphoric acid ester - Google Patents
Production of l-ascorbic acid-2-phosphoric acid esterInfo
- Publication number
- JPH0717989A JPH0717989A JP5159161A JP15916193A JPH0717989A JP H0717989 A JPH0717989 A JP H0717989A JP 5159161 A JP5159161 A JP 5159161A JP 15916193 A JP15916193 A JP 15916193A JP H0717989 A JPH0717989 A JP H0717989A
- Authority
- JP
- Japan
- Prior art keywords
- ascorbic acid
- isopropylidene
- acid
- salt
- ester
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、安定なＬ−アスコルビ
ン酸−２−リン酸エステル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 a stable L-ascorbic acid-2-phosphate ester.
【０００２】[0002]
【従来の技術】Ｌ−アスコルビン酸は、ビタミンＣ源と
して又は酸化防止剤として、医薬品、食品及び化粧品等
に広く用いられている。しかし、Ｌ−アスコルビン酸に
は、熱や光に弱く、容易に酸化され、不安定であるとい
う欠点がある。BACKGROUND OF THE INVENTION L-Ascorbic acid is widely used as a source of vitamin C or as an antioxidant in medicines, foods, cosmetics and the like. However, L-ascorbic acid has a drawback that it is weak against heat and light, is easily oxidized, and is unstable.
【０００３】かかるＬ−アスコルビン酸の欠点を克服し
た安定な誘導体としてＬ−アスコルビン酸−２−リン酸
エステルがすでに知られており、この化合物は生体中で
容易に分解してＬ−アスコルビン酸となり、活性を示す
ため有用な化合物である。L-ascorbic acid-2-phosphate ester is already known as a stable derivative that overcomes the drawbacks of L-ascorbic acid, and this compound is easily decomposed in the living body to give L-ascorbic acid. , Are useful compounds because of their activity.
【０００４】アスコルビン酸−２−リン酸エステルを製
造する方法としては、例えばアスコルビン酸を直接ホス
ホリル化する方法（特公昭４３−９２１９号公報、特公
昭４５−２３７４６号公報）及び酵素法による製造法
（特開昭６３−２１４９０号公報）が知られているが、
これらの方法はいずれも、多種の化合物の混合物が生成
し、分離・精製に手間がかかったり、収率が低かったり
するものであり、工業的に有利な方法とは言い難いもの
であった。As the method for producing ascorbic acid-2-phosphate ester, for example, a method in which ascorbic acid is directly phosphorylated (Japanese Patent Publication No. 43-9219 and Japanese Patent Publication No. 45-23746) and an enzymatic method are used. (Japanese Patent Laid-Open No. 63-21490) is known,
In all of these methods, a mixture of various compounds is produced, which requires time and effort for separation and purification, and the yield is low, and it is difficult to say that these methods are industrially advantageous.
【０００５】一方、近年のアスコルビン酸−２−リン酸
エステルの製造法としては、副反応を抑え収率を上げる
ため、アスコルビン酸の５位と６位のアルコール性水酸
基をアセトンで保護し、５，６−Ｏ−イソプロピリデン
−Ｌ−アスコルビン酸を製造し、これをホスホリル化
し、次いで保護基を脱離することによりアスコルビン酸
−２−リン酸エステルを得る方法が一般的である。On the other hand, as a recent method for producing ascorbic acid-2-phosphate ester, the alcoholic hydroxyl groups at the 5th and 6th positions of ascorbic acid are protected with acetone to prevent side reactions and increase the yield. , 6-O-isopropylidene-L-ascorbic acid is generally prepared, phosphorylated, and then the protecting group is eliminated to obtain ascorbic acid-2-phosphate ester.
【０００６】従って、５，６−Ｏ−イソプロピリデン−
Ｌ−アスコルビン酸は、アスコルビン酸−２−リン酸エ
ステルの製造において重要な中間体であり、これまでに
多くの製造法が見出されている。このような方法として
は、硫酸銅を触媒とする方法〔Ｃｈｅｍ．Ｂｅｒ．６９
Ｂ，８７９（１９３６）、Ｃａｒｂｏｈｙｄｒａｔｅ
Ｒｅｓ．４５巻，４５（１９７５）〕、ｐ−トルエンス
ルホン酸を用いる方法〔Ｇａｚｚ．Ｃｈｉｍ．Ｉｔａ
ｌ．９１巻，９６４（１９６１）〕、過剰の塩化水素を
用いる方法〔Ｅｘｐｅｒｉｅｎｔｉａ ６１９（１９６
３）、Ｃａｒｂｏｈｙｄｒａｔｅ Ｒｅｓ．１９巻，１
２７（１９７１）〕、塩化アセチルを用いる方法〔Ｃａ
ｎ．Ｊ．Ｃｈｅｍ．４７巻，２４９８（１９６９）、
Ｊ．Ａｍ．Ｃｈｅｍ．Ｓｏｃ．１０２巻，６３０４（１
９８０）〕、塩化亜鉛を用いる方法（特開昭５８−１３
１９７８号公報）、ヨウ化水素、五塩化アンチモン、五
フッ化アンチモンを用いる方法（特開昭６０−６９０７
９号公報）、濃硫酸を用いる方法（特開平４−２９９８
９号公報）、発煙硫酸を用いる方法（特開平２−２８６
６９３号公報）がある。Therefore, 5,6-O-isopropylidene-
L-ascorbic acid is an important intermediate in the production of ascorbic acid-2-phosphate ester, and many production methods have been found so far. As such a method, a method using copper sulfate as a catalyst [Chem. Ber. 69
B, 879 (1936), Carbohydrate
Res. 45, 45 (1975)], a method using p-toluenesulfonic acid [Gazz. Chim. Ita
l. 91, 964 (1961)], using excess hydrogen chloride [Experientia 619 (196.
3), Carbohydrate Res. Volume 19, 1
27 (1971)], a method using acetyl chloride [Ca
n. J. Chem. Volume 47, 2498 (1969),
J. Am. Chem. Soc. Volume 102, 6304 (1
980)], a method using zinc chloride (JP-A-58-13).
1978), hydrogen iodide, antimony pentachloride, and antimony pentafluoride (JP-A-60-6907).
No. 9), a method using concentrated sulfuric acid (JP-A-4-2998).
No. 9), a method using fuming sulfuric acid (JP-A-2-286).
693).
【０００７】さらに、５，６−Ｏ−イソプロピリデン−
Ｌ−アスコルビン酸のホスホリル化反応によるアスコル
ビン酸−２−リン酸エステルの製造法としては、特公昭
４３−９２１９号公報、特公昭４５−４４９７号公報、
特公昭４５−３０３２８号公報、特開昭４８−７２１６
３号公報、特公昭５９−４４３８号公報、Ｃａｒｂｏｈ
ｙｄｒａｔｅ Ｒｅｓ．６７巻，１２７〜１３８（１９
７８）、特開昭６３−２１４１９０号公報、特開平２−
２８６６９３号公報、特開平３−２０４８９１号公報記
載の方法がある。Further, 5,6-O-isopropylidene-
As a method for producing ascorbic acid-2-phosphate ester by phosphorylation reaction of L-ascorbic acid, JP-B-43-9219, JP-B-45-4497,
JP-B-45-30328, JP-A-48-7216
No. 3, Japanese Patent Publication No. 59-4438, Carboh
hydrate Res. 67, 127-138 (19
78), JP-A-63-214190, and JP-A-2-
There are methods described in JP-A-286693 and JP-A-3-204891.
【０００８】[0008]
【発明が解決しようとする課題】しかしながら、従来の
５，６−Ｏ−イソプロピリデン−Ｌ−アスコルビン酸の
製造法においては、反応時の発熱のため冷却下に反応を
行なわなくてはならなかったり、刺激性の強い試薬が必
要である等工業的に有利な方法と言い難いものであっ
た。However, in the conventional method for producing 5,6-O-isopropylidene-L-ascorbic acid, it is necessary to carry out the reaction under cooling due to the heat generated during the reaction. However, it is difficult to say that this method is industrially advantageous because it requires a highly irritating reagent.
【０００９】一方、５，６−Ｏ−イソプロピリデン−Ｌ
−アスコルビン酸のホスホリル化反応は、従来のいずれ
の方法も収率が低く、反応後、煩雑な精製工程を要する
ため、工業的に有利な方法ではなかった。On the other hand, 5,6-O-isopropylidene-L
-The phosphorylation reaction of ascorbic acid is not an industrially advantageous method because all the conventional methods have low yields and require a complicated purification step after the reaction.
【００１０】従って本発明の目的は、Ｌ−アスコルビン
酸−２−リン酸エステルを工業的に有利に製造する方法
を提供することにある。Therefore, an object of the present invention is to provide a method for industrially advantageously producing L-ascorbic acid-2-phosphate.
【００１１】[0011]
【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なった結果、５，６−Ｏ−イソプロ
ピリデン−Ｌ−アスコルビン酸を経由する特定の方法が
反応温度、反応後の処理操作、収率等の面で従来の方法
に比べて良好であり、Ｌ−アスコルビン酸−２−リン酸
エステルを工業的に有利に製造することができる方法で
あることを見出し、本発明を完成した。In view of such circumstances, the present inventors have conducted diligent research and as a result, have found that a specific method via 5,6-O-isopropylidene-L-ascorbic acid has a reaction temperature and a reaction It was found that this method is better than conventional methods in terms of subsequent processing operations, yields, etc., and that L-ascorbic acid-2-phosphate ester can be industrially advantageously produced. Completed the invention.
【００１２】本発明方法は、次の反応式で示される。The method of the present invention is represented by the following reaction formula.
【００１３】[0013]
【化１】 [Chemical 1]
【００１４】〔式中、Ｍはアルカリ金属又はアルカリ土
類金属を示し、ｎはその金属のイオン価数を示す〕[In the formula, M represents an alkali metal or alkaline earth metal, and n represents an ionic valence of the metal]
【００１５】すなわち、Ｌ−アスコルビン酸（１）とア
セトンとを、三フッ化ホウ素エチルエーテル錯化合物単
独又はこの錯化合物と酢酸との混合物の存在下に反応せ
しめて５，６−Ｏ−イソプロピリデン−Ｌ−アスコルビ
ン酸（２）を得、これにオキシ塩化リンと水とを１：
１．５〜１：２．５のモル比で反応させたリン酸化試薬
をpH８〜１２で反応させて保護エステル体（３）とし、
次いで加水分解にて５，６−位保護基を脱離させれば、
目的とするＬ−アスコルビン酸−２−リン酸エステル
（４）が得られる。また、必要により、更にアルカリ金
属化合物又はアルカリ土類金属化合物を反応せしめれ
ば、Ｌ−アスコルビン酸リン酸エステルの塩（５）が得
られる。That is, L-ascorbic acid (1) and acetone are reacted in the presence of a boron trifluoride ethyl ether complex compound alone or in the presence of a mixture of this complex compound and acetic acid to prepare 5,6-O-isopropylidene. -L-ascorbic acid (2) was obtained, and phosphorus oxychloride and water were added to the mixture at a ratio of 1:
The phosphorylation reagent reacted at a molar ratio of 1.5 to 1: 2.5 is reacted at pH 8 to 12 to give a protected ester body (3),
Then, by removing the 5,6-position protecting group by hydrolysis,
The target L-ascorbic acid-2-phosphate ester (4) is obtained. If necessary, an alkali metal compound or an alkaline earth metal compound is further reacted to obtain the salt (5) of L-ascorbic acid phosphoric acid ester.
【００１６】第一段階の水酸基を保護する方法、すなわ
ち５，６−Ｏ−イソプロピリデン−Ｌ−アスコルビン酸
を得る方法は、Ｌ−アスコルビン酸に対してアセトンを
５〜１０重量倍加え、室温にて撹拌下、三フッ化ホウ素
エチルエーテル錯化合物（以下「ＢＦ3・Ｅｔ2Ｏ」とい
う）を滴下して行なう。ここで用いるＢＦ3・Ｅｔ2Ｏ
は、酸触媒として作用するものであり、これを用いると
当該５，６−Ｏ−イソプロピリデン化反応が室温で進行
し、かつ収率も従来の方法に比べて向上する。ここでＢ
Ｆ3・Ｅｔ2Ｏに加えて酢酸を滴下すれば、ＢＦ3・Ｅｔ2
Ｏの使用量を減少させることができる。ＢＦ3・Ｅｔ2Ｏ
の滴下量は０．２〜０．６モル当量程度が好ましく、酢
酸を併用する場合は０．０４〜０．２モル当量とするこ
とが好ましい。滴下後、１時間程度撹拌し、析出した結
晶を濾取し、アセトン等で洗浄すれば５，６−Ｏ−イソ
プロピリデン−Ｌ−アスコルビン酸（２）が得られる。The method of protecting the hydroxyl group in the first step, that is, the method of obtaining 5,6-O-isopropylidene-L-ascorbic acid, is as follows. With stirring, the boron trifluoride ethyl ether complex compound (hereinafter referred to as "BF 3 .Et 2 O") is added dropwise. BF 3 · Et 2 O used here
Acts as an acid catalyst, and by using this, the 5,6-O-isopropylidene formation reaction proceeds at room temperature and the yield is improved as compared with the conventional method. Where B
If acetic acid is added dropwise to F 3 · Et 2 O, BF 3 · Et 2
The amount of O used can be reduced. BF 3 · Et 2 O
The addition amount of is preferably about 0.2 to 0.6 molar equivalent, and when acetic acid is used in combination, it is preferably 0.04 to 0.2 molar equivalent. After the dropping, the mixture is stirred for about 1 hour, and the precipitated crystals are collected by filtration and washed with acetone or the like to give 5,6-O-isopropylidene-L-ascorbic acid (2).
【００１７】得られた５，６−Ｏ−イソプロピリデン−
Ｌ−アスコルビン酸（２）は、ホスホリル化に付され
る。ここで用いるリン酸化試薬は、オキシ塩化リン１モ
ルに対し水１．５〜２．５モルを撹拌下滴下して調製さ
れる。リン酸化試薬におけるオキシ塩化リンと水とのモ
ル比は１：１．５〜１：２．５であることが必要であ
り、１：１．５より小さいと不純物の生成量が増加し、
発熱量が大きくなり、１：２．５より大きいと保護エス
テル体（３）の収量が著しく低下し、いずれも好ましく
ない。オキシ塩化リンと水との好ましいモル比は１：２
付近である。また、このホスホリル化反応時のpHは８〜
１２に調整することが必要である。このホスホリル化反
応はアルカリ条件で進行するが、従来の方法においては
pH１３以上とする必要があった。本発明方法において
は、pH８〜１２という穏和な条件で反応が進行するた
め、次の反応工程の加水分解反応に用いる酸の使用量も
少なくてすむ。反応は５，６−Ｏ−イソプロピリデン−
Ｌ−アスコルビン酸の溶液のpHを８〜１２に保ちつつ、
上記のリン酸化試薬を滴下して行う。pHの調整は水酸化
カリウム水溶液を用いるのが好ましく、反応温度は０〜
２０℃程度が好ましい。The resulting 5,6-O-isopropylidene-
L-ascorbic acid (2) is subject to phosphorylation. The phosphorylation reagent used here is prepared by dropwise adding 1.5 to 2.5 mol of water to 1 mol of phosphorus oxychloride with stirring. The molar ratio of phosphorus oxychloride to water in the phosphorylation reagent must be 1: 1.5 to 1: 2.5, and if it is less than 1: 1.5, the amount of impurities produced increases,
If the calorific value is large, and if it is larger than 1: 2.5, the yield of the protected ester form (3) is remarkably reduced, which is not preferable. The preferred molar ratio of phosphorus oxychloride to water is 1: 2.
It is in the vicinity. The pH during the phosphorylation reaction is 8 to
It is necessary to adjust to 12. This phosphorylation reaction proceeds under alkaline conditions, but in the conventional method
It was necessary to adjust the pH to 13 or higher. In the method of the present invention, since the reaction proceeds under mild conditions of pH 8 to 12, the amount of acid used for the hydrolysis reaction in the next reaction step can be small. The reaction is 5,6-O-isopropylidene-
While maintaining the pH of the L-ascorbic acid solution at 8 to 12,
The above phosphorylation reagent is added dropwise. It is preferable to use an aqueous potassium hydroxide solution to adjust the pH, and the reaction temperature is 0 to
About 20 ° C is preferable.
【００１８】得られた保護エステル体（３）は、加水分
解により５、６位の保護基を脱離すれば、Ｌ−アスコル
ビン酸−２−リン酸エステル（４）とすることができ
る。この加水分解は保護エステル体（３）に水を加え、
トリフルオロ酢酸等の酸によりpHを７未満、例えば２〜
５に調整することにより行なわれる。The resulting protected ester form (3) can be converted into L-ascorbic acid-2-phosphate ester (4) by removing the protecting groups at the 5th and 6th positions by hydrolysis. This hydrolysis involves adding water to the protected ester form (3),
PH less than 7, for example 2 to 3 with acid such as trifluoroacetic acid
This is done by adjusting to 5.
【００１９】得られたＬ−アスコルビン酸−２−リン酸
エステル（４）の粗生成物は、常法により、カラムクロ
マトグラフィー等で精製することができる。The obtained crude product of L-ascorbic acid-2-phosphate ester (4) can be purified by a conventional method such as column chromatography.
【００２０】Ｌ−アスコルビン酸−２−リン酸エステル
（４）は、必要により中和等により、マグネシウム塩、
カルシウム塩、ナトリウム塩等の塩とすることができ
る。The L-ascorbic acid-2-phosphate ester (4) is, if necessary, neutralized or the like to give a magnesium salt,
It may be a salt such as a calcium salt or a sodium salt.
【００２１】[0021]
【発明の効果】本発明方法によれば、Ｌ−アスコルビン
酸−２−リン酸エステルを穏和な条件で簡便な操作によ
り工業的に有利に製造することができる。Industrial Applicability According to the method of the present invention, L-ascorbic acid-2-phosphate ester can be industrially advantageously produced by a simple operation under mild conditions.
【００２２】[0022]
実施例１ ５，６−Ｏ−イソプロピリデン−Ｌ−アスコルビン酸の
製造：Ｌ−アスコルビン酸２０ｇにアセトン１００mlを
加え室温撹拌下、ＢＦ3・Ｅｔ2Ｏ５mlを滴下した。同温
度で１時間撹拌後、析出した結晶を濾取し、アセトンで
洗浄し、無色結晶の５，６−Ｏ−イソプロピリデン−Ｌ
−アスコルビン酸２２．１ｇ（収率９０％）を得た。融
点２１０℃（分解）Example 1 Production of 5,6-O-isopropylidene-L-ascorbic acid: To 20 g of L-ascorbic acid, 100 ml of acetone was added, and 5 ml of BF 3 .Et 2 O was added dropwise with stirring at room temperature. After stirring at the same temperature for 1 hour, the precipitated crystals were collected by filtration and washed with acetone to give colorless crystals of 5,6-O-isopropylidene-L.
-22.1 g of ascorbic acid (yield 90%) were obtained. Melting point 210 ° C (decomposition)
【００２３】実施例２ ５，６−Ｏ−イソプロピリデン−Ｌ−アスコルビン酸の
製造：Ｌ−アスコルビン酸２０ｇにアセトン１００mlを
加え、室温撹拌下、ＢＦ3・Ｅｔ2Ｏ２．５mlを滴下した
後、酢酸１８mlを滴下し、同温度で１時間反応を行なっ
た。以下実施例１と同様に処理し、無色結晶の５，６−
Ｏ−イソプロピリデン−Ｌ−アスコルビン酸２１．６ｇ
（収率８８％）を得た。Example 2 Production of 5,6-O-isopropylidene-L-ascorbic acid: 100 g of acetone was added to 20 g of L-ascorbic acid, and 2.5 ml of BF 3 .Et 2 O was added dropwise with stirring at room temperature. 18 ml of acetic acid was added dropwise and the reaction was carried out at the same temperature for 1 hour. Thereafter, the same treatment as in Example 1 was carried out to obtain colorless crystals of 5,6-
21.6 g of O-isopropylidene-L-ascorbic acid
(Yield 88%) was obtained.
【００２４】実施例３ Ｌ−アスコルビン酸−２−リン酸エステルマグネシウム
塩の製造：５，６−Ｏ−イソプロピリデン−Ｌ−アスコ
ルビン酸５．４ｇを、水４３mlとピリジン１１mlとの混
液に溶かし、これに下記方法により調製したリン酸化試
薬を、０〜１０℃に保ち、６０％ＫＯＨ水溶液でpHを８
に調整しながら滴下した。滴下後、同温度で１時間撹拌
したのちピリジンを減圧留去した。次いで、水を加えト
リフルオロ酢酸にてpH２．３に調整し、４０℃で３時間
撹拌した。反応終了後、反応混合物を約１００mlに減圧
濃縮し、濃縮液を活性炭８０ｇのカラムに添着し、次い
で水３００mlにて洗浄後、ピリジン−水混合溶液（ピリ
ジン２５mlに対して水５００ml、pH＝９．７）にて溶出
した（ｓｖ≒１）。目的物の溶出画分を合わせて約３０
mlに減圧濃縮した。Example 3 Production of L-ascorbic acid-2-phosphate magnesium salt: 5.4 g of 5,6-O-isopropylidene-L-ascorbic acid was dissolved in a mixed solution of 43 ml of water and 11 ml of pyridine, The phosphorylation reagent prepared by the following method was kept at 0 to 10 ° C, and the pH was adjusted to 8 with 60% KOH aqueous solution.
It was added dropwise while adjusting to. After the dropping, the mixture was stirred at the same temperature for 1 hour, and then pyridine was distilled off under reduced pressure. Next, water was added and the pH was adjusted to 2.3 with trifluoroacetic acid, and the mixture was stirred at 40 ° C. for 3 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to about 100 ml, the concentrated solution was impregnated on a column of 80 g of activated carbon, and then washed with 300 ml of water, and then a pyridine-water mixed solution (500 ml of water for 25 ml of pyridine, pH = 9) .7) was eluted (sv≈1). About 30 elution fractions of the target compound are combined
Concentrated under reduced pressure to ml.
【００２５】この濃縮液をＭｇＯにて中和した後、不溶
物を濾去した。濾液を約１０mlに減圧濃縮し活性炭２ｇ
を加えて３０分撹拌した後、濾過した。濾液に９０％メ
タノール３００mlを撹拌下加え、析出した結晶を濾取
し、無色結晶のＬ−アスコルビン酸−２−リン酸エステ
ルマグネシウム塩５．１ｇ（収率７０％）を得た。After neutralizing this concentrated solution with MgO, the insoluble matter was filtered off. The filtrate was concentrated under reduced pressure to about 10 ml and activated carbon 2 g
Was added, the mixture was stirred for 30 minutes, and then filtered. 300 ml of 90% methanol was added to the filtrate with stirring, and the precipitated crystals were collected by filtration to obtain 5.1 g (yield 70%) of colorless crystals of L-ascorbic acid-2-phosphate magnesium salt.
【００２６】リン酸化試薬の調製：オキシ塩化リン７．
６７ｇ（５０ミリモル）を水１．８ml（１００ミリモ
ル）中に室温撹拌下１時間で滴下し、リン酸化試薬を得
た。Preparation of phosphorylation reagent: phosphorus oxychloride 7.
67 g (50 mmol) was added dropwise to 1.8 ml (100 mmol) of water under stirring at room temperature for 1 hour to obtain a phosphorylation reagent.
【００２７】試験例１ ５，６−Ｏ−イソプロピリデン−Ｌ−アスコルビン酸
（２）の製造における三フッ化ホウ素エチルエーテル錯
化合物又はこれと酢酸との併用の効果を試験した。製造
の条件及び収率を表１に示す。Test Example 1 The effect of boron trifluoride ethyl ether complex compound or its combination with acetic acid in the production of 5,6-O-isopropylidene-L-ascorbic acid (2) was tested. The production conditions and yield are shown in Table 1.
【００２８】[0028]
【表１】 [Table 1]
【００２９】以上の結果より、酢酸のみでは反応は進行
せず化合物（２）は得られないことが判る。From the above results, it is understood that the reaction does not proceed with acetic acid alone and the compound (2) cannot be obtained.
【００３０】試験例２ ５，６−Ｏ−イソプロピリデン−Ｌ−アスコルビン酸
（２）のホスホリル化に用いるリン酸化試薬のオキシ塩
化リンと水とのモル比と５，６−イソプロピリデン−Ｌ
−アスコルビン酸−２−リン酸エステル（３）の生成率
との関係を調べた。反応条件及び生成率（％）を表３に
示す。なお、化合物（３）の生成率は、下記条件で高速
液体クロマトグラフィー（ＨＰＬＣ）により、標品との
ピーク面積比較法を用いて求めた。Test Example 2 5,6-O-isopropylidene-L-ascorbic acid (2) 5,6-isopropylidene-L and the molar ratio of phosphorus oxychloride, which is a phosphorylation reagent used for phosphorylation, to water
-The relationship with the production rate of ascorbic acid-2-phosphate ester (3) was investigated. Table 3 shows the reaction conditions and the production rate (%). The production rate of the compound (3) was determined by high performance liquid chromatography (HPLC) under the following conditions using a peak area comparison method with a standard product.
【００３１】[0031]
【表２】 カラム：ヌクレオシル（Ｎｕｃｌｅｏｓｉｌ）１００−
ＮＨ2（４．６mm×１５０mm） 移動相：アセトニトリル：０．１Ｍ ＫＨ2ＰＯ4水溶液
＝１：２（リン酸にてpH４．３に調整） 流量：１ml／min 検出波長：２５４nm[Table 2] Column: Nucleosil 100-
NH 2 (4.6 mm × 150 mm) Mobile phase: Acetonitrile: 0.1 M KH 2 PO 4 aqueous solution = 1: 2 (adjusted to pH 4.3 with phosphoric acid) Flow rate: 1 ml / min Detection wavelength: 254 nm
【００３２】[0032]
【表３】 [Table 3]
Claims (3)
スコルビン酸に、オキシ塩化リンと水とを１：１．５〜
１：２．５のモル比で反応させたリン酸化試薬をpH８〜
１２で反応させ、次いで得られたエステル体を加水分解
して５、６位の保護基を脱離させ、必要により生成物を
塩に変換することを特徴とするＬ−アスコルビン酸−２
−リン酸エステル又はその塩の製造法。1. 5,6-O-isopropylidene-L-ascorbic acid, phosphorus oxychloride and water 1: 1.5-
The phosphorylation reagent reacted at a molar ratio of 1: 2.5 has a pH of 8 to
L-ascorbic acid-2 characterized by reacting at 12, then hydrolyzing the obtained ester form to eliminate the protecting groups at the 5 and 6 positions, and converting the product into a salt if necessary.
-A method for producing a phosphoric acid ester or a salt thereof.
フッ化ホウ素エチルエーテル錯化合物又はその錯化合物
と酢酸との混合物の存在下に反応させ、得られた５，６
−Ｏ−イソプロピリデン−Ｌ−アスコルビン酸にオキシ
塩化リンと水とを１：１．５〜１：２．５のモル比で反
応させたリン酸化試薬をpH８〜１２で反応させ、次いで
得られたエステル体を加水分解して５、６位の保護基を
脱離させ、必要により生成物を塩に変換することを特徴
とするＬ−アスコルビン酸−２−リン酸エステル又はそ
の塩の製造法。2. L-ascorbic acid and acetone are reacted in the presence of a boron trifluoride ethyl ether complex compound or a mixture of the complex compound and acetic acid to obtain 5,6.
-O-isopropylidene-L-ascorbic acid was reacted with phosphorus oxychloride and water at a molar ratio of 1: 1.5 to 1: 2.5 to react with a phosphorylation reagent at pH 8 to 12, and then obtained. The method for producing L-ascorbic acid-2-phosphate ester or a salt thereof, which comprises hydrolyzing the ester compound to eliminate the protecting groups at the 5 and 6-positions and converting the product into a salt if necessary. .
フッ化ホウ素エチルエーテル錯化合物又はこの錯化合物
と酢酸との混合物の存在下に反応せしめることを特徴と
する５，６−Ｏ−イソプロピリデン−Ｌ−アスコルビン
酸の製造法。3. L-ascorbic acid and acetone are reacted in the presence of a boron trifluoride ethyl ether complex compound or a mixture of this complex compound and acetic acid, 5,6-O-isopropylidene. -A method for producing L-ascorbic acid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5159161A JP2867206B2 (en) | 1993-06-29 | 1993-06-29 | Method for producing L-ascorbic acid-2-phosphate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5159161A JP2867206B2 (en) | 1993-06-29 | 1993-06-29 | Method for producing L-ascorbic acid-2-phosphate |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP10256235A Division JP3096277B2 (en) | 1998-09-10 | 1998-09-10 | Process for producing 5,6-O-isopropylidene-L-ascorbic acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0717989A true JPH0717989A (en) | 1995-01-20 |
| JP2867206B2 JP2867206B2 (en) | 1999-03-08 |
Family
ID=15687606
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5159161A Expired - Fee Related JP2867206B2 (en) | 1993-06-29 | 1993-06-29 | Method for producing L-ascorbic acid-2-phosphate |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2867206B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1036795A3 (en) * | 1999-03-18 | 2002-03-06 | Showa Denko K K | Process for preparing ascorbic acid-2-monophosphate salt |
-
1993
- 1993-06-29 JP JP5159161A patent/JP2867206B2/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1036795A3 (en) * | 1999-03-18 | 2002-03-06 | Showa Denko K K | Process for preparing ascorbic acid-2-monophosphate salt |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2867206B2 (en) | 1999-03-08 |
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