JPS6312877B2 - - Google Patents
Info
- Publication number
- JPS6312877B2 JPS6312877B2 JP7805479A JP7805479A JPS6312877B2 JP S6312877 B2 JPS6312877 B2 JP S6312877B2 JP 7805479 A JP7805479 A JP 7805479A JP 7805479 A JP7805479 A JP 7805479A JP S6312877 B2 JPS6312877 B2 JP S6312877B2
- Authority
- JP
- Japan
- Prior art keywords
- isopropylidene
- lactone
- iil
- idurono
- base
- 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.)
- Expired
Links
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 17
- 239000000203 mixture Substances 0.000 claims description 10
- 239000002585 base Substances 0.000 claims description 8
- 150000002596 lactones Chemical group 0.000 claims description 8
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 claims description 4
- 239000003513 alkali Substances 0.000 claims description 2
- 150000007530 organic bases Chemical class 0.000 claims description 2
- 230000003647 oxidation Effects 0.000 claims description 2
- 238000007254 oxidation reaction Methods 0.000 claims description 2
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- BDBGJSXZKMTMGP-JYJDMEHSSA-N (3bs,6s,6ar)-6-hydroxy-2,2-dimethyl-3b,6,6a,7a-tetrahydro-3ah-furo[2,3]furo[2,4-b][1,3]dioxol-5-one Chemical compound O[C@@H]([C@H]1O2)C(=O)O[C@@H]1C1C2OC(C)(C)O1 BDBGJSXZKMTMGP-JYJDMEHSSA-N 0.000 claims 3
- 239000011541 reaction mixture Substances 0.000 claims 1
- 239000000243 solution Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 159000000000 sodium salts Chemical class 0.000 description 4
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000000862 absorption spectrum Methods 0.000 description 3
- 239000003729 cation exchange resin Substances 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 238000001308 synthesis method Methods 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- AVVWPBAENSWJCB-IVMDWMLBSA-N D-glucofuranose Chemical compound OC[C@@H](O)[C@H]1OC(O)[C@H](O)[C@H]1O AVVWPBAENSWJCB-IVMDWMLBSA-N 0.000 description 1
- 201000010374 Down Syndrome Diseases 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 238000010876 biochemical test Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- AVJBPWGFOQAPRH-FWMKGIEWSA-L dermatan sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@H](OS([O-])(=O)=O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](C([O-])=O)O1 AVJBPWGFOQAPRH-FWMKGIEWSA-L 0.000 description 1
- 238000011033 desalting Methods 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 229910002804 graphite Inorganic materials 0.000 description 1
- 239000010439 graphite Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- IAJILQKETJEXLJ-LECHCGJUSA-N iduronic acid Chemical compound O=C[C@@H](O)[C@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-LECHCGJUSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 238000004816 paper chromatography Methods 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000036632 reaction speed Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
Landscapes
- Saccharide Compounds (AREA)
Description
【発明の詳細な説明】
本発明は、１，２−Ｏ−イソプロピリデン−β
−Ｌ−イズロノ−６，３−ラクトンを高収率でか
つ高純度で選択的に分離する方法に係わる。DETAILED DESCRIPTION OF THE INVENTION The present invention provides 1,2-O-isopropylidene-β
The present invention relates to a method for selectively separating -L-idurono-6,3-lactone with high yield and high purity.
１，２−Ｏ−イソプロピリデン−β−Ｌ−イズ
ロノ−６，３−ラクトンは、生体内の結合組織、
軟骨組織、腱、角膜、動脈壁などに存在する酸性
ムコ多糖類のうちの特にコンドロイチン硫酸Ｂの
構成成分として知られているイズロン酸の化学合
成法における重要な中間物質であり、また代謝異
常症の１つであるダウン症（Hurler−Pfaundler
病）の診断法の研究および生化学研究分野におい
ても注目されている物質であつて、生化学試験に
使用される非常に高価な試薬である。 1,2-O-isopropylidene-β-L-idurono-6,3-lactone can be used in connective tissue in the body,
It is an important intermediate in the chemical synthesis of iduronic acid, which is known as a component of chondroitin sulfate B, which is an acidic mucopolysaccharide that exists in cartilage tissues, tendons, corneas, artery walls, etc. Down syndrome (Hurler-Pfaundler)
It is a substance that is attracting attention in research on diagnostic methods for diseases such as cancer and biochemical research, and is a very expensive reagent used in biochemical tests.
この１，２−Ｏ−イソプロピリデン−β−Ｌ−
イズロノ−６，３−ラクトン（以下IILと略称す
る）の製造について、従来、エム・エル・ウオル
フロム等（M.L.Wolfrom et al）による合成法
（メソツド・イン・カーボヒドレート・ケミスト
リ（Methos in Carbohydrate Chemistry）２、
32−34（1963））がよく知られており、一般的な合
成法として利用されている。この方法によれば、
IILは１，２−Ｏ−イソプロピリデン−α−Ｄ−
グルコフラノースを原料として過ヨウ素酸による
酸化およびシアノヒドリン反応を経て生成される
が、IILの異性体である１，２−Ｏ−イソプロピ
リデン−α−Ｄ−グルクロノ−６，３−ラクトン
（以下IGLと略称する）との混合物として得られ
る。そして、この方法によれば、得られた混合物
からIILを単離するにあたつては、フロレツクス
（Florex）XXXとセライト（Celite）との混合物
（混合比４：１）を担体とするカラムクロマトグ
ラフイによつてIILの分離が行なわれていた。し
かしながら、この分離操作法では、流出してくる
IILをペーパークロマトグラフイで確認しながら
分離するという繁雑な操作を必要とし、さらに分
離効率が必ずしも良くないため、多量の担体を使
用してもわずかの量のIILを分離できるにすぎな
かつた。 This 1,2-O-isopropylidene-β-L-
Regarding the production of Izurono-6,3-lactone (hereinafter abbreviated as IIL), the synthesis method (Methos in Carbohydrate Chemistry) by M. L. Wolfrom et al. 2 ,
32-34 (1963)) is well known and used as a general synthesis method. According to this method,
IIL is 1,2-O-isopropylidene-α-D-
It is produced from glucofuranose as a raw material through periodic acid oxidation and cyanohydrin reaction. (abbreviation)). According to this method, IIL is isolated from the resulting mixture using column chromatography using a mixture of Florex XXX and Celite (mixing ratio 4:1) as a carrier. Separation of IIL was performed using graphite. However, with this separation method, the
This requires a complicated operation of separating IIL while checking it using paper chromatography, and the separation efficiency is not always good, so even if a large amount of carrier is used, only a small amount of IIL can be separated.
本発明者等はこのようなIILとIGLとの混合物
から、簡単にかつ収率よく、しかも高純度でIIL
を単離しうる方法を見出し、本発明に至つた。 The present inventors have discovered that IIL can be easily and efficiently produced from a mixture of IIL and IGL with high purity.
We have discovered a method by which it is possible to isolate this, leading to the present invention.
本発明によるIILの単離法は、IILとIGLとの混
合物の水溶液にIILのラクトン環のみが開環する
PH域に液性を保ちながら塩基を添加する工程、お
よび得られたイズロノ酸の塩を未変化のIGLから
分離したのち、これをIILに変化させる工程を包
含することを特徴とする。 In the method for isolating IIL according to the present invention, only the lactone ring of IIL is opened in an aqueous solution of a mixture of IIL and IGL.
It is characterized by including a step of adding a base while maintaining the liquid property in the pH range, and a step of separating the obtained salt of idronoic acid from unchanged IGL and then converting it into IIL.
以下に本発明のIILの単離法について詳細に説
明する。 The method for isolating IIL of the present invention will be explained in detail below.
本発明方法の出発原料であるIILとIGLとの混
合物は、前述のエム・エル・ウオルフロム等の合
成法に従つて調製する。このようにして得られた
混合物を水に溶解し、激しく撹拌しながら、溶液
中のラクトンの全量に対してほぼ1/2当量（IILに
相当する量）のNaOHを含有する水溶液を滴加
する。この際、液性をIILのラクトン環のみが開
環するPH域、好ましくはPH６ないし７に保ちうる
速度でアルカリ液を添加することが重要である。
なおアルカリPH域ではIGLのラクトン環も開環
し、したがつて得られるIILの純度が低下するこ
とになるため、PHの調整は重要なフアクタであ
る。PHの調整にあたつてはPHメータあるいは精密
なPH試験紙等の通常の手段が利用できる。アルカ
リ液の滴加終了時、薄層クロマトグラフイを行な
い、反応前のIILとIGLとの混合物についてのク
ロマトグラムと比較すると、IILのスポツトが消
失し、代わつて原点に新たなスポツトが見られ
る。これは、IILのみが選択的に開環して、IGL
よりも速く消費されて１，２−Ｏ−イソプロピリ
デン−イズロン酸のナトリウム塩となつたことに
由来するものである。 The mixture of IIL and IGL, which is the starting material for the method of the present invention, is prepared according to the synthesis method of M.L. Wolfrom et al. mentioned above. The mixture thus obtained is dissolved in water and, with vigorous stirring, an aqueous solution containing approximately 1/2 equivalent of NaOH (an amount corresponding to IIL) relative to the total amount of lactone in the solution is added dropwise. . At this time, it is important to add the alkali solution at a rate that can maintain the liquid property in the pH range where only the lactone ring of IIL opens, preferably in the pH range of 6 to 7.
In addition, in the alkaline pH range, the lactone ring of IGL also opens, resulting in a decrease in the purity of the obtained IIL, so adjusting the pH is an important factor. Normal means such as a PH meter or precision PH test strips can be used to adjust the PH. When the alkaline solution was added dropwise, thin layer chromatography was performed and when compared with the chromatogram of the mixture of IIL and IGL before the reaction, the IIL spot disappeared and a new spot was seen at the origin. . This means that only IIL selectively opens and IGL
This is because it is consumed faster than the sodium salt of 1,2-O-isopropylidene-iduronic acid.
このようにして得られた反応液を減圧下で濃縮
し、得られる残渣をクロロホルムあるいは塩化メ
チレンなどの有機溶媒で洗浄したのち過する。
この液中にはIGLのみが抽出されてくる。一
方、洗浄して得られた１，２−Ｏ−イソプロピリ
デン−イズロン酸のナトリウム塩を再び水に溶解
し、ついで陽イオン交換樹脂を通過させるか、酸
性条件下有機溶媒を用いて１，２−Ｏ−イソプロ
ピリデン−イズロン酸を抽出する通常の脱塩法に
てナトリウムイオンを除去し、流出液または抽出
液を濃縮するとシロツプ状の物質が得られる。こ
れをノルマル−プロパノールあるいはアセトンな
どの有機溶媒と石油エーテルとの混合溶媒で処理
して結晶化されるとIILが結晶として単離できる。 The reaction solution thus obtained is concentrated under reduced pressure, and the resulting residue is washed with an organic solvent such as chloroform or methylene chloride, and then filtered.
Only IGL is extracted into this liquid. On the other hand, the sodium salt of 1,2-O-isopropylidene-iduronic acid obtained by washing was dissolved in water again, and then passed through a cation exchange resin or 1,2- The sodium ions are removed by a conventional desalting method for extracting -O-isopropylidene-iduronic acid, and the effluent or extract is concentrated to yield a syrup-like substance. When this is crystallized by treating it with a mixed solvent of an organic solvent such as normal-propanol or acetone and petroleum ether, IIL can be isolated as a crystal.
本発明によるIILの単離操作は上記のとおりで
あるが、本発明の方法は従来法に比して非常に操
作が簡便であり、さらに後述の実施例の結果から
も明らかなように高収率でかつ高純度でIILを単
離できる。 The procedure for isolating IIL according to the present invention is as described above, but the method of the present invention is much simpler to operate than conventional methods, and also has a high yield, as is clear from the results of the examples described later. IIL can be isolated with high efficiency and purity.
また、本発明によれば、添加する塩基として
は、NaOH以外のアルカリ塩（KOH等）、有機
塩基（たとえばトリエチルアミン、ピリジン等）
などもNaOHと同様にIILのラクトン環を選択的
に開環させうることが確認されている。しかしな
がら、これらの塩基を使用する場合には開環反応
時間はNaOHに比べて遅い。このように反応速
度および後処理の簡単さを考慮した場合、
NaOHを使用することが有利である。 Further, according to the present invention, the base to be added may include an alkali salt other than NaOH (KOH, etc.), an organic base (for example, triethylamine, pyridine, etc.)
It has been confirmed that similar to NaOH, it is possible to selectively open the lactone ring of IIL. However, when using these bases, the ring opening reaction time is slow compared to NaOH. Considering the reaction speed and ease of post-processing,
It is advantageous to use NaOH.
次に、本発明の方法の好適な１具体例である以
下の実施例により、本発明をさらに説明するが、
本発明はこれに限定されない。 Next, the present invention will be further explained by the following example, which is a preferred specific example of the method of the present invention.
The present invention is not limited to this.
実施例
IILとIGLとの等量混合物1.10ｇを水20mlに溶
解した。この水溶液を氷冷下撹拌しながら、溶液
中のIILに相当する当量のNaOHを含む0.12N
NaOH水溶液を滴加した。この間、PHメータで
厳重に監視しながらPHを6.0ないし7.0、好ましく
は6.8に維持しながら滴加を行なつた。Example 1.10 g of an equal mixture of IIL and IGL was dissolved in 20 ml of water. While stirring this aqueous solution under ice-cooling, 0.12N containing NaOH in an equivalent amount corresponding to IIL in the solution was added.
Aqueous NaOH solution was added dropwise. During this time, the dropwise addition was carried out while maintaining the pH at 6.0 to 7.0, preferably 6.8, while strictly monitoring with a PH meter.
添加後、薄層クロマドグラフイ（シリカゲル
Ｇ）によりIILの消失を確認したのち、約40℃の
水浴上で減圧下、水溶液を濃縮した。これにより
白色残渣が得られた。 After the addition, disappearance of IIL was confirmed by thin layer chromatography (silica gel G), and then the aqueous solution was concentrated under reduced pressure on a water bath at about 40°C. This gave a white residue.
ついで、この残渣をCHCl3またはCH2Cl2で数
回洗浄し、洗液を集めた。この洗液からはIGLが
回収された。これは、赤外吸収スペクトル、混融
試験、薄層クロマトグラフイの結果で同定確認し
た。 The residue was then washed several times with CHCl 3 or CH 2 Cl 2 and the washings were collected. IGL was recovered from this washing solution. This identity was confirmed by the results of infrared absorption spectra, fusion tests, and thin layer chromatography.
一方、有機溶媒に不溶な白色残渣は１，２−Ｏ
−イソプロピリデン−イゾロン酸のNa塩体0.62
ｇであつた。この化合物の赤外吸収スペクトルに
よればラクトン環特有の吸収（1765cm-1）は消失
し、かつ1610cm-1にはカルボキシレート（−
COO-）特有の吸収が認められた。 On the other hand, the white residue insoluble in organic solvents is 1,2-O
-Sodium salt of isopropylidene-isolonic acid 0.62
It was hot at g. According to the infrared absorption spectrum of this compound, the absorption characteristic of the lactone ring (1765 cm -1 ) disappears, and at 1610 cm -1 the carboxylate (-
COO - ) Specific absorption was observed.
得られたナトリウム塩体0.62ｇを再び水に溶解
し、陽イオン交換樹脂のカラム層を通し、流出液
を減圧下で濃縮した。これにより無色のシロツプ
が得られた。これを結晶化することにより
IIL0.50ｇが得られた。融点（137℃）、赤外吸収
スペクトル、比色定性等により、この生成物が
IILであることを確認した。また、この生成物の
クロマトグラフイによれば唯一のスポツトしか認
められず、ほぼ純粋であることが確認された。 0.62 g of the obtained sodium salt was dissolved in water again, passed through a column layer of cation exchange resin, and the effluent was concentrated under reduced pressure. This gave a colorless syrup. By crystallizing this
0.50 g of IIL was obtained. The melting point (137℃), infrared absorption spectrum, colorimetry, etc. indicate that this product is
I confirmed that it was IIL. Furthermore, chromatography of this product revealed only one spot, confirming that it was almost pure.
なお、ナトリウム塩体を陽イオン交換樹脂を通
す間に１，２−Ｏ−イソプロピリデン−イズロン
酸が生成されるが、流出液の濃縮段階あるいは結
晶化段階においてC6の酸性基とC3の水酸基との
間で脱水を生じラクトン環型となつて安定化し、
直ちにIILに変化するものと考えられる。 Note that 1,2-O-isopropylidene-iduronic acid is produced when the sodium salt is passed through a cation exchange resin, but the acidic group of C 6 and the acid group of C 3 are formed during the concentration step of the effluent or the crystallization step. Dehydration occurs between the hydroxyl group and the lactone ring form becomes stable.
It is thought that it will immediately change to IIL.
以上本発明をその具体例について詳述したが、
本発明はこの特定の実施例に限定されるものでは
なく、本発明の精神を逸脱しないで幾多の変化変
形がなし得ることはもちろんである。 The present invention has been described in detail with respect to specific examples thereof, but
It goes without saying that the invention is not limited to this particular embodiment, and that many changes and modifications may be made without departing from the spirit of the invention.
Claims (1)
ズロノ−６，３−ラクトンと１，２−Ｏ−イソプ
ロピリデン−α−Ｄ−グルクロノ−６，３−ラク
トンとの混合物の水溶液に１，２−Ｏ−イソプロ
ピリデン−β−Ｌ−イズロノ−６，３−ラクトン
のラクトン環のみが開環するPH域に液性を保ちな
がら塩基を添加する工程および得られたイズロノ
酸の塩を未変化の１，２−Ｏ−イソプロピリデン
−α−Ｄ−グルクロノ−６，３−ラクトンから分
離したのち、これを１，２−Ｏ−イソプロピリデ
ン−β−Ｌ−イズロノ−６，３−ラクトンに変化
させる工程を包含することを特徴とする、１，２
−Ｏ−イソプロピリデン−β−Ｌ−イズロノ−
６，３−ラクトンの単離法。 ２ 塩基の添加の間、反応混合物の液性をPH６な
いし７に保つことを特徴とする特許請求の範囲第
１項記載の方法。 ３ 塩基はアルカリ、有機塩基の中から選ばれる
ことを特徴とする特許請求の範囲第１項または第
２項記載の方法。 ４ 塩基はNaOHであることを特徴とする特許
請求の範囲第３項記載の方法。 ５ 添加する塩基の量は反応混合物中の１，２−
Ｏ−イソプロピリデン−β−Ｌ−イズロノ−６，
３−ラクトンと等モル量あることを特徴とする特
許請求の範囲第１項ないし第４項のいずれか１項
に記載の方法。 ６ １，２−Ｏ−イソプロピリデン−β−Ｌ−イ
ズロノ−６，３−ラクトンと１，２−Ｏ−イソプ
ロピリデン−α−Ｄ−グルクロノ−６，３−ラク
トンとの混合物は１，２−Ｏ−イソプロピリデン
−α−Ｄ−グルコフラノースを原料として過ヨウ
素酸による酸化およびシアノヒドリン反応により
合成したものであることを特徴とする特許請求の
範囲第１項ないし第５項のいずれか１項に記載の
方法。[Scope of Claims] 1 1,2-O-isopropylidene-β-L-idurono-6,3-lactone and 1,2-O-isopropylidene-α-D-glucurono-6,3-lactone A step of adding a base to an aqueous solution of the mixture while maintaining the liquid property in a pH range where only the lactone ring of 1,2-O-isopropylidene-β-L-idurono-6,3-lactone opens, and After separating the acid salt from unchanged 1,2-O-isopropylidene-α-D-glucurono-6,3-lactone, it was converted into 1,2-O-isopropylidene-β-L-idurono-6. , 3-lactone.
-O-isopropylidene-β-L-idurono-
Method for isolating 6,3-lactone. 2. The method according to claim 1, characterized in that during the addition of the base, the liquid nature of the reaction mixture is maintained at pH 6 to 7. 3. The method according to claim 1 or 2, wherein the base is selected from alkali and organic bases. 4. The method according to claim 3, wherein the base is NaOH. 5 The amount of base added depends on the 1,2-
O-isopropylidene-β-L-idurono-6,
The method according to any one of claims 1 to 4, characterized in that the amount is equimolar to 3-lactone. 6 A mixture of 1,2-O-isopropylidene-β-L-idurono-6,3-lactone and 1,2-O-isopropylidene-α-D-glucurono-6,3-lactone is 1,2- Claims 1 to 5 are characterized in that the product is synthesized from O-isopropylidene-α-D-glucofuranose by oxidation with periodic acid and cyanohydrin reaction. Method described.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7805479A JPS562996A (en) | 1979-06-22 | 1979-06-22 | Isolation of 1,2-o-isopropylidene-beta-l-idurono-6,3-lactone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7805479A JPS562996A (en) | 1979-06-22 | 1979-06-22 | Isolation of 1,2-o-isopropylidene-beta-l-idurono-6,3-lactone |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS562996A JPS562996A (en) | 1981-01-13 |
| JPS6312877B2 true JPS6312877B2 (en) | 1988-03-23 |
Family
ID=13651130
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP7805479A Granted JPS562996A (en) | 1979-06-22 | 1979-06-22 | Isolation of 1,2-o-isopropylidene-beta-l-idurono-6,3-lactone |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS562996A (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS58156287A (en) * | 1982-03-12 | 1983-09-17 | Pioneer Electronic Corp | Video reproducer |
| JPS5961389A (en) * | 1982-09-30 | 1984-04-07 | Sony Corp | Chromaticity adjusting circuit |
-
1979
- 1979-06-22 JP JP7805479A patent/JPS562996A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS562996A (en) | 1981-01-13 |
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