JPH0481401A - Cyclodextrin derivative - Google Patents
Cyclodextrin derivativeInfo
- Publication number
- JPH0481401A JPH0481401A JP19546790A JP19546790A JPH0481401A JP H0481401 A JPH0481401 A JP H0481401A JP 19546790 A JP19546790 A JP 19546790A JP 19546790 A JP19546790 A JP 19546790A JP H0481401 A JPH0481401 A JP H0481401A
- Authority
- JP
- Japan
- Prior art keywords
- water
- cyclodextrin
- derivative
- chloride
- compound
- 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.)
- Pending
Links
Landscapes
- Polysaccharides And Polysaccharide Derivatives (AREA)
Abstract
Description
【発明の詳細な説明】
［産業上の利用分野］
本発明はシクロデキストリン誘導体に関し、更に詳しく
は高い水溶性を有するシクロデキストリン誘導体に関す
る。DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to cyclodextrin derivatives, and more particularly to cyclodextrin derivatives having high water solubility.
［従来の技術］
一般に医薬、農薬等の薬品類等は用途上、水溶性を有す
ることか求められる。近年、これらの水溶性を向上させ
る手段の一つとして、上記薬品類等をシクロデキストリ
ンに包接させることによって水溶性を向上させる方法が
提案されている。[Prior Art] Generally, chemicals such as medicines and agricultural chemicals are required to be water-soluble due to their use. In recent years, as one means for improving the water solubility of these substances, a method has been proposed in which the above-mentioned chemicals and the like are included in cyclodextrin to improve the water solubility.
［発明が解決しようとする課題］
しかしながら、このようなシクロデキストリン包接化合
物においても、シクロデキストリン自体の水への溶解度
に限度があるため、その水溶性は実用上未だ不十分であ
った。このため、シクロデキストリンの水に対する溶解
度を向上させるため、シクロデキストリンをメチル化、
ヒドロキシエチル化、ヒドロキシプロピル化するか、あ
るいはエピクロルヒドリンを用いて架橋させたポリマー
を合成する等の方法が行なわれているが、未だ十分な効
果は得られていなかった。[Problems to be Solved by the Invention] However, even in such a cyclodextrin clathrate compound, the solubility of cyclodextrin itself in water is limited, so its water solubility is still insufficient for practical use. Therefore, in order to improve the solubility of cyclodextrin in water, cyclodextrin is methylated and
Methods such as hydroxyethylation, hydroxypropylation, or synthesis of crosslinked polymers using epichlorohydrin have been used, but sufficient effects have not yet been obtained.
従って、本発明の目的は、水に対して極めて高い溶解性
を有するシクロデキストリン誘導体を提供することにあ
る。Therefore, an object of the present invention is to provide a cyclodextrin derivative having extremely high solubility in water.
［課題を解決するための手段］
本発明者は前記課題に鑑みて鋭意研究の結果、本発明の
上記目的は、少なくとも１つのアンモニウム基を有する
シクロデキストリン誘導体を提供することにより達成さ
れることを見出した。[Means for Solving the Problems] In view of the above problems, the present inventors have conducted extensive research and found that the above objects of the present invention can be achieved by providing a cyclodextrin derivative having at least one ammonium group. I found it.
以下に本発明を更に詳細に説明する。The present invention will be explained in more detail below.
本発明の少なくとも１つのアンモニウム基を有するシク
ロデキストリン（以下、ＣＤと称す）誘導体においてア
ンモニウム基としては好ましくはＮ Ｈ４”Ｘ−基（Ｘ
は／）ロゲン原子を表わす）であり、このような化合物
としては具体的には、例えばモノトリメチルアンモニウ
ム（クロライド）βＣＤ、ジトリメチルアンモニウム（
クロライド）β−ＣＤ、ヘプタトリメチルアンモニウム
（クロライド）β−ＣＤ等が挙げられる。これらＣＤ誘
導体の合成反応について以下に示す。In the cyclodextrin (hereinafter referred to as CD) derivative having at least one ammonium group of the present invention, the ammonium group is preferably an N H4''X- group (X
represents a rogen atom), and specific examples of such compounds include monotrimethylammonium (chloride) βCD, ditrimethylammonium (
chloride) β-CD, heptatrimethylammonium (chloride) β-CD, and the like. Synthetic reactions for these CD derivatives are shown below.
モノトリメチルアンモニウム（タロライト）β−ＣＤヘ
プタトリメチルアンモニウム（クロライド）β−ＣＤ（
９）また、上記反応についての具体的合成例について以
下に示す。Monotrimethylammonium (talolite) β-CD Heptatrimethylammonium (chloride) β-CD (
9) Further, specific synthesis examples for the above reaction are shown below.
■モノトリメチルアンモニウム（クロライド）β−ＣＤ
の合成
■−１：β−ＣＤを室温下ピリジンに溶解し、これにピ
リジンに溶解したパラトルエンスルホン酸クロライドを
２０°Ｃにて滴下する。滴下終了後−昼夜、室温で攪拌
し、反応終了後、ピリジンを４０℃以下で減圧留去し、
残渣を大量のアセトン中に加え再沈殿する。沈殿物を集
め、水より再結晶を繰り返し精製し、β−ＣＤモノトシ
レート（１）を得る。（収率：２５％）
得られたβ−ＣＤモノトシレートをＤＭＦ中でＫＩと７
０〜８０°Ｃで一昼夜反応させ、反応終了後ＤＭＦを減
圧下で留去し、残渣を大量のアセトンより再沈殿する。■Monotrimethylammonium (chloride) β-CD
Synthesis 1-1: β-CD is dissolved in pyridine at room temperature, and para-toluenesulfonic acid chloride dissolved in pyridine is added dropwise at 20°C. After completion of the dropwise addition - Stir at room temperature day and night. After completion of the reaction, pyridine was distilled off under reduced pressure at 40°C or below,
Add the residue to a large amount of acetone and reprecipitate. The precipitate is collected and purified by repeated recrystallization from water to obtain β-CD monotosylate (1). (Yield: 25%) The obtained β-CD monotosylate was mixed with KI and 7 in DMF.
The reaction is carried out at 0 to 80°C for one day, and after the reaction is completed, DMF is distilled off under reduced pressure, and the residue is reprecipitated from a large amount of acetone.
沈殿物はｎ−ブタノール／エタノール／水より再結晶し
精製し化合物（２）を得る。（収率：６０％）
更に、化合物（２）をＤＭＦ中に溶解し、０°Ｃまで冷
却する。次にトリメチルアミンを０℃で加え、０〜５°
Ｃにおいて１２時間反応させる。反応終了後、ＤＭＦ、
トリメチルアミンを減圧下で留去し、残渣を大量の
アセトンより再沈殿を行なう。The precipitate is purified by recrystallization from n-butanol/ethanol/water to obtain compound (2). (Yield: 60%) Furthermore, compound (2) is dissolved in DMF and cooled to 0°C. Then add trimethylamine at 0°C and
React at C for 12 hours. After the reaction is complete, DMF,
Trimethylamine is distilled off under reduced pressure, and the residue is reprecipitated from a large amount of acetone.
沈殿物を集めて、水／エタノールの系より再結晶し化合
物（３）を得る。（収率：６０％）（３）を水に溶解し
Ｃ２−型アニオン交換樹脂を通すことによりモノトリメ
チルアンモニウム（クロライド）β−ＣＤ （４）をほ
ぼ定量的に得る。（収率：９０％）
■−２：水にナトリウムアンドを溶解し、その系に前記
（１）を加える。次いで、８０〜９０℃に加熱し３時間
反応させる。室温まで放冷後、濾過し、水を減圧下で濃
縮する。残渣を大量のメタノールより再沈殿を行なう。The precipitate is collected and recrystallized from a water/ethanol system to obtain compound (3). (Yield: 60%) Monotrimethylammonium (chloride) β-CD (4) is obtained almost quantitatively by dissolving (3) in water and passing it through a C2-type anion exchange resin. (Yield: 90%) ①-2: Dissolve sodium and in water and add the above (1) to the system. Next, the mixture is heated to 80 to 90°C and reacted for 3 hours. After cooling to room temperature, it is filtered and the water is concentrated under reduced pressure. The residue is reprecipitated from a large amount of methanol.
沈殿物を集めて水より再結晶し化合物（５）を得る。（
収率ニア０％）更に化合物（５）をＤＭＦ溶媒に溶解し
、少量の１０％パラジウム炭素を加え水素添加を行なう
。The precipitate is collected and recrystallized from water to obtain compound (5). (
(yield near 0%) Furthermore, compound (5) is dissolved in a DMF solvent, and a small amount of 10% palladium on carbon is added to perform hydrogenation.
（圧カニ ８〜１０ａｔｍ、温度：３０〜４０°Ｃ）２
４時間後室温まで放冷し濾過する。溶媒を減圧下で留去
した後、残渣を大量のアセトンより再沈殿を行なう。(Pressure crab 8-10 atm, temperature: 30-40°C) 2
After 4 hours, the mixture is allowed to cool to room temperature and filtered. After distilling off the solvent under reduced pressure, the residue is reprecipitated from a large amount of acetone.
沈殿物を集めて、水／エタノールより再結晶し化合物（
６）を得る。（収率：６０％）
次に化合物（６）とに２ＣＯ３をＤＭＦに溶解し、０〜
５°Ｃに冷却する。その系に冷却したヨウ化メチルを加
え添加後３０〜４０°Ｃで１２時間反応させる。The precipitate was collected and recrystallized from water/ethanol to obtain the compound (
6) is obtained. (Yield: 60%) Next, dissolve compound (6) and 2CO3 in DMF, and
Cool to 5°C. Cooled methyl iodide is added to the system, and after addition, the mixture is allowed to react at 30-40°C for 12 hours.
反応終了後、室温まで放冷し減圧下でＤＭＦ、ヨウ化メ
チルを留去、残渣を大量のアセトンより再沈殿を行なう
。沈殿物を集めて、水／エタノールの系より再結晶し化
合物（３）を得る。（収率：２５％）
以下、■−１と同様にモノトリメチルアンモニウム（ク
ロライド）β−ＣＤ （４）を得る。After the reaction is completed, the mixture is allowed to cool to room temperature, DMF and methyl iodide are distilled off under reduced pressure, and the residue is reprecipitated from a large amount of acetone. The precipitate is collected and recrystallized from a water/ethanol system to obtain compound (3). (Yield: 25%) Monotrimethylammonium (chloride) β-CD (4) is obtained in the same manner as in ①-1.
■ジトリメチルアンモニウム（クロライド）β−ＣＤの
合成は■に準する。(2) The synthesis of ditrimethylammonium (chloride) β-CD follows the procedure (2).
■へブタトリメチルアンモニウム（クロライド）β−Ｃ
Ｄの合成
りＭＦ中に室温でβ−ＣＤを溶解し、メタンスルホニル
ブロマイドを加え、添加後６０〜７０℃で２４時間攪拌
する。反応終了後、ＤＭＦを減圧下で留去し残渣を大量
のメタノールより再沈殿する。更に塩基で中和復水冷水
に加え濾過した後、沈殿物を氷冷水で洗浄し減圧乾燥し
化合物（７）を得る。■ Hebutatrimethylammonium (chloride) β-C
Synthesis of D β-CD is dissolved in MF at room temperature, methanesulfonyl bromide is added, and after the addition, the mixture is stirred at 60 to 70°C for 24 hours. After the reaction is completed, DMF is distilled off under reduced pressure and the residue is reprecipitated from a large amount of methanol. Further, the condensate neutralized with a base is added to cold water and filtered, and the precipitate is washed with ice-cold water and dried under reduced pressure to obtain compound (7).
（収率：８０％）
化合物（７）をＤＭＦに溶解し、０℃まで冷却する。次
にトリメチルアミンをＯｏＣで加え０〜５℃において１
２時間反応させる。反応終了後ＤＭＦ。(Yield: 80%) Compound (7) is dissolved in DMF and cooled to 0°C. Next, add trimethylamine at OoC at 0-5℃ for 1
Let react for 2 hours. DMF after the reaction is completed.
トリメチルアミンを減圧下で留去し、残渣を大量のジエ
チルエーテルより再沈殿を行なう。沈殿物は集めて水／
エタノールの系より再結晶し化合物（８）を得る。（収
率：２０％）
次に化合物（８）を水に溶解し、Ｃ２−型アニオン交換
樹脂を通すことによりヘプタトリメチルアンモニウム（
クロライド）β−ＣＤ （９）をほぼ定量的に得る。（
収率：９０％）
なお、目的物の確認はＮＭＲスペクトル、マススペクト
ル、元素分析などの方法を用いて行なった。Trimethylamine is distilled off under reduced pressure, and the residue is reprecipitated from a large amount of diethyl ether. Collect the sediment and add water/
Recrystallization from an ethanol system yields compound (8). (Yield: 20%) Next, compound (8) was dissolved in water and passed through a C2-type anion exchange resin to obtain heptatrimethylammonium (
chloride) β-CD (9) is obtained almost quantitatively. (
(Yield: 90%) The target product was confirmed using methods such as NMR spectrum, mass spectrum, and elemental analysis.
前記の如く得られるシクロデキストリン誘導体の水に対
する溶解度を調べた。結果を以下に記す。The solubility of the cyclodextrin derivative obtained as described above in water was investigated. The results are described below.
本発明においてはＣＤとしてα型ＣＤ、β型ＣＤ、及び
γ型ＣＤのいずれも用いることができる。In the present invention, any of α-type CD, β-type CD, and γ-type CD can be used as CD.
本発明の高い水溶性を有するＣＤ誘導体は、例・えば医
薬、農薬等の薬品、芳香剤、化粧品、洗剤、塗料、染料
、食料品の食品添加物等に用いることができる。The highly water-soluble CD derivative of the present invention can be used, for example, in medicines, chemicals such as agricultural chemicals, fragrances, cosmetics, detergents, paints, dyes, food additives for foodstuffs, and the like.
［発明の効果］
以上詳細に述べたように、本発明によりアンモニウム基
をシクロデキストリンに確実に導入することで水に対す
る溶解度を大幅に向上させることか出来、この結果水溶
性の高いシクロデキストリン包接化合物を得ることかで
きる。[Effects of the Invention] As described in detail above, the present invention makes it possible to significantly improve the solubility in water by reliably introducing ammonium groups into cyclodextrin, resulting in highly water-soluble cyclodextrin inclusion. It is possible to obtain a compound.
Claims (1)
トリン誘導体。Cyclodextrin derivatives having at least one ammonium group.
Priority Applications (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP19546790A JPH0481401A (en) | 1990-07-24 | 1990-07-24 | Cyclodextrin derivative |
| DE69127256T DE69127256T2 (en) | 1990-05-21 | 1991-05-20 | CYCLODEXTRIN DERIVATIVE |
| EP91909367A EP0485614B1 (en) | 1990-05-21 | 1991-05-20 | Cyclodextrin derivative |
| KR1019920700037A KR927003645A (en) | 1990-05-21 | 1991-05-20 | Cyclodextrin derivatives |
| EP95119260A EP0710673A3 (en) | 1990-05-21 | 1991-05-20 | Cyclodextrin derivatives |
| CA002063454A CA2063454A1 (en) | 1990-05-21 | 1991-05-20 | Cyclodextrin derivatives |
| US07/776,296 US5241059A (en) | 1990-05-21 | 1991-05-20 | Cyclodextrin derivatives |
| PCT/JP1991/000666 WO1991018022A1 (en) | 1990-05-21 | 1991-05-20 | Cyclodextrin derivative |
| EP95119259A EP0710672A3 (en) | 1990-05-21 | 1991-05-25 | Cyclodextrin derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP19546790A JPH0481401A (en) | 1990-07-24 | 1990-07-24 | Cyclodextrin derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0481401A true JPH0481401A (en) | 1992-03-16 |
Family
ID=16341566
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP19546790A Pending JPH0481401A (en) | 1990-05-21 | 1990-07-24 | Cyclodextrin derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0481401A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005056609A1 (en) * | 2003-12-15 | 2005-06-23 | National University Of Singapore | Cationic oligomer of a saccharide for resolving enantiomers and asymmetric synthesis |
| JP2011006448A (en) * | 2002-06-13 | 2011-01-13 | Novartis Ag | Quaternized ammonium cyclodextrin compound |
-
1990
- 1990-07-24 JP JP19546790A patent/JPH0481401A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011006448A (en) * | 2002-06-13 | 2011-01-13 | Novartis Ag | Quaternized ammonium cyclodextrin compound |
| WO2005056609A1 (en) * | 2003-12-15 | 2005-06-23 | National University Of Singapore | Cationic oligomer of a saccharide for resolving enantiomers and asymmetric synthesis |
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