JPH069709A - Cyclodextrin derivative and production thereof - Google Patents
Cyclodextrin derivative and production thereofInfo
- Publication number
- JPH069709A JPH069709A JP21832692A JP21832692A JPH069709A JP H069709 A JPH069709 A JP H069709A JP 21832692 A JP21832692 A JP 21832692A JP 21832692 A JP21832692 A JP 21832692A JP H069709 A JPH069709 A JP H069709A
- Authority
- JP
- Japan
- Prior art keywords
- cyclodextrin
- reaction
- acetyl
- producing
- hydroxyl group
- 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
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は新規なシクロデキストリ
ン誘導体及びその製造方法に関するものである。FIELD OF THE INVENTION The present invention relates to a novel cyclodextrin derivative and a method for producing the same.
【０００２】[0002]
【従来の技術】シクロデキストリンは分子内に疎水性の
空洞を有し、外側は親水性で水中油型ミセルに似た機能
を示す化合物である。このようなシクロデキストリンは
その空洞径に応じて疎水性のゲスト分子を取り込み水溶
液中で複合体を形成し、調製法によっては固体の包接化
合物を単離することもできる。この立体選択的な相互作
用によりゲスト分子の物理化学的性質を微妙に変化させ
ることができるため、製剤への有効利用が期待でき、各
方面で種々に利用され、またその利用が図られている化
合物である。Cyclodextrin is a compound that has a hydrophobic cavity in its molecule, is hydrophilic on the outside, and functions like an oil-in-water micelle. Such a cyclodextrin incorporates a hydrophobic guest molecule depending on its cavity diameter to form a complex in an aqueous solution, and a solid inclusion compound can be isolated depending on the preparation method. The physicochemical properties of the guest molecule can be subtly changed by this stereoselective interaction, so that it can be expected to be used effectively in pharmaceutical preparations, and it is used in various fields and is being used. It is a compound.
【０００３】特にシクロデキストリンの２，３又は６位
の水酸基を部分的に残してなるシクロデキストリン誘導
体の場合は、その水酸基との相互作用により包接能が大
幅に変化するため、ゲスト分子の種類、その物性等を大
きく変化させうることが期待できる。Particularly, in the case of a cyclodextrin derivative in which the hydroxyl group at the 2, 3 or 6 position of cyclodextrin is partially left, the inclusion ability is significantly changed by the interaction with the hydroxyl group, so that the type of guest molecule is different. It can be expected that the physical properties and the like can be greatly changed.
【０００４】例えば、特開平3-137103号公報に開示され
る３位および６位の水酸基をメチル化したジメチルシク
ロデキストリンは、油に溶け易くなり、界面活性を呈
し、吸湿性が低下するという特性を有するため製剤への
用途が著しく拡大するという利点を有する。For example, the dimethylcyclodextrin disclosed in JP-A-3-137103, in which the hydroxyl groups at the 3- and 6-positions are methylated, is easily dissolved in oil, exhibits surface activity, and decreases hygroscopicity. Therefore, it has an advantage that the application to the formulation is remarkably expanded.
【０００５】このようなシクロデキストリン誘導体に用
いられる中間物質の合成については、J. Carbohydr. Ch
em.,7 293-308 (1988) ; Carbohydr. Res., 187 203-22
1 (1989) ; Carbohydr. Res., 192 366-369 (1989)等の
論文に詳細に記載されている。Regarding the synthesis of the intermediate substance used for such a cyclodextrin derivative, J. Carbohydr. Ch.
em., 7 293-308 (1988); Carbohydr. Res., 187 203-22
1 (1989); Carbohydr. Res., 192 366-369 (1989) and others.
【０００６】[0006]
【発明が解決しようとする課題】しかしながら、このよ
うな２，３又は６位の水酸基を部分的に残してなるシク
ロデキストリン誘導体の合成は、その過程において特定
の水酸基を選択的に反応させる必要があるため非常に困
難であり、かつ複雑であった。However, in the synthesis of a cyclodextrin derivative in which such a hydroxyl group at the 2, 3 or 6-position is partially left, it is necessary to selectively react a specific hydroxyl group in the process. It was very difficult and complicated because of it.
【０００７】すなわち、本発明の目的は、２，３あるい
は６位のいずれかに、又は２，６位あるいは３，６位に
アセチル基を導入した新規なシクロデキストリン誘導体
及びその製造方法を提供することにある。That is, an object of the present invention is to provide a novel cyclodextrin derivative in which an acetyl group is introduced at either the 2,3 or 6-position, or at the 2,6 or 3,6 position, and a method for producing the same. Especially.
【０００８】また、本発明の目的は上記シクロデキスト
リン誘導体を簡便に製造することができる方法を提供す
ることにある。Another object of the present invention is to provide a method for easily producing the above cyclodextrin derivative.
【０００９】[0009]
【課題を解決するための手段】本発明者等は、前記課題
に鑑みて鋭意研究の結果、本発明の上記目的は、下記式
（１），（２）又は（３）で表わされるアセチルシクロ
デキストリン誘導体、又は下記式（４）又は（５）で表
わされるジアセチル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 The inventors of the present invention have conducted extensive studies in view of the above problems, and as a result, the above object of the present invention is to achieve the acetylcyclo structure represented by the following formula (1), (2) or (3) It has been found that this can be achieved by providing a dextrin derivative or a diacetylcyclodextrin derivative represented by the following formula (4) or (5).
【００１０】[0010]
【化３】 [Chemical 3]
【００１１】また、本発明の目的は下記シクロデキスト
リン誘導体の製造方法により達成される。The object of the present invention is also achieved by the following method for producing a cyclodextrin derivative.
【００１２】（１）（６−Ｏ−tert−ブチルジメチルシ
リル）シクロデキストリンの２位及び３位の水酸基をベ
ンジル化、アリル化又はピラニル化した後、脱シリル化
して得られたシクロデキストリン誘導体の６位の水酸基
をアセチル化した後、保護基を除去する、６−アセチル
−シクロデキストリンの製造方法。(1) A cyclodextrin derivative obtained by benzylating, allylating or pyranylating the hydroxyl groups at the 2- and 3-positions of (6-O-tert-butyldimethylsilyl) cyclodextrin and then desilylating A method for producing 6-acetyl-cyclodextrin, which comprises acetylating the hydroxyl group at the 6-position and then removing the protective group.
【００１３】（２）２位の水酸基がベンジル化又はアリ
ル化された（６−Ｏ−tert−ブチルジメチルシリル）シ
クロデキストリンを脱シリル化した後ベンジル化、アリ
ル化又はピラニル化し、次いで２位のベンジル基又はア
リル基を脱離せしめた後アセチル化する、２−アセチル
−シクロデキストリンの製造方法。(2) Dehydroxylation of (6-O-tert-butyldimethylsilyl) cyclodextrin in which the 2-position hydroxyl group is benzylated or allylated, followed by benzylation, allylation or pyranylation, and then the 2-position A method for producing 2-acetyl-cyclodextrin, which comprises desorbing a benzyl group or an allyl group and then acetylating.
【００１４】（３）（２，６−ジ−Ｏ−tert−ブチルジ
メチルシリル）シクロデキストリンの３位の水酸基をア
セチル化した後、脱シリル化する、３−アセチル−シク
ロデキストリンの製造方法。(3) A method for producing 3-acetyl-cyclodextrin, which comprises acetylating the hydroxyl group at the 3-position of (2,6-di-O-tert-butyldimethylsilyl) cyclodextrin and then desilylating.
【００１５】（４）２位の水酸基がベンジル化又はアリ
ル化された（６−Ｏ−tert−ブチルジメチルシリル）シ
クロデキストリンの３位の水酸基をアセチル化した後、
２位のベンジル基又はアリル基を脱離せしめ、次いで脱
シリル化する、３−アセチル−シクロデキストリンの製
造方法。(4) The hydroxyl group at the 2-position is benzylated or allylated, and after the hydroxyl group at the 3-position of (6-O-tert-butyldimethylsilyl) cyclodextrin is acetylated,
A method for producing 3-acetyl-cyclodextrin, which comprises removing the benzyl group or the allyl group at the 2-position and then desilylating.
【００１６】（５）シクロデキストリンにＮ−アセチル
イミダゾールを反応させる６−アセチル−シクロデキス
トリンの製造方法。(5) A method for producing 6-acetyl-cyclodextrin by reacting cyclodextrin with N-acetylimidazole.
【００１７】（６）シクロデキストリンに塩化アセチル
を反応させる６−アセチル−シクロデキストリンの製造
方法。(6) A method for producing 6-acetyl-cyclodextrin by reacting cyclodextrin with acetyl chloride.
【００１８】（７）２位の水酸基がベンジル化又はアリ
ル化された（６−Ｏ−ｔ−ブチルジメチルシリル）シク
ロデキストリンを脱シリル化した後、アセチル化する、
３，６−ジアセチルシクロデキストリンの製造方法。(7) Desilylation of (6-Ot-butyldimethylsilyl) cyclodextrin in which the 2-position hydroxyl group is benzylated or allylated, followed by acetylation.
A method for producing 3,6-diacetylcyclodextrin.
【００１９】（８）２位の水酸基がベンジル化又はアリ
ル化された（６−Ｏ−ｔ−ブチルジメチルシリル）シク
ロデキストリンの３位の水酸基をベンジル化、アリル化
又はピラニル化した後に脱シリル化を行ない、次いで２
位のベンジル基又はアリル基を脱離せしめた後アセチル
化する、２，６−ジアセチルシクロデキストリンの製造
方法。(8) The 2-position hydroxyl group is benzylated or allylated (6-Ot-butyldimethylsilyl) cyclodextrin The 3-position hydroxyl group is benzylated, allylated or pyranylated, and then desilylated. And then 2
A method for producing 2,6-diacetylcyclodextrin, which comprises removing the benzyl group or allyl group at the position and then acetylating.
【００２０】（９）（２，６−ジ−Ｏ−tert−ブチルジ
メチルシリル）シクロデキストリンの３位の水酸基をベ
ンジル化、アリル化又はピラニル化した後に脱シリル化
を行ない、次いでアセチル化を行なう、２，６−ジアセ
チルシクロデキストリンの製造方法。(9) The hydroxyl group at the 3-position of (2,6-di-O-tert-butyldimethylsilyl) cyclodextrin is benzylated, allylated or pyranylated, then desilylated, and then acetylated. A method for producing 2,6-diacetylcyclodextrin.
【００２１】以下に本発明を更に具体的に説明する。The present invention will be described in more detail below.
【００２２】本発明において、シクロデキストリンはｎ
が６のものをα−シクロデキストリン、ｎが７のものを
β−シクロデキストリン、ｎが８のものをγ−シクロデ
キストリンという。In the present invention, cyclodextrin is n
6 is referred to as α-cyclodextrin, n is referred to as β-cyclodextrin, and n is referred to as γ-cyclodextrin.
【００２３】以下に、本発明のモノアセチルシクロデキ
ストリンの具体的反応例を示す。但し以下場合によりシ
クロデキストリンをＣＤと略記する。Specific reaction examples of the monoacetylcyclodextrin of the present invention are shown below. However, in the following cases, cyclodextrin is abbreviated as CD.
【００２４】[0024]
【化４】 [Chemical 4]
【００２５】[0025]
【化５】 [Chemical 5]
【００２６】上記反応例（１）及び（２）は具体的には
以下のような反応により行なわれる。 反応［１］ β−ＣＤ（ｎ＝７）を脱水ピリジン中に溶解し、窒素雰
囲気下０〜５℃に冷却する。次いで脱水ピリジンに溶解
した tＢＤＭＳｉ・Ｃｌを滴下し、滴下終了後０〜５℃
で１時間、室温で12時間攪拌する。反応終了後、大量の
水より再沈殿を行ない沈殿を濾別、よく水洗し乾燥させ
る。その後シリカゲルカラムクロマトグラフィーにより
精製し、得られた［Ａ］はエタノールより３回再結晶を
行なった。（収率：約80％）The above reaction examples (1) and (2) are specifically carried out by the following reactions. Reaction [1] β-CD (n = 7) is dissolved in dehydrated pyridine and cooled to 0 to 5 ° C under a nitrogen atmosphere. Then, t BDMSi.Cl dissolved in dehydrated pyridine was added dropwise, and 0 to 5 ° C after the addition was completed.
Stir for 1 hour and at room temperature for 12 hours. After completion of the reaction, reprecipitation is carried out with a large amount of water, the precipitate is filtered off, washed well with water and dried. Then, it was purified by silica gel column chromatography, and the obtained [A] was recrystallized from ethanol three times. (Yield: about 80%)
【００２７】反応［２］ ［Ａ］を脱水ＤＭＦに溶解後ＢａＯ，Ｂａ（ＯＨ）2 ・
８Ｈ2 Ｏを続いて添加する。その系に室温で臭化ベンジ
ルを滴下し、滴下終了後ヨウ化ナトリウムを加え24時間
攪拌する。反応終了後メタノールを加え攪拌、次いで不
溶物を濾別、濾液に塩化メチレンを加え１Ｍ−Ｈ2 ＳＯ
4 、水の順で洗浄し有機相を乾燥後、減圧下40℃以下で
濃縮する。残渣に少量のエタノールを加え、大量の水よ
り再沈殿する。沈殿物はよく乾燥後シリカゲルカラムク
ロマトグラフィーにより精製し、得られた［Ｂ］はエタ
ノールより再結晶を行なった。（収率：約70％）Reaction [2] After dissolving [A] in dehydrated DMF, BaO, Ba (OH) 2 ·
8H 2 O is subsequently added. Benzyl bromide is added dropwise to the system at room temperature, and after completion of the addition, sodium iodide is added and the mixture is stirred for 24 hours. After completion of the reaction, methanol was added and stirred, then the insoluble matter was filtered off, and methylene chloride was added to the filtrate to give 1M-H 2 SO.
4. Wash with water in this order, dry the organic phase, and then concentrate at 40 ° C or lower under reduced pressure. Add a small amount of ethanol to the residue and reprecipitate from a large amount of water. The precipitate was thoroughly dried and purified by silica gel column chromatography, and the obtained [B] was recrystallized from ethanol. (Yield: about 70%)
【００２８】反応［３］ ［Ｂ］を脱水塩化メチレンに溶解し、窒素雰囲気下０〜
５℃に冷却する。次いでその系に三フッ化ホウ素のジエ
チルエーテル錯体を滴下し、滴下終了後０〜５℃で２時
間、室温で12時間反応させる。反応終了後、有機相を氷
冷水で洗浄し有機相は乾燥後減圧下濃縮し、残渣をシリ
カゲルカラムクロマトグラフィーにより精製し、得られ
た［Ｃ］はジエチルエーテル／メタノール系より再結晶
を行なった。（収率：約70％）Reaction [3] Dissolve [B] in dehydrated methylene chloride, and dissolve in a nitrogen atmosphere at 0-
Cool to 5 ° C. Then, a diethyl ether complex of boron trifluoride is added dropwise to the system, and after completion of the addition, the reaction is carried out at 0 to 5 ° C for 2 hours and at room temperature for 12 hours. After completion of the reaction, the organic phase was washed with ice cold water, the organic phase was dried and then concentrated under reduced pressure, the residue was purified by silica gel column chromatography, and the obtained [C] was recrystallized from a diethyl ether / methanol system. . (Yield: about 70%)
【００２９】反応［４］ ［Ｃ］をＴＨＦに溶解し、その系に３，４−ジヒドロ−
２Ｈピランを加え攪拌する。そして室温で塩酸１〜２滴
を加え12時間反応させる。反応終了後、その系にＫＯＨ
を添加し、室温で30分間攪拌する。ＫＯＨを濾別後、溶
液を減圧下濃縮する。残渣はアルミナカラムクロマトグ
ラフィーにより分離・精製し［Ｄ］を得た。（収率：約
65％）Reaction [4] [C] was dissolved in THF and 3,4-dihydro- was added to the system.
Add 2H pyran and stir. Then, add 1-2 drops of hydrochloric acid at room temperature and react for 12 hours. After the reaction is completed, KOH is added to the system.
Is added and stirred at room temperature for 30 minutes. After filtering off KOH, the solution is concentrated under reduced pressure. The residue was separated and purified by alumina column chromatography to obtain [D]. (Yield: about
65%)
【００３０】反応［５］ ［Ｄ］をエタノール／酢酸＝２／１溶液に溶解し、10％
Ｐｄ／Ｃを触媒として添加後、水素添加を行なう（40
℃，５kg／cm2 ）。水素圧が減少しなくなった時点で反
応を終了させ、Ｐｄ／Ｃを濾別、溶液を減圧下で濃縮
し、残渣をアルミナカラムクロマトグラフィーで分離・
精製し［Ｅ］を得た。（収率：約85％）Reaction [5] [D] was dissolved in an ethanol / acetic acid = 2/1 solution to give 10%.
After adding Pd / C as a catalyst, hydrogenation is performed (40
℃, 5kg / cm 2 ). The reaction is terminated when the hydrogen pressure does not decrease, Pd / C is filtered off, the solution is concentrated under reduced pressure, and the residue is separated by alumina column chromatography.
Purification yielded [E]. (Yield: about 85%)
【００３１】反応［６］−１ ［Ｅ］を脱水ピリジンに溶解し、室温で無水酢酸を滴下
する。滴下終了後60℃で12時間反応させる。反応終了後
ピリジンを減圧下濃縮し、残渣に少量のエタノールを加
え、大量の氷冷水より再沈殿を行なう。沈殿物を濾別し
よく乾燥後、アルミナカラムクロマトグラフィーにより
分離・精製し［Ｆ］を得た。（収率：約80％）Reaction [6] -1 [E] is dissolved in dehydrated pyridine, and acetic anhydride is added dropwise at room temperature. After completion of dropping, the mixture is reacted at 60 ° C for 12 hours. After completion of the reaction, pyridine is concentrated under reduced pressure, a small amount of ethanol is added to the residue, and reprecipitation is performed with a large amount of ice-cooled water. The precipitate was filtered off, dried well, and then separated and purified by alumina column chromatography to obtain [F]. (Yield: about 80%)
【００３２】反応［６］−２ ［Ｅ］を脱水ピリジン（あるいはトリエチルアミン）に
溶解し、窒素雰囲気下塩化メチルに溶解した塩化アセチ
ル（又は臭化アセチル）を滴下する。滴下終了後０〜５
℃で２時間、室温で６時間反応させる。反応終了後ピリ
ジンを減圧下濃縮し、残渣に少量のエタノールを加え、
大量の氷冷水より再沈殿を行なう。沈殿物を濾別しよく
乾燥後、アルミナカラムクロマトグラフィーにより分離
・精製し［Ｆ］を得た。Reaction [6] -2 [E] is dissolved in dehydrated pyridine (or triethylamine), and acetyl chloride (or acetyl bromide) dissolved in methyl chloride is added dropwise under a nitrogen atmosphere. 0-5 after dropping
The reaction is carried out at 0 ° C for 2 hours and at room temperature for 6 hours. After the reaction was completed, pyridine was concentrated under reduced pressure, a small amount of ethanol was added to the residue,
Reprecipitate from a large amount of ice-cold water. The precipitate was filtered off, dried well, and then separated and purified by alumina column chromatography to obtain [F].
【００３３】反応［７］ ［Ｆ］をＴＨＦに溶解し、そこに塩酸を加え、40℃で30
分間攪拌させる。反応終了後放冷し、室温でＫＯＨを加
え30分間攪拌する。ＫＯＨを濾別後ＴＨＦを減圧下濃縮
し、残渣をシリカゲルカラムクロマトグラフィーにより
分離・精製し、２−アセチルβ−ＣＤ［Ｇ］を得た。
（収率：約55％）Reaction [7] [F] is dissolved in THF, hydrochloric acid is added thereto, and the mixture is heated at 40 ° C. for 30 minutes.
Let stir for a minute. After completion of the reaction, the mixture is allowed to cool, KOH is added at room temperature and the mixture is stirred for 30 minutes. After KOH was filtered off, THF was concentrated under reduced pressure, and the residue was separated and purified by silica gel column chromatography to obtain 2-acetyl β-CD [G].
(Yield: about 55%)
【００３４】反応［８］ ［Ａ］を脱水ＤＭＦに溶解し、窒素雰囲気下10℃に冷却
する。その系にＮａＨを添加し、その温度で２時間攪
拌、次いで臭化ベンジルをゆっくり滴下し、さらにヨウ
化ナトリウムを加える。添加後10℃で１時間、室温で24
時間攪拌する。反応終了後メタノールを加え30分間攪拌
し、そして濾過する。濾液は減圧下40℃以下にて濃縮
し、残渣は少量のメタノールより再沈殿させ、濾過し、
濾物は乾燥後シリカゲルカラムクロマトグラフィーによ
り分離する。得られた［Ｈ］はエタノールより再結晶し
精製した。（収率：約60％）Reaction [8] [A] is dissolved in dehydrated DMF and cooled to 10 ° C. under a nitrogen atmosphere. NaH is added to the system and stirred at that temperature for 2 hours, then benzyl bromide is slowly added dropwise and more sodium iodide is added. After addition, 1 hour at 10 ℃, 24 at room temperature
Stir for hours. After the reaction is complete, methanol is added and the mixture is stirred for 30 minutes and filtered. The filtrate was concentrated under reduced pressure at 40 ° C or lower, the residue was reprecipitated from a small amount of methanol, filtered,
The filter cake is dried and then separated by silica gel column chromatography. The obtained [H] was recrystallized from ethanol for purification. (Yield: about 60%)
【００３５】反応［９］ ［Ｂ］にかえて［Ｈ］を用い、得られた化合物の再結晶
を行なわない以外は反応［３］と同様にして［Ｉ］を得
た。（収率：約70％）Reaction [9] [I] was obtained in the same manner as in Reaction [3] except that [H] was used in place of [B] and the obtained compound was not recrystallized. (Yield: about 70%)
【００３６】反応［10］−１ ［Ｅ］にかえて［Ｉ］を用い、アルミナカラムクロマト
グラフィーにかえてシリカゲルカラムクロマトグラフィ
ーにて分離・精製した以外は反応［６］−１と同様にし
て［Ｊ］を得た。（収率：約70％）The reaction [6] -1 was carried out in the same manner as in the reaction [6] -1, except that [I] was used instead of the reaction [10] -1 [E], and separation and purification were performed by silica gel column chromatography instead of alumina column chromatography. I got [J]. (Yield: about 70%)
【００３７】反応［10］−２ ［Ｅ］にかえて［Ｉ］を用い、アルミナカラムクロマト
グラフィーにかえてシリカゲルカラムクロマトグラフィ
ーにて分離・精製した以外は反応［６］−２と同様にし
て［Ｊ］を得た。Reaction [6] -2 was carried out in the same manner as Reaction [6] -2 except that [I] was used in place of Reaction [10] -2 [E] and was separated and purified by silica gel column chromatography instead of alumina column chromatography. I got [J].
【００３８】反応［11］ ［Ｄ］にかえて［Ｊ］を用い、アルミナカラムクロマト
グラフィーにかえてシリカゲルカラムクロマトグラフィ
ーにて分離・精製した以外は反応［５］と同様にして６
−アセチルβ−ＣＤ［Ｋ］を得た。（収率：約80％）Reaction [11] 6 was carried out in the same manner as in Reaction [5] except that [J] was used in place of [D] and was separated and purified by silica gel column chromatography instead of alumina column chromatography.
-Acetyl β-CD [K] was obtained. (Yield: about 80%)
【００３９】反応［12］ β−ＣＤ（ｎ＝７）を脱水ＤＭＦに溶解し、室温でイミ
ダゾールを添加する。次いでアルゴン雰囲気下 tＢＤＭ
Ｓｉ・Ｃｌを加え溶解させる。その系をゆっくりと加熱
し90〜 100℃で24時間反応させる。反応終了後放冷し、
減圧下ＤＭＦを留去し残渣を塩化メチレン／水系で抽出
し、有機相は１Ｍ−Ｈ2 ＳＯ4 、水、ＮａＨＣＯ3 水溶
液で洗浄後乾燥する。有機相は減圧下濃縮し、残渣は塩
化メチレン／メタノール系より再結晶し精製し［Ｌ］を
得た。（収率：約65％）Reaction [12] β-CD (n = 7) is dissolved in dehydrated DMF, and imidazole is added at room temperature. Then under argon atmosphere t BDM
Si.Cl is added and dissolved. The system is slowly heated and reacted at 90-100 ° C for 24 hours. Allow to cool after the reaction,
The residue was distilled off under reduced pressure DMF and extracted with methylene chloride / water, the organic phase is 1M-H 2 SO 4, dried after washed with water, aqueous NaHCO 3. The organic phase was concentrated under reduced pressure, and the residue was recrystallized from a methylene chloride / methanol system and purified to obtain [L]. (Yield: about 65%)
【００４０】反応［13］−１ ［Ｅ］にかえて［Ｌ］を用い、反応条件を 100℃，36時
間としアルミナカラムクロマトグラフィーにかえてシリ
カゲルカラムクロマトグラフィーにて分離・精製した以
外は反応［６］−１と同様にして［Ｍ］を得た。（収
率：約90％）Reactions except that [L] was used in place of the reaction [13] -1 [E], the reaction conditions were 100 ° C. for 36 hours, and the separation and purification was performed by silica gel column chromatography instead of alumina column chromatography. [M] was obtained in the same manner as in [6] -1. (Yield: about 90%)
【００４１】反応［13］−２ ［Ｌ］を脱水ＤＭＦ（あるいＴＨＦ）、ピリジン混合溶
媒（あるいはトリエチルアミンのみ）に溶解し窒素雰囲
気下０〜５℃でＤＭＦ又はＴＨＦに溶解した塩化アセチ
ル（又は臭化アセチル）を滴下する。滴下終了後０〜５
℃で２時間、室温で12時間反応させる。反応終了後溶媒
を減圧下濃縮し、残渣に少量のアセトンを加え、大量の
氷冷水により再沈殿を行なう。沈殿物を濾別、乾燥後シ
リカゲルクロマトグラフィーにより分離・精製し［Ｍ］
を得た。（収率：約90％）Reaction [13] -2 [L] was dissolved in dehydrated DMF (or THF) and pyridine mixed solvent (or only triethylamine) and dissolved in DMF or THF at 0-5 ° C. under a nitrogen atmosphere to obtain acetyl chloride (or Acetyl bromide) is added dropwise. 0-5 after dropping
React at 2 ° C for 2 hours and at room temperature for 12 hours. After completion of the reaction, the solvent is concentrated under reduced pressure, a small amount of acetone is added to the residue, and reprecipitation is performed with a large amount of ice-cooled water. The precipitate is filtered off, dried and then separated and purified by silica gel chromatography [M].
Got (Yield: about 90%)
【００４２】反応［14］ ［Ｂ］にかえて［Ｍ］を用い、得られた化合物の再結晶
を行なわない以外は反応［３］と同様にして３−アセチ
ルβ−ＣＤ［Ｎ］を得た。（収率：約50％）Reaction [14] 3-Acetyl β-CD [N] was obtained in the same manner as in Reaction [3] except that [M] was used instead of [B] and the obtained compound was not recrystallized. It was (Yield: about 50%)
【００４３】反応［15］−１ ［Ｅ］にかえて［Ｂ］を用い、アルミナカラムクロマト
グラフィーにかえてシリカゲルカラムクロマトグラフィ
ーにて分離・精製した以外は反応［６］−１と同様にし
て［Ｏ］を得た。（収率：約80％）The reaction [6] -1 was carried out in the same manner as in the reaction [6] -1, except that [B] was used in place of the reaction [15] -1 [E] and was separated and purified by silica gel column chromatography instead of alumina column chromatography. [O] was obtained. (Yield: about 80%)
【００４４】反応［15］−２ ［Ｌ］にかえて［Ｂ］を用いた以外は反応［13］−２と
同様にして［Ｏ］を得た。[O] was obtained in the same manner as in Reaction [13] -2 except that [B] was used instead of Reaction [15] -2 [L].
【００４５】反応［16］ ［Ｄ］にかえて［Ｏ］を用い、アルミナカラムクロマト
グラフィーにかえてシリカゲルカラムクロマトグラフィ
ーにて分離し、更に、得られた［Ｐ］をメタノールによ
り再結晶し精製した以外は反応［５］と同様にして
［Ｐ］を得た。（収率：約65％）Reaction [16] Using [O] instead of [D] and separating by silica gel column chromatography instead of alumina column chromatography, the obtained [P] was recrystallized from methanol for purification. [P] was obtained in the same manner as in the reaction [5] except for the above. (Yield: about 65%)
【００４６】反応［17］ ［Ｂ］にかえて［Ｐ］を用いた以外は反応［３］と同様
にして３−アセチルＣＤ［Ｎ］を得た。（収率：約50
％）Reaction [17] 3-Acetyl CD [N] was obtained in the same manner as in Reaction [3] except that [P] was used instead of [B]. (Yield: about 50
%)
【００４７】上記反応［１］において、β−ＣＤにかえ
てα−ＣＤを用いる場合は、β−ＣＤを脱水ピリジン中
に溶解するかわりにα−ＣＤを脱水ピリジン／脱水ＤＭ
Ｆ＝４／３溶液に溶解し、更に得られた［Ａ］をエタノ
ールにより再結晶するかわりに塩化メチレン／エタノー
ル溶液より再結晶した以外は反応［１］と同様の操作で
行なうことができる。When α-CD is used instead of β-CD in the above reaction [1], α-CD is dehydrated pyridine / dehydrated DM instead of dissolving β-CD in dehydrated pyridine.
The reaction can be performed in the same manner as in the reaction [1] except that it is dissolved in a F = 4/3 solution and that the obtained [A] is recrystallized from a methylene chloride / ethanol solution instead of being recrystallized from ethanol.
【００４８】また、β−ＣＤにかえてγ−ＣＤを用いる
場合は、［Ａ］をエタノールにより再結晶するかわりに
塩化メチレン／メタノール溶液より再結晶した以外は反
応［１］と同様の操作で行なうことができる。When γ-CD is used instead of β-CD, the same operation as in Reaction [1] is performed except that [A] is recrystallized from a methylene chloride / methanol solution instead of being recrystallized from ethanol. Can be done.
【００４９】反応［18］ β−ＣＤ（ｎ＝７）を脱水ピリジンに溶解し窒素雰囲気
下室温で攪拌する。その系に脱水ピリジンに溶解したＮ
−アセチルイミダゾールを滴下して行く。滴下終了後、
室温で１時間次いで40〜50℃で約30時間攪拌させる。反
応終了後減圧下ピリジンを留去し、残渣はシリカゲルカ
ラムクロマトグラフィーにより分離・精製し目的物
［Ｋ］を得る。（収率：約80％）Reaction [18] β-CD (n = 7) is dissolved in dehydrated pyridine and stirred at room temperature under a nitrogen atmosphere. N dissolved in dehydrated pyridine in the system
-Acetylimidazole is added dropwise. After the dropping is completed,
Allow to stir at room temperature for 1 hour and then at 40-50 ° C for about 30 hours. After completion of the reaction, pyridine is distilled off under reduced pressure, and the residue is separated and purified by silica gel column chromatography to obtain the desired product [K]. (Yield: about 80%)
【００５０】反応［19］ β−ＣＤ（ｎ＝７）を脱水ピリジンに溶解し、窒素雰囲
気下−５℃で攪拌する。その系に塩化メチレンに溶解し
た塩化アセチルをゆっくり滴下して行く。滴下終了後−
５℃で２時間、５℃で６時間反応させる。反応終了後ピ
リジン、塩化メチレンを室温、減圧下で留去し、残渣を
クロロホルム／水系で抽出する。クロロホルム層は１Ｍ
硫酸で洗浄、中和後乾燥し濃縮する。残渣はシリカゲル
カラムクロマトグラフィーにより分離・精製し目的物
［Ｋ］を得る。（収率：約65％）Reaction [19] β-CD (n = 7) is dissolved in dehydrated pyridine and stirred at -5 ° C under a nitrogen atmosphere. Acetyl chloride dissolved in methylene chloride is slowly added dropwise to the system. After completion of dropping
The reaction is carried out at 5 ° C for 2 hours and 5 ° C for 6 hours. After completion of the reaction, pyridine and methylene chloride are distilled off at room temperature under reduced pressure, and the residue is extracted with chloroform / water system. Chloroform layer is 1M
Wash with sulfuric acid, neutralize, dry and concentrate. The residue is separated and purified by silica gel column chromatography to obtain the desired product [K]. (Yield: about 65%)
【００５１】上記反応［18］及び［19］において、β−
ＣＤにかえてα−ＣＤを用いる場合は、β−ＣＤを脱水
ピリジン中に溶解するかわりにα−ＣＤを脱水ピリジン
／脱水ＤＭＦ＝４／３溶液に溶解した以外は反応［18］
及び［19］と同様の操作で行なうことができる。In the above reactions [18] and [19], β-
When α-CD was used instead of CD, the reaction was carried out except that α-CD was dissolved in a dehydrated pyridine / dehydrated DMF = 4/3 solution instead of dissolving β-CD in dehydrated pyridine [18].
And the same operation as [19].
【００５２】次にジアセチルシクロデキストリンの具体
的反応例を示す。Next, specific reaction examples of diacetylcyclodextrin will be shown.
【００５３】[0053]
【化６】 [Chemical 6]
【００５４】上記反応例（２）は具体的には以下のよう
な反応により行なわれる。 反応［１］ β−ＣＤ（ｎ＝７）を脱水ピリジン中に溶解し、窒素雰
囲気下０〜５℃に冷却する。次いで脱水ピリジンに溶解
した tＢＤＭＳｉ・Ｃｌを滴下し、滴下終了後０〜５℃
で１時間、室温で12時間攪拌する。反応終了後、大量の
水より再沈殿を行ない沈殿を濾別、よく水洗し乾燥させ
る。その後シリカゲルカラムクロマトグラフィーにより
精製し、得られた［Ａ］はエタノールより再結晶を行な
った。（収率：約80％）The above reaction example (2) is specifically carried out by the following reaction. Reaction [1] β-CD (n = 7) is dissolved in dehydrated pyridine and cooled to 0 to 5 ° C under a nitrogen atmosphere. Then, t BDMSi.Cl dissolved in dehydrated pyridine was added dropwise, and 0 to 5 ° C after the addition was completed.
Stir for 1 hour and at room temperature for 12 hours. After completion of the reaction, reprecipitation is carried out with a large amount of water, the precipitate is filtered off, washed well with water and dried. After that, the product was purified by silica gel column chromatography, and the obtained [A] was recrystallized from ethanol. (Yield: about 80%)
【００５５】反応［２］ ［Ａ］を脱水ＤＭＦに溶解後、ＢａＯ，Ｂａ（ＯＨ）2
・８Ｈ2 Ｏを続いて添加する。その系に室温で臭化ベン
ジルを滴下し、滴下終了後ヨウ化ナトリウムを加え24時
間攪拌する。反応終了後メタノールを加え、攪拌、次い
で不溶物を濾別する。濾液に塩化メチレンを加え、１Ｍ
−Ｈ2 ＳＯ4 、水の順で洗浄し、有機相を乾燥後、減圧
下40℃以下で濃縮する。残渣に少量のエタノールを加
え、大量の水より再沈殿する。沈殿物はよく乾燥後シリ
カゲルカラムクロマトグラフィーにより精製し、得られ
た［Ｂ］はエタノールより再結晶を行なった。（収率：
約70％）Reaction [2] [A] was dissolved in dehydrated DMF and then BaO, Ba (OH) 2
• Add 8H 2 O subsequently. Benzyl bromide is added dropwise to the system at room temperature, and after completion of the addition, sodium iodide is added and the mixture is stirred for 24 hours. After completion of the reaction, methanol is added, the mixture is stirred, and the insoluble matter is filtered off. Add methylene chloride to the filtrate and add 1M
-H 2 SO 4 and water are washed in this order, the organic phase is dried, and then concentrated under reduced pressure at 40 ° C or lower. Add a small amount of ethanol to the residue and reprecipitate from a large amount of water. The precipitate was thoroughly dried and purified by silica gel column chromatography, and the obtained [B] was recrystallized from ethanol. (yield:
About 70%)
【００５６】反応［３］ ［Ｂ］を脱水塩化メチレンに溶解し、窒素雰囲気下０〜
５℃に冷却する。次いでその系に三フッ化ホウ素のジエ
チルエーテル錯体を滴下し、滴下終了後０〜５℃で２時
間、室温で12時間反応させる。反応終了後、有機相を氷
冷水で洗浄し、有機相は乾燥後減圧下濃縮し、残渣をシ
リカゲルカラムクロマトグラフィーにより精製し、得ら
れた［Ｃ］はジエチルエーテル／メタノール系より再結
晶を行なった。（収率：約70％）Reaction [3] Dissolve [B] in dehydrated methylene chloride, and dissolve in a nitrogen atmosphere at 0-
Cool to 5 ° C. Then, a diethyl ether complex of boron trifluoride is added dropwise to the system, and after completion of the addition, the reaction is carried out at 0 to 5 ° C for 2 hours and at room temperature for 12 hours. After completion of the reaction, the organic phase was washed with ice-cold water, the organic phase was dried and concentrated under reduced pressure, the residue was purified by silica gel column chromatography, and the obtained [C] was recrystallized from a diethyl ether / methanol system. It was (Yield: about 70%)
【００５７】反応［４］−１ ［Ｃ］を脱水ピリジンに溶解し、室温で無水酢酸を滴下
する。滴下終了後60℃で12時間反応させる。反応終了後
ピリジンを減圧下濃縮し、残渣に少量のエタノールを加
え、大量の氷冷水より再沈殿を行なう。沈殿物を濾別
し、よく乾燥後シリカゲルカラムクロマトグラフィーに
より分離・精製し［Ｄ］を得た。（収率：約85％）Reaction [4] -1 [C] is dissolved in dehydrated pyridine, and acetic anhydride is added dropwise at room temperature. After completion of dropping, the mixture is reacted at 60 ° C for 12 hours. After completion of the reaction, pyridine is concentrated under reduced pressure, a small amount of ethanol is added to the residue, and reprecipitation is performed with a large amount of ice-cooled water. The precipitate was filtered off, dried well, and then separated and purified by silica gel column chromatography to obtain [D]. (Yield: about 85%)
【００５８】反応［４］−２ ［Ｃ］を脱水ピリジンに溶解し、窒素雰囲気下０〜５℃
で塩化メチルに溶解した塩化アセチル（又は臭化アセチ
ル）を滴下する。滴下終了後０〜５℃で２時間、室温で
６時間反応させる。反応終了後ピリジンを減圧下濃縮
し、残渣に少量のエタノールを加え、大量の氷冷水より
再沈殿を行なう。沈殿物を濾別し、よく乾燥後シリカゲ
ルカラムクロマトグラフィーにより分離・精製し［Ｄ］
を得た。Reaction [4] -2 [C] was dissolved in dehydrated pyridine, and the mixture was heated at 0 to 5 ° C. under a nitrogen atmosphere.
Then, acetyl chloride (or acetyl bromide) dissolved in methyl chloride is added dropwise. After completion of dropping, the mixture is reacted at 0 to 5 ° C for 2 hours and at room temperature for 6 hours. After completion of the reaction, pyridine is concentrated under reduced pressure, a small amount of ethanol is added to the residue, and reprecipitation is performed with a large amount of ice-cooled water. The precipitate is filtered off, dried well and then separated and purified by silica gel column chromatography [D].
Got
【００５９】反応［５］ ［Ｄ］をエタノール／酢酸＝２／１溶液に溶解し、10％
Ｐｄ／Ｃを触媒として添加後、水素添加を行なう（40
℃，５kg／cm2 ）。水素圧が減少しなくなった時点で反
応を終了させ、Ｐｄ／Ｃを濾別、溶液を減圧下で濃縮し
残渣をシリカゲルカラムクロマトグラフィーで分離・精
製し３，６−ジアセチルＣＤ［Ｅ］を得た。（収率：約
80％）Reaction [5] [D] was dissolved in an ethanol / acetic acid = 2/1 solution to give 10%.
After adding Pd / C as a catalyst, hydrogenation is performed (40
℃, 5kg / cm 2 ). When the hydrogen pressure has stopped decreasing, the reaction is terminated, Pd / C is filtered off, the solution is concentrated under reduced pressure, and the residue is separated and purified by silica gel column chromatography to obtain 3,6-diacetyl CD [E]. It was (Yield: about
80%)
【００６０】反応［６］ ［Ｂ］をＴＨＦに溶解し、３，４−ジヒドロ−２Ｈピラ
ンを滴下する。その系に塩酸を１〜２滴添加し、室温で
12時間攪拌する。反応終了後、その系にＫＯＨを加え、
室温で30分攪拌する。ＫＯＨを濾別後、溶液を減圧下濃
縮する。残渣はアルミナカラムクロマトグラフィーによ
り分離・精製し［Ｆ］を得た。（収率：約70％）Reaction [6] [B] is dissolved in THF and 3,4-dihydro-2Hpyran is added dropwise. Add 1-2 drops of hydrochloric acid to the system at room temperature
Stir for 12 hours. After the reaction is completed, KOH is added to the system,
Stir for 30 minutes at room temperature. After filtering off KOH, the solution is concentrated under reduced pressure. The residue was separated and purified by alumina column chromatography to obtain [F]. (Yield: about 70%)
【００６１】反応［７］ ［Ｂ］にかえて［Ｆ］を用い、得られた化合物について
再結晶を行なわない以外は反応［３］と同様にして
［Ｇ］を得た。（収率：約70％）Reaction [7] [G] was obtained in the same manner as in Reaction [3] except that [F] was used in place of [B] and the obtained compound was not recrystallized. (Yield: about 70%)
【００６２】反応［８］ ［Ｄ］にかえて［Ｇ］を用いた以外は反応［５］と同様
にして［Ｈ］を得た。（収率：約85％）Reaction [8] [H] was obtained in the same manner as in Reaction [5] except that [G] was used instead of [D]. (Yield: about 85%)
【００６３】反応［９］−１ ［Ｃ］にかえて［Ｈ］を用いた以外は反応［４］−１と
同様にして［Ｉ］を得た。（収率：約80％）[I] was obtained in the same manner as in Reaction [4] -1 except that [H] was used instead of Reaction [9] -1 [C]. (Yield: about 80%)
【００６４】反応［９］−２ ［Ｃ］にかえて［Ｈ］にした以外は反応［４］−２と同
様にして［Ｉ］を得た。[I] was obtained in the same manner as in the reaction [4] -2 except that the reaction [9] -2 [C] was changed to [H].
【００６５】反応［10］ ［Ｉ］をＴＨＦに溶解し、そこに塩酸を加え40℃で30分
間攪拌させる。反応終了後放冷し、室温でＫＯＨを加え
30分間攪拌する。ＫＯＨを濾別後ＴＨＦを減圧下濃縮
し、残渣をシリカゲルカラムクロマトグラフィーにより
分離・精製して［Ｊ］を得た。（収率：約55％）Reaction [10] [I] is dissolved in THF, hydrochloric acid is added thereto, and the mixture is stirred at 40 ° C. for 30 minutes. After the reaction is complete, let cool and add KOH at room temperature.
Stir for 30 minutes. After KOH was filtered off, THF was concentrated under reduced pressure, and the residue was separated and purified by silica gel column chromatography to obtain [J]. (Yield: about 55%)
【００６６】反応［11］ β−ＣＤ（ｎ＝７）を脱水ＤＭＦに溶解し、室温でイミ
ダゾールを添加する。次いでアルゴン雰囲気下 tＢＤＭ
Ｓｉ・Ｃｌを加え溶解させる。その系をゆっくりと加熱
し90〜 100℃で24時間反応させる。反応終了後放冷し、
減圧下ＤＭＦを留去し残渣を塩化メチレン／水系で抽出
し、有機相は１Ｍ−Ｈ2 ＳＯ4 、水、ＮａＨＣＯ3 水溶
液で洗浄後乾燥する。有機相は減圧下濃縮し、残渣を塩
化メチレン／メタノール系より再結晶し精製し［Ｋ］を
得た。（収率：約65％）Reaction [11] β-CD (n = 7) is dissolved in dehydrated DMF, and imidazole is added at room temperature. Then under argon atmosphere t BDM
Si.Cl is added and dissolved. The system is slowly heated and reacted at 90-100 ° C for 24 hours. Allow to cool after the reaction,
The residue was distilled off under reduced pressure DMF and extracted with methylene chloride / water, the organic phase is 1M-H 2 SO 4, dried after washed with water, aqueous NaHCO 3. The organic phase was concentrated under reduced pressure, and the residue was recrystallized from a methylene chloride / methanol system and purified to obtain [K]. (Yield: about 65%)
【００６７】反応［12］ ［Ｂ］にかえて［Ｋ］を用いた以外は反応［６］と同様
にして［Ｌ］を得た。（収率：約70％）Reaction [12] [L] was obtained in the same manner as in Reaction [6] except that [K] was used instead of [B]. (Yield: about 70%)
【００６８】反応［13］ ［Ｂ］にかえて［Ｌ］を用い、反応を室温で12時間行な
うかわりに室温で24時間行ない、更にジエチルエーテル
／メタノール系による再結晶を行なわない以外は反応
［３］と同様にして［Ｍ］を得た。（収率：約60％）Reaction [13] Reaction [13] was repeated except that [L] was used in place of [B], the reaction was carried out at room temperature for 24 hours instead of at room temperature for 12 hours, and recrystallization with a diethyl ether / methanol system was not carried out. [M] was obtained in the same manner as 3]. (Yield: about 60%)
【００６９】反応［14］−１ ［Ｃ］にかえて［Ｍ］を用いた以外は反応［４］−１と
同様にして［Ｎ］を得た。（収率：約80％）[N] was obtained in the same manner as in Reaction [4] -1 except that [M] was used instead of Reaction [14] -1 [C]. (Yield: about 80%)
【００７０】反応［14］−２ ［Ｃ］にかえて［Ｍ］にした以外は反応［４］−２と同
様にして［Ｎ］を得た。[N] was obtained in the same manner as in the reaction [4] -2 except that the reaction [14] -2 [C] was changed to [M].
【００７１】反応［15］ ［Ｉ］にかえて［Ｎ］を用いた以外は反応［10］と同様
にして２，６−ジアセチルＣＤ［Ｊ］を得た。（収率：
約60％）Reaction [15] 2,6-diacetyl CD [J] was obtained in the same manner as in the reaction [10] except that [N] was used instead of [I]. (yield:
(About 60%)
【００７２】上記反応［１］において、β−ＣＤにかえ
てα−ＣＤを用いる場合は、β−ＣＤを脱水ピリジン中
に溶解するかわりにα−ＣＤを脱水ピリジン／脱水ＤＭ
Ｆ＝４／３溶液に溶解した以外は反応［１］と同様の操
作で行なうことができる。When α-CD is used instead of β-CD in the above reaction [1], α-CD is dehydrated in pyridine / dehydrated DM instead of being dissolved in dehydrated pyridine.
The same operation as in the reaction [1] can be carried out except that it is dissolved in a F = 4/3 solution.
【００７３】また、β−ＣＤにかえてγ−ＣＤを用いる
場合は、反応［１］と同様の操作で行なうことができ
る。When γ-CD is used instead of β-CD, the same operation as in the reaction [1] can be performed.
【００７４】[0074]
【発明の効果】以上詳細に説明したように、本発明によ
り、２，３あるいは６位のいずれかに、又は２，６位あ
るいは３，６位にアセチル基を導入した新規なシクロデ
キストリン誘導体が得られる。また油に溶けやすく、界
面活性を呈し吸湿性の低下した、シクロデキストリン誘
導体が得られる。INDUSTRIAL APPLICABILITY As described in detail above, according to the present invention, a novel cyclodextrin derivative in which an acetyl group is introduced at either the 2,3 or 6-position or at the 2,6- or 3,6-position is provided. can get. In addition, a cyclodextrin derivative which is easily soluble in oil, exhibits surface activity, and has reduced hygroscopicity can be obtained.
【００７５】更に、本発明によれば、反応段階ごとにシ
クロデキストリンの持つ水酸基の特定の位置を狙って化
学修飾するため確実に目的物が得られる。Furthermore, according to the present invention, the target compound is surely obtained because the chemical modification is aimed at a specific position of the hydroxyl group of cyclodextrin in each reaction step.
Claims (11)
されるアセチルシクロデキストリン誘導体。 【化１】 1. An acetylcyclodextrin derivative represented by the following formula (1), (2) or (3). [Chemical 1]
ル）シクロデキストリンの２位及び３位の水酸基をベン
ジル化、アリル化又はピラニル化した後、脱シリル化し
て得られたシクロデキストリン誘導体の６位の水酸基を
アセチル化した後保護基を除去する、６−アセチル−シ
クロデキストリンの製造方法。2. A cyclodextrin derivative obtained by benzylating, allylating or pyranylating hydroxyl groups at the 2- and 3-positions of (6-O-tert-butyldimethylsilyl) cyclodextrin, and then desilylating the derivative. A method for producing 6-acetyl-cyclodextrin, which comprises acetylating the hydroxyl group at the position and then removing the protecting group.
された（６−Ｏ−tert−ブチルジメチルシリル）シクロ
デキストリンを脱シリル化した後ベンジル化、アリル化
又はピラニル化し、次いで２位のベンジル基又はアリル
基を脱離せしめた後アセチル化する、２−アセチル−シ
クロデキストリンの製造方法。3. A (6-O-tert-butyldimethylsilyl) cyclodextrin having a benzylated or allylated hydroxyl group at the 2-position is desilylated, then benzylated, allylated or pyranylated, and then benzyl at the 2-position. A method for producing 2-acetyl-cyclodextrin, which comprises eliminating a group or an allyl group and then acetylating the group.
ルシリル）シクロデキストリンの３位の水酸基をアセチ
ル化した後、脱シリル化する、３−アセチル−シクロデ
キストリンの製造方法。4. A method for producing 3-acetyl-cyclodextrin, which comprises acetylating the hydroxyl group at the 3-position of (2,6-di-O-tert-butyldimethylsilyl) cyclodextrin and then desilylating.
された（６−Ｏ−tert−ブチルジメチルシリル）シクロ
デキストリンの３位の水酸基をアセチル化した後、２位
のベンジル基又はアリル基を脱離せしめ、次いで脱シリ
ル化する、３−アセチル−シクロデキストリンの製造方
法。5. A hydroxyl group at the 2-position is benzylated or allylated, and the hydroxyl group at the 3-position of (6-O-tert-butyldimethylsilyl) cyclodextrin is acetylated, and then the benzyl group or the allyl group at the 2-position is added. A method for producing 3-acetyl-cyclodextrin, which comprises desorbing and then desilylating.
ダゾールを反応させる６−アセチル−シクロデキストリ
ンの製造方法。6. A method for producing 6-acetyl-cyclodextrin, which comprises reacting cyclodextrin with N-acetylimidazole.
応させる６−アセチル−シクロデキストリンの製造方
法。7. A method for producing 6-acetyl-cyclodextrin, which comprises reacting cyclodextrin with acetyl chloride.
アセチルシクロデキストリン誘導体。 【化２】 8. A diacetylcyclodextrin derivative represented by the following formula (4) or (5). [Chemical 2]
された（６−Ｏ−ｔ−ブチルジメチルシリル）シクロデ
キストリンを脱シリル化した後アセチル化する、３，６
−ジアセチルシクロデキストリンの製造方法。9. A (6-Ot-butyldimethylsilyl) cyclodextrin in which the hydroxyl group at the 2-position is benzylated or allylated is desilylated and then acetylated.
-Method for producing diacetylcyclodextrin.
化された（６−Ｏ−ｔ−ブチルジメチルシリル）シクロ
デキストリンの３位の水酸基をベンジル化、アリル化又
はピラニル化した後に脱シリル化を行ない、次いで２位
のベンジル基又はアリル基を脱離せしめた後アセチル化
する、２，６−ジアセチルシクロデキストリンの製造方
法。10. A hydroxyl group at the 2-position is benzylated or allylated (6-Ot-butyldimethylsilyl) cyclodextrin. The hydroxyl group at the 3-position is benzylated, allylated or pyranylated, and then desilylated. A process for producing 2,6-diacetylcyclodextrin, which comprises performing benzyl group or allyl group at the 2-position and then acetylating.
チルシリル）シクロデキストリンの３位の水酸基をベン
ジル化、アリル化又はピラニル化した後に脱シリル化を
行ない、次いでアセチル化を行なう、２，６−ジアセチ
ルシクロデキストリンの製造方法。11. A dehydroxylation is carried out after benzylation, allylation or pyranylation of the hydroxyl group at the 3-position of (2,6-di-O-tert-butyldimethylsilyl) cyclodextrin, followed by acetylation. A method for producing 2,6-diacetylcyclodextrin.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP21832692A JP2762859B2 (en) | 1992-04-30 | 1992-07-24 | Cyclodextrin derivative and method for producing the same |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4-137799 | 1992-04-30 | ||
| JP13779992 | 1992-04-30 | ||
| JP21832692A JP2762859B2 (en) | 1992-04-30 | 1992-07-24 | Cyclodextrin derivative and method for producing the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH069709A true JPH069709A (en) | 1994-01-18 |
| JP2762859B2 JP2762859B2 (en) | 1998-06-04 |
Family
ID=26470997
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP21832692A Expired - Fee Related JP2762859B2 (en) | 1992-04-30 | 1992-07-24 | Cyclodextrin derivative and method for producing the same |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2762859B2 (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0678525A1 (en) * | 1994-04-22 | 1995-10-25 | Consortium für elektrochemische Industrie GmbH | Partially acylated beta-cyclodextrins |
| EP0680975A1 (en) * | 1994-04-22 | 1995-11-08 | Consortium für elektrochemische Industrie GmbH | Acylated gamma-cyclodextrins |
| CN1058668C (en) * | 1995-07-04 | 2000-11-22 | 本田技研工业株式会社 | Suspension arm for vehicle |
| JP2003321474A (en) * | 2002-04-30 | 2003-11-11 | Kentetsuku:Kk | Clathrate compound |
| CN110252400A (en) * | 2019-06-21 | 2019-09-20 | 华侨大学 | A kind of preparation method of walnut shell graft beta-cyclodextrin type catalyst and 2- Amino 3 cyano -4H- pyran derivate |
| JP2021181573A (en) * | 2017-03-02 | 2021-11-25 | 国立大学法人大阪大学 | Host-group-containing polymerizable monomer, polymer material, method for producing the same, and clathrate compound and method for producing the same |
-
1992
- 1992-07-24 JP JP21832692A patent/JP2762859B2/en not_active Expired - Fee Related
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0678525A1 (en) * | 1994-04-22 | 1995-10-25 | Consortium für elektrochemische Industrie GmbH | Partially acylated beta-cyclodextrins |
| EP0680975A1 (en) * | 1994-04-22 | 1995-11-08 | Consortium für elektrochemische Industrie GmbH | Acylated gamma-cyclodextrins |
| US5633368A (en) * | 1994-04-22 | 1997-05-27 | Consortium f ur elektrochemische Industrie GmbH | Partially acylated β-cyclodextrins |
| US5654422A (en) * | 1994-04-22 | 1997-08-05 | Consortium Fur Elektrochemische Industrie Gmbh | Acylated γ-cyclodextrins |
| CN1088716C (en) * | 1994-04-22 | 2002-08-07 | 电化学工业有限公司（国际） | Partially acylated -cyclodextrins |
| CN1102154C (en) * | 1994-04-22 | 2003-02-26 | 电化学工业有限公司（国际） | Acylierte gamma-cyclodextrine |
| CN1058668C (en) * | 1995-07-04 | 2000-11-22 | 本田技研工业株式会社 | Suspension arm for vehicle |
| JP2003321474A (en) * | 2002-04-30 | 2003-11-11 | Kentetsuku:Kk | Clathrate compound |
| JP2021181573A (en) * | 2017-03-02 | 2021-11-25 | 国立大学法人大阪大学 | Host-group-containing polymerizable monomer, polymer material, method for producing the same, and clathrate compound and method for producing the same |
| CN110252400A (en) * | 2019-06-21 | 2019-09-20 | 华侨大学 | A kind of preparation method of walnut shell graft beta-cyclodextrin type catalyst and 2- Amino 3 cyano -4H- pyran derivate |
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| Publication number | Publication date |
|---|---|
| JP2762859B2 (en) | 1998-06-04 |
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