JPH05271307A - Fixation of cyclodextrin - Google Patents
Fixation of cyclodextrinInfo
- Publication number
- JPH05271307A JPH05271307A JP10220592A JP10220592A JPH05271307A JP H05271307 A JPH05271307 A JP H05271307A JP 10220592 A JP10220592 A JP 10220592A JP 10220592 A JP10220592 A JP 10220592A JP H05271307 A JPH05271307 A JP H05271307A
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- Prior art keywords
- reaction
- cyclodextrin
- silica gel
- derivative
- reacted
- 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.)
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- Polysaccharides And Polysaccharide Derivatives (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明はシクロデキストリンの固
定化方法に関し、詳しくは無機物質、特にシリカゲルに
シクロデキストリンを固定化する方法に関する。TECHNICAL FIELD The present invention relates to a method for immobilizing cyclodextrin, and more particularly to a method for immobilizing cyclodextrin on an inorganic substance, particularly silica gel.
【０００２】[0002]
【従来の技術】シクロデスキトリンは、その環状空洞内
に種々の有機系化合物を取りこみ包接化合物を形成し、
これらの化合物は近年吸着・分離剤として利用されてい
る。しかしながら、シクロデキストリンはそれ自身水溶
性であり、特定の有機溶媒のみに溶解するものであるた
め、種々の系から化合物を包接して単離することは困難
である。2. Description of the Related Art Cyclodesquitrin incorporates various organic compounds in its annular cavity to form an inclusion compound,
These compounds have recently been used as adsorption / separation agents. However, since cyclodextrin itself is water-soluble and dissolves only in a specific organic solvent, it is difficult to include and isolate a compound from various systems.
【０００３】このような問題を解決する１つの方法とし
て、無機物質、例えばシリカゲル等にシクロデキストリ
ンを化学結合させることにより、不溶性とし、かつ取り
扱い容易な吸着・分離剤として利用する方法が提案され
ている。As one method for solving such a problem, a method has been proposed in which cyclodextrin is chemically bonded to an inorganic substance such as silica gel to make it insoluble and to be used as an adsorption / separation agent which is easy to handle. There is.
【０００４】シリカゲルにシクロデキストリンを化学結
合させる方法としては、例えば、米国特許第 4,539,399
号明細書、特開昭 61-129566号公報及びジャーナル オ
ブリキッド クロマトグラフィー（J. Liquid chromato
gr. , ９（２＆３） 607-620（1986））の各々にはシリ
カゲルに対しシリル化剤として３−グリシドキシプロピ
ルトリメトキシシラン、γ−アミノプロピルトリエトキ
シシラン、３−イソシアネートプロピルトリエトキシシ
ランをそれぞれ反応させ、その各々の末端のエポキシ基
又はイソシアネート基に対し、シクロデキストリンを反
応せしめる方法が提案されている。A method for chemically bonding cyclodextrin to silica gel is described in, for example, US Pat. No. 4,539,399.
Specification, JP-A-61-129566 and Journal of Obliqued Chromatography (J. Liquid chromato
Gr., 9 (2 & 3) 607-620 (1986)), silica gels have 3-glycidoxypropyltrimethoxysilane, γ-aminopropyltriethoxysilane, 3-isocyanatopropyltriethoxysilane as silylating agents. Has been proposed, and a cyclodextrin is allowed to react with the epoxy group or isocyanate group at each terminal thereof.
【０００５】[0005]
【発明が解決しようとする課題】しかしながら、上記の
方法においては、いずれもシリル化剤がシリカゲル表面
と十分に反応していない等のため担持量が1000μモル／
シリカゲル１g 以下程度であり少なく、この結果、シク
ロデキストリンの固定量も、 100μモル／シリカゲル１
g 以下程度と非常に少ないという欠点を有していた。However, in any of the above methods, the supported amount is 1000 μmol / min because the silylating agent does not sufficiently react with the silica gel surface.
As little as 1 g of silica gel or less, as a result, the fixed amount of cyclodextrin was also 100 μmol / silica gel 1
It had a drawback that it was very small, less than g.
【０００６】従って本発明の目的は、シクロデキストリ
ンを無機物質、特にシリカゲルに固定化する方法におい
て、無機物質に対するシクロデキストリンの固定量を著
しく増大させるシクロデキストリンの固定化方法を提供
することにある。Accordingly, it is an object of the present invention to provide a method for immobilizing cyclodextrin on an inorganic substance, particularly silica gel, in which the amount of cyclodextrin immobilized on the inorganic substance is remarkably increased.
【０００７】[0007]
【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、アリル
オキシカルボン酸誘導体、アリルオキシアルコール誘導
体、下記一般式［Ｉ］で表わされる化合物又は下記一般
式［II］で表わされる化合物をシクロデキストリンある
いはシクロデキストリン誘導体と反応させた後に活性化
シリカゲルと反応させるか、又は活性化シリカゲルと反
応させた後にシクロデキストリンあるいはシクロデキス
トリン誘導体と反応させることを特徴とするシクロデキ
ストリンの固定化方法、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-mentioned problems, the present inventors have earnestly studied, and as a result, the above-mentioned object of the present invention was found to be an allyloxycarboxylic acid derivative, an allyloxyalcohol derivative, A compound represented by the formula [II] or a compound represented by the following general formula [II] is reacted with cyclodextrin or a cyclodextrin derivative and then reacted with activated silica gel, or with an activated silica gel and then reacted with cyclodextrin or a cyclodextrin derivative. It was found to be achieved by a method of immobilizing cyclodextrin characterized by reacting.
【０００８】[0008]
【化３】 （式中、Ｒ1 はメトキシ基、エトキシ基、塩素原子等を
表わし、Ｒ2 はメチル基、エチル基等を表わし、Ｒ3 は
水素原子、メチル基等を表わす。また、ｘ3 は１〜３の
整数を表わし、ｙ1 は１〜５の整数を表わす。）[Chemical 3] (In the formula, R 1 represents a methoxy group, an ethoxy group, a chlorine atom, etc., R 2 represents a methyl group, an ethyl group, etc., R 3 represents a hydrogen atom, a methyl group, etc., and x 3 represents 1 to 1). Represents an integer of 3, and y 1 represents an integer of 1 to 5.)
【０００９】[0009]
【化４】 （式中、Ｒ4 はメトキシ基、エトキシ基等を表わし、Ｒ
5 はメチル基、エチル基等を表わす。また、ｘ4 は１〜
３の整数を表わし、ｙ2 は１〜５の整数を表わす。）[Chemical 4] (In the formula, R 4 represents a methoxy group, an ethoxy group or the like, and R 4
5 represents a methyl group, an ethyl group or the like. Also, x 4 is 1 to
Represents an integer of 3, and y 2 represents an integer of 1 to 5. )
【００１０】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.
【００１１】本発明に用いられるシクロデキストリン
（以下ＣＤと略記する）としてはグルコース単位が６，
７及び８個からなるα，β及びγ−シクロデキストリン
がいずれも使用可能である。The cyclodextrin (hereinafter abbreviated as CD) used in the present invention has 6 glucose units.
Any of α and β and γ-cyclodextrin consisting of 7 and 8 can be used.
【００１２】また、本発明に用いるＣＤ誘導体として
は、以下のものが挙げられる。 （１）少なくとも１つのヒドロキシル基を有するα，
β，γ−ＣＤ誘導体。 （２）少なくとも１つの脱離基 を有するα，β，γ−ＣＤ誘導体。 （３）少なくとも１つのメタクリル酸型基（又はアクリ
ル酸型基）を有するα，β，γ−ＣＤ誘導体。The CD derivatives used in the present invention include the following. (1) α having at least one hydroxyl group,
β, γ-CD derivatives. (2) at least one leaving group An α, β, γ-CD derivative having (3) An α, β, γ-CD derivative having at least one methacrylic acid type group (or acrylic acid type group).
【００１３】本発明に用いられるアリルオキシカルボン
酸誘導体及びアリルオキシアルコール誘導体としては、
好ましくは下記の各々の式で表されるものが挙げられ
る。The allyloxycarboxylic acid derivative and allyloxyalcohol derivative used in the present invention include
Preferred are those represented by the following formulas.
【００１４】[0014]
【化５】 （式中、ｘ1 は１〜５の整数であり、ｘ2 は２〜６の整
数である。）[Chemical 5] (In the formula, x 1 is an integer of 1 to 5, and x 2 is an integer of 2 to 6.)
【００１５】また、本発明に用いられる「活性化シリカ
ゲル」とは、希硝酸中でシリカゲルを１時間以上還流さ
せることにより表面に水酸基を数多く生じさせたものを
いう。The "activated silica gel" used in the present invention refers to silica gel in which a large number of hydroxyl groups are formed on the surface by refluxing silica gel in dilute nitric acid for 1 hour or more.
【００１６】本発明のシクロデキストリンの固定化方法
は、アリルオキシカルボン酸誘導体、アリルオキシアル
コール誘導体、メタクリル酸アルキルジアルコキシメチ
ルシラン又は３−アミノアルキルジアルコキシメチルシ
ラン（以下、これらを「本発明の誘導体」と称す）と、
ＣＤあるいはＣＤ誘導体、及び活性化シリカゲルとを順
次反応させることを特徴としているが、このような反応
は、本発明の誘導体をＣＤ又はＣＤ誘導体と反応させた
後に活性化シリカゲルと反応させることで行なうことも
できるが、また、本発明の誘導体をまず活性化シリカゲ
ルと反応させた後にＣＤ又はＣＤ誘導体と反応させるこ
とにより行なうこともできる。The method for immobilizing cyclodextrin of the present invention includes an allyloxycarboxylic acid derivative, an allyloxy alcohol derivative, an alkyldialkoxymethylsilane methacrylate or a 3-aminoalkyldialkoxymethylsilane (hereinafter referred to as "the present invention"). "Derivative"),
The method is characterized in that CD or a CD derivative and activated silica gel are sequentially reacted. Such a reaction is performed by reacting the derivative of the present invention with CD or a CD derivative and then with activated silica gel. Alternatively, it can also be carried out by first reacting the derivative of the present invention with activated silica gel and then with CD or a CD derivative.
【００１７】以下に、本発明のＣＤの固定化方法の具体
的反応例を挙げる。Specific reaction examples of the method for immobilizing CD of the present invention will be described below.
【００１８】[0018]
【化６】 [Chemical 6]
【００１９】[0019]
【化７】 [Chemical 7]
【００２０】[0020]
【化８】 [Chemical 8]
【００２１】上記反応は具体的には以下のように行なう
ことができる。The above reaction can be specifically carried out as follows.
【００２２】反応例（１） 反応［１］ ３−アリルオキシプロピオン酸（ｘ1 ＝２）をメタノー
ル中で１Ｍ−ＫＯＨのメタノール溶液と反応させ中和点
を反応終了とし、その後メタノールを濃縮乾固させる。
得られた白色固体をイソプロピルアルコールより再結晶
を行ない［Ａ］を得る。（［Ａ］Ｍ；Ｋ，収率：約85
％）Reaction Example (1) Reaction [1] 3-allyloxypropionic acid (x 1 = 2) was reacted with 1 M-KOH in methanol in methanol to complete the reaction at the neutralization point, and then methanol was concentrated to dryness. Harden.
The obtained white solid is recrystallized from isopropyl alcohol to obtain [A]. ([A] M; K, yield: about 85
%)
【００２３】反応［２］ ３−アリルオキシプロピオン酸（ｘ1 ＝２）を塩化チオ
ニル中で還流６時間反応させる。反応終了後、減圧下塩
化チオニルを留去し、残渣を減圧蒸留することにより
［Ｂ］を得る。（［Ｂ］収率：約80％）Reaction [2] 3-allyloxypropionic acid (x 1 = 2) is reacted in thionyl chloride at reflux for 6 hours. After completion of the reaction, thionyl chloride was distilled off under reduced pressure, and the residue was distilled under reduced pressure to obtain [B]. ([B] Yield: about 80%)
【００２４】反応［３］ ［Ａ］を脱水ＤＭＦ（あるいはＤＭＳＯ）中に溶解さ
せ、窒素雰囲気下60℃に加温する。次いでモノトシル
（あるいはモノアイオド）β−ＣＤ誘導体（ｎ＝７，Ｒ
1 ；ＣＨ3 ＣＯ−）のＤＭＦ溶液を滴下する。滴下終了
後 100℃で24時間攪拌し、反応終了後ＤＭＦを減圧下留
去し、残渣を塩化メチレン／水で抽出する。塩化メチレ
ン相は乾燥後濃縮し、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［Ｃ］を得る。（［Ｃ］収率：
約55％）Reaction [3] [A] is dissolved in dehydrated DMF (or DMSO) and heated to 60 ° C. under a nitrogen atmosphere. Next, monotosyl (or monoiodo) β-CD derivative (n = 7, R
1; CH 3 CO-) is added dropwise in DMF. After completion of dropping, the mixture is stirred at 100 ° C. for 24 hours, after completion of reaction, DMF is distilled off under reduced pressure, and the residue is extracted with methylene chloride / water. The methylene chloride phase is dried and then concentrated, and the residue is purified by silica gel column chromatography to obtain [C]. ([C] Yield:
55%)
【００２５】反応［４］ モノヒドロキシβ−ＣＤ誘導体（ｎ＝７，Ｒ1 ；ＣＨ3
−）を脱水ＴＨＦ中に溶解させ、トリエチルアミンを加
え窒素気流下０〜５℃に下げる。その後［Ｂ］をゆっく
り滴下し、滴下終了後０〜５℃で２時間、室温で12時間
攪拌する。反応終了後ＴＨＦを減圧下で留去し、残渣を
塩化メチレン／水で抽出する。塩化メチレン相は乾燥後
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［Ｃ］を得る。（［Ｃ］収率：約75％）Reaction [4] Monohydroxy β-CD derivative (n = 7, R 1 ; CH 3
-) Is dissolved in dehydrated THF, triethylamine is added, and the temperature is lowered to 0 to 5 ° C under a nitrogen stream. After that, [B] is slowly added dropwise, and after completion of the addition, the mixture is stirred at 0 to 5 ° C. for 2 hours and at room temperature for 12 hours. After completion of the reaction, THF is distilled off under reduced pressure, and the residue is extracted with methylene chloride / water. The methylene chloride phase is dried and then concentrated, and the residue is purified by silica gel column chromatography to obtain [C]. ([C] yield: about 75%)
【００２６】反応［５］ ３−アリルオキシプロピオン酸（ｘ1 ＝２）とモノヒド
ロキシβ−ＣＤ誘導体（ｎ＝７，Ｒ1 ＝ＣＨ3 −）とを
脱水クロロホルム中に溶解させ、その系に４−ピロリジ
ノピリジンを添加する。さらに室温下でジシクロヘキシ
ルカルボジイミドを添加し、その後還流下24時間反応さ
せる。反応終了後濾過し、クロロホルムを減圧下濃縮、
残渣を塩化メチレン／水で抽出する。塩化メチレン相は
乾燥後濃縮し、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［Ｃ］を得る。（［Ｃ］収率：約40
％）Reaction [5] 3-allyloxypropionic acid (x 1 = 2) and a monohydroxy β-CD derivative (n = 7, R 1 ═CH 3 —) were dissolved in dehydrated chloroform and added to the system. 4-Pyrrolidinopyridine is added. Further, dicyclohexylcarbodiimide is added at room temperature, and then the mixture is reacted under reflux for 24 hours. After completion of the reaction, it is filtered, chloroform is concentrated under reduced pressure,
The residue is extracted with methylene chloride / water. The methylene chloride phase is dried and then concentrated, and the residue is purified by silica gel column chromatography to obtain [C]. ([C] Yield: about 40
%)
【００２７】反応［６］ ［Ｃ］（ｘ1 ＝２，Ｒ1 ；ＣＨ3 ＣＯ−）とトリエトキ
シシラン（ｙ＝３，Ｒ2 ；Ｃ2 Ｈ5 Ｏ−）をＴＨＦ中に
溶解し、アルゴン雰囲気下攪拌する。その系に室温でヘ
キサクロロ白金酸６水和物のＴＨＦ溶液をゆっくり滴下
し、滴下終了後80℃で24時間攪拌する。反応終了後、遠
心分離により沈澱物を取り除き、ＴＨＦを減圧下留去さ
せ、残渣はよく乾燥させる。得られた［Ｄ］は分解しや
すいので窒素雰囲気下で保存する。（［Ｄ］収率：約80
％）Reaction [6] Dissolve [C] (x 1 = 2, R 1 ; CH 3 CO-) and triethoxysilane (y = 3, R 2 ; C 2 H 5 O-) in THF, Stir under argon atmosphere. A THF solution of hexachloroplatinic acid hexahydrate is slowly added dropwise to the system at room temperature, and after completion of the addition, the mixture is stirred at 80 ° C for 24 hours. After the reaction is completed, the precipitate is removed by centrifugation, THF is distilled off under reduced pressure, and the residue is dried well. Since the obtained [D] is easily decomposed, it is stored in a nitrogen atmosphere. ([D] Yield: about 80
%)
【００２８】反応［７］ 脱水トルエン中に活性化シリカゲルを分散させ、室温下
窒素雰囲気で［Ｄ］（Ｒ2 ；Ｃ2 Ｈ5 Ｏ−，ｙ＝３，ｘ
1 ＝２，Ｒ1 ；ＣＨ3 ＣＯ−）を添加し、その後 100℃
で12時間攪拌させる。反応終了後、反応シリカゲルを濾
別し、よくアセトンで洗浄し、減圧下80〜90℃で乾燥す
ることで［Ｅ］を得る。（［Ｅ］固定量：約 550μモル
／シリカゲル１g ）Reaction [7] Activated silica gel is dispersed in dehydrated toluene, and [D] (R 2 ; C 2 H 5 O-, y = 3, x in a nitrogen atmosphere at room temperature.
1 = 2, R 1 ; CH 3 CO-), and then 100 ° C
Let stir for 12 hours. After completion of the reaction, the reaction silica gel is filtered off, washed well with acetone, and dried under reduced pressure at 80 to 90 ° C. to obtain [E]. ([E] fixed amount: about 550 μmol / silica gel 1 g)
【００２９】反応例（２） 反応［８］ ３−アリルオキシプロピオン酸（ｘ1 ＝２）をＴＨＦ中
で攪拌、さらにピリジンを加える。次いで室温でＴＨＦ
に溶解した臭化トリチルを滴下、滴下終了後還流下12時
間攪拌する。反応終了後濾過し、ＴＨＦピリジンを減圧
下留去させ、残渣をベンゼン／クロロホルムで再結晶し
［Ｆ］を得る。（［Ｆ］収率：約70％）Reaction Example (2) Reaction [8] 3-allyloxypropionic acid (x 1 = 2) is stirred in THF, and pyridine is added. Then THF at room temperature
Trityl bromide dissolved in was added dropwise, and after the addition was completed, the mixture was stirred under reflux for 12 hours. After completion of the reaction, filtration is performed, THF pyridine is distilled off under reduced pressure, and the residue is recrystallized from benzene / chloroform to obtain [F]. ([F] yield: about 70%)
【００３０】反応［９］ ［Ｆ］（ｘ1 ＝２，Ｒ3 ；（Ｃ6 Ｈ5 ）3 Ｃ−）とトリ
エトキシシラン（ｙ＝３，Ｒ2 ；Ｃ2 Ｈ5 Ｏ−）との反
応 反応［６］に準ずる。（［Ｇ］収率：約90％）Reaction [9] of [F] (x 1 = 2, R 3 ; (C 6 H 5 ) 3 C-) with triethoxysilane (y = 3, R 2 ; C 2 H 5 O-) Reaction According to Reaction [6]. ([G] yield: about 90%)
【００３１】反応［10］ ［Ｇ］（ｘ1 ＝２，Ｒ3 ；（Ｃ6 Ｈ5 ）3 Ｃ−，ｙ＝
３，Ｒ2 ＝Ｃ2 Ｈ5 Ｏ−）と活性化シリカゲルとの反応 反応［７］に準ずる。（［Ｈ］担持量：約2200μモル／
シリカ１g ）Reaction [10] [G] (x 1 = 2, R 3 ; (C 6 H 5 ) 3 C-, y =
3, R 2 = C 2 H 5 O-) and reaction with activated silica gel According to the reaction [7]. (Amount of [H] supported: Approx. 2200 μmol /
Silica 1g)
【００３２】反応［11］ ［Ｈ］をアセトン／ＨＢｒ水溶液中に分散させ、室温で
30分攪拌させる。反応終了後、反応シリカゲルを濾別、
よくアセトンで洗浄し、減圧下80〜90℃で乾燥すること
で［Ｉ］を得る。（［Ｈ］→［Ｉ］転化率 約 100％）Reaction [11] Disperse [H] in an acetone / HBr aqueous solution and let it stand at room temperature.
Let stir for 30 minutes. After the reaction is completed, the reaction silica gel is filtered off,
After washing well with acetone and drying under reduced pressure at 80 to 90 ° C, [I] is obtained. ([H] → [I] conversion rate about 100%)
【００３３】反応［12］ ［Ｉ］をＳＯＣｌ2 中に分散させ、還流下12時間攪拌す
る。反応終了後、反応シリカゲルを濾別、脱水アセトン
でよく洗浄し、減圧下80〜90℃で乾燥することで［Ｊ］
を得る。（［Ｉ］→［Ｊ］転化率 約 100％）Reaction [12] [I] is dispersed in SOCl 2 and stirred under reflux for 12 hours. After completion of the reaction, the reaction silica gel is separated by filtration, washed thoroughly with dehydrated acetone, and dried under reduced pressure at 80 to 90 ° C [J].
To get ([I] → [J] conversion rate about 100%)
【００３４】反応［13］ ［Ｊ］を脱水ＴＨＦ中分散させ、窒素雰囲気下トリエチ
ルアミンを加え、０〜５℃でＴＨＦに溶解したモノヒド
ロキシβ−ＣＤ誘導体（ｎ＝７，Ｒ1 ＝ＣＨ3−）を滴
下し、滴下終了後０〜５℃で２時間、室温で24時間反応
させる。反応終了後、反応シリカゲルを濾別し、濾物は
メタノール中で還流させ末端反応基をつぶす（約12時
間）。終了後、反応シリカゲルを濾別し、減圧下80〜90
℃で乾燥することで［Ｋ］を得る。（［Ｋ］ＣＤ固定
量：約 500μモル／シリカ１g ）Reaction [13] [J] was dispersed in dehydrated THF, triethylamine was added under a nitrogen atmosphere, and the monohydroxy β-CD derivative (n = 7, R 1 ═CH 3 —) was dissolved in THF at 0 to 5 ° C. ) Is added dropwise, and after completion of the addition, the mixture is reacted at 0 to 5 ° C. for 2 hours and at room temperature for 24 hours. After completion of the reaction, the reaction silica gel is filtered off, and the residue is refluxed in methanol to destroy the terminal reactive groups (about 12 hours). After the reaction is completed, the reaction silica gel is filtered off and the pressure is reduced to 80-90.
[K] is obtained by drying at ℃. (Fixed amount of [K] CD: about 500 μmol / g of silica)
【００３５】反応［14］ ［Ａ］（ｘ1 ＝２，Ｍ；Ｋ）とトリエトキシシラン（ｙ
＝３，Ｒ2 ；Ｃ2 Ｈ5Ｏ−）をＤＭＦ中に溶解し、アル
ゴン雰囲気下攪拌する。その系に室温でヘキサクロロ白
金酸６水和物のＤＭＦ溶液をゆっくり滴下、滴下終了後
80℃で24時間攪拌する。反応終了後、遠心分離により沈
澱物を取り除き、ＤＭＦを減圧下留去させ、残渣はよく
乾燥させる。得られた［Ｌ］は分解しやすいので窒素雰
囲気下で保存する。（［Ｌ］収率：約70％）Reaction [14] [A] (x 1 = 2, M; K) and triethoxysilane (y
= 3, R 2; C 2 H 5 O-) was dissolved in DMF, and stirred under an argon atmosphere. A DMF solution of hexachloroplatinic acid hexahydrate was slowly added dropwise to the system at room temperature, and after the addition was completed
Stir at 80 ° C for 24 hours. After completion of the reaction, the precipitate is removed by centrifugation, DMF is distilled off under reduced pressure, and the residue is thoroughly dried. Since the obtained [L] is easily decomposed, it is stored in a nitrogen atmosphere. ([L] yield: about 70%)
【００３６】反応［15］ ［Ｌ］（ｘ1 ＝２，Ｍ；Ｋ，Ｒ2 ；Ｃ2 Ｈ5 Ｏ−，ｙ＝
３）と活性化シリカゲルの反応 反応［７］に準ずる。（［Ｍ］担持量：約2000μモル／
シリカ１g ）Reaction [15] [L] (x 1 = 2, M; K, R 2 ; C 2 H 5 O-, y =
3) Reaction with activated silica gel Follow the reaction [7]. ([M] supported amount: about 2000 μmol /
Silica 1g)
【００３７】反応［16］ ［Ｍ］（ｘ1 ＝２，Ｍ；Ｋ，Ｒ2 ；Ｃ2 Ｈ5 Ｏ−）とＳ
ＯＣｌ2 との反応 反応［12］に準ずる。（［Ｍ］→［Ｊ］転化率 約 100
％）Reaction [16] [M] (x 1 = 2, M; K, R 2 ; C 2 H 5 O-) and S
Reaction with OCl 2 According to Reaction [12]. ([M] → [J] conversion rate approx. 100
%)
【００３８】反応［17］ ［Ｍ］（ｘ1 ＝２，Ｍ；Ｋ，Ｒ2 ；Ｃ2 Ｈ5 Ｏ−）をＴ
ＨＦ中に分散させ、窒素雰囲気下室温でモノトシル（あ
るいはモノアイオド）β−ＣＤ誘導体（ｎ＝７，Ｒ1 ；
ＣＨ3 ＣＯ−）のＴＨＦ溶液を滴下する。滴下終了後、
還流下48時間反応させる。反応終了後、反応シリカゲル
を濾別し、熱水でよく洗浄後、減圧下80〜90℃で乾燥す
ることで［Ｋ］を得る。（［Ｋ］ＣＤ固定量：約 300μ
モル／シリカゲル１g ）The reaction [17] [M] (x 1 = 2, M; K, R 2 ; C 2 H 5 O-) was converted to T.
Dispersed in HF, at room temperature under nitrogen atmosphere, monotosyl (or monoiodo) β-CD derivative (n = 7, R 1 ;
CH 3 CO-) in THF is added dropwise. After finishing the dropping
React under reflux for 48 hours. After completion of the reaction, the reaction silica gel is filtered off, washed thoroughly with hot water, and dried at 80 to 90 ° C. under reduced pressure to obtain [K]. ([K] CD fixed amount: about 300μ
Mol / silica gel 1 g)
【００３９】反応例（３） 反応［18］ ３−アリルオキシプロピオン酸（ｘ1 ＝２）を塩化チオ
ニル中で還流下６時間反応させる。反応終了後、減圧下
塩化チオニルを留去し、残渣を減圧蒸留することにより
［Ｎ］を得る。（［Ｎ］収率：約80％）Reaction Example (3) Reaction [18] 3-allyloxypropionic acid (x 1 = 2) is reacted in thionyl chloride for 6 hours under reflux. After completion of the reaction, thionyl chloride was distilled off under reduced pressure, and the residue was distilled under reduced pressure to obtain [N]. ([N] yield: about 80%)
【００４０】反応［19］ ［Ｎ］とトリメトキシシラン（Ｒ1 ；ＣＨ3 Ｏ−，ｙ＝
３）をＴＨＦ中に溶解し、アルゴン雰囲気下攪拌する。
その系に室温でヘキサクロロ白金酸６水和物のＴＨＦ溶
液をゆっくり滴下、滴下終了後80℃で24時間攪拌する。
反応終了後、遠心分離により沈澱物を取り除き、ＴＨＦ
を減圧下留去させ、残渣［Ｏ］を得る。該化合物は分解
しやすいので窒素雰囲気下で保存する。（［Ｏ］収率：
約70％）Reaction [19] [N] with trimethoxysilane (R 1 ; CH 3 O-, y =
3) is dissolved in THF and stirred under an argon atmosphere.
A THF solution of hexachloroplatinic acid hexahydrate is slowly added dropwise to the system at room temperature, and after completion of the addition, the mixture is stirred at 80 ° C for 24 hours.
After the reaction is completed, the precipitate is removed by centrifugation, and THF is added.
Is distilled off under reduced pressure to obtain a residue [O]. Since the compound is easily decomposed, it is stored under a nitrogen atmosphere. ([O] yield:
About 70%)
【００４１】反応［20］ 脱水トルエン中に活性化シリカゲルを分散させ、室温下
窒素雰囲気で［Ｏ］のトルエン溶液を加え、その後 100
℃で12時間反応させる。反応終了後、反応シリカゲルを
濾別し、よくトルエンで洗浄し、減圧下80〜90℃で乾燥
することで［Ｐ］を得る。（［Ｐ］固定量：約1500μモ
ル／シリカゲル１g ）Reaction [20] Activated silica gel is dispersed in dehydrated toluene, and a toluene solution of [O] is added in a nitrogen atmosphere at room temperature.
Incubate for 12 hours at ℃. After completion of the reaction, the reaction silica gel is filtered off, washed well with toluene, and dried at 80 to 90 ° C. under reduced pressure to obtain [P]. (Fixed amount of [P]: about 1500 μmol / g of silica gel)
【００４２】反応［21］（［ａ］の場合） ［Ｐ］を脱水ピリジン中で分散させ、系を窒素雰囲気下
０〜５℃に冷却する。その系にβ−ＣＤのピリジン溶液
をゆっくり滴下する。滴下終了後０〜５℃で２時間、次
いで室温で12時間反応させる。反応終了後、反応シリカ
ゲルを濾別し、よくＤＭＦで洗浄後メタノール中で還流
させる（約12時間）。終了後、反応シリカゲルを濾別
し、減圧下80〜90℃で乾燥し［Ｑ］を得る。（［Ｐ］へ
のＣＤ固定量：約 350μモル／シリカゲル１g ）Reaction [21] (for [a]) [P] is dispersed in dehydrated pyridine and the system is cooled to 0-5 ° C under a nitrogen atmosphere. A β-CD pyridine solution is slowly added dropwise to the system. After completion of dropping, the mixture is reacted at 0 to 5 ° C for 2 hours and then at room temperature for 12 hours. After completion of the reaction, the reaction silica gel is filtered off, washed well with DMF and then refluxed in methanol (about 12 hours). After completion, the reaction silica gel is filtered off and dried under reduced pressure at 80 to 90 ° C. to obtain [Q]. (Amount of CD fixed to [P]: about 350 μmol / g of silica gel)
【００４３】反応［21］（［ｂ］の場合）（Ｒ2 ；ＣＨ
3 ＣＯ−，ｍ＝７） 反応［21］［ａ］において、脱水ピリジンを脱水ＴＨＦ
／トリエチルアミンとし、β−ＣＤのピリジン溶液をβ
−ＣＤのＴＨＦ溶液とした以外は同様にして［Ｑ］を得
る。（［Ｐ］へのＣＤ固定量：約 450μモル／シリカゲ
ル１g ）Reaction [21] (for [b]) (R 2 ; CH
3 CO-, m = 7) In the reaction [21] [a], dehydrated pyridine was replaced with dehydrated THF.
/ Triethylamine and β-CD pyridine solution is β
[Q] is obtained in the same manner except that a THF solution of CD is used. (Amount of CD fixed on [P]: about 450 μmol / g of silica gel)
【００４４】[0044]
【化９】 [Chemical 9]
【００４５】[0045]
【化１０】 [Chemical 10]
【００４６】[0046]
【化１１】 [Chemical 11]
【００４７】反応例（４） 反応［１］ 水酸化ナトリウム水溶液に０〜５℃においてアリルオキ
シエタノール（ｘ2 ＝２）のＴＨＦ溶液を滴下し、その
後０℃以下で１時間攪拌する。次いでｐ−トルエンスル
ホン酸クロライドのＴＨＦ溶液を滴下し、滴下終了後も
０℃以下で３時間攪拌する。反応終了後分液し、水相を
塩化メチレンで抽出、ＴＨＦ相と合わせて乾燥後減圧下
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［Ａ］を得る。（［Ａ］収率：約85％）Reaction Example (4) Reaction [1] A THF solution of allyloxyethanol (x 2 = 2) was added dropwise to an aqueous solution of sodium hydroxide at 0 to 5 ° C, and then stirred at 0 ° C or lower for 1 hour. Then, a THF solution of p-toluenesulfonic acid chloride is added dropwise, and after completion of the addition, the mixture is stirred at 0 ° C. or lower for 3 hours. After completion of the reaction, liquid separation is performed, the aqueous phase is extracted with methylene chloride, combined with the THF phase, dried and concentrated under reduced pressure, and the residue is purified by silica gel column chromatography to obtain [A]. ([A] yield: about 85%)
【００４８】反応［２］ ＴＨＦ中、窒素気流下ＮａＨを分散させ、室温でモノヒ
ドロキシβ−ＣＤ誘導体（ｎ＝７，Ｒ2 ；ＣＨ3 −）の
ＴＨＦ溶液を滴下する。滴下終了後２時間攪拌し、次い
で［Ａ］（ｘ2 ＝２）のＴＨＦ溶液をゆっくり滴下し、
滴下終了後還流下で24時間反応させる。反応終了後濾過
し、濾液は減圧下留去、残渣を塩化メチレン／水より抽
出し、塩化メチレン相は乾燥後減圧下濃縮する。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
［Ｂ］を得る。（［Ｂ］収率：約55％）Reaction [2] NaH is dispersed in THF under a nitrogen stream, and a THF solution of a monohydroxy β-CD derivative (n = 7, R 2 ; CH 3 —) is added dropwise at room temperature. After completion of dropping, the mixture is stirred for 2 hours, and then a THF solution of [A] (x 2 = 2) is slowly added dropwise,
After completion of dropping, the mixture is reacted under reflux for 24 hours. After completion of the reaction, the mixture is filtered, the filtrate is distilled off under reduced pressure, the residue is extracted with methylene chloride / water, and the methylene chloride phase is dried and then concentrated under reduced pressure. The residue is purified by silica gel column chromatography to obtain [B]. ([B] Yield: about 55%)
【００４９】反応［３］ ［Ｂ］（ｘ2 ＝２，ｎ＝７，Ｒ2 ；ＣＨ3 −）とジメト
キシメチルシラン（ｙ＝２，Ｒ3 ；ＣＨ3 Ｏ−）をＴＨ
Ｆ中に溶解し、アルゴン雰囲気下攪拌する。その系に室
温でヘキサクロロ白金酸６水和物のＴＨＦ溶液をゆっく
り滴下、滴下終了後80℃で24時間攪拌する。反応終了
後、遠心分離により沈澱物を取り除き、ＴＨＦを減圧下
留去させ、残渣はよく乾燥させる。得られた［Ｃ］は分
解しやすいので窒素雰囲気下で保存する。（［Ｃ］収
率：約85％）Reaction [3] [B] (x 2 = 2, n = 7, R 2 ; CH 3 —) and dimethoxymethylsilane (y = 2, R 3 ; CH 3 O—) were mixed with TH.
Dissolve in F and stir under argon atmosphere. A THF solution of hexachloroplatinic acid hexahydrate is slowly added dropwise to the system at room temperature, and after completion of the addition, the mixture is stirred at 80 ° C for 24 hours. After the reaction is completed, the precipitate is removed by centrifugation, THF is distilled off under reduced pressure, and the residue is dried well. Since the obtained [C] is easily decomposed, it is stored in a nitrogen atmosphere. ([C] yield: about 85%)
【００５０】反応［４］ 脱水トルエン中に活性化シリカゲルを分散させ、室温下
窒素雰囲気で［Ｃ］（Ｒ3 ；ＣＨ3 Ｏ−，ｙ＝２，ｘ2
＝２，ｎ＝７，Ｒ2 ；ＣＨ3 −）を添加し、その後 100
℃で12時間攪拌させる。反応終了後、反応シリカゲルを
濾別し、よくアセトンで洗浄し、減圧下80〜90℃で乾燥
することで［Ｄ］を得る。（［Ｄ］固定量：約 600μモ
ル／シリカゲル１g ）Reaction [4] Activated silica gel is dispersed in dehydrated toluene, and [C] (R 3 ; CH 3 O--, y = 2, x 2 in a nitrogen atmosphere at room temperature.
= 2, n = 7, R 2 ; CH 3 −) was added, and then 100
Allow to stir at ℃ for 12 hours. After completion of the reaction, the reaction silica gel is filtered off, washed well with acetone, and dried at 80 to 90 ° C. under reduced pressure to obtain [D]. ([D] Fixed amount: about 600 μmol / silica gel 1 g)
【００５１】反応［５］ 脱水ＴＨＦ中アリルオキシエタノール（ｘ2 ＝２）を溶
解し、さらにトリエチルアミンを加える。窒素雰囲気下
０〜５℃に系を冷却し、そこにモノ酸塩化β−ＣＤ誘導
体（ｎ＝７，Ｒ1 ；ＣＨ3 ＣＯ−）のＴＨＦ溶液をゆっ
くり滴下し、滴下終了後０〜５℃で２時間、続いて室温
で６時間反応させる。反応終了後ＴＨＦ、トリエチルア
ミンを減圧下で留去、残渣を塩化メチレン／水より抽出
し、塩化メチレン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［Ｅ］を
得る。（［Ｅ］収率：約75％）Reaction [5] Allyloxyethanol (x 2 = 2) is dissolved in dehydrated THF, and triethylamine is further added. The system was cooled to 0 to 5 ° C under a nitrogen atmosphere, and a THF solution of a mono-acidified β-CD derivative (n = 7, R 1 ; CH 3 CO-) was slowly added dropwise thereto, and 0 to 5 ° C after the addition was completed. For 2 hours and then 6 hours at room temperature. After completion of the reaction, THF and triethylamine are distilled off under reduced pressure, the residue is extracted with methylene chloride / water, the methylene chloride phase is dried and then concentrated under reduced pressure, and the residue is purified by silica gel column chromatography to obtain [E]. ([E] yield: about 75%)
【００５２】反応［６］ ［Ｅ］（ｘ2 ＝２，ｎ＝７，Ｒ1 ；ＣＨ3 ＣＯ−）とジ
メトキシメチルシラン（Ｒ3 ；ＣＨ3 Ｏ−，ｙ＝２）と
の反応 反応［３］に準ずる。（［Ｆ］収率：約80％）Reaction [6] Reaction of [E] (x 2 = 2, n = 7, R 1 ; CH 3 CO-) with dimethoxymethylsilane (R 3 ; CH 3 O-, y = 2) 3]. ([F] yield: about 80%)
【００５３】反応［７］ ［Ｆ］（ｘ2 ＝２，ｎ＝７，Ｒ1 ；ＣＨ3 ＣＯ−，Ｒ
3 ；ＣＨ3 Ｏ−，ｙ＝２）と活性化シリカゲルとの反応 反応［４］に準ずる。（［Ｇ］固定量：約 550μモル／
シリカ１g ）Reaction [7] [F] (x 2 = 2, n = 7, R 1 ; CH 3 CO-, R
3; CH 3 O-, y = 2) and pursuant to Reaction with activated silica gel [4]. ([G] fixed amount: about 550 μmol /
Silica 1g)
【００５４】反応例（５） 反応［８］ 脱水ピリジン中にアリルオキシエタノール（ｘ2 ＝２）
を溶解させ、室温で塩化トリチルを添加する。その後60
℃で３時間反応させる。反応終了後ピリジンを減圧下留
去、残渣をエーテル／水より抽出し、エーテル相は乾燥
後減圧下濃縮する。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［Ｈ］を得る。（［Ｈ］収率：約
90％）Reaction Example (5) Reaction [8] Allyloxyethanol (x 2 = 2) in dehydrated pyridine
Is dissolved and trityl chloride is added at room temperature. Then 60
React at ℃ for 3 hours. After completion of the reaction, pyridine is distilled off under reduced pressure, the residue is extracted with ether / water, and the ether phase is dried and then concentrated under reduced pressure. The residue is purified by silica gel column chromatography to obtain [H]. ([H] yield: approx.
90%)
【００５５】反応［９］ ［Ｈ］（ｘ2 ＝２，Ｒ4 ；（Ｃ6 Ｈ5 ）3 Ｃ−）とメチ
ルトリクロロシラン（Ｒ3 ；Ｃｌ，ｙ＝３）との反応 反応［３］に準ずる。（［Ｉ］収率：約75％）Reaction [9] Reaction of [H] (x 2 = 2, R 4 ; (C 6 H 5 ) 3 C-) with methyltrichlorosilane (R 3 ; Cl, y = 3) Reaction [3] According to. ([I] yield: about 75%)
【００５６】反応［10］ ［Ｉ］（ｘ2 ＝２，Ｒ4 ；（Ｃ6 Ｈ5 ）3 Ｃ−，Ｒ3 ；
Ｃｌ，ｙ＝３）と活性化シリカゲルとの反応 反応［４］に準ずる。（［Ｊ］担持量：約2000μモル／
シリカゲル１g ）Reaction [10] [I] (x 2 = 2, R 4 ; (C 6 H 5 ) 3 C-, R 3 ;
Reaction of Cl, y = 3) with activated silica gel According to the reaction [4]. (Amount of [J] supported: about 2000 μmol /
Silica gel 1g)
【００５７】反応［11］ ［Ｊ］をアセトン／ＨＢｒ水溶液中に分散させ、室温で
30分攪拌させる。反応終了後、反応シリカゲルを濾別、
よくアセトンで洗浄し、減圧下80〜90℃で乾燥すること
で［Ｋ］を得る。（［Ｊ］→［Ｋ］転化率 約 100％）Reaction [11] [J] was dispersed in an acetone / HBr aqueous solution, and the mixture was stirred at room temperature.
Let stir for 30 minutes. After the reaction is completed, the reaction silica gel is filtered off,
After washing well with acetone and drying under reduced pressure at 80 to 90 ° C, [K] is obtained. ([J] → [K] conversion rate approx. 100%)
【００５８】反応［12］ ［Ｋ］（ｘ2 ＝２）を脱水ＴＨＦ中に分散させ、窒素気
流下トリエチルアミンを加え、系を０〜５℃に冷却す
る。その系にモノ酸塩化β−ＣＤ誘導体（ｎ＝７，Ｒ
5 ；ＣＨ3 −）のＴＨＦ溶液をゆっくり滴下する。滴下
終了後０〜５℃で２時間、室温で24時間反応させる。反
応終了後、反応シリカゲルを濾別し、濾物はよくメタノ
ールで洗浄し、減圧下80〜90℃で乾燥することで［Ｌ］
を得る。（［Ｌ］ＣＤ固定量：約 600μモル／シリカゲ
ル１g ）Reaction [12] [K] (x 2 = 2) is dispersed in dehydrated THF, triethylamine is added under a nitrogen stream, and the system is cooled to 0 to 5 ° C. Mono-acidified β-CD derivative (n = 7, R
5 ; CH 3- ) in THF is slowly added dropwise. After completion of dropping, the mixture is reacted at 0 to 5 ° C for 2 hours and at room temperature for 24 hours. After completion of the reaction, the reaction silica gel is filtered off, and the residue is thoroughly washed with methanol and dried under reduced pressure at 80 to 90 ° C [L].
To get (Amount of [L] CD fixed: 600 μmol / g of silica gel)
【００５９】反応例（６） 反応［13］ 水酸化ナトリウム水溶液に０〜５℃においてアリルオキ
シエタノール（ｘ2 ＝２）のＴＨＦ溶液を滴下し、その
後０℃以下で１時間攪拌する。次いでｐ−トルエンスル
ホン酸クロリドのＴＨＦ溶液を滴下し、滴下終了後も０
℃以下で３時間攪拌する。反応終了後分液し、水相を塩
化メチレンで抽出、ＴＨＦ相と合わせて乾燥後減圧下濃
縮し、残渣をシリカゲルカラムクロマトグラフィーより
精製し［Ｍ］を得る。（［Ｍ］収率：約85％）Reaction Example (6) Reaction [13] A THF solution of allyloxyethanol (x 2 = 2) was added dropwise to an aqueous sodium hydroxide solution at 0 to 5 ° C, and then stirred at 0 ° C or lower for 1 hour. Then, a THF solution of p-toluenesulfonic acid chloride was added dropwise, and after completion of the addition, 0 was added.
Stir below 3 ° C for 3 hours. After completion of the reaction, the mixture is separated, the aqueous phase is extracted with methylene chloride, combined with the THF phase, dried and concentrated under reduced pressure, and the residue is purified by silica gel column chromatography to obtain [M]. ([M] yield: about 85%)
【００６０】反応［14］ ［Ｍ］とヨウ化ナトリウムをアセトン中で還流下12時間
攪拌する。反応終了後濾過し、アセトンを減圧下濃縮す
る。残渣をシリカゲルカラムクロマトグラフィーより精
製し［Ｎ］を得る。（［Ｎ］収率：約90％）Reaction [14] [M] and sodium iodide are stirred in acetone under reflux for 12 hours. After completion of the reaction, the mixture is filtered and acetone is concentrated under reduced pressure. The residue is purified by silica gel column chromatography to obtain [N]. ([N] yield: about 90%)
【００６１】反応［15］ ［Ｎ］とトリエトキシシラン（Ｒ1 ；Ｃ2 Ｈ5 Ｏ−，ｙ
＝３）をＴＨＦ中に溶解し、アルゴン雰囲気下攪拌す
る。その系に室温でヘキサクロロ白金酸６水和物のＴＨ
Ｆ溶液をゆっくり滴下、滴下終了後80℃で24時間攪拌す
る。反応終了後、遠心分離より沈澱物を取り除き、ＴＨ
Ｆは減圧下濃縮し、残渣［Ｏ］を得る。該化合物は分解
しやすいので窒素雰囲気下で保存する。（［Ｏ］収率：
約80％）Reaction [15] [N] and triethoxysilane (R 1 ; C 2 H 5 O-, y
= 3) is dissolved in THF and stirred under an argon atmosphere. In the system, TH of hexachloroplatinic acid hexahydrate was added to the system at room temperature.
Solution F is slowly added dropwise, and after completion of addition, the mixture is stirred at 80 ° C for 24 hours. After the reaction is completed, the precipitate is removed by centrifugation and TH
F is concentrated under reduced pressure to obtain a residue [O]. Since the compound is easily decomposed, it is stored under a nitrogen atmosphere. ([O] yield:
About 80%)
【００６２】反応［16］ 脱水トルエン中に活性化シリカゲルを分散させ、室温下
窒素雰囲気で［Ｏ］のトルエン溶液を加え、その後 100
℃で12時間反応させる。反応終了後、反応シリカゲルを
濾別し、よくトルエンで洗浄し、減圧下80〜90℃で乾燥
することで［Ｐ］を得る。（［Ｐ］固定量：約1800μモ
ル／シリカゲル１g ）Reaction [16] Activated silica gel is dispersed in dehydrated toluene, and a toluene solution of [O] is added in a nitrogen atmosphere at room temperature, and then 100
Incubate for 12 hours at ℃. After completion of the reaction, the reaction silica gel is filtered off, washed well with toluene, and dried at 80 to 90 ° C. under reduced pressure to obtain [P]. (Fixed amount of [P]: 1800 μmol / g of silica gel)
【００６３】反応［17］（［ａ］の場合） 脱水ＤＭＦ中に［Ｐ］を分散させ、その系に窒素雰囲気
下室温で別途濾過したβ−ＣＤ（ｍ＝７）のＮａアルコ
ラートのＤＭＦ溶液を滴下する。滴下終了後ゆっくり加
熱し 120℃で24時間攪拌する。反応終了後、反応シリカ
ゲルを濾別し、ＤＭＦ，水でよく洗浄し、減圧下80〜90
℃で乾燥することで［Ｑ］を得る。（［Ｐ］へのＣＤの
固定量：約 250μモル／シリカゲル１g ） なおγ−ＣＤ（ｍ＝８）の場合は、滴下終了後50℃で12
時間、80℃では12時間、そして 120℃では24時間反応さ
せることが必要である。Reaction [17] (in the case of [a]) [P] was dispersed in dehydrated DMF, and a DMF solution of β-CD (m = 7) Na alcoholate was separately filtered in a nitrogen atmosphere at room temperature in the system. Is dripped. After dripping, heat slowly and stir at 120 ° C for 24 hours. After the reaction was completed, the reaction silica gel was filtered off, washed well with DMF and water, and then under reduced pressure at 80-90.
[Q] is obtained by drying at [deg.] C. (Amount of CD fixed to [P]: about 250 μmol / g of silica gel) In the case of γ-CD (m = 8), 12 at 50 ° C. after completion of dropping.
It is necessary to react for 12 hours at 80 ° C and 24 hours at 120 ° C.
【００６４】反応［17］（［ｂ］の場合）（Ｒ2 ；ＣＨ
3 −，ｍ＝７） 反応［17］［ａ］において、ＤＭＦをＴＨＦとし、温度
120℃を還流下とする以外は同様にして［Ｑ］を得る。
（［Ｐ］へのＣＤ誘導体固定量：約 400μモル／シリカ
ゲル１g ）Reaction [17] (for [b]) (R 2 ; CH
3- , m = 7) In reaction [17] [a], DMF was set to THF, and temperature was
[Q] is obtained in the same manner except that the reflux is carried out at 120 ° C.
(Amount of CD derivative immobilized on [P]: about 400 μmol / silica gel 1 g)
【００６５】反応［18］ 反応［15］において［Ｎ］を［Ｍ］とした以外は同様に
して［Ｒ］を得る。Reaction [18] [R] is obtained in the same manner as in Reaction [15] except that [N] is changed to [M].
【００６６】反応［19］ 反応［16］において［Ｏ］を［Ｒ］とした以外は同様に
して［Ｓ］を得る。Reaction [19] [S] is obtained in the same manner as in reaction [16] except that [O] is changed to [R].
【００６７】反応［20］ 反応［17］［ａ］及び［17］［ｂ］において［Ｐ］を
［Ｓ］とした以外は同様にして［Ｑ］を得る。Reaction [20] [Q] is obtained in the same manner as in Reactions [17] [a] and [17] [b] except that [P] is changed to [S].
【００６８】[0068]
【化１２】 [Chemical 12]
【００６９】反応例（７） 活性化シリカゲルとメタクリル酸プロピルジエトキシメ
チルシランを脱水トルエン中少量のハイドロキノン存在
下６時間還流させる。反応終了後放冷し、反応シリカゲ
ルを濾過し、トルエン，メタノールで洗浄し、80〜90℃
下で減圧乾燥させる。次いで重合管中に反応シリカゲル
及び別途合成したメタクリルエステル型ＣＤ誘導体、そ
して開始剤としてアゾビスイソブチロニトリルのトルエ
ン溶液を入れ、凍結・脱気を繰り返した後封管する。封
管後、重合管を70〜80℃で24時間振とうさせる。反応終
了後放冷し、濾過する。濾物はトルエン，メタノールで
よく洗浄し、80〜90℃下で減圧乾燥させる。（ＣＤ固定
量：約 500μモル／シリカゲル１g ）Reaction Example (7) Activated silica gel and propyldiethoxymethylsilane methacrylate are refluxed in dehydrated toluene for 6 hours in the presence of a small amount of hydroquinone. After completion of the reaction, the mixture is allowed to cool, the reaction silica gel is filtered, washed with toluene and methanol, and 80 to 90 ° C.
Dry under reduced pressure. Next, a reaction silica gel, a separately synthesized methacrylic ester type CD derivative, and a toluene solution of azobisisobutyronitrile as an initiator are put in a polymerization tube, and after repeating freezing and deaeration, the tube is sealed. After sealing the tube, the polymerization tube is shaken at 70-80 ° C for 24 hours. After completion of the reaction, the mixture is allowed to cool and filtered. The filter cake is thoroughly washed with toluene and methanol, and dried under reduced pressure at 80 to 90 ° C. (CD fixed amount: about 500 μmol / silica gel 1 g)
【００７０】[0070]
【化１３】 [Chemical 13]
【００７１】反応例（８） 活性化シリカゲルを脱水トルエン中で３−アミノプロピ
ルジエトキシメチルシランと３時間還流させる。反応終
了後放冷し、反応シリカゲルを濾別し、トルエン，メタ
ノールでよく洗浄後乾燥する。得られた反応シリカゲル
を脱水塩化メチレン中メタクリル酸無水物と０〜５℃で
１時間、その後室温で24時間反応させる。反応終了後、
反応シリカゲルを濾別し、塩化メチレン，メタノールで
よく洗浄する。その後80〜90℃で減圧乾燥する。次いで
重合管中に、得られた反応シリカゲル、ＣＤ誘導体（メ
タクリルエステル型）、アゾビスイソブチロニトリルの
ＤＭＦ溶液を入れ、凍結・脱気を繰り返した後封管す
る。封管後、重合管を70〜80℃で24時間振とうさせる。
反応終了後放冷し、濾過する。濾物をＤＭＦ，メタノー
ルでよく洗浄し、80〜90℃下で減圧乾燥する。（ＣＤ固
定量：約 400μモル／シリカゲル１g ）Reaction Example (8) Activated silica gel is refluxed with 3-aminopropyldiethoxymethylsilane in dehydrated toluene for 3 hours. After completion of the reaction, the mixture is allowed to cool, the reaction silica gel is filtered off, washed well with toluene and methanol, and then dried. The reaction silica gel obtained is reacted with methacrylic anhydride in dehydrated methylene chloride at 0-5 ° C. for 1 hour and then at room temperature for 24 hours. After the reaction,
The reaction silica gel is filtered off and washed well with methylene chloride and methanol. Then, it is dried under reduced pressure at 80 to 90 ° C. Then, the obtained reaction silica gel, the CD derivative (methacryl ester type), and a DMF solution of azobisisobutyronitrile are placed in a polymerization tube, and the tube is sealed after repeating freezing and deaeration. After sealing the tube, the polymerization tube is shaken at 70-80 ° C for 24 hours.
After completion of the reaction, the mixture is allowed to cool and filtered. The filter cake is thoroughly washed with DMF and methanol, and dried under reduced pressure at 80 to 90 ° C. (CD fixed amount: about 400 μmol / silica gel 1 g)
【００７２】本発明のＣＤの固定化方法により合成した
固定相を用いて下記ダンシルアミノ酸１２種類について
下記条件にて光学分割を行なった。Using the stationary phase synthesized by the CD immobilization method of the present invention, 12 kinds of the following dansyl amino acids were subjected to optical resolution under the following conditions.
【００７３】[0073]
【化１４】 使用ＨＰＬＣ機種：Ｗaters 社製 Ｍodel−6000Ａ 使用カラム内容 長さ： 150mm，内径： 4.6mm（このカ
ラム内にＣＤ固定相を充填） ＨＰＬＣ測定条件 溶離液：トリエチルアミン及び酢酸
緩衝溶液／メタノール＝50／50 ｐＨ： 5.0 流速：
1.0ml／分 光学分割の程度（つまりＲ体、Ｌ体の分離度）の善し悪
しはその百分率で示す。[Chemical 14] HPLC model used: Waters Model Del-6000A Used column content Length: 150 mm, inner diameter: 4.6 mm (CD stationary phase is packed in this column) HPLC measurement conditions Eluent: triethylamine and acetic acid buffer solution / methanol = 50/50 pH: 5.0 Flow rate:
1.0 ml / min The degree of optical resolution (that is, the degree of separation of R body and L body) is shown as a percentage.
【００７４】すなわち、クロマトグラム上に現われる光
学異性体のピーク２本について分離の程度を数値で表わ
した。つまり、ピークからベースラインまでの高さをｈ
とし、ピークから二つのピークの谷間の底までの高さを
ｈ′とすると、分離度Ｒ′は下記式で表わされる。 Ｒ′（％）＝ｈ′／ｈ× 100 従って全く分離されない場合は分離度０％、２本のピー
クがベースラインまで分離されれば 100％である。結果
を表１に示す。That is, the degree of separation of the two peaks of the optical isomers appearing on the chromatogram was expressed numerically. In other words, the height from the peak to the baseline is h
And the height from the peak to the bottom of the valley between the two peaks is h ', the resolution R'is expressed by the following equation. R ′ (%) = h ′ / h × 100 Therefore, the degree of separation is 0% when not separated at all, and 100% when two peaks are separated up to the baseline. The results are shown in Table 1.
【００７５】[0075]
【表１】 但し、固定相Ａは米国特許第 4,539,399号明細書に記載
の方法により合成されたものであり、固定相Ｂは本発明
の反応例（６）により合成されたものである。[Table 1] However, stationary phase A was synthesized by the method described in US Pat. No. 4,539,399, and stationary phase B was synthesized by reaction example (6) of the present invention.
【００７６】上記結果より、新規に合成した固定相Ｂが
光学分割において大いに優れていることは明らかであ
る。From the above results, it is clear that the newly synthesized stationary phase B is very excellent in optical resolution.
【００７７】[0077]
【発明の効果】シクロデキストリンを無機質固体に固定
化することでその包接作用を利用し、優れた不溶性分離
・吸着剤となり得る。By immobilizing cyclodextrin on an inorganic solid, it can be used as an excellent insoluble separating / adsorbing agent by utilizing its inclusion effect.
【００７８】また、特にシリカゲルに対しスペーサーの
担持量を多くすることでその後の反応においてシクロデ
キストリンの固定量を増大でき、それによってシクロデ
キストリンの機能を大幅に上げることが出来る。Further, in particular, by increasing the amount of spacers supported on silica gel, the amount of cyclodextrin fixed can be increased in the subsequent reaction, whereby the function of cyclodextrin can be greatly enhanced.
Claims (4)
ロデキストリンあるいはシクロデキストリン誘導体と反
応させた後に活性化シリカゲルと反応させるか、又は活
性化シリカゲルと反応させた後にシクロデキストリンあ
るいはシクロデキストリン誘導体と反応させることを特
徴とするシクロデキストリンの固定化方法。1. An allyloxycarboxylic acid derivative is reacted with cyclodextrin or a cyclodextrin derivative and then reacted with activated silica gel, or is reacted with activated silica gel and then reacted with cyclodextrin or a cyclodextrin derivative. A method for immobilizing cyclodextrin, which comprises:
ロデキストリンあるいはシクロデキストリン誘導体と反
応させた後に活性化シリカゲルと反応させるか、又は活
性化シリカゲルと反応させた後にシクロデキストリンあ
るいはシクロデキストリン誘導体と反応させることを特
徴とするシクロデキストリンの固定化方法。2. A reaction of an allyloxy alcohol derivative with cyclodextrin or a cyclodextrin derivative and then with activated silica gel, or with an activated silica gel and then with cyclodextrin or a cyclodextrin derivative. A characteristic method for immobilizing cyclodextrin.
を、シクロデキストリンあるいはシクロデキストリン誘
導体と反応させた後に活性化シリカゲルと反応させる
か、又は活性化シリカゲルと反応させた後にシクロデキ
ストリンあるいはシクロデキストリン誘導体と反応させ
ることを特徴とするシクロデキストリンの固定化方法。 【化１】 （式中、Ｒ1 はメトキシ基、エトキシ基、塩素原子等を
表わし、Ｒ2 はメチル基、エチル基等を表わし、Ｒ3 は
水素原子、メチル基等を表わす。また、ｘ3 は１〜３の
整数を表わし、ｙ1 は１〜５の整数を表わす。）3. A compound represented by the following general formula [I] is reacted with cyclodextrin or a cyclodextrin derivative and then reacted with activated silica gel, or is reacted with activated silica gel and then cyclodextrin or cyclodextrin. A method for immobilizing cyclodextrin, which comprises reacting with a derivative. [Chemical 1] (In the formula, R 1 represents a methoxy group, an ethoxy group, a chlorine atom, etc., R 2 represents a methyl group, an ethyl group, etc., R 3 represents a hydrogen atom, a methyl group, etc., and x 3 represents 1 to 1). Represents an integer of 3, and y 1 represents an integer of 1 to 5.)
を、シクロデキストリンあるいはシクロデキストリン誘
導体と反応させた後に活性化シリカゲルと反応させる
か、又は活性化シリカゲルと反応させた後にシクロデキ
ストリンあるいはシクロデキストリン誘導体と反応させ
ることを特徴とするシクロデキストリンの固定化方法。 【化２】 （式中、Ｒ4 はメトキシ基、エトキシ基等を表わし、Ｒ
5 はメチル基、エチル基等を表わす。また、ｘ4 は１〜
３の整数を表わし、ｙ2 は１〜５の整数を表わす。）4. A compound represented by the following general formula [II] is reacted with cyclodextrin or a cyclodextrin derivative and then reacted with activated silica gel, or is reacted with activated silica gel and then cyclodextrin or cyclodextrin. A method for immobilizing cyclodextrin, which comprises reacting with a derivative. [Chemical 2] (In the formula, R 4 represents a methoxy group, an ethoxy group or the like, and R 4
5 represents a methyl group, an ethyl group or the like. Also, x 4 is 1 to
Represents an integer of 3, and y 2 represents an integer of 1 to 5. )
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4102205A JP3048085B2 (en) | 1992-03-27 | 1992-03-27 | Method for immobilizing cyclodextrin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4102205A JP3048085B2 (en) | 1992-03-27 | 1992-03-27 | Method for immobilizing cyclodextrin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH05271307A true JPH05271307A (en) | 1993-10-19 |
| JP3048085B2 JP3048085B2 (en) | 2000-06-05 |
Family
ID=14321166
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4102205A Expired - Lifetime JP3048085B2 (en) | 1992-03-27 | 1992-03-27 | Method for immobilizing cyclodextrin |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3048085B2 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2760752A1 (en) * | 1997-03-14 | 1998-09-18 | Inst Francais Du Petrole | CHIRAL COMPOUNDS, THEIR SYNTHESIS AND THEIR SUPPORT |
| EP0985681A1 (en) * | 1998-09-11 | 2000-03-15 | Institut Français du Pétrole | Chloro-, hydroxy- and alcoxysilanes derivatives of polysaccharides or oligosaccharides, polymerizables and crosslinkables, process for their preparation and their use as substrate materials |
| CN114573733A (en) * | 2022-03-22 | 2022-06-03 | 安徽徽科生物工程技术有限公司 | Organic silicon modified cyclodextrin organic matter, preparation method, drug delivery device and application |
-
1992
- 1992-03-27 JP JP4102205A patent/JP3048085B2/en not_active Expired - Lifetime
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2760752A1 (en) * | 1997-03-14 | 1998-09-18 | Inst Francais Du Petrole | CHIRAL COMPOUNDS, THEIR SYNTHESIS AND THEIR SUPPORT |
| EP0864586A3 (en) * | 1997-03-14 | 1999-01-20 | Institut Français du Pétrole | Chiral compounds, synthesis and use on a support |
| US6342592B1 (en) | 1997-03-14 | 2002-01-29 | Institut Francais Du Petrole And Chiralsep | Chiral compounds, their synthesis and use as a support |
| US7067640B1 (en) | 1997-03-14 | 2006-06-27 | Eka Chemicals Ab | Cross-linked chiral compounds and methods of making thereof |
| EP0985681A1 (en) * | 1998-09-11 | 2000-03-15 | Institut Français du Pétrole | Chloro-, hydroxy- and alcoxysilanes derivatives of polysaccharides or oligosaccharides, polymerizables and crosslinkables, process for their preparation and their use as substrate materials |
| FR2784109A1 (en) * | 1998-09-11 | 2000-04-07 | Inst Francais Du Petrole | CHLORO-, HYDROXY- AND ALKOXYSILANE DERIVATIVES OF POLYSACCHARIDES OR OLIGOSACCHARIDES, POLYMERISABLE AND CROSSLINKABLE, THEIR SYNTHESIS AND THEIR USE AS SOURCES OF NEW MATERIALS SUPPORTS |
| AU769340B2 (en) * | 1998-09-11 | 2004-01-22 | Eka Chemicals Ab | Chloro-,hydroxy- and alkoxysilane derivatives of polysaccharides or oligosaccharides, polymerizable and cross-linkable, their synthesis and their use as source of novel support materials |
| CN114573733A (en) * | 2022-03-22 | 2022-06-03 | 安徽徽科生物工程技术有限公司 | Organic silicon modified cyclodextrin organic matter, preparation method, drug delivery device and application |
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| Publication number | Publication date |
|---|---|
| JP3048085B2 (en) | 2000-06-05 |
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