JPH04351603A - Cyclodextrin derivative - Google Patents
Cyclodextrin derivativeInfo
- Publication number
- JPH04351603A JPH04351603A JP3154067A JP15406791A JPH04351603A JP H04351603 A JPH04351603 A JP H04351603A JP 3154067 A JP3154067 A JP 3154067A JP 15406791 A JP15406791 A JP 15406791A JP H04351603 A JPH04351603 A JP H04351603A
- Authority
- JP
- Japan
- Prior art keywords
- cyclodextrin
- beta
- precipitate
- bishydroxy
- dmf
- 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
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical class O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 title claims abstract description 17
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 7
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 abstract description 26
- 229920000858 Cyclodextrin Polymers 0.000 abstract description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 14
- 239000003814 drug Substances 0.000 abstract description 4
- 239000003905 agrochemical Substances 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 3
- HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 abstract description 2
- 239000002537 cosmetic Substances 0.000 abstract description 2
- 239000003599 detergent Substances 0.000 abstract description 2
- 239000000975 dye Substances 0.000 abstract description 2
- 239000002778 food additive Substances 0.000 abstract description 2
- 235000013373 food additive Nutrition 0.000 abstract description 2
- 239000003205 fragrance Substances 0.000 abstract description 2
- GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 abstract description 2
- 239000001116 FEMA 4028 Substances 0.000 abstract 6
- 229960004853 betadex Drugs 0.000 abstract 6
- 229920001450 Alpha-Cyclodextrin Polymers 0.000 abstract 1
- 229940043377 alpha-cyclodextrin Drugs 0.000 abstract 1
- 235000011175 beta-cyclodextrine Nutrition 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 239000011248 coating agent Substances 0.000 abstract 1
- 238000000576 coating method Methods 0.000 abstract 1
- 229940080345 gamma-cyclodextrin Drugs 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 36
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 239000002244 precipitate Substances 0.000 description 21
- 238000003786 synthesis reaction Methods 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- 230000015572 biosynthetic process Effects 0.000 description 16
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000000034 method Methods 0.000 description 3
- RNVYQYLELCKWAN-UHFFFAOYSA-N solketal Chemical compound CC1(C)OCC(CO)O1 RNVYQYLELCKWAN-UHFFFAOYSA-N 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000001226 reprecipitation Methods 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 1
- CVOUQICGLVQMOF-UHFFFAOYSA-N [2-phenyl-5-(phenylmethoxymethyl)-1,3-dioxan-5-yl]methanol Chemical compound C1OC(C=2C=CC=CC=2)OCC1(CO)COCC1=CC=CC=C1 CVOUQICGLVQMOF-UHFFFAOYSA-N 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- CZZYITDELCSZES-UHFFFAOYSA-N diphenylmethane Chemical compound C=1C=CC=CC=1CC1=CC=CC=C1 CZZYITDELCSZES-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- ITYJDNHFRZSTJY-UHFFFAOYSA-N methanesulfonyl bromide Chemical compound CS(Br)(=O)=O ITYJDNHFRZSTJY-UHFFFAOYSA-N 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000003973 paint Substances 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
Landscapes
- 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誘
導体に関し、更に詳しくは極めて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。FIELD OF THE INVENTION The present invention relates to cyclodextrin derivatives, and more particularly to cyclodextrin derivatives having extremely high water solubility.
【０００２】0002
【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が求められる。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。BACKGROUND OF THE INVENTION In general, drugs 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.
【０００３】0003
【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 cyclodextrin clathrate compounds, the solubility in water of cyclodextrin itself is limited, so that its water solubility is still insufficient for practical use. Therefore, to improve the solubility of cyclodextrin in water,
Methylation, hydroxyethylation of cyclodextrin,
Methods such as hydroxypropylation or synthesis of crosslinked polymers using epichlorohydrin have been used, but sufficient effects have not yet been obtained.
【０００４】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。[0004] Accordingly, an object of the present invention is to provide a cyclodextrin derivative having extremely high solubility in water.
【０００５】[0005]
【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
一つのヒドロキシル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-mentioned problems, the present inventors have conducted extensive research and found that the above-mentioned objects of the present invention can be achieved by providing a cyclodextrin derivative having at least one hydroxyl group. I found it.
【０００６】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.
【０００７】本発明はヒドロキシル基をシクロデキスト
リン（以下、ＣＤと略記する）分子に確実に導入するこ
とにより水に対する溶解度を大幅に向上させるものであ
るが、この結果得られる本発明のＣＤ誘導体としては、
具体的には、モノ−（ビスヒドロキシ）β−ＣＤ、ジ−
（ビスヒドロキシ）β−ＣＤ、ヘプタ−（ビスヒドロキ
シ）β−ＣＤ、モノ−（トリスヒドロキシ）β−ＣＤ、
ジ−（トリスヒドロキシ）β−ＣＤ、ヘプタ−（トリス
ヒドロキシ）β−ＣＤ等が挙げられる。The present invention significantly improves the solubility in water by steadily introducing a hydroxyl group into a cyclodextrin (hereinafter abbreviated as CD) molecule, and the resulting CD derivative of the present invention teeth,
Specifically, mono-(bishydroxy)β-CD, di-
(bishydroxy)β-CD, hepta-(bishydroxy)β-CD, mono-(trishydroxy)β-CD,
Examples include di-(trishydroxy)β-CD, hepta-(trishydroxy)β-CD, and the like.
【０００８】また、本発明に用いられるＣＤとしては、
α−ＣＤ、β−ＣＤ、γ−ＣＤ等のいずれも用いること
ができる。[0008] Furthermore, the CD used in the present invention includes:
Any of α-CD, β-CD, γ-CD, etc. can be used.
【０００９】以下に、本発明の少なくとも１つのヒドロ
キシル基を有するＣＤ誘導体の合成反応例を示す。An example of the synthesis reaction of the CD derivative having at least one hydroxyl group according to the present invention will be shown below.
【００１０】0010
【化１】[Chemical formula 1]
【００１１】[0011]
【化２】[Case 2]
【００１２】0012
【化３】[Chemical formula 3]
【００１３】[0013]
【化４】
上記合成反応は具体的には以下の合成例に従って行なう
ことができる。embedded image The above synthesis reaction can be specifically carried out according to the following synthesis example.
【００１４】（Ａ）モノ−（ビスヒドロキシ）β−ＣＤ
の合成
β−ＣＤを脱水ピリジンに室温で溶解し、その系に２０
℃以下でピリジンに溶解したｐ−トルエンスルホニルク
ロライドを滴下する。滴下終了後、室温でさらに一昼夜
撹拌する。反応終了後ピリジンを減圧下４０℃以下にて
留去し、残渣を大量のアセトンより再沈殿を行ない、沈
殿物を集めて水より再結晶を３度行なう。（収率：約２
５％）(A) Mono-(bishydroxy)β-CD
Synthesized β-CD was dissolved in dehydrated pyridine at room temperature, and 20
p-Toluenesulfonyl chloride dissolved in pyridine is added dropwise below .degree. After completion of the dropwise addition, the mixture was further stirred at room temperature overnight. After the reaction is completed, pyridine is distilled off under reduced pressure at a temperature below 40°C, the residue is reprecipitated from a large amount of acetone, and the precipitate is collected and recrystallized from water three times. (Yield: approx. 2
5%)
【００１５】得られたβ−ＣＤモノトシレートを
ＤＭＦに溶解し、ＫＩと７０〜８０℃下一昼夜反応させ
る。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を行ない、沈殿物は集めてｎ−ブタ
ノール／エタノール／水系より再結晶を行なう。（収率
：約６０％）The obtained β-CD monotosylate is dissolved in DMF and reacted with KI at 70 to 80° C. overnight. After the reaction is completed, DMF is distilled off under reduced pressure, the residue is reprecipitated from a large amount of acetone, and the precipitate is collected and recrystallized from an n-butanol/ethanol/water system. (Yield: about 60%)
【００１６】次にＤＭＦ中で２，２−ジメ
チル−１，３−ジオキソラン−４−メタノールとＮａＨ
を室温、窒素気流下反応させ、１時間後系を３０〜４０
℃に上げ、そこにＤＭＦに溶解したβ−ＣＤモノアイオ
ダイドを滴下し、滴下終了後９０〜１００℃で一昼夜反
応させる。反応終了後ＤＭＦを減圧下留去し、残渣を大
量のアセトンより再沈殿させ、沈殿物は熱メタノールに
溶解させ、濾過後再度大量のアセトンより再沈殿させる
。沈殿物は集めてメタノールで再結晶を行なう。（収率
：約３０％）Next, in DMF, 2,2-dimethyl-1,3-dioxolane-4-methanol and NaH
were reacted at room temperature under a nitrogen stream, and after 1 hour the system was heated to 30-40%
℃, β-CD monoiodide dissolved in DMF was added dropwise thereto, and after the dropwise addition was completed, the mixture was allowed to react overnight at 90 to 100°C. After the reaction is complete, DMF is distilled off under reduced pressure, and the residue is reprecipitated from a large amount of acetone.The precipitate is dissolved in hot methanol, filtered, and then reprecipitated again from a large amount of acetone. The precipitate is collected and recrystallized with methanol. (Yield: about 30%)
【００１７】さらに、沈殿物を酢酸に溶解
し、室温で塩酸／酢酸＝１／１溶液を滴下し、約１時間
撹拌後、溶媒を減圧下濃縮し、残渣を大量のアセトンよ
り再沈殿を行なう。沈殿物は集めて、よくアセトン、メ
タノールで洗浄し減圧乾燥することで目的物を得る。（
収率：約８０％）Further, the precipitate is dissolved in acetic acid, a 1/1 solution of hydrochloric acid/acetic acid is added dropwise at room temperature, and after stirring for about 1 hour, the solvent is concentrated under reduced pressure, and the residue is reprecipitated from a large amount of acetone. . The precipitate is collected, thoroughly washed with acetone and methanol, and dried under reduced pressure to obtain the desired product. (
Yield: about 80%)
【００１８】（Ｂ）ジ−（ビスヒドロキシ）β−ＣＤの
合成
β−ＣＤを室温下ピリジンに溶解し、これにピリジンに
溶解したジフェニルメタンｐ，ｐ′−ジスルホニルクロ
ライドを５℃にて滴下する。滴下終了後、２０℃以下に
て一昼夜撹拌する。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より再沈殿を行な
う。
沈殿物を集め、水より再結晶を繰り返し精製する。（収
率：約１５％）(B) Synthesis of di-(bishydroxy) β-CD β-CD is dissolved in pyridine at room temperature, and diphenylmethane p,p'-disulfonyl chloride dissolved in pyridine is added dropwise to this at 5°C. . After the dropwise addition is completed, the mixture is stirred at 20° C. or lower all day and night. After the reaction is completed, pyridine is distilled off under reduced pressure at a temperature below 40°C, and the residue is reprecipitated from a large amount of acetone. The precipitate is collected and purified by repeated recrystallization from water. (Yield: about 15%)
【００１９】得られた化合物をＤＭＦ中でＫＩと７０〜
８０℃下一昼夜反応させ、終了後ＤＭＦを減圧下留去し
、残渣を大量のアセトンより再沈殿させる。沈殿物は集
めてｎ−ブタノール／エタノール／水系より再結晶し精
製する。（収率：約５５％）The obtained compound was mixed with KI in DMF at 70~
The reaction was carried out at 80° C. for a day and night, and after completion, DMF was distilled off under reduced pressure, and the residue was reprecipitated from a large amount of acetone. The precipitate is collected and purified by recrystallization from n-butanol/ethanol/water system. (Yield: approx. 55%)
【００２０】次にＤＭＦ中で２，２−ジメチル−１，３
−ジオキソラン−４−メタノールとＮａＨを室温、窒素
気流下で反応させ、１時間後系を３０〜４０℃に上げ、
そこにＤＭＦに溶解した沈殿物を滴下し、滴下終了後９
０〜１００℃で一昼夜反応させる。反応終了後ＤＭＦを
減圧下留去し、残渣を大量のアセトンより再沈殿させ、
沈殿物は熱エタノールに溶解させ、濾過後再度大量のア
セトンより再沈殿させる。沈殿物は集めてエタノールで
再結晶を行なう。（収率：約２０％）Next, in DMF, 2,2-dimethyl-1,3
-Dioxolane-4-methanol and NaH are reacted at room temperature under a nitrogen stream, and after 1 hour the system is raised to 30-40°C.
Drop the precipitate dissolved in DMF there, and after the dropping is completed,
React overnight at 0 to 100°C. After the reaction was completed, DMF was distilled off under reduced pressure, and the residue was reprecipitated from a large amount of acetone.
The precipitate is dissolved in hot ethanol, filtered, and reprecipitated again from a large amount of acetone. The precipitate is collected and recrystallized with ethanol. (Yield: approx. 20%)
【００２１】さらに、沈殿物を酢酸に溶解し、室温で塩
酸／酢酸＝１／１溶液を滴下し、約１時間撹拌後、溶媒
を減圧下濃縮し、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、よくアセトン、メタノールで洗
浄し減圧乾燥することで目的物を得る。（収率：約７０
％）Further, the precipitate is dissolved in acetic acid, a 1/1 solution of hydrochloric acid/acetic acid is added dropwise at room temperature, and after stirring for about 1 hour, the solvent is concentrated under reduced pressure, and the residue is reprecipitated from a large amount of acetone. . Collect the precipitate, wash thoroughly with acetone and methanol, and dry under reduced pressure to obtain the desired product. (Yield: approx. 70
%)
【００２２】（Ｃ）ヘプタ（ビスヒドロキシ）β−ＣＤ
の合成
ＤＭＦ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、次いで６０〜７０℃で２４時間撹拌
する。
反応終了後ＤＭＦを減圧下留去し、残渣を大量のメタノ
ールより再沈殿させる。そして中和後氷冷水に加え、濾
過し、沈殿物を氷冷水でよく洗浄し乾燥することでβ−
ＣＤヘプタブロマイドを得る。（収率：約８０％）(C) Hepta(bishydroxy)β-CD
Synthesis of β-CD is dissolved in DMF at room temperature, methanesulfonyl bromide is added, and then stirred at 60-70°C for 24 hours. After the reaction is complete, DMF is distilled off under reduced pressure, and the residue is reprecipitated from a large amount of methanol. After neutralization, the β-
CD heptabromide is obtained. (Yield: about 80%)
【０
０２３】次にＤＭＦ中で２，２−ジメチル−１，３−ジ
オキソラン−４−メタノールとＮａＨを室温、窒素気流
下で反応させ、１時間後系を３０〜４０℃に上げ、そこ
にＤＭＦに溶解したβ−ＣＤヘプタブロマイドを滴下し
、滴下終了後９０〜１００℃で一昼夜反応させる。反応
終了後ＤＭＦを減圧下留去し、残渣を大量のジエチルエ
ーテルより再沈殿させ、沈殿物は熱エタノールに溶解し
、濾過後再度大量のジエチルエーテルより再沈殿させる
。
沈殿物を集めてエタノールで再結晶を行なう。（収率：
約１０％）0
[023] Next, 2,2-dimethyl-1,3-dioxolane-4-methanol and NaH were reacted in DMF at room temperature under a nitrogen stream, and after 1 hour the system was raised to 30-40°C, and DMF was added thereto. Dissolved β-CD heptabromide is added dropwise, and after completion of the addition, the mixture is allowed to react overnight at 90 to 100°C. After the reaction is complete, DMF is distilled off under reduced pressure, and the residue is reprecipitated from a large amount of diethyl ether.The precipitate is dissolved in hot ethanol, filtered, and then reprecipitated again from a large amount of diethyl ether. Collect the precipitate and recrystallize it with ethanol. (yield:
approximately 10%)
【００２４】さらに、沈殿物を酢酸に溶解し、室温で塩
酸／酢酸＝１／１溶液を滴下し、約２時間撹拌後、溶媒
を減圧下濃縮し、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、よくアセトン、メタノールで洗
浄し減圧乾燥することで目的物を得る。（収率：約７０
％）Further, the precipitate is dissolved in acetic acid, a 1/1 solution of hydrochloric acid/acetic acid is added dropwise at room temperature, and after stirring for about 2 hours, the solvent is concentrated under reduced pressure, and the residue is reprecipitated from a large amount of acetone. . Collect the precipitate, wash thoroughly with acetone and methanol, and dry under reduced pressure to obtain the desired product. (Yield: approx. 70
%)
【００２５】（Ｄ）モノ−（トリスヒドロキシ）β−Ｃ
Ｄの合成
β−ＣＤモノトシレート、β−ＣＤモノアイオダイドま
での合成は（Ａ）モノ−（ビスヒドロキシ）β−ＣＤの
合成を参照。(D) Mono-(trishydroxy)β-C
Synthesis of D For the synthesis of β-CD monotosylate and β-CD monoiodide, refer to (A) Synthesis of mono-(bishydroxy)β-CD.
【００２６】次にＤＭＦ中で２−フェニル−５−ベンジ
ルオキシメチル−５−ヒドロキシメチル−１，３−ジオ
キサンとＮａＨを室温、窒素気流下で反応させ、１時間
後系を３０〜４０℃に上げ、そこにＤＭＦに溶解したβ
−ＣＤモノアイオダイドを滴下し、滴下終了後９０〜１
００℃で一昼夜反応させる。反応終了後ＤＭＦを減圧下
留去し、残渣を大量のアセトンより再沈殿させ、沈殿物
は熱エタノールに溶解させ、濾過後再度大量のアセトン
より再沈殿させる。沈殿物は集めてエタノールで再結晶
を行なう。（収率：約１５％）Next, 2-phenyl-5-benzyloxymethyl-5-hydroxymethyl-1,3-dioxane and NaH were reacted in DMF at room temperature under a nitrogen stream, and after 1 hour the system was heated to 30-40°C. β dissolved in DMF
-Drop CD monoiodide, 90 to 1 after completion of dropping
React at 00°C overnight. After the reaction is completed, DMF is distilled off under reduced pressure, and the residue is reprecipitated from a large amount of acetone.The precipitate is dissolved in hot ethanol, filtered, and then reprecipitated again from a large amount of acetone. The precipitate is collected and recrystallized with ethanol. (Yield: about 15%)
【００２７】さらに沈殿物を酢酸に溶解し、５％Ｐｄ／
Ｃを加え水素添加を行なう（室温下５ｋｇ／ｃｍ２加圧
）。２４時間反応させ、Ｐｄ／Ｃを濾別、酢酸を減圧下
留去し、残渣を大量のアセトンより再沈殿させる。沈殿
物はアセトン、メタノールでよく洗浄し、減圧乾燥する
ことで目的物を得る。（収率：約８０％）Further, the precipitate was dissolved in acetic acid, and 5% Pd/
Add C and perform hydrogenation (at room temperature and under pressure of 5 kg/cm2). After reacting for 24 hours, Pd/C is filtered off, acetic acid is distilled off under reduced pressure, and the residue is reprecipitated from a large amount of acetone. The precipitate is thoroughly washed with acetone and methanol, and dried under reduced pressure to obtain the desired product. (Yield: about 80%)
【００２８】（Ｅ）ジ−（トリスヒドロキシ）β−ＣＤ
の合成
β−ＣＤアイオダイドの合成は（Ｂ）ジ−（ビスヒドロ
キシ）β−ＣＤの合成を参照。化合物■及び目的物■の
合成は上記（Ｄ）モノー（トリスヒドロキシ）β−ＣＤ
の合成と同様に行なう。
■：（収率：約５％） ■：（収率：約８０％）
(E) Di-(trishydroxy)β-CD
For the synthesis of β-CD iodide, see (B) Synthesis of di-(bishydroxy)β-CD. The synthesis of compound (1) and target compound (2) is the above (D) mono(trishydroxy)β-CD
Proceed in the same way as for the synthesis. ■: (Yield: approx. 5%) ■: (Yield: approx. 80%)
【００２９】（Ｆ）ヘプタ−（トリスヒドロキシ）β−
ＣＤの合成
β−ＣＤヘプタブロマイドの合成は（Ｃ）ヘプタ−（ビ
スヒドロキシ）β−ＣＤの合成を参照。化合物■及び目
的物■の合成は上記（Ｂ）ジ−（ビスヒドロキシ）β−
ＣＤの合成と同様に行なう。ただし再沈殿溶媒をジエチ
ルエーテルで行ない、再沈殿後減圧乾燥する。
■：（収率：約５％） ■：（収率：約６０％）
(F) Hepta-(trishydroxy)β-
Synthesis of CD For the synthesis of β-CD heptabromide, see (C) Synthesis of hepta-(bishydroxy)β-CD. The synthesis of compound (1) and target compound (2) is based on the above (B) di-(bishydroxy)β-
This is done in the same way as for CD synthesis. However, the reprecipitation solvent is diethyl ether, and the reprecipitation is followed by drying under reduced pressure. ■: (Yield: approx. 5%) ■: (Yield: approx. 60%)
【００３０】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。The target product was confirmed using methods such as NMR spectrum, mass spectrum, and elemental analysis.
【００３１】その他のＣＤ誘導体についても上記方法に
準じて同様に合成することができる。Other CD derivatives can also be synthesized in the same manner as described above.
【００３２】上記の如く得られるＣＤ誘導体の水に対す
る溶解度を調べた結果を以下に示す。The results of examining the water solubility of the CD derivative obtained as described above are shown below.
【００３３】[0033]
【表１】[Table 1]
【００３４】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 pharmaceuticals, chemicals such as agricultural chemicals, fragrances, cosmetics, detergents,
It can be used in paints, dyes, food additives, etc.
【００３５】以上詳細に述べたように、本発明によりヒ
ドロキシル基をＣＤに確実に導入することにより、ＣＤ
の水に対する溶解度を大幅に向上させることができ、こ
の結果水溶性の高いＣＤ包接化合物を得ることができる
。As described in detail above, by reliably introducing a hydroxyl group into CD according to the present invention, CD
As a result, a highly water-soluble CD clathrate compound can be obtained.
Claims (1)
するシクロデキストリン誘導体。1. A cyclodextrin derivative having at least one hydroxyl group.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3154067A JPH04351603A (en) | 1991-05-29 | 1991-05-29 | Cyclodextrin derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3154067A JPH04351603A (en) | 1991-05-29 | 1991-05-29 | Cyclodextrin derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH04351603A true JPH04351603A (en) | 1992-12-07 |
Family
ID=15576173
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3154067A Pending JPH04351603A (en) | 1991-05-29 | 1991-05-29 | Cyclodextrin derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH04351603A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998013456A1 (en) * | 1996-09-26 | 1998-04-02 | Henkel-Ecolab Gmbh & Co. Ohg | Washing or laundering post-treatment agents |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61500788A (en) * | 1983-12-21 | 1986-04-24 | ヤンセン・フア−マセウテイカ・エヌ・ヴエ− | Pharmaceutical preparations containing water-labile or slightly soluble drugs and methods for their production |
| JPS63122701A (en) * | 1986-11-12 | 1988-05-26 | Wako Pure Chem Ind Ltd | Novel cyclodextrin derivative and production thereof |
-
1991
- 1991-05-29 JP JP3154067A patent/JPH04351603A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61500788A (en) * | 1983-12-21 | 1986-04-24 | ヤンセン・フア−マセウテイカ・エヌ・ヴエ− | Pharmaceutical preparations containing water-labile or slightly soluble drugs and methods for their production |
| JPS63122701A (en) * | 1986-11-12 | 1988-05-26 | Wako Pure Chem Ind Ltd | Novel cyclodextrin derivative and production thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998013456A1 (en) * | 1996-09-26 | 1998-04-02 | Henkel-Ecolab Gmbh & Co. Ohg | Washing or laundering post-treatment agents |
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