JP4950521B2 - Trehalose derivatives and process for producing the same - Google Patents
Trehalose derivatives and process for producing the same Download PDFInfo
- Publication number
- JP4950521B2 JP4950521B2 JP2006063079A JP2006063079A JP4950521B2 JP 4950521 B2 JP4950521 B2 JP 4950521B2 JP 2006063079 A JP2006063079 A JP 2006063079A JP 2006063079 A JP2006063079 A JP 2006063079A JP 4950521 B2 JP4950521 B2 JP 4950521B2
- Authority
- JP
- Japan
- Prior art keywords
- derivative
- hexopyranose
- alkyl
- free
- 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.)
- Expired - Fee Related
Links
- 0 C*(CC(C1OCc2ccccc2)OCc2ccccc2)OC(COCc2ccccc2)[C@]1OCc1ccccc1 Chemical compound C*(CC(C1OCc2ccccc2)OCc2ccccc2)OC(COCc2ccccc2)[C@]1OCc1ccccc1 0.000 description 2
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Saccharide Compounds (AREA)
Description
非還元性二糖トレハロース誘導体及びその中間体とその製造法に関するものである。 The present invention relates to a non-reducing disaccharide trehalose derivative, an intermediate thereof, and a production method thereof.
二つのグルコースがアノマー酸素原子を介してグリコシド結合した非還元性二糖であるトレハロースは天然物中に広く見出され、生体においては重要なエネルギー源の一つになっている。抗酸化作用を持つことから、食品添加剤としても広く利用されている。また、有用な腸内細菌であるビフィズス菌の活性化等の効果も見出されている。
アノマー位がアルキルで分岐した1-Ｃ-アルキル-ヘキソピラノシドは、アノマー位のかさ高さから糖加水分解酵素の水解に対して耐性を示すことや、酵素阻害剤としての機能が報告されている（例えば、非特許文献１−２を参照）。そのようなことから、1-Ｃ-アルキル-ヘキソピラノースを糖鎖中に組み込むことで、新たな機能の発現が大いに期待される（例えば、非特許文献３を参照）。1-Ｃ-アルキル-ヘキソピラノースとヘキソピラノースとを組み合わせた非還元性二糖には、トレハラーゼ阻害剤や、有用な食品添加剤としての新たな機能が期待できる。
Trehalose, a non-reducing disaccharide in which two glucoses are glycosidically bonded via an anomeric oxygen atom, is widely found in natural products and has become one of the important energy sources in living organisms. Due to its antioxidant activity, it is widely used as a food additive. In addition, effects such as activation of bifidobacteria which are useful intestinal bacteria have been found.
It has been reported that 1-C-alkyl-hexopyranoside branched by alkyl at the anomeric position exhibits resistance to hydrolysis of sugar hydrolase from the bulk of the anomeric position, and functions as an enzyme inhibitor ( For example, refer nonpatent literature 1-2). For this reason, expression of a new function is greatly expected by incorporating 1-C-alkyl-hexopyranose into a sugar chain (see, for example, Non-Patent Document 3). A non-reducing disaccharide in which 1-C-alkyl-hexopyranose and hexopyranose are combined can be expected to have a new function as a trehalase inhibitor or a useful food additive.
本発明は、アノマー水酸基遊離の1-Ｃ-アルキル-ヘキソピラノース誘導体とアノマー水酸基遊離のヘキソピラノース誘導体を、プロトン酸あるいはルイス酸の存在下で、縮合させることで容易に非還元性二糖トレハロース誘導体を製造することができる。
アノマー水酸基遊離の1-Ｃ-アルキル-ヘキソピラノース誘導体とアノマー水酸基遊離のヘキソピラノース誘導体を、温和な条件下で効率良く縮合させて、非還元性二糖トレハロース誘導体を製造することである。 An anomeric hydroxyl group-free 1-C-alkyl-hexopyranose derivative and an anomeric hydroxyl group-free hexopyranose derivative are efficiently condensed under mild conditions to produce a non-reducing disaccharide trehalose derivative.
本発明者らは前記の事情に鑑み鋭意研究した結果、アノマー水酸基遊離の1-Ｃ-アルキル-ヘキソピラノース誘導体とアノマー水酸基遊離のヘキソピラノース誘導体を、僅か数モル％のトリフルオロメタンスルホン酸またはビストリフルオロメタンスルホンイミド等のプロトン酸、あるいは僅か数モル％のビスマストリフラート等のルイス酸を用いることで、温和な条件下で効率良く非還元性二糖トレハロース誘導体が得られることを見出し、本発明に到達した。 As a result of diligent research in view of the above circumstances, the present inventors have found that an anomeric hydroxyl group-free 1-C-alkyl-hexopyranose derivative and an anomeric hydroxyl group-free hexopyranose derivative are only a few mol% of trifluoromethanesulfonic acid or bistrifluoromethanesulfone. It has been found that a non-reducing disaccharide trehalose derivative can be obtained efficiently under mild conditions by using a protonic acid such as imide or a Lewis acid such as only a few mol% of bismuth triflate.
すなわち、本発明は、トリフルオロメタンスルホン酸またはビストリフルオロメタンスルホンイミド等のプロトン酸、あるいはビスマストリフラート等のルイス酸の存在下、アノマー水酸基遊離の1-Ｃ-アルキル-ヘキソピラノース誘導体とアノマー水酸基遊離のヘキソピラノース誘導体を反応させて得られる非還元性二糖トレハロース誘導体（１）およびその中間体（２）、（３）、（４）、とそれらの製造法である。
本発明は、アノマー水酸基遊離の1-Ｃ-アルキル-ヘキソピラノース誘導体とアノマー水酸基遊離のヘキソピラノース誘導体を、僅か数モル％のトリフルオロメタンスルホン酸またはビストリフルオロメタンスルホンイミド等のプロトン酸、あるいは僅か数モル％のビスマストリフラート等のルイス酸を用いることで、温和な条件下で効率良く非還元性二糖トレハロース誘導体を製造することができる。本発明は、前述した食品添加剤やトレハラーゼ阻害剤として期待される有用な非還元性二糖トレハラーゼ誘導体を提供できる。 The present invention relates to an anomeric hydroxyl group-free 1-C-alkyl-hexopyranose derivative and an anomeric hydroxyl group-free hexopyranose derivative having only a few mol% of a protonic acid such as trifluoromethanesulfonic acid or bistrifluoromethanesulfonimide, or only a few mol%. By using a Lewis acid such as bismuth triflate, a non-reducing disaccharide trehalose derivative can be produced efficiently under mild conditions. The present invention can provide useful non-reducing disaccharide trehalase derivatives expected as food additives and trehalase inhibitors described above.
以下、本発明を詳細に説明する。
本発明は、トリフルオロメタンスルホン酸またはビストリフルオロメタンスルホンイミド等のプロトン酸、あるいはビスマストリフラート等のルイス酸の存在下、アノマー水酸基遊離の1-Ｃ-アルキル-ヘキソピラノース誘導体とアノマー水酸基遊離のヘキソピラノース誘導体を反応させて得られる非還元性二糖トレハロース誘導体とその製造法である。
Hereinafter, the present invention will be described in detail.
The present invention relates to 1-C-alkyl-hexopyranose derivatives free of anomeric hydroxyl groups and hexopyranose derivatives free of anomeric hydroxyl groups in the presence of a protonic acid such as trifluoromethanesulfonic acid or bistrifluoromethanesulfonimide, or a Lewis acid such as bismuth triflate. A non-reducing disaccharide trehalose derivative obtained by reaction and a method for producing the same.
本発明の原料の1つに使用するアノマー水酸基遊離の1-Ｃ-アルキル-ヘキソピラノース誘導体は、T. Yamanoiらが記載（Letters in Organic Chemistry, 2005年, 2巻, 242ページ]の方法により、糖水酸基が保護された糖ラクトン誘導体に、Grignard試薬あるいはアルキルリチウムを反応させて製造することができる。1-Ｃ-アルキル-ヘキソピラノース誘導体のアノマー水酸基以外の水酸基は周知の保護基で保護することができる。例えば、アセチル基やベンゾイル基等のアシル型保護基や、メチル基、アリル基やベンジル基等のエーテル型保護基、イソプロピリデン基やベンジリデン基等のアセタール型保護基等を挙げることができる。 An anomeric hydroxyl group-free 1-C-alkyl-hexopyranose derivative used as one of the raw materials of the present invention can be obtained by the method described by T. Yamanoi et al. (Letters in Organic Chemistry, 2005, Vol. 2, page 242). It can be produced by reacting a sugar lactone derivative protected with a hydroxyl group with Grignard reagent or alkyllithium.Hydroxyl groups other than the anomeric hydroxyl group of the 1-C-alkyl-hexopyranose derivative can be protected with a known protecting group. For example, acyl-type protecting groups such as acetyl group and benzoyl group, ether-type protecting groups such as methyl group, allyl group and benzyl group, acetal-type protecting groups such as isopropylidene group and benzylidene group, and the like can be mentioned.
本発明の他の原料の一つとして使用されるアノマー水酸基遊離のヘキソピラノース誘導体は、周知のものを使用できる。2,3,4,6-テトラ-Ｏ-ベンジル-グルコピラノース、2,3,4,6-テトラ-Ｏ-ベンジル-マンノピラノース、2,3,4,6-テトラ-Ｏ-ベンジル-ガラクトピラノース、2,3,4-トリ-Ｏ-ベンジル-フコピラノース、２-アジド‐3,4,6-トリ-Ｏ-ベンジル-２-デオキシ-グルコピラノース、3,4,6-トリ-Ｏ-ベンジル-２-ベンジルオキシカルボニルアミノ-２-デオキシ-グルコピラノース、2,3,4,6-テトラ-Ｏ-アセチル-グルコピラノース、2,3,4,6-テトラ-Ｏ-アセチル-マンノピラノース、2,3,4,6-テトラ-Ｏ-アセチル-ガラクトピラノース、2,3,4-トリ-Ｏ-アセチル-フコピラノース、3,4,6-トリ-Ｏ-アセチル-２-アジド-２-デオキシ-グルコピラノース、3,4,6-トリ-Ｏ-アセチル‐２-ベンジルオキシカルボニルアミノ-２-デオキシ-グルコピラノース、2,3,4,6-テトラ-Ｏ-ベンゾイル-グルコピラノース、2,3,4,6-テトラ-Ｏ-ベンゾイル-マンノピラノース、2,3,4,6-テトラ-Ｏ-ベンゾイル-ガラクトピラノース、2,3,4-トリ-Ｏ-ベンゾイル-フコピラノース、２-アジド‐3,4,6-トリ-Ｏ-ベンゾイル-２-デオキシ-グルコピラノース、3,4,6-トリ-Ｏ-ベンゾイル-２-ベンジルオキシカルボニルアミノ-２-デオキシ-グルコピラノース、1,2：3,4-ジ-O-イソプロピリデンガラクトピラノースなどが挙げられる。 As the anomeric hydroxyl group-free hexopyranose derivative used as another raw material of the present invention, a well-known one can be used. 2,3,4,6-tetra-O-benzyl-glucopyranose, 2,3,4,6-tetra-O-benzyl-mannopyranose, 2,3,4,6-tetra-O-benzyl-galacto Pyranose, 2,3,4-Tri-O-benzyl-fucopyranose, 2-azido-3,4,6-tri-O-benzyl-2-deoxy-glucopyranose, 3,4,6-tri-O-benzyl -2-benzyloxycarbonylamino-2-deoxy-glucopyranose, 2,3,4,6-tetra-O-acetyl-glucopyranose, 2,3,4,6-tetra-O-acetyl-mannopyranose, 2,3,4,6-tetra-O-acetyl-galactopyranose, 2,3,4-tri-O-acetyl-fucopyranose, 3,4,6-tri-O-acetyl-2-azido-2-deoxy -Glucopyranose, 3,4,6-tri-O-acetyl-2-benzyloxycarbonylamino-2-deoxy-glucopyranose, 2,3,4,6-tetra-O-benzoyl-glucopyranose, 2,3 , 4,6-Tetra-O -Benzoyl-mannopyranose, 2,3,4,6-tetra-O-benzoyl-galactopyranose, 2,3,4-tri-O-benzoyl-fucopyranose, 2-azido-3,4,6-tri- O-benzoyl-2-deoxy-glucopyranose, 3,4,6-tri-O-benzoyl-2-benzyloxycarbonylamino-2-deoxy-glucopyranose, 1,2: 3,4-di-O-isopropyl Examples include redengalactopyranose.
プロトン酸は、テトラフルオロボロン酸や周知のパーフルオロアルキルスルホン酸誘導体を使用することができる。例えば、パーフルオロアルキルスルホン酸誘導体として、トリフルオロメタンスルホン酸、ヘプタデカフルオロオクタンスルホン酸等を挙げることができるが、特にビス（トリフルオロメタン）スルホンイミドが好ましい。ルイス酸としては、三フッ化ホウ素、トリフルオロメタンスルホン酸トリメチルシリルや金属塩としてイッテリビウム、イットリウム、ランタン、スカンジウム、銅、スズ、ジルコニウム等で構成される周知のトリフレート塩およびパークレートを挙げることができるが、特に、ビスマストリフレートが好ましい。 As the protonic acid, tetrafluoroboronic acid or a known perfluoroalkylsulfonic acid derivative can be used. For example, examples of the perfluoroalkylsulfonic acid derivative include trifluoromethanesulfonic acid, heptadecafluorooctanesulfonic acid, and the like, and bis (trifluoromethane) sulfonimide is particularly preferable. Examples of Lewis acids include boron trifluoride, trimethylsilyl trifluoromethanesulfonate, and known triflate salts and parkrates composed of ytterbium, yttrium, lanthanum, scandium, copper, tin, zirconium, etc. as metal salts. However, bismuth triflate is particularly preferable.
溶媒は、アルコールを除く周知の有機溶媒を使用することができる。例えば、ジエチルエーテル、ベンゼン、トルエン、ジクロロメタン、アセトニトリル、テトラヒドロフラン、ジメチルホルムアミド等を挙げることができる。 As the solvent, a well-known organic solvent excluding alcohol can be used. For example, diethyl ether, benzene, toluene, dichloromethane, acetonitrile, tetrahydrofuran, dimethylformamide and the like can be mentioned.
アノマー水酸基遊離の1-Ｃ-アルキル-ヘキソピラノース誘導体とアノマー水酸基遊離のヘキソピラノース誘導体の使用量については特に制限はない。1-Ｃ-アルキル-ヘキソピラノース誘導体に対して過剰に用いることもできるが、通常１〜１０当量の範囲である。好ましくは、アルコールに対して１〜２．０当量で使用する。また逆に、ヘキソピラノース誘導体を1-Ｃ-アルキル-ヘキソピラノース誘導体に対して過剰に用いることが出来るのは言うまでもない。 There are no particular restrictions on the amounts of the 1-C-alkyl-hexopyranose derivative free of anomeric hydroxyl group and the hexopyranose derivative free of anomeric hydroxyl group. Although it can be used in excess relative to the 1-C-alkyl-hexopyranose derivative, it is usually in the range of 1 to 10 equivalents. Preferably, it is used at 1 to 2.0 equivalents with respect to the alcohol. Conversely, it goes without saying that the hexopyranose derivative can be used in excess of the 1-C-alkyl-hexopyranose derivative.
プロトン酸やルイス酸の使用量についても特に制限はない。通常、1-Ｃ-アルキル-ヘキソピラノース誘導体に対して０．１〜２００モル％用いることができるが、好ましくは０．５〜３０モル％で使用する。 There are no particular restrictions on the amount of protonic acid or Lewis acid used. Usually, it can be used in an amount of 0.1 to 200 mol%, preferably 0.5 to 30 mol% based on the 1-C-alkyl-hexopyranose derivative.
反応温度は特に制限はないが、通常−５０℃〜６０℃で行う。好ましくは、−２０℃〜３０℃の範囲である。反応時間は反応温度、原料の種類等によって異なるが、数分から数十時間の範囲である。 Although reaction temperature does not have a restriction | limiting in particular, Usually, it carries out at -50 degreeC-60 degreeC. Preferably, it is the range of -20 degreeC-30 degreeC. The reaction time varies depending on the reaction temperature, the type of raw material, etc., but is in the range of several minutes to several tens of hours.
精製は通常の糖の精製に用いる方法で行う。例えば、シリカゲルによる薄層クロマトグラフィーまたはカラムクロマトグラフィー等が挙げられる。 Purification is performed by a method used for normal sugar purification. For example, thin layer chromatography using silica gel or column chromatography can be used.
以下に実施例を挙げて本発明を具体的に説明するが、以下の実施例により何等の制限をうけるものではない。 EXAMPLES The present invention will be specifically described below with reference to examples, but the present invention is not limited to the following examples.
[実施例１]
セプタムキャップをした二口ナスフラスコに乾燥剤として無水硫酸カルシウム（Drierite）（約100 mg）とビス（トリフルオロメタン）スルホンイミド（Tf2NH）(1.8 mg, 0.0066 mmol)を入れ、アルゴン置換した。この中に2,3,4,6-テトラ-Ｏ-ベンジル-D-グルコピラノース(48.2 mg, 0.087 mmol)をアセトニトリル(1.0 ml)に溶解してシリンジで加えて、反応容器を0 ℃に冷却した後に、1-C-メチル-2,3,4,6-テトラ-O-ベンジル-D-グルコピラノース (72.4 mg, 0.13 mmol)をアセトニトリル(1.0 ml)に溶解してシリンジで加えた。反応混合物を2時間撹拌した後に、飽和の重曹水と酢酸エチルを加えて、有機層を抽出した。有機層をNa2SO4で乾燥して、無機物を濾別後、溶媒を減圧留去して粗生成物を得た。粗生成物を薄層クロマトグラフィー(展開溶媒 ヘキサン：酢酸エチル＝4：１)で単離して、前に示した式（２）の化合物をオイルとして得た(44.3 mg, 収率47％)。
13C-NMR(150 MHz,CDCl3) δ101.0 (1-C-メチル-D-グルコピラノシドのアノマー炭素), 90.2 (グルコピラノシドの１位の炭素).
[Example 1]
An anhydrous calcium sulfate (Drierite) (about 100 mg) and bis (trifluoromethane) sulfonimide (Tf 2 NH) (1.8 mg, 0.0066 mmol) were added as a desiccant to a two-necked eggplant flask with a septum cap, and the atmosphere was replaced with argon. 2,3,4,6-Tetra-O-benzyl-D-glucopyranose (48.2 mg, 0.087 mmol) was dissolved in acetonitrile (1.0 ml) and added with a syringe, and the reaction vessel was cooled to 0 ° C. Then, 1-C-methyl-2,3,4,6-tetra-O-benzyl-D-glucopyranose (72.4 mg, 0.13 mmol) was dissolved in acetonitrile (1.0 ml) and added by syringe. The reaction mixture was stirred for 2 hours, saturated aqueous sodium hydrogen carbonate and ethyl acetate were added, and the organic layer was extracted. The organic layer was dried over Na 2 SO 4 , the inorganic substance was filtered off, and the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was isolated by thin layer chromatography (developing solvent hexane: ethyl acetate = 4: 1) to obtain the compound of formula (2) shown above as an oil (44.3 mg, 47% yield).
13 C-NMR (150 MHz, CDCl 3 ) δ 101.0 (anomeric carbon of 1-C-methyl-D-glucopyranoside), 90.2 (carbon at position 1 of glucopyranoside).
[実施例2]
セプタムキャップをした二口ナスフラスコに乾燥剤として無水硫酸カルシウム（Drierite）（約100 mg）とビス（トリフルオロメタン）スルホンイミド（Tf2NH）(4.3 mg, 0.015 mmol)を入れ、アルゴン置換した。この中に２-アジド‐3,4,6-トリ-Ｏ-ベンジル-２-デオキシ-グルコピラノース (36.3 mg, 0.076 mmol)をアセトニトリル(1.0 ml)に溶解してシリンジで加えて、反応容器を0 ℃に冷却した後に、1-C-メチル-2,3,4,6-テトラ-O-ベンジル-D-グルコピラノース (50.7 mg, 0.091 mmol)をアセトニトリル(1.0 ml)に溶解してシリンジで加えた。反応混合物を2時間撹拌した後に、飽和の重曹水と酢酸エチルを加えて、有機層を抽出した。有機層をNa2SO4で乾燥して、無機物を濾別後、溶媒を減圧留去して粗生成物を得た。粗生成物を薄層クロマトグラフィー(展開溶媒 ヘキサン：酢酸エチル＝4：１)で単離して、前に示した式（３）の化合物をオイルとして得た(42.8 mg, 収率56％)。
13C-NMR(150 MHz,CDCl3) δ101.2 (1-C-メチル-D-グルコピラノシドのアノマー炭素), 90.6 (２-アジド‐デオキシ-グルコピラノシドの１位の炭素).
[Example 2]
An anhydrous calcium sulfate (Drierite) (about 100 mg) and bis (trifluoromethane) sulfonimide (Tf 2 NH) (4.3 mg, 0.015 mmol) were placed as a desiccant in a two-necked eggplant flask with a septum cap and purged with argon. 2-Azido-3,4,6-tri-O-benzyl-2-deoxy-glucopyranose (36.3 mg, 0.076 mmol) was dissolved in acetonitrile (1.0 ml) and added with a syringe. After cooling to 0 ° C., 1-C-methyl-2,3,4,6-tetra-O-benzyl-D-glucopyranose (50.7 mg, 0.091 mmol) was dissolved in acetonitrile (1.0 ml) with a syringe. added. The reaction mixture was stirred for 2 hours, saturated aqueous sodium hydrogen carbonate and ethyl acetate were added, and the organic layer was extracted. The organic layer was dried over Na 2 SO 4 , the inorganic substance was filtered off, and the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was isolated by thin layer chromatography (developing solvent hexane: ethyl acetate = 4: 1) to give the compound of formula (3) shown above as an oil (42.8 mg, yield 56%).
13 C-NMR (150 MHz, CDCl 3 ) δ 101.2 (anomeric carbon of 1-C-methyl-D-glucopyranoside), 90.6 (carbon at position 1 of 2-azido-deoxy-glucopyranoside).
[実施例3]
セプタムキャップをした二口ナスフラスコに乾燥剤として無水硫酸カルシウム（Drierite）（約100 mg）とビスマストリフレート（Bi(OTf)3）(5.5 mg, 0.084 mmol)を入れ、アルゴン置換した。この中に2,3,4,6-テトラ-O-ベンジル-D-マンノピラノース (61.6 mg, 0.11 mmol)をアセトニトリル(1.0 ml)に溶解してシリンジで加えて、反応容器を0 ℃に冷却した後に、1-C-メチル-2,3,4,6-テトラ-O-ベンジル-D-グルコピラノース (99.5 mg, 0.17 mmol)をアセトニトリル(1.0 ml)に溶解してシリンジで加えた。反応混合物を2時間撹拌した後に、飽和の重曹水と酢酸エチルを加えて、有機層を抽出した。有機層をNa2SO4で乾燥して、無機物を濾別後、溶媒を減圧留去して粗生成物を得た。粗生成物を薄層クロマトグラフィー(展開溶媒 ヘキサン：酢酸エチル＝4：１)で単離して、前に示した式（４）の化合物をオイルとして得た(90.8 mg, 収率75％)。
13C-NMR(150 MHz,CDCl3) δ101.2 (1-C-メチル-D-グルコピラノシドのアノマー炭素), 90.7 (マンノピラノシドの１位の炭素).
[Example 3]
An anhydrous calcium sulfate (Drierite) (about 100 mg) and bismuth triflate (Bi (OTf) 3 ) (5.5 mg, 0.084 mmol) were placed in a two-necked eggplant flask with a septum cap as a desiccant and purged with argon. 2,3,4,6-Tetra-O-benzyl-D-mannopyranose (61.6 mg, 0.11 mmol) was dissolved in acetonitrile (1.0 ml) and added with a syringe, and the reaction vessel was brought to 0 ° C. After cooling, 1-C-methyl-2,3,4,6-tetra-O-benzyl-D-glucopyranose (99.5 mg, 0.17 mmol) was dissolved in acetonitrile (1.0 ml) and added by syringe. The reaction mixture was stirred for 2 hours, saturated aqueous sodium hydrogen carbonate and ethyl acetate were added, and the organic layer was extracted. The organic layer was dried over Na 2 SO 4 , the inorganic substance was filtered off, and the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was isolated by thin layer chromatography (developing solvent hexane: ethyl acetate = 4: 1) to give the compound of formula (4) shown above as an oil (90.8 mg, 75% yield).
13 C-NMR (150 MHz, CDCl 3 ) δ 101.2 (anomer carbon of 1-C-methyl-D-glucopyranoside), 90.7 (carbon at position 1 of mannopyranoside).
本発明で得られた非還元性二糖トレハロース誘導体は、その水酸基の保護基を脱保護することで、機能性食品添加剤やトレハラーゼ阻害剤として有望であり、さらには医薬品、農薬、化粧品、試薬などの合成中間体として有用である。 The non-reducing disaccharide trehalose derivative obtained in the present invention is promising as a functional food additive or trehalase inhibitor by deprotecting the protecting group of the hydroxyl group, and further, a pharmaceutical, an agricultural chemical, a cosmetic, a reagent. It is useful as a synthetic intermediate.
Claims (6)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2006063079A JP4950521B2 (en) | 2006-03-08 | 2006-03-08 | Trehalose derivatives and process for producing the same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2006063079A JP4950521B2 (en) | 2006-03-08 | 2006-03-08 | Trehalose derivatives and process for producing the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2007238502A JP2007238502A (en) | 2007-09-20 |
| JP4950521B2 true JP4950521B2 (en) | 2012-06-13 |
Family
ID=38584386
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006063079A Expired - Fee Related JP4950521B2 (en) | 2006-03-08 | 2006-03-08 | Trehalose derivatives and process for producing the same |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP4950521B2 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9572825B2 (en) | 2013-05-07 | 2017-02-21 | BioBlast Pharma Ltd. | Compositions and methods for treating huntington's disease |
| US10493023B2 (en) | 2013-05-07 | 2019-12-03 | Seelos Therapeutics, Inc. | Treatment of protein aggregation myopathic and neurodegenerative diseases by parenteral administration of trehalose |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5091508B2 (en) * | 2007-03-09 | 2012-12-05 | 公益財団法人野口研究所 | Glycoside derivatives and non-reducing disaccharides and their production |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH07110871B2 (en) * | 1991-12-09 | 1995-11-29 | 株式会社ディ・ディ・エス研究所 | Method for producing glycosyl derivative |
-
2006
- 2006-03-08 JP JP2006063079A patent/JP4950521B2/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9572825B2 (en) | 2013-05-07 | 2017-02-21 | BioBlast Pharma Ltd. | Compositions and methods for treating huntington's disease |
| US10493023B2 (en) | 2013-05-07 | 2019-12-03 | Seelos Therapeutics, Inc. | Treatment of protein aggregation myopathic and neurodegenerative diseases by parenteral administration of trehalose |
| US10751353B2 (en) | 2013-05-07 | 2020-08-25 | Seelos Therapeutics, Inc. | Compositions and methods for treating an aggregation disease or disorder |
| US10869831B2 (en) | 2013-05-07 | 2020-12-22 | Seelos Therapeutics, Inc. | Treatment of protein aggregation myopathic and neurodegenerative diseases by parenteral administration of trehalose |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2007238502A (en) | 2007-09-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2857395A1 (en) | Process for preparation of 3-((2s,5s)-4-methylene-5-(3-oxopropyl)tetrahydrofuran-2-yl)propanol derivatives and intermediates useful thereof | |
| Srinivas et al. | Ruthenium catalyzed synthesis of 2, 3-unsaturated C-glycosides from glycals | |
| Sipos et al. | Preparation of 1-C-glycosyl aldehydes by reductive hydrolysis | |
| Chen et al. | CF3SO3H–SiO2 as catalyst for Ferrier rearrangement: an efficient procedure for the synthesis of pseudoglycosides | |
| JP4950521B2 (en) | Trehalose derivatives and process for producing the same | |
| JP4559362B2 (en) | Glycerin carbonate glycoside | |
| CA1267891A (en) | Process for the preparation of sphingosine derivatives | |
| van Kalkeren et al. | Protective group-free synthesis of 3, 4-dihydroxytetrahydrofurans from carbohydrates: formal total synthesis of sphydrofuran | |
| Dondoni et al. | Stereoselective Conjugate Addition of Nitrogen and Carbon Nucleophiles to Sugar‐Derived Enones: Synthesis of Sialic Acid Analogues | |
| JP5091508B2 (en) | Glycoside derivatives and non-reducing disaccharides and their production | |
| Wang et al. | Synthesis of trifluoromethylated analogues of β-l-fucofuranose and β-l-4, 6-dideoxyxylohexopyranose | |
| Khong et al. | Total synthesis of phenylpropanoid glycoside osmanthuside-B 6 facilitated by double isomerisation of glucose–rhamnose orthoesters | |
| JP5155578B2 (en) | Fructofuranoside derivative and its production method | |
| Kawashima et al. | Preparation of the monoacylates of 2-substituted (Z)-but-2-ene-1, 4-diols using porcine pancreas lipase | |
| Pelyvás et al. | En route to thromboxane compounds from carbohydrates, I. Synthesis of the unsaturated sugar precursors | |
| FR2699535A1 (en) | Etoposide derivatives, process for their preparation, their use as a medicament and their use for the preparation of a medicament for anticancer treatment | |
| CN112794858B (en) | Preparation method of compound with 3,4-trans-3, 6-anhydro-hexofuranose structure | |
| Zlatev et al. | Deoxygenation of 5-O-benzoyl-1, 2-isopropylidene-3-O-imidazolylthiocarbonyl-α-d-xylofuranose using dimethyl phosphite: an efficient alternate method towards a 3′-deoxynucleoside glycosyl donor | |
| JP5305697B2 (en) | Method for producing α-D-mannopyranoside derivative | |
| CN108314689A (en) | 4,11- diacyl bergenin derivative synthetic methods | |
| JP5252841B2 (en) | Trichloroethyloxycarbonylated α-galactosaminide derivatives | |
| JP2018534313A (en) | Method for preparing 6-azido-2,4-diacetamide-2,4,6-trideoxy-D-mannose | |
| Goursaud et al. | New synthesis of 2, 6-anhydro-β-d-fructofuranoses, pivotal [2.2. 1] bicyclic acetals for the conversion of d-fructose into 2, 2, 5-trisubstituted tetrahydrofurans | |
| JP2007238501A (en) | Method for producing fructofuranoside derivative and non-reductive disaccharide fructofuranoside derivative | |
| JP6027119B2 (en) | Synthesis of 10-α / β-D-arabinofuranosyl-undecene as a potential antimycobacterial agent |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20090306 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20120227 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20120309 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20150316 Year of fee payment: 3 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 Ref document number: 4950521 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |