JP2009215242A - Sugar-binding type spiro crown ether derivative - Google Patents

Sugar-binding type spiro crown ether derivative Download PDF

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JP2009215242A
JP2009215242A JP2008061715A JP2008061715A JP2009215242A JP 2009215242 A JP2009215242 A JP 2009215242A JP 2008061715 A JP2008061715 A JP 2008061715A JP 2008061715 A JP2008061715 A JP 2008061715A JP 2009215242 A JP2009215242 A JP 2009215242A
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sugar
crown ether
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JP5394645B2 (en
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Takashi Yamanoi
孝 山ノ井
Yoshinobu Oda
慶喜 小田
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Noguchi Institute
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Abstract

<P>PROBLEM TO BE SOLVED: To provide a sugar-binding type spiro crown ether derivative that contains an anomer carbon atom of a hemiketal structure in the cyclic carbon atom of a crown ether in which a sugar molecule and the crown ether forms a spiro structure and a method for producing the same. <P>SOLUTION: The sugar-binding type spiro crown ether derivative is obtained by using 2,3,4,6-tri-O-benzyl-1C-vinyl-α-D-glucopyranose, an ethylene glycol derivative and bismuth (III) triflate as an activator. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

本発明は、ヘミケタール構造のアノマー炭素原子をクラウンエーテルの環状炭素原子に含み、糖分子とクラウンエーテルがスピロ構造となる糖結合型スピロクラウンエーテル誘導体（以後、糖結合型スピロクラウンエーテル誘導体と称する）、およびその製造法に関するものである。具体的には、糖分子のヘミケタール構造のアノマー炭素原子をクラウンエーテルの環状炭素原子に含み、糖分子とクラウンエーテルがスピロ構造となる式［１］〜［３］の糖結合型スピロクラウンエーテル誘導体、および式［４］の１−C−ビニル化糖誘導体を出発原料とした、式［１］〜［３］の糖結合型スピロクラウンエーテル誘導体の製造法に関するものである。   The present invention relates to a sugar-bonded spirocrown ether derivative containing an anomeric carbon atom of a hemiketal structure in the cyclic carbon atom of a crown ether and having a sugar molecule and a crown ether having a spiro structure (hereinafter referred to as a sugar-bonded spirocrown ether derivative). , And its manufacturing method. Specifically, the sugar-bonded spiro crown ether derivatives of the formulas [1] to [3], in which the anomeric carbon atom of the hemiketal structure of the sugar molecule is contained in the cyclic carbon atom of the crown ether, and the sugar molecule and the crown ether have a spiro structure. And a method for producing a sugar-bonded spirocrown ether derivative of the formulas [1] to [3] using a 1-C-vinylated sugar derivative of the formula [4] as a starting material.

クラウンエーテルは、エチレンオキシ鎖の繰り返し構造からなる環状化合物である。クラウンエーテルは、自由度の非常に高い化合物であり、その環の大きさによって、様々なイオンを取り込むことが知られており、例えば有機合成化学の分野では、金属イオンを取り込ませ、不斉触媒として広く利用されている（例えば非特許文献１を参照）。また最近では、クラウンエーテルがアンモニウムイオンの認識に適していることが判り、特にタンパク質中のリジン残基に由来するアミノ基と結合して、タンパク質の物性や機能を改変しうることが明らかになってきた（非特許文献２、３を参照）。しかし、クラウンエーテルは生体内のナトリウムイオンや、カリウムイオンを認識し、環内に取り込んでしまい、生体内のバランスを壊し人体に猛毒となることが言われている。そのため、クラウンエーテルを制御するシステムを構築することが求められている。   Crown ether is a cyclic compound having a repeating structure of ethyleneoxy chain. Crown ether is a compound with a very high degree of freedom, and is known to incorporate various ions depending on the size of the ring. For example, in the field of synthetic organic chemistry, metal ions can be incorporated to form asymmetric catalysts. Widely used (see, for example, Non-Patent Document 1). Recently, it has been found that crown ethers are suitable for recognition of ammonium ions, and in particular, it can be seen that they can modify the physical properties and functions of proteins by binding to amino groups derived from lysine residues in proteins. (See Non-Patent Documents 2 and 3). However, it is said that crown ether recognizes sodium ions and potassium ions in the living body and takes them into the ring, breaking the balance in the living body and becoming extremely toxic to the human body. Therefore, it is required to construct a system for controlling crown ether.

一方、糖分子（糖鎖）は、生体内においてその種類や構造に応じて、特定の細胞やレクチンに対する認識能を持つことが最近の研究で解明されつつある。その為、糖分子は医薬送達システム（Drug Delivery System; DDS）として期待されており、生物学、薬学、医学の分野で重要視されている。これらの背景から、糖結合型スピロクラウンエーテル誘導体は、生体内においてDDSとして利用できることが期待される。
Toshiyuki, I.ら、「Synthesis of Chiralazacrown Ethers Derived From α-D-Glucose and Their Catalytic Properties on The Asymmetric Michael Addition」、Heterocycles, 2001年, 55巻, 37ページ. Reinhoudt, R. D.ら、「The Effect of Crown Ethers on Enzyme-catalysed Reactions in Organic Solvents」、Journal of Chemical Society Chemical Communications, 1989年, 359ページ. Paul, D.ら、「Chemical Activation of Cytochrome c Proteins via Crown Ether Complexation: Cold-Active Synzymes for Enantiomer-Selective Sulfoxide Oxidation in Methanol」、Journal of The American Chemical Society, 2003年, 125巻, 11478ページ. On the other hand, recent studies have revealed that sugar molecules (sugar chains) have the ability to recognize specific cells and lectins in vivo according to their types and structures. Therefore, sugar molecules are expected as a drug delivery system (DDS) and are regarded as important in the fields of biology, pharmacy, and medicine. From these backgrounds, it is expected that sugar-linked spirocrown ether derivatives can be used as DDS in vivo.
Toshiyuki, I. et al., `` Synthesis of Chiralazacrown Ethers Derived From α-D-Glucose and Their Catalytic Properties on The Asymmetric Michael Addition '', Heterocycles, 2001, 55, 37. Reinhoudt, RD et al., `` The Effect of Crown Ethers on Enzyme-catalysed Reactions in Organic Solvents '', Journal of Chemical Society Chemical Communications, 1989, p. 359. Paul, D. et al., `` Chemical Activation of Cytochrome c Proteins via Crown Ether Complexation: Cold-Active Synzymes for Enantiomer-Selective Sulfoxide Oxidation in Methanol '', Journal of The American Chemical Society, 2003, 125, 11478.

本発明では、糖分子のヘミケタール構造のアノマー炭素原子が、クラウンエーテルの環状炭素原子の一部になり、糖分子とクラウンエーテルがスピロ構造となる糖結合型スピロクラウンエーテル誘導体、およびその製造法を提供することを課題とする。   In the present invention, a sugar-bonded spiro crown ether derivative in which the anomeric carbon atom of the hemiketal structure of a sugar molecule becomes a part of the cyclic carbon atom of the crown ether, and the sugar molecule and the crown ether have a spiro structure, and a method for producing the same. The issue is to provide.

糖分子のヘミケタール構造のアノマー炭素原子をクラウンエーテルの環状炭素原子に含み、糖分子とクラウンエーテルがスピロ構造となる糖結合型スピロクラウンエーテル誘導体を製造するにあたり、式［４］の１−C−ビニル化糖を原料に用い、エチレングリコール誘導体に対し、活性化剤としてビスマス(III)トリフレートを作用させる事で合成することが出来る。その後、種々の化学変換を行い式［１］〜［３］の新規な糖結合型スピロクラウンエーテル誘導体を製造することができる。   In producing a sugar-bonded spirocrown ether derivative in which the anomeric carbon atom of the hemiketal structure of a sugar molecule is contained in the cyclic carbon atom of the crown ether and the sugar molecule and the crown ether have a spiro structure, 1-C— of the formula [4] Synthesis can be performed by using bismuth (III) triflate as an activator for ethylene glycol derivatives using vinylated sugar as a raw material. Thereafter, various chemical transformations can be performed to produce novel sugar-linked spirocrown ether derivatives of the formulas [1] to [3].

具体的には、グルコースの２、３、４、６位をベンジル基で保護し、１位にビニル基を導入した糖誘導体である2,3,4,6-トリ-O-ベンジル-1C-ビニル-α-D-グルコピラノースと、一つの水酸基をベンゾイル基で保護したエチレングリコール誘導体を用い、ビスマス(III)トリフレートを活性化剤に用いることで、糖結合型スピロクラウンエーテル誘導体を製造することができることを見出し、本発明に到達した。   Specifically, 2,3,4,6-tri-O-benzyl-1C- is a sugar derivative in which glucose positions 2, 3, 4, and 6 are protected with a benzyl group and a vinyl group is introduced at the 1-position. A sugar-linked spirocrown ether derivative is produced by using vinyl-α-D-glucopyranose and an ethylene glycol derivative in which one hydroxyl group is protected with a benzoyl group and using bismuth (III) triflate as an activator. The present invention has been found.

すなわち、本発明は、下記式［１］〜［３］の糖結合型スピロクラウンエーテル誘導体、および下記式［４］の１−C−ビニル化糖誘導体を原料に用いた、下記式［１］〜［３］の糖結合型スピロクラウンエーテル誘導体の製造法に関するものである。

Figure 2009215242
（R1は、ヘミケタール構造のアノマー炭素原子をクラウンエーテルの環状炭素原子に含む糖分子を示す。R2はCH2、C=O、またはCHOHを表す。nは0から3までの整数を表す。） That is, the present invention uses the sugar-bonded spirocrown ether derivatives of the following formulas [1] to [3] and the 1-C-vinylated sugar derivative of the following formula [4] as raw materials. The present invention relates to a method for producing a sugar-bonded spirocrown ether derivative of [3].
Figure 2009215242
 (R 1 represents a sugar molecule containing an anomeric carbon atom of the hemiketal structure in the cyclic carbon atom of the crown ether. R 2 represents CH 2 , C═O, or CHOH. N represents an integer from 0 to 3. .)

Figure 2009215242
（R3はOBn、OAc、OBz、NHAcまたはN3を表す。Bnはベンジル基、Acはアセチル基、Bzはベンゾイル基を表す。）
Figure 2009215242
 (R 3 represents OBn, OAc, OBz, NHAc or N 3. Bn represents a benzyl group, Ac represents an acetyl group, and Bz represents a benzoyl group.)

Figure 2009215242
（R4はOBn、OAc、OBz、NHAcまたはN3を表す。Bnはベンジル基、Acはアセチル基、Bzはベンゾイル基を表す。）
Figure 2009215242
 (R 4 represents OBn, OAc, OBz, NHAc or N 3. Bn represents a benzyl group, Ac represents an acetyl group, and Bz represents a benzoyl group.)

Figure 2009215242
（R5はOBn、OAc、OBz、NHAcまたはN3を表す。Bnはベンジル基、Acはアセチル基、Bzはベンゾイル基を表す。）
Figure 2009215242
 (R 5 represents OBn, OAc, OBz, NHAc or N 3. Bn represents a benzyl group, Ac represents an acetyl group, and Bz represents a benzoyl group.)

以下、本発明を詳細に説明する。
本発明は、糖分子のヘミケタール構造のアノマー炭素原子をクラウンエーテルの環状炭素原子に含み、糖分子とクラウンエーテルがスピロ構造となる糖結合型スピロクラウンエーテル誘導体を製造するにあたり、式［４］の１−C−ビニル化糖を原料とし、エチレングリコール誘導体に対し、活性化剤としてビスマス(III)トリフレートを作用させる事で式［１］〜［３］の新規な糖結合型スピロクラウンエーテル誘導体を製造する。 The present invention will be described in detail below.
The present invention provides a saccharide-bonded spiro crown ether derivative containing an anomeric carbon atom of the hemiketal structure of a sugar molecule in the cyclic carbon atom of the crown ether, wherein the sugar molecule and the crown ether have a spiro structure. A novel sugar-linked spirocrown ether derivative of the formulas [1] to [3] by using bismuth (III) triflate as an activator for an ethylene glycol derivative using 1-C-vinylated sugar as a raw material Manufacturing.

式［２］の糖結合型スピロクラウンエーテル誘導体は、次のようにして合成する。
2,3,4,6-トリ-O-ベンジル-1C-ビニル-α-D-グルコピラノースを、ジクロロメタン中、5 mol%のビスマス(III)トリフレートを用い、モノベンゾイル−テトラエチレングリコールと反応させる。次に、オゾン酸化を行いさらに酸化することで、ビニル基をカルボキシル基へと変換し、その後、ベンゾイル基を脱保護し、塩基にDIEAを用いPyBOPにて脱水縮合させることで、式［２］に示す糖結合型スピロクラウンエーテル誘導体を得る。 The sugar-bonded spirocrown ether derivative of the formula [2] is synthesized as follows.
Reaction of 2,3,4,6-tri-O-benzyl-1C-vinyl-α-D-glucopyranose with monobenzoyl-tetraethylene glycol using 5 mol% bismuth (III) triflate in dichloromethane Let Next, ozone is oxidized and further oxidized to convert the vinyl group to a carboxyl group, and then the benzoyl group is deprotected and dehydrated and condensed with PyBOP using DIEA as a base. A sugar-linked spirocrown ether derivative shown in FIG.

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受けるものではない。   Hereinafter, the present invention will be described in detail with reference to examples. However, the present invention is not limited to the following examples.

（工程１）
2,3,4,6-トリ-O-ベンジル-1-C-ビニル-α-D-グルコピラノース(256.5 mg/ 0.45 mmol)と、ビスマス(III)トリフレート(15.2 mg/ 0.023 mmol)と、ドライアライト(379.6 mg)をナスフラスコに入れ、アルゴン雰囲気下でジクロロメタン(3.5 mL)に溶解させ0℃にした。その後、モノベンゾイル−テトラエチレングリコール(165.3 mg/ 0.55 mmol)を加え2時間撹拌した。次に、炭酸水素ナトリウム水溶液を用いて反応を停止させ、酢酸エチルと炭酸水素ナトリウム水溶液を用いて有機層を抽出し、無水硫酸ナトリウムによって乾燥させた。薄層クロマトグラフィー（展開溶媒比ヘキサン：酢酸エチル=2:1）によって精製を行った。
1H-NMR (600 MHz, CDCl3) δ 3.34 (1H, d, J = 9.6 Hz, H-2), 3.48-3.70 (14H, m, H-4, Ha-6, OCH2CH2O), 3.76〜3.79 (3H, m, Hb-6, OCH2CH2O), 3.85 (1H, m, H-5), 4.10 (1H, t, J = 9.7Hz, H-3), 5.27 ( 1H, dd, J = 2.0 Hz, J = 11.0 Hz, CH=CHaHb), 5.54 (1H, dd, J = 2.1 Hz, J = 11.0 Hz, CH=CHaHb), 5.99 (1H, m, CH=CH2), 13C-NMR (150 MHz, CDCl3) δ61.4 (OCH2CH2O), 64.10 (OCH2CH2O), 68.79 (C-6), 69.15 (OCH2CH2O), 70.00 (OCH2CH2O), 70.59 (OCH2CH2O), 70.64 (OCH2CH2O), 70.64 (OCH2CH2O), 70.73 (OCH2CH2O), 71.54 (C-5), 78.48 (C-4), 82.99 (C-3), 84.29 (C-2), 99.46 (C-1), 118.78 (CH=CH2), 135.28 (CH=CH2). (Process 1)
2,3,4,6-tri-O-benzyl-1-C-vinyl-α-D-glucopyranose (256.5 mg / 0.45 mmol), bismuth (III) triflate (15.2 mg / 0.023 mmol), Dry allite (379.6 mg) was placed in an eggplant flask and dissolved in dichloromethane (3.5 mL) under an argon atmosphere at 0 ° C. Then, monobenzoyl-tetraethylene glycol (165.3 mg / 0.55 mmol) was added and stirred for 2 hours. Next, the reaction was stopped using an aqueous sodium hydrogen carbonate solution, and the organic layer was extracted using ethyl acetate and an aqueous sodium hydrogen carbonate solution, and dried over anhydrous sodium sulfate. Purification was performed by thin layer chromatography (developing solvent ratio hexane: ethyl acetate = 2: 1).
1 H-NMR (600 MHz, CDCl 3) δ 3.34 (1H, d, J = 9.6 Hz, H-2), 3.48-3.70 (14H, m, H-4, H a -6, OCH 2 CH 2 O ), 3.76-3.79 (3H, m, H b -6, OCH 2 CH 2 O), 3.85 (1H, m, H-5), 4.10 (1H, t, J = 9.7Hz, H-3), 5.27 (1H, dd, J = 2.0 Hz, J = 11.0 Hz, CH = CH a H b ), 5.54 (1H, dd, J = 2.1 Hz, J = 11.0 Hz, CH = CH a H b ), 5.99 (1H , m, CH = CH 2 ), 13 C-NMR (150 MHz, CDCl 3 ) δ61.4 (OCH 2 CH 2 O), 64.10 (OCH 2 CH 2 O), 68.79 (C-6), 69.15 (OCH 2 CH 2 O), 70.00 (OCH 2 CH 2 O), 70.59 (OCH 2 CH 2 O), 70.64 (OCH 2 CH 2 O), 70.64 (OCH 2 CH 2 O), 70.73 (OCH 2 CH 2 O) , 71.54 (C-5), 78.48 (C-4), 82.99 (C-3), 84.29 (C-2), 99.46 (C-1), 118.78 (CH = CH 2 ), 135.28 (CH = CH 2 ).

（工程２）
次に、工程１で得られた生成物(220.9 mg/ 0.26 mmol)をジクロロメタン(10.0 mL)に溶かし、オゾンガスをバブリングさせ、6時間後に、トリフェニルホスフィン(260.4 mg/ 0.99 mmol)を加えた。24時間後、t-ブタノール(4.0 mL)と純水(1.0 mL)の混合溶媒中、亜塩素酸ナトリウム(238.5 mg/ 2.64 mmol)、リン酸二水素ナトリウム(122.2 mg/ 0.78 mmol)、２−メチル−２−ブテン(121.6 μL/ 1.15 mmol)を加えた。４８時間後、ジクロロメタンと食塩水を用いて有機層を抽出し、無水硫酸ナトリウムによって乾燥させた。薄層クロマトグラフィー（展開溶媒比クロロホルム：メタノール＝5：1）によって精製を行った。その後、テトラヒドロフラン中、水酸化ナトリウム水溶液を用いて脱ベンゾイル化を行った。
1H-NMR (600 MHz, CDCl3) δ3.37-4.00 (22 H, m, H-2, H-3, H-4, H-5, H-6, OCH2CH2O), 13C-NMR (150 MHz, CDCl3) δ60.4 (OCH2CH2O), 62.6 (OCH2CH2O), 68.5-70.4 (OCH2CH2O, H-6), 78.1 (C-5), 82.4 (C-4), 82.9 (C-2, C-3), 99.7 (C-1), 172.3 (C=O) (Process 2)
Next, the product obtained in Step 1 (220.9 mg / 0.26 mmol) was dissolved in dichloromethane (10.0 mL), ozone gas was bubbled, and 6 hours later, triphenylphosphine (260.4 mg / 0.99 mmol) was added. After 24 hours, in a mixed solvent of t-butanol (4.0 mL) and pure water (1.0 mL), sodium chlorite (238.5 mg / 2.64 mmol), sodium dihydrogen phosphate (122.2 mg / 0.78 mmol), 2- Methyl-2-butene (121.6 μL / 1.15 mmol) was added. After 48 hours, the organic layer was extracted with dichloromethane and brine and dried over anhydrous sodium sulfate. Purification was performed by thin layer chromatography (developing solvent ratio chloroform: methanol = 5: 1). Thereafter, debenzoylation was performed using an aqueous sodium hydroxide solution in tetrahydrofuran.
1 H-NMR (600 MHz, CDCl 3 ) δ3.37-4.00 (22 H, m, H-2, H-3, H-4, H-5, H-6, OCH 2 CH 2 O), 13 C-NMR (150 MHz, CDCl 3 ) δ60.4 (OCH 2 CH 2 O), 62.6 (OCH 2 CH 2 O), 68.5-70.4 (OCH 2 CH 2 O, H-6), 78.1 (C-5 ), 82.4 (C-4), 82.9 (C-2, C-3), 99.7 (C-1), 172.3 (C = O)

（工程３）
式［２］の糖結合型スピロクラウンエーテル誘導体の合成
工程２で得られた化合物(20.4 mg/ 0.027 mmol)を、ジクロロメタン(3.0 mL)に溶かし、PyBOP (28.3 mg/ 0.054 mmol)、DIEA (9.3 μL/ 0.054 mmol)を加えた後48時間撹拌した。酢酸エチルとクエン酸水溶液を用いて有機層を抽出し、さらに酢酸エチルと炭酸水素ナトリウム水溶液を用いて有機層を抽出し、無水硫酸ナトリウムによって乾燥させた。薄層クロマトグラフィー（展開溶媒比クロロホルム：メタノール＝15：1）によって精製を行い、式［２］の糖結合型スピロクラウンエーテル誘導体(6.8 mg)を得た。
13C-NMR (150 MHz, CDCl3):δ 99.7 (C-1), 168.6 (C=O). (Process 3)
Synthesis of sugar-linked spirocrown ether derivative of formula [2] The compound obtained in Step 2 (20.4 mg / 0.027 mmol) was dissolved in dichloromethane (3.0 mL), and PyBOP (28.3 mg / 0.054 mmol), DIEA (9.3 (μL / 0.054 mmol) was added, followed by stirring for 48 hours. The organic layer was extracted with ethyl acetate and aqueous citric acid solution, and further extracted with ethyl acetate and aqueous sodium hydrogen carbonate solution, and dried over anhydrous sodium sulfate. Purification was performed by thin layer chromatography (developing solvent ratio chloroform: methanol = 15: 1) to obtain a sugar-linked spirocrown ether derivative (6.8 mg) of the formula [2].
13 C-NMR (150 MHz, CDCl 3 ): δ 99.7 (C-1), 168.6 (C = O).

クラウンエーテル構造を持つことから、タンパク質中のアミノ基と結合して、タンパク質の物性や機能を改変するような性質を持ち、さらに糖分子を有することで、特定のタンパク質を選択することが出来ることから、DDSとしての利用が高まり、新しい医薬として重要な化合物になると考えられる。   Because it has a crown ether structure, it can bind to amino groups in proteins to modify the physical properties and functions of the protein, and it can select specific proteins by having sugar molecules. Therefore, the use as DDS will increase and it will be an important compound as a new medicine.

Claims (4)

ヘミケタール構造のアノマー炭素原子をクラウンエーテルの環状炭素原子に含み、糖分子とクラウンエーテルがスピロ構造となる下記式[１]で示される糖結合型スピロクラウンエーテル誘導体。
Figure 2009215242
 （R1は、ヘミケタール構造のアノマー炭素原子をクラウンエーテルの環状炭素原子に含む糖分子を示す。R2はCH2、C=O、またはCHOHを表す。nは0から3までの整数を表す。） A sugar-linked spirocrown ether derivative represented by the following formula [1], wherein an anomeric carbon atom having a hemiketal structure is contained in the cyclic carbon atom of the crown ether, and the sugar molecule and the crown ether have a spiro structure.
Figure 2009215242
 (R 1 represents a sugar molecule containing an anomeric carbon atom of the hemiketal structure in the cyclic carbon atom of the crown ether. R 2 represents CH 2 , C═O, or CHOH. N represents an integer from 0 to 3. .) 下記式[２]に示される糖結合型スピロクラウンエーテル誘導体。
Figure 2009215242
 （R3はOBn、OAc、OBz、NHAcまたはN3を表す。Bnはベンジル基、Acはアセチル基、Bzはベンゾイル基を表す。） A sugar-linked spirocrown ether derivative represented by the following formula [2].
Figure 2009215242
 (R 3 represents OBn, OAc, OBz, NHAc or N 3. Bn represents a benzyl group, Ac represents an acetyl group, and Bz represents a benzoyl group.) 下記式[３]に示される糖結合型スピロクラウンエーテル誘導体。
Figure 2009215242
 （R4はOBn、OAc、OBz、NHAcまたはN3を表す。Bnはベンジル基、Acはアセチル基、Bzはベンゾイル基を表す。） A sugar-linked spirocrown ether derivative represented by the following formula [3].
Figure 2009215242
 (R 4 represents OBn, OAc, OBz, NHAc or N 3. Bn represents a benzyl group, Ac represents an acetyl group, and Bz represents a benzoyl group.) 下記式[４]に示される１−C−ビニル化糖誘導体
Figure 2009215242
 （R5はOBn、OAc、OBz、NHAcまたはN3を表す。Bnはベンジル基、Acはアセチル基、Bzはベンゾイル基を表す。）を原料に用い、エチレングリコール誘導体に対し、ビスマス(III)トリフレートを活性化剤として反応させることを特徴とする請求項１〜３記載の糖結合型スピロクラウンエーテル誘導体の製造法。 1-C-vinylated sugar derivative represented by the following formula [4]
Figure 2009215242
 (R 5 represents OBn, OAc, OBz, NHAc or N 3. Bn represents a benzyl group, Ac represents an acetyl group, and Bz represents a benzoyl group.) The raw material is bismuth (III) The method for producing a sugar-linked spirocrown ether derivative according to claim 1, wherein triflate is reacted as an activator.
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