JP6981639B2 - Sugar manufacturing method - Google Patents

Description

The present invention relates to a method for producing sugar. In particular, the present invention relates to a method for producing a stereoselective sugar chain.

A sugar chain is a substance having a structure in which monosaccharides are bonded to each other via an oxygen atom called a glycosidic bond. Glycosidic bonds are roughly classified into α-glycosidic bonds and β-glycosidic bonds, and it is indispensable to make these two types of glycosidic bonds separately, that is, to control the stereoselectivity of the glycosylation reaction when using sugar chains as functional compounds. Is.

Methods for producing such sugar chains have been actively researched and developed. The most important reaction step in the method for producing a sugar chain is a glycosylation reaction between sugar and alcohol, and the stereoselectivity, efficiency or convenience of the reaction are attracting attention as important factors.

For example, in the method of synthesizing a sugar chain as a material for medical and agricultural chemicals or as a lead compound, in order to achieve high stereoselectivity, the hydroxyl group and amino group on the 2-position carbon of the sugar are sterically controlled by acetyl group and phthalimide group, respectively. It is necessary to introduce the group. However, it is also known that the steric control group needs to be introduced into the sugar in advance and also causes a decrease in the reactivity of the sugar in the glycosylation reaction (Carbohydr. Res., 310, pp. 43). −51, 1998). On the other hand, when a benzyl group is introduced into the hydroxyl group on the 2-position carbon, the stereoselectivity is low, and the obtained sugar chain becomes a mixture of two types of stereoisomers (J. Am. Chem. Soc., 129). , pp.10922-10928, 2007).

If stereochemistry cannot be controlled by the glycosylation reaction, the isomers need to be separated and purified (Org. Lett., 17, pp. 1525-1528, 2015). It is also known that in the electrolytic glycosylation reaction, in the case of a reaction with a highly reactive alcohol such as methanol, high stereoselectivity is exhibited even in the presence of one type of electrolyte, but the highly reactive alcohol is used. Due to its limitations, it cannot be applied to the synthesis of sugar chains (Albert A. Bowers, University of Illinois, Chicago, Doctoral Thesis, 2007).

Carbohydr. Res., 310, pp. 43-51, 1998 J. Am. Chem. Soc., 129, pp.10922-10928, 2007 Org. Lett., 17, pp.1525-1528, 2015 Albert A. Bowers, University of Illinois, Chicago, Dissertation, 2007

In this way, even in the production of medical and agrochemical products, not only the reactivity as a chemical reaction and the stereoselectivity, but also the high stereoselectivity that does not require the separation and purification operation by silica gel chromatograph, which is a problem especially for industrial production. It has been desired to develop a new method for producing a sugar chain that realizes selectivity without using a stereocontrol group.

The present inventors have performed an electrolytic glycosylation reaction using a single electrolyte in a mutual manner with a glycosylation reaction intermediate so as not to impair the original reactivity and selectivity of the glycosyl triflate intermediate. As a result of focusing on the coexistence of an electrolyte having a weak counter anion, the desired O-glycosylation reaction proceeds with extremely high stereoselectivity in the presence of two or more electrolytes containing a triflate anion. We found that and completed the following inventions.

一般式（１）中、Ｒ¹およびＲ²は、それぞれ独立に、直鎖、分枝もしくは環状構造を有するアルキル基、ベンジル基、ｐ−メトキシベンジル基、ｐ−メチルベンジル基、アセチル基、トリメチルアセチル基、ベンゾイル基、トリメチルシリル基またはｔ−ブチルジメチルシリル基を示し、Ｒ¹およびＲ²は互いに結合して環を形成していてもよく、Ｒ³は、環状構造を有しないアルキル基、ベンジル基、ｐ−メトキシベンジル基、ｐ−メチルベンジル基、アセチル基、トリメチルアセチル基、ベンゾイル基、トリメチルシリル基またはｔ−ブチルジメチルシリル基を示し、Ｙ¹はフタルイミド基、ベンジルオキシ基、ｐ−メトキシベンジルオキシ基、ｐ−メチルベンジルオキシ基、アジド基、アセチルオキシ基、ベンゾイルオキシ基、メトキシ基、メトキシメチル基またはトリメチルシロキシ基を示し、Ｚ¹は、テルロアリール基、セレノアリール基、チオアリール基、チオメチル基、チオエチル基、チオオクチル基、チオノニル基およびチオデシル基から選ばれる脱離基を示す；

一般式（２）中、Ｒ⁴およびＲ⁵は、それぞれ独立に、水素原子、直鎖、分枝もしくは環状構造を有するアルキル基、アセチル基、ベンジル基、ｐ−メトキシベンジル基、ｐ−メチルベンジル基、トリメチルアセチル基、ベンゾイル基、トリメチルシリル基またはｔ−ブチルジメチルシリル基を示し、Ｒ⁴およびＲ⁵は互いに結合して環を形成していてもよく、Ｒ⁶は、水素原子、環状構造を有しないアルキル基、ベンジル基、ｐ−メトキシベンジル基、ｐ−メチルベンジル基、アセチル基、トリメチルアセチル基、ベンゾイル基、トリメチルシリル基またはｔ−ブチルジメチルシリル基を示し、Ｙ²はフタルイミド基、ベンジルオキシ基、ｐ−メトキシベンジルオキシ基、ｐ−メチルベンジルオキシ基、アジド基、アセチルオキシ基、ベンゾイルオキシ基、メトキシ基、メトキシメチル基またはトリメチルシロキシ基を示し、Ｚ²は反応性基を示す；
（Ｒ⁷）₄Ａ⁺ＯＳ（＝Ｏ）₂Ｒ^- （３−１）
一般式（３−１）中、Ｒ⁷は炭素数が１以上のアルキル基、パーフルオロアルキル基、フェニル基、ベンジル基またはポリエチレングリコール基を示し、
Ａは、窒素原子またはリン原子を示し、
Ｒは、フッ素原子またはフッ化アルキル基を表す；
Ｒ⁷ ₄Ａ⁺Ｘ^- （３−２）
一般式（３−２）中、Ｒ⁷は炭素数が１以上のアルキル基、パーフルオロアルキル基、フェニル基、ベンジル基またはポリエチレングリコール基を示し、
Ａは、窒素原子またはリン原子を示し、
Ｘは、ビス（トリフルオロメタンスルホニル）アミド、ビス（フルオロメタンスルホニル）アミドまたはＢ（Ｃ₆Ｆ₅）₄を示す。
＜２＞前記一般式（１）に示す糖と、前記一般式（２）に示す糖とを、一般式（３−１）に示す電解質および一般式（３−２）に示す電解質の存在下で、非プロトン性有機溶媒中で電解酸化反応させること含み、
前記一般式（１）におけるＲ¹およびＲ²は互いに結合して環を形成しておらず、
Ｙ¹はベンジルオキシ基、ｐ−メトキシベンジルオキシ基、ｐ−メチルベンジルオキシ基、メトキシ基、メトキシメチル基、トリメチルシロキシ基またはアジド基であり、
前記一般式（２）中、Ｚ²はアルコキシ基またはアリールチオ基を示し、かつ、Ｒ⁴およびＲ⁵は互いに結合して環を形成しておらず、
前記一般式（３−１）中、Ｒは、トリフルオロメチル基を示し、
前記一般式（３−２）中、Ｘは、ビス（トリフルオロメタンスルホニル）アミドまたはビス（フルオロメタンスルホニル）アミドを示す、＜１＞に記載の糖の製造方法。
＜３＞前記一般式（３−１）に示す電解質が、テトラブチルアンモニウムトリフラートであり、前記一般式（３−２）に示す電解質が、テトラブチルアンモニウムビス（トリフルオロメタンスルホニル）アミドおよびテトラブチルアンモニウムビス（フルオロメタンスルホニル）アミドの少なくとも一方である、＜１＞または＜２＞に記載の糖の製造方法。
＜４＞脱離基を有する一般式（１）に示す糖と一般式（２）に示す糖を、一般式（３）に示す電解質から選ばれた２以上の電解質の存在下に、非プロトン性有機溶媒中で電解酸化反応させることを特徴とする立体選択的な糖の製造方法。

ここで、式（１）中、Ｒ¹、Ｒ²は、直鎖、分枝、環状構造を有するアルキル基、またはベンジル基を示し、Ｒ³は、環状構造を有しないアルキル基、またはベンジル基を示し、Ｙ¹はベンジロキシ基またはアジド基を、Ｚ¹は、テルロアリール基、セレノアリール基、チオアリール基またはチオエチル基から選ばれた脱離基を示し、ｍは、１以上の整数を示す。
また、式（２）中、Ｒ⁴、Ｒ⁵は、水素原子、直鎖、分枝、環状構造を有するアルキル基、アセチル基、ベンジル基を示し、Ｒ⁶は環状構造を有しないアルキル基、アセチル基、ベンジル基を示し、Ｙ²はベンジロキシ基、アジド基またはフタルイミド基を、Ｚ²はアルコキシ基またはアリールチオ基を示し、ｎは、１以上の整数を示す。
Ｒ⁷ ₄Ａ⁺Ｘ^- （３）
（式（３）中、Ｒ⁷は炭素数が１以上のアルキル基、パーフルオロアルキル基またはポリエチレングリコール基を示し、Ａは、窒素原子、リン原子を示し、Ｘはトリフラート、ビス（トリフルオロメタンスルホニル）アミド、ビス（フルオロメタンスルホニル）アミドを示す。 <1> A polysaccharide composed of a sugar represented by the general formula (1) and / or a sugar represented by two or more general formulas (1), a sugar represented by the general formula (2) and / or two or more general formulas. Electrolytic oxidation reaction of a polysaccharide composed of the sugar represented by (2) in an aprotic organic solvent in the presence of an electrolyte represented by the general formula (3-1) and an electrolyte represented by the general formula (3-2). Method of producing sugar, including letting;

In the general formula (1), R ¹ and R ² are independently linear, branched or cyclic structures such as an alkyl group, a benzyl group, a p-methoxybenzyl group, a p-methylbenzyl group, an acetyl group and a trimethyl. It represents an acetyl group, a benzoyl group, a trimethylsilyl group or a t-butyldimethylsilyl group, and R ¹ and R ² may be bonded to each other to form a ring, and R ³ is an alkyl group having no cyclic structure, benzyl. Group, p-methoxybenzyl group, p-methylbenzyl group, acetyl group, trimethylacetyl group, benzoyl group, trimethylsilyl group or t-butyldimethylsilyl group, Y ¹ is phthalimide group, benzyloxy group, p-methoxybenzyl An oxy group, a p-methylbenzyloxy group, an azido group, an acetyloxy group, a benzoyloxy group, a methoxy group, a methoxymethyl group or a trimethylsiloxy group, and Z ¹ is a tellroaryl group, a serenoaryl group, a thioaryl group or a thiomethyl group. , Thioethyl group, thiooctyl group, thiononyl group and thiodecyl group;

In the general formula (2), R ⁴ and R ⁵ are independently hydrogen atom, linear, branched or cyclic group having an alkyl group, an acetyl group, a benzyl group, a p-methoxybenzyl group, and a p-methylbenzyl group, respectively. A group, a trimethylacetyl group, a benzoyl group, a trimethylsilyl group or a t-butyldimethylsilyl group, and R ⁴ and R ⁵ may be bonded to each other to form a ring, and R ⁶ has a hydrogen atom and a cyclic structure. It indicates an alkyl group, a benzyl group, a p-methoxybenzyl group, a p-methylbenzyl group, an acetyl group, a trimethylacetyl group, a benzoyl group, a trimethylsilyl group or a t-butyldimethylsilyl group, and Y ² is a phthalimide group or a benzyloxy group. Group, p-methoxybenzyloxy group, p-methylbenzyloxy group, azido group, acetyloxy group, benzoyloxy group, methoxy group, methoxymethyl group or trimethylsiloxy group, Z ² indicates a reactive group;
_{^{(R 7) 4 A + OS}} (= O) 2 R - (3-1)
In the general formula (3-1), R ⁷ represents an alkyl group having one or more carbon atoms, a perfluoroalkyl group, a phenyl group, a benzyl group or a polyethylene glycol group.
A indicates a nitrogen atom or a phosphorus atom.
R represents a fluorine atom or an alkyl fluoride group;
_{^{R 7 4 A + X - (}} 3-2)
In the general formula (3-2), R ⁷ represents an alkyl group having one or more carbon atoms, a perfluoroalkyl group, a phenyl group, a benzyl group or a polyethylene glycol group.
A indicates a nitrogen atom or a phosphorus atom.
X represents a bis (trifluoromethanesulfonyl) amide, a bis (fluoromethanesulfonyl) amide or B (C ₆ F ₅ ) ₄ .
<2> The sugar represented by the general formula (1) and the sugar represented by the general formula (2) are mixed in the presence of an electrolyte represented by the general formula (3-1) and an electrolyte represented by the general formula (3-2). Including electrolytic oxidation reaction in an aprotic organic solvent
^{R 1} and R ² in the general formula (1) are not bonded to each other to form a ring.
Y ¹ is a benzyloxy group, a p-methoxybenzyloxy group, a p-methylbenzyloxy group, a methoxy group, a methoxymethyl group, a trimethylsiloxy group or an azido group.
In the general formula (2), Z ² represents an alkoxy group or an arylthio group, and R ⁴ and R ⁵ are not bonded to each other to form a ring.
In the general formula (3-1), R represents a trifluoromethyl group.
The method for producing a sugar according to <1>, wherein X in the general formula (3-2) represents a bis (trifluoromethanesulfonyl) amide or a bis (fluoromethanesulfonyl) amide.
<3> The electrolyte represented by the general formula (3-1) is tetrabutylammonium triflate, and the electrolytes represented by the general formula (3-2) are tetrabutylammonium bis (trifluoromethanesulfonyl) amide and tetrabutylammonium. The method for producing a sugar according to <1> or <2>, which is at least one of bis (fluoromethanesulfonyl) amides.
<4> The sugar represented by the general formula (1) and the sugar represented by the general formula (2) having a leaving group are aprotic in the presence of two or more electrolytes selected from the electrolytes represented by the general formula (3). A method for producing a stereoselective sugar, which comprises subjecting it to an electrolytic oxidation reaction in a sex organic solvent.

Here, in the formula (1), R ¹ and R ² represent a linear, branched, alkyl group or benzyl group having a cyclic structure, and R ³ is an alkyl group or benzyl group having no cyclic structure. , Y ¹ represents a benzyloxy group or an azido group, Z ¹ represents a desorption group selected from a tellroaryl group, a selenoaryl group, a thioaryl group or a thioethyl group, and m represents an integer of 1 or more.
Further, in the formula (2), R ⁴ and R ⁵ represent a hydrogen atom, a linear group, a branch, an alkyl group having a cyclic structure, an acetyl group and a benzyl group, and R ⁶ is an alkyl group having no cyclic structure. It represents an acetyl group and a benzyl group, Y ² represents a benzyloxy group, an azido group or a phthalimide group, Z ² represents an alkoxy group or an arylthio group, and n represents an integer of 1 or more.
_{^{R 7 4 A + X - (}} 3)
(In the formula (3), R ⁷ represents an alkyl group having one or more carbon atoms, a perfluoroalkyl group or a polyethylene glycol group, A represents a nitrogen atom and a phosphorus atom, and X represents a trifurate and a bis (trifluoromethanesulfonyl). ) Amides, bis (fluoromethanesulfonyl) amides.

<5> The method for producing a sugar according to any one of <1> to <4>, wherein either or both of the electrolyte and the aprotic organic solvent are ionic liquids.
<6> Among the produced sugars, a polysaccharide composed of the sugar represented by the general formula (1) and / or two or more sugars represented by the general formula (1), and the polysaccharide represented by the general formula (2). A sugar α in which a sugar and / or a polysaccharide composed of a polysaccharide represented by two or more general formulas (2) is α-bonded, and a sugar represented by the general formula (1) and / or two or more general formulas. A polysaccharide in which a polysaccharide composed of the sugar represented by (1) and a polysaccharide composed of the sugar represented by the general formula (2) and / or two or more sugars represented by the general formula (2) are β-bonded. [Amount of sugar β / (amount of sugar α + amount of sugar β)] × 100, which is the mass ratio of the sugar β to the total mass of β, is 85% or more, <1> to <5>. The method for producing a sugar according to any one of the above.
<7> The electrolyte represented by the general formula (3-1) and the electrolyte represented by the general formula (3-2) are used in a molar ratio of 1: 0.2 to 5.0, <1> to <. 6> The method for producing sugar according to any one of.
<8> Tetrabutylammonium triflate and at least one of tetrabutylammonium bis (trifluoromethanesulfonyl) amide and tetrabutylammonium bis (fluoromethanesulfonyl) amide are contained in a molar ratio of 1: 0.2 to 5.0. Electrolyte composition.
<9> The method for producing a sugar according to any one of <1> to <7>, which uses the electrolyte composition according to <8>.

The in <4>, the description of the general formula (1) to (3) (including the same reference numerals in the description of ¹ such as R) and the preferred ranges, etc., described later to the general formula (1) to (3) ( It is the same as (including the explanation of the code such as R ^{1) and the preferable range.} However, m and n are preferably integers of 1 to 3, and more preferably 1. Further, it is required that at least one of the two or more kinds of electrolytes selected from the electrolytes represented by the general formula (3) has triflate as a counter anion.

(B) The method according to (a), wherein either or both of the electrolyte and the aprotic organic solvent are further ionic liquids.

According to the present invention, it is possible to provide a sugar chain useful as a raw material for medical and agricultural chemicals, a raw material such as a lead compound, or a synthetic intermediate under mild conditions, which is safe, environmentally friendly, and at low cost.

Hereinafter, the contents of the present invention will be described in detail. In the specification of the present application, "~" is used to mean that the numerical values described before and after it are included as the lower limit value and the upper limit value.
In the present specification, Bu indicates a butyl group, TfO indicates a triflate, Bn indicates a benzyl group, Ac indicates an acetyl group, Phth indicates a phthalimide group, and MOM indicates a methoxymethyl group.

一般式（１）中、Ｒ¹およびＲ²は、それぞれ独立に、直鎖、分枝もしくは環状構造を有するアルキル基、ベンジル基、ｐ−メトキシベンジル基、ｐ−メチルベンジル基、アセチル基、トリメチルアセチル基、ベンゾイル基、トリメチルシリル基またはｔ−ブチルジメチルシリル基を示し、Ｒ¹およびＲ²は互いに結合して環を形成していてもよく、Ｒ³は、環状構造を有しないアルキル基、ベンジル基、ｐ−メトキシベンジル基、ｐ−メチルベンジル基、アセチル基、トリメチルアセチル基、ベンゾイル基、トリメチルシリル基またはｔ−ブチルジメチルシリル基を示し、Ｙ¹はフタルイミド基、ベンジルオキシ基、ｐ−メトキシベンジルオキシ基、ｐ−メチルベンジルオキシ基、アジド基、アセチルオキシ基、ベンゾイルオキシ基、メトキシ基、メトキシメチルオキシ基またはトリメチルシロキシ基を示し、Ｚ¹は、テルロアリール基、セレノアリール基、チオアリール基、チオメチル基、チオエチル基、チオオクチル基、チオノニル基およびチオデシル基から選ばれる脱離基を示す。

一般式（２）中、Ｒ⁴およびＲ⁵は、それぞれ独立に、水素原子、直鎖、分枝もしくは環状構造を有するアルキル基、アセチル基、ベンジル基、ｐ−メトキシベンジル基、ｐ−メチルベンジル基、トリメチルアセチル基、ベンゾイル基、トリメチルシリル基またはｔ−ブチルジメチルシリル基を示し、Ｒ⁴およびＲ⁵は互いに結合して環を形成していてもよく、Ｒ⁶は、水素原子、環状構造を有しないアルキル基、ベンジル基、ｐ−メトキシベンジル基、ｐ−メチルベンジル基、アセチル基、トリメチルアセチル基、ベンゾイル基、トリメチルシリル基またはｔ−ブチルジメチルシリル基を示し、Ｙ²はフタルイミド基、ベンジルオキシ基、ｐ−メトキシベンジルオキシ基、ｐ−メチルベンジルオキシ基、アジド基、アセチルオキシ基、ベンゾイルオキシ基、メトキシ基、メトキシメチル基またはトリメチルシロキシ基を示し、Ｚ²は反応性基を示す。
（Ｒ⁷）₄Ａ⁺ＯＳ（＝Ｏ）₂Ｒ^- （３−１）
一般式（３−１）中、Ｒ⁷は炭素数が１以上のアルキル基、パーフルオロアルキル基、フェニル基、ベンジル基またはポリエチレングリコール基を示し、Ａは、窒素原子またはリン原子を示し、Ｒは、フッ素原子またはフッ化アルキル基を表す。
Ｒ⁷ ₄Ａ⁺Ｘ^- （３−２）
一般式（３−２）中、Ｒ⁷は炭素数が１以上のアルキル基、パーフルオロアルキル基、フェニル基、ベンジル基またはポリエチレングリコール基を示し、Ａは、窒素原子またはリン原子を示し、Ｘは、ビス（トリフルオロメタンスルホニル）アミド、ビス（フルオロメタンスルホニル）アミドまたはＢ（Ｃ₆Ｆ₅）₄を示す。 The method for producing a sugar (sometimes referred to as "sugar chain") of the present invention comprises a sugar represented by the general formula (1) and / or a polysaccharide composed of two or more sugars represented by the general formula (1). The sugar represented by the general formula (2) and / or the polysaccharide composed of two or more sugars represented by the general formula (2) are combined with the electrolyte represented by the general formula (3-1) and the general formula (3-2). It is characterized by comprising an electrolytic oxidation reaction in an aprotic organic solvent in the presence of the indicated electrolyte.

In the general formula (1), R ¹ and R ² are independently linear, branched or cyclic structures such as an alkyl group, a benzyl group, a p-methoxybenzyl group, a p-methylbenzyl group, an acetyl group and a trimethyl. It represents an acetyl group, a benzoyl group, a trimethylsilyl group or a t-butyldimethylsilyl group, and R ¹ and R ² may be bonded to each other to form a ring, and R ³ is an alkyl group having no cyclic structure, benzyl. Group, p-methoxybenzyl group, p-methylbenzyl group, acetyl group, trimethylacetyl group, benzoyl group, trimethylsilyl group or t-butyldimethylsilyl group, Y ¹ is phthalimide group, benzyloxy group, p-methoxybenzyl Indicates an oxy group, a p-methylbenzyloxy group, an azido group, an acetyloxy group, a benzoyloxy group, a methoxy group, a methoxymethyloxy group or a trimethylsiloxy group, and Z ¹ is a tellroaryl group, a serenoaryl group, a thioaryl group or a thiomethyl group. Indicates a desorption group selected from a group, a thioethyl group, a thiooctyl group, a thiononyl group and a thiodecyl group.

In the general formula (2), R ⁴ and R ⁵ are independently hydrogen atom, linear, branched or cyclic group having an alkyl group, an acetyl group, a benzyl group, a p-methoxybenzyl group, and a p-methylbenzyl group, respectively. A group, a trimethylacetyl group, a benzoyl group, a trimethylsilyl group or a t-butyldimethylsilyl group, and R ⁴ and R ⁵ may be bonded to each other to form a ring, and R ⁶ has a hydrogen atom and a cyclic structure. It indicates an alkyl group, a benzyl group, a p-methoxybenzyl group, a p-methylbenzyl group, an acetyl group, a trimethylacetyl group, a benzoyl group, a trimethylsilyl group or a t-butyldimethylsilyl group, and Y ² is a phthalimide group or a benzyloxy group. Group, p-methoxybenzyloxy group, p-methylbenzyloxy group, azido group, acetyloxy group, benzoyloxy group, methoxy group, methoxymethyl group or trimethylsiloxy group, and Z ² indicates a reactive group.
_{^{(R 7) 4 A + OS}} (= O) 2 R - (3-1)
In the general formula (3-1), R ⁷ represents an alkyl group having one or more carbon atoms, a perfluoroalkyl group, a phenyl group, a benzyl group or a polyethylene glycol group, and A represents a nitrogen atom or a phosphorus atom, and R Represents a fluorine atom or an alkyl fluoride group.
_{^{R 7 4 A + X - (}} 3-2)
In the general formula (3-2), R ⁷ represents an alkyl group having one or more carbon atoms, a perfluoroalkyl group, a phenyl group, a benzyl group or a polyethylene glycol group, A represents a nitrogen atom or a phosphorus atom, and X Indicates a bis (trifluoromethanesulfonyl) amide, a bis (fluoromethanesulfonyl) amide or B (C ₆ F ₅ ) _4.

In the present invention, a sugar having a leaving group selected from a tellroaryl group, a selenoaryl group, a thioaryl group, a thioalkyl group and the like (preferably a sugar having a thioaryl group as a leaving group) is used as a specific two or more types of electrolytes. In the presence, it is electrochemically activated to promote the glycosylation reaction. With such a configuration, sugar having an excellent stereoselectivity can be obtained.
The reason for this is presumed, but in the present invention, a polysaccharide composed of the sugar represented by the general formula (1) and / or the sugar represented by two or more general formulas (1) (hereinafter referred to as "sugar (1)"). (May be), but it is thought to be based on the fact that it was stored in an anion-capped state. That is, in the conventional method, when the glycosylation reaction is allowed to proceed in a state where the amount of the _{electrolyte (for example, Bu 4 NOTf) represented by the general formula (3-1) is large, the sugar (1) is stored in a capped state.} The selectivity of the obtained sugar chain is lowered. _{On the other hand, if the concentration of the electrolyte (for example, Bu 4} NOTf) represented by the general formula (3-1) is lowered, the supporting electrolyte disappears as the capping progresses. In the present invention, the electrolyte represented by the general formula (3-1) (Bu ₄ NOTf, etc.) is used as the first type of supporting electrolyte, and the electrolyte represented by the general formula (3-2) is used in combination as the second type of supporting electrolyte. By doing so, it is presumed that the stereoselectivity was successfully improved.

Specifically, according to the method for producing a sugar of the present invention, among the produced sugars, the sugar is composed of the sugar represented by the general formula (1) and / or two or more sugars represented by the general formula (1). Polysaccharide (sugar (1)), sugar represented by the general formula (2) and / or polysaccharide composed of two or more sugars represented by the general formula (2) (hereinafter, may be referred to as "sugar (2)"). [Amount of sugar β / (amount of sugar β / ( Amount of sugar α + amount of sugar β)] × 100 can be 85% or more. The value of [amount of sugar β / (amount of sugar α + amount of sugar β)] × 100 can be further set to 88% or more and 90% or more.
In particular, it is highly valuable in that the above-mentioned high yield of sugar β can be achieved while the yield is 60% or more, further 65% or more, particularly 70% or more.
That is, in the present invention, a sugar α in which the sugar (1) and the sugar (2) are α-bonded, and a sugar β in which the sugar (1) and the sugar (2) are β-bonded are included, and the sugar α and the sugar α. Obtaining a composition in which [amount of sugar β / (amount of sugar α + amount of sugar β)] × 100, which is the mass ratio of sugar β to the total mass of sugar β, is 85% or more and less than 100%. Can be done.

<Sugar (1)>
The sugar represented by the general formula (1) used in the present invention will be described.
R ¹ and R ² independently represent an alkyl group, a benzyl group, an acetyl group, a trimethylacetyl group, a benzoyl group, a trimethylsilyl group or a t-butyldimethylsilyl group having a linear, branched or cyclic structure, respectively. R ¹ and R ² may be coupled to each other to form a ring.

Examples of R ¹ include alkyl groups having a linear, branched or cyclic structure (preferably methyl group, methoxymethyl group, methoxyethoxymethyl group, more preferably methyl group), benzyl group, p. -Methylbenzyl group, p-methylbenzyl group, acetyl group, trimethylacetyl group, benzoyl group, trimethylsilyl group, t-butyldimethylsilyl group, monosaccharide and oligosaccharide can be mentioned, and may be linear, branched or cyclic. Alkyl group, benzyl group, p-methoxybenzyl group, p-methylbenzyl group, acetyl group, trimethylacetyl group, benzoyl group, trimethylsilyl group or t-butyldimethylsilyl group having a structure are preferable, and linear, branched and cyclic. An alkyl group or a benzyl group having a structure is more preferable, and a benzyl group is further preferable.

Examples of R ² include an alkyl group having a linear, branched or cyclic structure (preferably a methyl group, a methoxymethyl group, a methoxyethoxymethyl group, more preferably a methyl group), a benzyl group, a p-methoxybenzyl group. , P-Methylbenzyl group, acetyl group, trimethylacetyl group, benzoyl group, trimethylsilyl group, t-butyldimethylsilyl group, monosaccharide and oligosaccharide, etc., and have a linear, branched or cyclic structure. Group, benzyl group, p-methoxybenzyl group, p-methylbenzyl group, acetyl group, trimethylacetyl group, benzoyl group, trimethylsilyl group or t-butyldimethylsilyl group are preferable, and alkyl having a linear, branched and cyclic structure. A group or a benzyl group is more preferable, and a benzyl group is further preferable.

Further, R ¹ and R ² may be coupled to each other to form a ring. Specifically, a benzylidene group is exemplified as a specific example in which ^{R 1} and R ^{2 are bonded to each other to form a ring. An example is an example in which one} of R 1 and R ² is an alkyl group and the other is a benzyl group, which are ring-bonded to each other to form a ring. An embodiment in which R ¹ and R ² are bonded to form a benzylidene group is shown below.

Examples of R ³ include an alkyl group having no cyclic structure (preferably a methyl group, a methoxymethyl group, a methoxyethoxymethyl group, more preferably a methyl group), a benzyl group, a p-methoxybenzyl group, and a p-methylbenzyl group. Examples include groups, acetyl groups, trimethylacetyl groups, benzoyl groups, trimethylsilyl groups, t-butyldimethylsilyl groups, monosaccharides and oligosaccharides, and alkyl groups, benzyl groups and p-methoxybenzyl groups having no cyclic structure. , P-Methylbenzyl group, acetyl group, trimethylacetyl group, benzoyl group, trimethylsilyl group or t-butyldimethylsilyl group, more preferably alkyl group or benzyl group having no cyclic structure, and further benzyl group. preferable.
Here, the alkyl group having no cyclic structure means a linear or branched alkyl group.
In the present invention, ^{among R 1 to} R ³ , R ² may contain a substituent different from R ¹ and R ^3. With such a configuration, sugar α and sugar β can be more easily separated when separated by a column or the like.

Y ¹ represents a phthalimide group, a benzyloxy group, a p-methoxybenzyloxy group, a p-methylbenzyloxy group, an azido group, an acetyloxy group, a benzoyloxy group, a methoxy group, a methoxymethyloxy group or a trimethylsiloxy group, and phthalimide. Group, benzyloxy group, p-methoxybenzyloxy group, p-methylbenzyloxy group, azido group, acetyloxy group, benzoyloxy group, methoxy group, or trimethylsiloxy group are preferable, and benzyloxy group and p-methoxybenzyloxy group are preferable. A group, a p-methylbenzyloxy group, a methoxy group, a methoxymethyl group, a trimethylsiloxy group or an azido group is more preferable, and a benzyloxy group or an azido group is further preferable.

Z ¹ is a tellroaryl group, a selenoaryl group, a thioaryl group (eg, thiophenyl group, thiop-methoxyphenyl group, thiop-methylphenyl group, thiop-fluorophenyl group, thioo or p-difluorophenyl group). It represents a desorbing group selected from a thioalkyl group (eg, thiomethyl group, thioethyl group, thiooctyl group, thiononyl group and thiodecyl group), preferably a tellroaryl group, a selenoaryl group, a thioaryl group or a thioalkyl group, preferably a thioaryl group or a thiomethyl group. More preferably, a thioaryl group is even more preferred, and a thiop-fluorophenyl group is even more preferred.

一般式（１−１）におけるＲ¹、Ｒ²、Ｒ³、Ｙ¹およびＺ¹は、それぞれ、一般式（１）におけるＲ¹、Ｒ²、Ｒ³、Ｙ¹およびＺ¹と同義である。
糖は３糖以上であってもよい。
また、糖同士の結合様式として、６位や３位で結合している糖であってもよい。 The polysaccharide composed of two or more sugars represented by the general formula (1) means a polysaccharide formed by reacting the monosaccharides represented by the general formula (1) with each other, and for example, the following general formula (1-1). ) Is exemplified.
General formula (1-1)

^{R 1, R 2, R 3} , Y 1 and Z ¹ in the general formula (1-1), respectively, the same meanings as ^{R 1, R 2, R 3} , Y 1 and Z ¹ in the general formula (1) ..
The sugar may be 3 or more sugars.
Further, as the bonding mode between sugars, sugars bonded at the 6-position or the 3-position may be used.

In the general formula (1), when a plurality of R ¹ , R ² , R ³ , and Y ¹ exist, the respective R ¹ , R ² , R ³ , and Y ¹ may be the same or different. However, it is preferable that they are the same.

As the sugar (1) preferably used in the present invention, R ¹ , R ² and R ³ are all benzyl groups, Y ¹ is a benzyloxy group or an azide group, and Z ¹ is a thiop-fluorophenyl group.

Only one type of sugar (1) may be used, or two or more types may be used, but only one type is preferable.

<Sugar (2)>
The sugar represented by the general formula (2) used in the present invention will be described.
R ⁴ and R ⁵ are independently hydrogen atom, linear, branched or cyclic structure alkyl group, acetyl group, benzyl group, p-methoxybenzyl group, p-methylbenzyl group, trimethylacetyl group, benzoyl. A group, a trimethylsilyl group or a t-butyldimethylsilyl group is shown. R ⁴ and R ⁵ may be coupled to each other to form a ring.

Examples of R ⁴ are hydrogen atoms, linear, branched or cyclic groups having an alkyl group (preferably a methyl group, a methoxymethyl group, a methoxyethoxymethyl group, more preferably a methyl group), an acetyl group, a benzyl group. , P-methoxybenzyl group, p-methylbenzyl group, trimethylacetyl group, benzoyl group, trimethylsilyl group or t-butyldimethylsilyl group, hydrogen atom, linear, branched or cyclic structure alkyl group, acetyl. A group or a benzyl group is preferable, and a benzyl group is more preferable.

Examples of R ⁵ are hydrogen atoms, linear, branched or cyclically structured alkyl groups (preferably methyl groups, methoxymethyl groups, methoxyethoxymethyl groups, more preferably methyl groups), acetyl groups, benzyl groups. , P-methoxybenzyl group, p-methylbenzyl group, trimethylacetyl group, benzoyl group, trimethylsilyl group or t-butyldimethylsilyl group, hydrogen atom, linear, branched, alkyl group having cyclic structure, acetyl group. Alternatively, a benzyl group is preferable, and a hydrogen atom is more preferable.

Further, R ⁴ and R ⁵ may be coupled to each other to form a ring. Specifically, a benzylidene group is exemplified as a specific example in which ^{R 4} and R ^{5 are bonded to each other to form a ring.} An example is an example in which one of R ⁴ and R ⁵ is an alkyl group and the other is a benzyl group, which are ring-bonded to each other to form a ring.

R ⁶ is a hydrogen atom, an alkyl group having no cyclic structure (preferably a methyl group, a methoxymethyl group, a methoxyethoxymethyl group, more preferably a methyl group), a benzyl group, a p-methoxybenzyl group, or a p-methylbenzyl group. A group, an acetyl group, a trimethylacetyl group, a benzoyl group, a trimethylsilyl group or a t-butyldimethylsilyl group, and an alkyl group, an acetyl group or a benzyl group having no cyclic structure is preferable, and an acetyl group is more preferable.

Y ² includes a phthalimide group, a benzyloxy group, a p-methoxybenzyloxy group, a p-methylbenzyloxy group, an azido group, an acetyloxy group, a benzoyloxy group, a methoxy group, a methoxymethyloxy group or a trimethylsiloxy group, respectively. It can be a phthalimide group, a benzyloxy group, a p-methoxybenzyloxy group, a p-methylbenzyloxy group, an azido group, an acetyloxy group, a benzoyloxy group, a methoxy group or a trimethylsiloxy group, preferably a benzyloxy group, an azide. Groups or phthalimide groups are more preferred, and phthalimide groups are even more preferred.

Z ² represents a reactive group, an alkoxy group (eg, methoxy group, octyloxy group) or arylthio group (thiop-methylphenyl group, thiop-fluorophenyl group, thiophenyl group), thioethyl group, monosaccharide and oligo. Examples include sugars, such as an alkoxy group, an arylthio group or a thioethyl group, more preferably an alkoxy group or an arylthio group, further preferably an arylthio group, and even more preferably a thiop-fluorophenyl group. In the present invention, although Z ² is a reactive group, it is highly valuable in that a sugar chain can be synthesized without being protected by a protecting group as it is.

一般式（２−１）におけるＲ⁴、Ｒ⁵、Ｒ⁶、Ｙ²およびＺ²は、それぞれ、一般式（２）におけるＲ⁴、Ｒ⁵、Ｒ⁶、Ｙ²およびＺ²と同義である。
糖は３糖以上であってもよい。
また、糖同士の結合様式として、６位や３位で結合している糖であってもよい。 The polysaccharide composed of two or more sugars represented by the general formula (2) refers to a polysaccharide formed by reacting the monosaccharides represented by the general formula (2), for example, the following general formula (2-1). ) Is exemplified.
General formula (2-1)

^{R 4, R 5, R 6} , Y 2 and Z ² in the general formula (2-1), respectively, the same meanings as ^{R 4, R 5, R 6} , Y 2 and Z ² in the general formula (2) ..
The sugar may be 3 or more sugars.
Further, as the bonding mode between sugars, sugars bonded at the 6-position or the 3-position may be used.

In the general formula (2), when a plurality of R ⁴ , R ⁵ , R ⁶ , and Y ² exist, the respective R ⁴ , R ⁵ , R ⁶ , and Y ² may be the same or different. However, it is preferable that they are the same.

As the sugar (2) preferably used in the present invention, R ⁴ is a benzyl group, R ⁵ is a hydrogen atom, R ⁶ is an acetyl group, Y ² is a phthalimide group, and Z ² is a thiop-fluorophenyl group. ..

Only one type of sugar (2) may be used, or two or more types may be used, but only one type is preferable.

<Electrolyte represented by general formula (3-1)>
R ⁷ represents an alkyl group having one or more carbon atoms (which may be an alkyl group having a linear, branched or cyclic structure), a perfluoroalkyl group, a phenyl group, a benzyl group or a polyethylene glycol group. Alkyl groups having 1 or more carbon atoms, perfluoroalkyl groups, or polyethylene glycol groups are preferable, alkyl groups having 1 to 8 carbon atoms are more preferable, and methyl groups, ethyl groups, propyl groups, butyl groups, pentyl groups, and hexyls. Groups, cyclohexyl groups, methoxymethyl groups, 2-methoxyethoxymethyl groups or nonafluorobutyl groups are more preferred, and butyl groups are even more preferred.
^{R 7} in the general formula (3-1) may be the same or different. It is preferably the same.
A represents a nitrogen atom or a phosphorus atom, and a nitrogen atom is preferable.

R represents a fluorine atom or an alkyl fluoride group, preferably a fluorine atom or a trifluoromethyl group, and more preferably a trifluoromethyl group.

As the electrolyte represented by the general formula (3-1), it is particularly preferable that R ⁷ is a butyl group, A is a nitrogen atom, and R is a trifluoromethyl group.
Only one type of electrolyte represented by the general formula (3-1) may be used, or two or more types may be used, but only one type is preferable.

<Electrolyte represented by general formula (3-2)>
R ⁷ represents an alkyl group having one or more carbon atoms (which may be an alkyl group having a linear, branched or cyclic structure), a perfluoroalkyl group, a phenyl group, a benzyl group or a polyethylene glycol group. Alkyl groups having 1 or more carbon atoms, perfluoroalkyl groups, or polyethylene glycol groups are preferable, alkyl groups having 1 to 8 carbon atoms are more preferable, and methyl groups, ethyl groups, propyl groups, butyl groups, pentyl groups, and hexyls. Groups, cyclohexyl groups, methoxymethyl groups, 2-methoxyethoxymethyl groups or nonafluorobutyl groups are more preferred, and butyl groups are even more preferred.
A represents a nitrogen atom or a phosphorus atom, and a nitrogen atom is preferable.
X represents a bis (trifluoromethanesulfonyl) amide, a bis (fluoromethanesulfonyl) amide or B (C ₆ F ₅ ) _4, with a preferred bis (trifluoromethanesulfonyl) amide or bis (fluoromethanesulfonyl) amide.

As the electrolyte represented by the general formula (3-2), it is particularly preferable that R ⁷ is a butyl group, A is a nitrogen atom, and R is a bis (trifluoromethanesulfonyl) amide or a bis (fluoromethanesulfonyl) amide. ..
Only one type of electrolyte represented by the general formula (3-2) may be used, or two or more types may be used, but only one type is preferable.

In the present invention, it is preferable that the electrolyte represented by the general formula (3-1) has a stronger nucleophilicity than the electrolyte represented by the general formula (3-2).

In the present invention, the molar ratio of the sugar (2) to the sugar (1) to be administered to the reaction system during production is preferably 1: 1 to 1-3, preferably 1: 1 to 1: 1.2. Is more preferable.
The molar ratio of the electrolyte represented by the general formula (3-1) to the sugar (1) to be administered to the reaction system during production is preferably 1: 1 to 1-3, preferably 1: 1 to 1.2. It is more preferable to have.
Further, the molar ratio of the electrolyte represented by the general formula (3-2) to the electrolyte represented by the general formula (3-1) to be administered to the reaction system during production is preferably 1: 0.2 to 5.0. , 1: 0.2 to 3.5, more preferably 1: 0.3 to 3.1.

In the conventional chemical glycosylation method, an acetyloxy group or a benzoyloxy group is used as a substituent ^{of Y 1} of the sugar (1) because it is easy to control the steric chemistry by the involvement of an adjacent group, and the steric chemistry can be controlled. The use of benzyloxy groups and azido groups as substituents ^{for Y 1} has been avoided because of the absence. The present invention is a stereoselective method for synthesizing a sugar chain using a sugar having a benzyloxy group or an azide group, which is easy to introduce and remove as a substituent of ^{Y 1, unlike the conventional method.}

Since the method of the present invention carries out an electrochemical glycosylation reaction, safety during work is ensured, and there is almost no generation of hazardous waste such as metal oxidant residue, and other safety and environmental aspects. At the same time, it is an advantageous method in terms of cost, which is regarded as important as an industrial production method.

The method of the present invention is most suitable for one-pot synthesis of sterically selective sugar chains using a liquid phase electrolytic automatic synthesis system, but it is a manual that isolates and purifies at each stage of sugar chain elongation by glycosylation reaction. It does not prevent the application of sugar chains to the synthetic process in Japan.

The present invention also comprises tetrabutylammonium triflate and at least one of the tetrabutylammonium bis (trifluoromethanesulfonyl) amide and the tetrabutylammonium bis (fluoromethanesulfonyl) amide 1: 0.2 to 5.0 (preferably). Discloses an electrolyte composition comprising a molar ratio of 1: 0.2 to 3.5, more preferably 1: 0.3 to 3.1). In such an electrolyte composition, [amount of sugar β / (amount of sugar α + amount of sugar β)] × 100, which is the mass ratio of sugar β to the total mass of sugar α and sugar β, is 85. It is preferably used for producing a composition having a percentage of% or more and less than 100%.

Hereinafter, the present invention will be further described with reference to examples, but the present invention is not limited to such examples.

<Example 1>

A carbon fiber (after time-heating and carbonization treatment) was attached to the H-type separable electrolytic cell as an anode, and a platinum plate (10 mm × 20 mm, gas burner heat-treated) was attached as a cathode, dried under reduced pressure, and then substituted with argon. Electrolyte Bu ₄ NOTf (0.25 mg, 98 mg), Bu ₄ NNTf ₂ (392 mg, 0.75 mmol) and sugar (1a) (146 mg, 0.25 mmol) are added to the anode side, and electrolyte Bu ₄ NNTf is added to the cathode side. _{After adding 2} (1.0 mmol, 523 mg), a solvent (dichloromethane, 10 mL) was added to both poles. Further, Tf ₂ NH (70 mg, 0.25 mmol) was added to the cathode, and then the electrolytic cell was cooled in a low temperature bath set at −80 ° C. and stirred. After 10 minutes, energization (8.0 mA) was started, and energization was performed for 50 minutes and 10 seconds so as to reach 1.0 F / mol. After the energization was completed, a solution (1.0 mL) of sugar (2a) (165 mg, 0.30 mmol) was added (1.0 mL / min) from a syringe pump. Then, the temperature was raised to −60 ° C., the temperature was maintained at −60 ° C. for 1 hour, and then triethylamine (0.40 mL) was added to terminate the reaction. After stirring at the same temperature for about 10 minutes, pull up the electrolytic cell from the low temperature bath, confirm that it has returned to room temperature, transfer the reaction solution of both poles to the eggplant flask, distill off the solvent with an evaporator, and then short-circuit. It was passed through a column (silica; the solvent used was a mixture of hexane / ethyl acetate (EtOAc) (volume ratio: 2: 1)). The solvent was distilled off with an evaporator, and the mixture was further vacuum dried to obtain a disaccharide (3a). From the comparison with the internal standard substance peak (tetrachloroethane: 0.25 mmol, 41.9 mg) in NMR, the NMR yield of (3a) was found to be 69% (0.17 mmol), and the α / β ratio was 5:95. ..

. TLC (hexane / EtOAc 5: 2): R f 0.35 1 H NMR (CDCl 3, 600 MHz) chemical shift values 7.88 - 7.83 (m, 2 H ), 7.76 - 7.72 (m, 2 H), 7.43 (dd , J = 8.4, 5.4 Hz, 2 H), 7.39 --7.22 (m, 18 H), 7.15 --7.11 (m, 2 H), 6.92 (pseudo-t, J = 9.0 Hz, 2 H), 5.73 (dd) , J = 10.2, 9.6 Hz, 1 H), 5.63 (d, J = 10.8 Hz, 1 H), 4.83 (d, J = 10.8 Hz, 1 H), 4.78 (d, J = 10.8 Hz, 1 H) , 4.74 (d, J = 10.8 Hz, 1 H), 4.68 (d, J = 11.4 Hz, 1 H), 4.56 (d, J = 12.0 Hz, 1 H), 4.49 (d, J = 10.8 Hz, 1 H), 4.44 (d, J = 11.4 Hz, 1 H), 4.38 (d, J = 12.0 Hz, 1 H), 4.25 (pseudo-t, J = 10.2 Hz, 1 H), 4.23 --4.22 (m, 1 H), 4.02 (pseudo-t, J = 9.6 Hz, 1 H), 3.97 (dd, J = 11.4, 3.6 Hz, 1 H), 3.87 (dd, J = 10.8, 1.2 Hz, 1 H), 3.77 (ddd, J = 9.6, 3.0, 1.2 Hz, 1 H), 3.69 --3.61 (m, 3 H), 3.30 --3.26 (m, 2 H), 3.19 (dt, J = 9.6, 2.4 Hz, 1 H) , 1.80 (s, 3 H). ¹³ C NMR (CDCl ₃ , 150 MHz) Chemical shift value 170.5, 167.8, 167.2, 163.0 (d, J = 247.4 Hz), 137.98, 137.96, 137.91, 136.1 (d, J = 8.6 Hz), 134.4, 134.1, 131.7, 131.2, 128.5, 128.38, 128.36, 127.80, 127.76, 127.73, 127.71, 127.69, 127.65, 127.63, 125.9 (d, J = 3.0 Hz), 123.69, 123.49, 123.69, 123.49, 115.9 (d, J = 21.9 Hz), 101.2, 83.3, 82.8, 79.0, 75.3, 75.1, 74.8, 74.5, 73.3, 73.1, 71.5, 68.4, 68.0, 66.4, 53.8, 20.4. HRMS (ESI) m / z calcd for C ₅₆ H ₅₃ FKN ₄ O ₁₁ S [M + K] ⁺ , 1047.3047; found, 1047.3046.

<Example 2>

A carbon fiber (after time-heating and carbonization treatment) was attached to the H-type separable electrolytic cell as an anode, and a platinum plate (10 mm × 20 mm, gas burner heat-treated) was attached as a cathode, dried under reduced pressure, and then substituted with argon. Electrolyte Bu ₄ NOTf (157 mg, 0.40 mmol), Bu ₄ NNTf ₂ (610 mg, 1.2 mmol) and sugar (1b) (260 mg, 0.40 mmol) are added to the anode side, and electrolyte Bu ₄ NNTf is added to the cathode side. _{After adding 2} (1.6 mmol, 814 mg), a solvent (dichloromethane, 16 mL) was added to both poles. Further, Tf ₂ NH (112 mg, 0.40 mmol) was added to the cathode, and then the electrolytic cell was cooled in a low temperature bath set at −80 ° C. and stirred. After 10 minutes, energization (16.0 mA) was started, and energization was performed for 42 minutes and 13 seconds so as to reach 1.0 F / mol. After the energization was completed, a solution (1.0 mL) of sugar (2a) (265 mg, 0.48 mmol) was added (1.0 mL / min) from a syringe pump. Then, the temperature was raised to −60 ° C., the temperature was maintained at −60 ° C. for 1 hour, and then triethylamine (0.60 mL) was added to terminate the reaction. After stirring at the same temperature for about 10 minutes, pull up the electrolytic cell from the low temperature bath, confirm that it has returned to room temperature, transfer the reaction solution of both poles to the eggplant flask, distill off the solvent with an evaporator, and then short-circuit. It was passed through a column (mixture of silica gel, solvent Hexane / EtOAc (volume ratio: 2: 1)). The solvent was distilled off with an evaporator, and the mixture was further vacuum dried to obtain a disaccharide (3b). From the comparison with the internal standard substance peak (tetrachloroethane: 0.40 mmol, 67.1 mg) in NMR, the NMR yield of (3b) was determined to be 64% (0.26 mmol), and the α / β ratio was 2:98.

. TLC (hexane / EtOAc 5: 2): R f 0.35 1 H NMR (CDCl 3, 600 MHz) chemical shift values 7.88 - 7.85 (m, 2 H ), 7.76 - 7.74 (m, 2 H), 7.43 - 7.40 (m, 2 H), 7.35 --7.25 (m, 20 H), 7.13 --7.12 (m, 2 H), 6.89 (pseudo-t, J = 8.4 Hz, 2 H), 5.73 (pseudo-t, J = 9.6 Hz, 1 H), 5.60 (d, J = 10.8 Hz, 1 H), 4.88 (d, J = 10.8 Hz, 1 H), 4.782 (d, J = 11.4 Hz, 1 H), 4.777 (d, J = 11.4 Hz, 1 H), 4.77 (d, J = 10.8 Hz, 1 H), 4.69 (d, J = 11.4 Hz, 1 H), 4.53 --4.40 (m, 6 H), 4.35 (d, J) = 8.4 Hz, 1 H), 4.25 (pseudo-t, J = 10.2 Hz, 1 H), 3.96 (pseudo-t, J = 10.2 Hz, 1 H), 3.82 (dd, J = 10.8, 7.2 Hz, 1 H), 3.71 (d, J = 9.6 Hz, 2 H), 3.69 (dd, J = 10.8, 4.8 Hz, 1 H), 3.64 (pseudo-t, J = 9.6 Hz, 2 H), 3.51 (pseudo- t, J = 9.0 Hz, 2 H), 3.32 --3.26 (m, 2 H). ¹³ C NMR (CDCl ₃ , 150 MHz) Chemical shift value 170.7, 167.9, 167.2, 163.0 (d, J = 247.2 Hz), 138.6, 138.3, 138.2, 138.1, 137.7, 136.0 (d, J = 8.3 Hz), 134.3, 134.1, 131.7, 131.2, 128.36, 128.33, 128.30, 127.78, 127.75, 127.63, 127.57, 127.54, 127.48, 126.0, 123.7, 123.5, 115.9 (d, J = 21.6 Hz) ), 102.8, 84.8, 82.8, 82.4, 79.3, 77.5, 75.4, 75.1, 75.0, 74.8, 74.3, 73.14, 73.09, 71.5, 68.7, 67.8, 53.7, 20.4. HRMS (ESI) m / z calcd for C ₆₃ H ₆₀ FNO ₁₂ S [M + Na] +, 1096.3712; found, 1096.3716.

<Comparative Example 1>
_{In Example 1, Bu 4} NOTf (1.0 mmol) was used as the electrolytes on the anode side and the cathode side, and the others were carried out in the same manner. The NMR yield was found to be 79%, and the α / β ratio was found to be 16:84.

<Comparative Example 2>
_{In Example 1, Bu 4} NNTf ₂ (1.0 mmol) was used as the electrolytes on the anode side and the cathode side, and the others were carried out in the same manner. The NMR yield was determined to be 35%, and the α / β ratio was determined to be 28:72.

<Example 3>
In Example 1, Bu ₄ NOTf (0.75 mmol) and Bu ₄ NNTf ₂ (0.25 mmol) were used as the anode side electrolyte, and Bu ₄ NNTf ₂ (1.0 mmol) was used as the cathode side electrolyte. Others went in the same way. The NMR yield was determined to be 76%, and the α / β ratio was determined to be 10:90.

<Example 4>
In Example 1, Bu ₄ NOTf (0.5 mmol) and Bu ₄ NNTf ₂ (0.5 mmol) were used as the anode side electrolyte, and Bu ₄ NNTf ₂ (1.0 mmol) was used as the cathode side electrolyte. Others went in the same way. The NMR yield was determined to be 76%, and the α / β ratio was determined to be 6:94.

<Example 5>
In Example 1, Bu ₄ NOTf (0.25 mmol) and Bu ₄ NN (SO ₂ F) ₂ (0.75 mmol) were used as the anode side electrolyte, and Bu ₄ NN (SO ₂ F) was used as the cathode side electrolyte. ) ₂ (1.0 mmol) was used, and the others were carried out in the same manner. The NMR yield was determined to be 69%, and the α / β ratio was determined to be 5:95.

<Example 6>
In Example 1, as an electrolyte on the anode side, with Bu ₄ NOTf (0.25mmol) and _{Bu 4 NB (C 6 F 5} ) 4 (0.75mmol), as an electrolyte on the cathode side, Bu ₄ NB (C ₆ F ₅ ) ₄ (1.0 mmol) was used, and the others were carried out in the same manner. The NMR yield was determined to be 65%, and the α / β ratio was determined to be 4:96.

実施例１において、糖（２ａ）（０．１７ｍｍｏｌ）を、上記糖（７）（０．２０ｍｍｏｌ）に変更し、他は同様に行った。ＮＭＲ収率は６７％、α／β比は５：９５と求まった。 <Example 7>

In Example 1, the sugar (2a) (0.17 mmol) was changed to the above sugar (7) (0.20 mmol), and the others were carried out in the same manner. The NMR yield was found to be 67%, and the α / β ratio was determined to be 5:95.

. TLC (Hexane / EtOAc 1: 1): R f 0.65 1 H NMR (CDCl 3, 600 MHz) chemical shift values 7.88 - 7.78 (m, 4 H ), 7.74 - 7.66 (m, 4 H), 7.37 - 7.21 (m, 24 H), 7.12 (dd, J = 7.8, 2.4 Hz, 2 H), 6.84 (pseudo-t, J = 9.0 Hz, 2 H), 5.68 (pseudo-t, J = 10.2 Hz, 1 H) ), 5.65 (pseudo-t, J = 10.8 Hz, 1 H), 5.51 (d, J = 10.2 Hz, 1 H), 5.43 (d, J = 8.4 Hz, 1 H), 4.80 (d, J = 10.8) Hz, 1 H), 4.76 (d, J = 10.8 Hz, 1 H), 4.72 (d, J = 11.4 Hz, 1 H), 4.58 (d, J = 12.0 Hz, 1 H), 4.49 (d, J) = 11.4 Hz, 1 H), 4.46 (d, J = 12.0 Hz, 1 H), 4.44 (d, J = 12.0 Hz, 1 H), 4.43 (d, J = 11.4 Hz, 1 H), 4.38 (d) , J = 12.0 Hz, 1 H), 4.37 (d, J = 11.4 Hz, 1 H), 4.19 (pseudo-t, J = 10.2 Hz, 1 H), 4.16 (d, J = 8.4 Hz, 1 H) , 4.13 (dd, J = 10.2, 9.0 Hz, 1 H), 4.07 (pseudo-t, J = 9.6 Hz, 1 H), 4.04 (pseudo-t, J = 9.6 Hz, 1 H), 3.86 (dd, J = 10.8, 2.4 Hz, 1 H), 3.73 (d, J = 9.6 Hz, 1 H), 3.67 --3.62 (m, 2 H), 3.60 (pseudo-t, J = 9.6 Hz, 1 H), 3.56 (d, J = 10.2 Hz, 1 H), 3.52 (ddd, J = 9.6, 4.2, 1.2 Hz, 1 H), 3.49 --3.43 (m, 2 H), 3.24 (dd, J = 9.6, 7.8 H) z, 1 H), 3.18 (pseudo-t, J = 9.6 Hz, 1 H), 3.05 (dt, J = 9.6, 2.4 Hz, 1 H), 1.84 (s, 3 H), 1.77 (s, 3 H) ). ¹³ C NMR (CDCl ₃ , 150 MHz) Chemical shift values 170.6, 170.2, 167.8, 167.2, 163.0 (d, J = 247.4 Hz), 138.2, 138.0, 137.9, 137.7, 137.5, 136.0 (d, J = 8.4) Hz), 134.4, 134.1, 131.7, 131.2, 128.5, 128.40, 128.36, 128.3, 127.83, 127.78, 127.7, 127.65, 127.59, 127.5, 127.4, 125.8, 123.7, 123.5, 115.9 (d, J = 21.8 Hz), 83.2 , 82.6, 78.5, 75.3, 74.9, 74.7, 74.3, 73.7, 73.1, 73.0, 72.7, 72.1, 70.4, 68.4, 67.9, 67.5, 66.3, 55.2, 53.8, 20.5, 20.3.
HRMS (ESI) m / z calcd for C ₇₉ H ₇₄ FN ₅ NaO ₁₈ S [M + Na] ⁺ , 1454.4623; found, 1454.4638.

実施例１において、糖（１ａ）を、上記糖（１ｃ）（０．４ｍｍｏｌ）に変更し、他は同様に行った。ＮＭＲ収率は６０％、α／β比は９：９１と求まった。 <Example 8>

In Example 1, the sugar (1a) was changed to the above sugar (1c) (0.4 mmol), and the others were carried out in the same manner. The NMR yield was determined to be 60%, and the α / β ratio was determined to be 9:91.

. TLC (Hexane / EtOAc 2: 1): R f 0.30 1 H NMR (CDCl 3, 600 MHz) chemical shift values 7.87 - 7.84 (m, 2 H ), 7.75 - 7.72 (m, 2 H), 7.44 - 7.24 (m, 17 H), 6.92 (pseudo-t, J = 9.0 Hz, 2 H), 5.72 (dd, J = 10.2, 9.0 Hz, 1 H), 5.63 (d, J = 10.2 Hz, 1 H), 4.82 (d, J = 10.8 Hz, 1 H), 4.73 (d, J = 6.0 Hz, 1 H), 4.71 (d, J = 10.8 Hz, 1 H), 4.60 (d, J = 6.0 Hz, 1 H) ), 4.56 (d, J = 12.0 Hz, 1 H), 4.48 (d, J = 12.0 Hz, 1 H), 4.40 (d, J = 12.0 Hz, 1 H), 4.26 (pseudo-t, J = 10.2) Hz, 1 H), 4.23 (d, J = 8.4 Hz, 1 H), 4.02 (pseudo-t, J = 9.0 Hz, 1 H), 3.97 (dd, J = 10.8, 3.0 Hz, 1 H), 3.87 (d, J = 10.8 Hz, 1 H), 3.77 (ddd, J = 10.2, 3.0, 1.8 Hz, 1 H), 3.73 (dd, J = 10.8, 1.8 Hz, 1 H), 3.60 (dd, J = 10.8, 5.6 Hz, 1 H), 3.56 (pseudo-t, J = 9.0 Hz, 2 H), 3.28 --3.21 (m, 4 H), 3.20 --3.17 (m, 2 H), 1.78 (s, 3 H) ). ¹³ C NMR (CDCl ₃ , 150 MHz) Chemical shift values 170.5, 167.8, 167.2, 163.0 (d, J = 247.2 Hz), 138.0, 137.8, 137.7, 136.0 (d, J = 8.1 Hz), 134.4, 134.2 , 131.7, 131.2, 128.5, 128.41, 128.36, 127.84, 127.82, 127.7, 127.6, 126.0 (d, J) = 3.3 Hz), 123.7, 123.5, 115.9 (d, J = 21.8 Hz), 101.0, 98.3, 83.0, 82.9, 78.9, 75.7, 75.2, 75.0, 74.3, 73.4, 73.1, 71.4, 68.7, 67.9, 66.2, 56.4 , 53.8, 20.4. HRMS (ESI) m / z calcd for C ₅₁ H ₅₁ FN ₄ NaO ₁₂ S [M + Na] ⁺ , 985.3100; found, 985.3096.

実施例１において、糖（１ａ）を、上記糖（５）（０．１０ｍｍｏｌ）に変更し、糖（２ａ）を上記糖（４）（０．１２ｍｍｏｌ）に変更し、他は同様に行った。ＮＭＲ収率は４７％、α／β比は１：９９と求まった。 <Example 9>

In Example 1, the sugar (1a) was changed to the above sugar (5) (0.10 mmol), the sugar (2a) was changed to the above sugar (4) (0.12 mmol), and the others were carried out in the same manner. .. The NMR yield was found to be 47%, and the α / β ratio was found to be 1:99.

TLC (hexane / EtOAc 1: 1): R _f 0.20. ¹ H NMR (CDCl ₃ , 600 MHz) Chemical shift value 7.91 --7.88 (m, 2 H), 7.84 --7.81 (m, 2 H), 7.79 --7.77 (m, 4 H), 7.74 --7.70 (m, 2 H), 7.38 (dd, J = 8.4, 5.4 Hz, 2 H), 7.35 (d, J = 7.2 Hz, 2 H), 7.31 --7.23 (m) , 3 H), 7.22 (d, J = 7.2 Hz, 2 H), 7.19-7.16 (m, 4 H), 7.14-7.11 (m, 3 H), 7.08 (pseudo-t, J = 7.8 Hz, 2 H), 6.94 (pseudo-t, J = 7.2 Hz, 1 H), 6.92-6.87 (m, 4 H), 6.66 (pseudo-t, J = 7.2 Hz, 1 H), 5.64 (pseudo-t, J) = 9.0 Hz, 2 H), 5.57 (dd, J = 10.8, 9.0 Hz, 1 H), 5.56 (d, J = 10.8 z, 1 H), 5.39 (d, J = 8.4 Hz, 1 H), 5.19 (d, J = 8.4 Hz, 1 H), 5.08 (pseudo-t, J = 9.0 Hz, 1 H), 4.93 (d, J = 11.4 Hz, 1 H), 4.64 (d, J = 11.4 Hz, 1) H), 4.60 (d, J = 12.0 Hz, 1 H), 4.43 (d, J = 12.0 Hz, 1 H), 4.39 (d, J = 12.0 Hz, 1 H), 4.38 --4.35 (m, 2 H) ), 4.32 (d, J = 12.0 Hz, 2 H), 4.28 (d, J = 10.8 Hz, 1 H), 4.16 (pseudo-t, J = 10.2 Hz, 1 H), 4.155 (dd, J = 10.8) , 8.4 Hz, 1 H), 4.147 (pseudo-t, J = 9.0 Hz, 1 H), 4.12 (pseudo-t, J = 9.0 Hz, 1 H), 4.01 (pseudo-t, J = 9.6 Hz, 1 H), 3.91 --3.39 (m, 2 H), 3.86 (dd, J = 10.8, 3.0 Hz, 1 H), 3.83 (pseudo-t, J = 9.0 Hz, 1 H), 3.79 (d, J = 10.2 Hz, 1) H), 3.67 (d, J = 10.2 Hz, 1 H), 3.47 (d, J = 10.2 Hz, 1 H), 3.40 (dt, J = 10.2, 3.0 Hz, 1 H), 3.27 (dd, J = 10.8, 3.0 Hz, 1 H), 3.25 (d, J = 11.4 Hz, 1 H), 3.08 (dd, J = 9.0, 8.4 Hz, 1 H), 3.03 (dd, J = 11.4, 3.0 Hz, 1 H) ), 3.01 (pseudo-t, J = 9.6 Hz, 1 H), 2.69 (dd, J = 9.6, 1.8 Hz, 1 H), 2.61 (dd, J = 9.6, 1.8 Hz, 1 H), 2.01 (s) , 3 H), 1.97 (s, 3 H), 1.92 (s, 3 H), 1.81 (s, 3 H), 1.69 (s, 3 H). ¹³ C NMR (CDCl ₃ , 150 MHz) Chemical shift value 170.44, 170.37, 170.1, 169.9, 169.3, 168.0, 167.7, 167.5, 167.2, 162.9 (d, J = 248.7 Hz), 138.4, 138.1, 137.9, 137.7, 135.9 (d, J = 8.3 Hz), 134.5, 134.4, 134.3, 134.1, 131.51, 131.45, 131.3, 131.2, 131.1, 128.2, 128.14, 128.05, 127.9, 127.7, 127.5, 127.34, 127.29, 127.1, 127.04, 126.99, 125.9 (d, J = 3.3 Hz), 123.7, 123.6, 123.50, 123.46, 115.9 (d, J = 21.8 Hz), 100.6, 96.7, 95.8, 82.9, 80.5, 78.7, 74.7, 74.6, 74.0, 73.7, 73.5, 73.1, 73.0, 72.2, 71 .9, 71.4, 71.2, 70.9, 70.6, 68.2, 68.0, 67.8, 66.8, 65.6, 61.3, 55.6, 54.8, 53.6, 20.6, 20.5, 20.4, 20.3, 20.2. HRMS (ESI) m / z calcd for C ₉₂ H ₈₇ FN ₆ NaO ₂₇ S [M + Na] ⁺ , 1781.5216; found, 1781.5240.

As described above, according to the method for producing sugar of the present invention, it was found that a sugar chain in which sugar and sugar are bound by β bond can be obtained in a high ratio.

Claims (6)

A polysaccharide composed of the sugar represented by the general formula (1) and / or two or more sugars represented by the general formula (1), and
The sugar represented by the general formula (2) and / or the polysaccharide composed of two or more sugars represented by the general formula (2) are combined with the electrolyte represented by the general formula (3-1) and the general formula (3-2). in the presence of electrolytes having, including that to the electrolytic oxidation reaction in an aprotic organic solvent, a method of manufacturing sugars hydrogen atom below Z ¹ and below R ⁴ to R ⁶ are formed by bonding;

In the general formula (1), R ¹ and R ² independently have an alkyl group, a benzyl group, a p-methoxybenzyl group, a p-methylbenzyl group, an acetyl group, and a trimethyl having a linear, branched or cyclic structure, respectively. It represents an acetyl group, a benzoyl group, a trimethylsilyl group or a t-butyldimethylsilyl group, and R ¹ and R ² may be bonded to each other to form a ring.
R ³ represents an alkyl group, a benzyl group, a p-methoxybenzyl group, a p-methylbenzyl group, an acetyl group, a trimethylacetyl group, a benzoyl group, a trimethylsilyl group or a t-butyldimethylsilyl group having no cyclic structure.
Y ¹ represents base Njiruokishi group, p- methoxybenzyl group, p- methylbenzyl group, azido group, main butoxy group, a methoxymethyl group or trimethylsiloxy group,
Z ¹ represents a leaving group selected from a tellroaryl group, a selenoaryl group, a thioaryl group, a thiomethyl group, a thioethyl group, a thiooctyl group, a thiononyl group and a thiodecyl group;

In the general formula (2), R ⁴ and R ⁵ are independently hydrogen atom, linear, branched or cyclic group having an alkyl group, an acetyl group, a benzyl group, a p-methoxybenzyl group and a p-methylbenzyl group, respectively. It represents a group, a trimethylacetyl group, a benzoyl group, a trimethylsilyl group or a t-butyldimethylsilyl group, and R ⁴ and R ⁵ may be bonded to each other to form a ring.
R ⁶ contains a hydrogen atom, an alkyl group having no cyclic structure, a benzyl group, a p-methoxybenzyl group, a p-methylbenzyl group, an acetyl group, a trimethylacetyl group, a benzoyl group, a trimethylsilyl group or a t-butyldimethylsilyl group. Show,
One of R ^{4 to} R ⁶ is a hydrogen atom,
Y ² represents base Njiruokishi group, p- methoxybenzyl group, p- methylbenzyl group, azido group, main butoxy group, a methoxymethyl group or trimethylsiloxy group,
Z ² indicates an alkoxy group, an arylthio group or a thioethyl group ;
_{^{(R 7) 4 A + OS}} (= O) 2 R - (3-1)
In the general formula (3-1), R ⁷ represents an alkyl group having 1 to 8 carbon atoms, a perfluoroalkyl group, a phenyl group, or a benzyl group , and A represents a nitrogen atom or a phosphorus atom.
R represents a fluorine atom or an alkyl fluoride group;
_{^{R 7 4 A + X - (}} 3-2)
In the general formula (3-2), R ⁷ represents an alkyl group having 1 to 8 carbon atoms, a perfluoroalkyl group, a phenyl group, or a benzyl group .
A indicates a nitrogen atom or a phosphorus atom.
X indicates a bis (trifluoromethanesulfonyl) amide, a bis (fluoromethanesulfonyl) amide or B (C ₆ F ₅ ) ₄ ; The sugar represented by the general formula (1) and the sugar represented by the general formula (2) are not mixed in the presence of the electrolyte represented by the general formula (3-1) and the electrolyte represented by the general formula (3-2). Including electrolytic oxidation reaction in a protonic organic solvent,
^{R 1} and R ² in the general formula (1) are not bonded to each other to form a ring.
Y ¹ is a benzyloxy group, a p-methoxybenzyloxy group, a p-methylbenzyloxy group, a methoxy group, a methoxymethyl group, a trimethylsiloxy group or an azido group.
In the general formula (2), Z ² represents an alkoxy group or an arylthio group, and R ⁴ and R ⁵ are not bonded to each other to form a ring.
In the general formula (3-1), R represents a trifluoromethyl group.
The method for producing a sugar according to claim 1, wherein in the general formula (3-2), X represents a bis (trifluoromethanesulfonyl) amide or a bis (fluoromethanesulfonyl) amide. The electrolyte represented by the general formula (3-1) is tetrabutylammonium triflate.
The sugar according to claim 1 or 2, wherein the electrolyte represented by the general formula (3-2) is at least one of tetrabutylammonium bis (trifluoromethanesulfonyl) amide and tetrabutylammonium bis (fluoromethanesulfonyl) amide. Production method. The method for producing a sugar according to any one of claims 1 to 3 , wherein either or both of the electrolyte and the aprotic organic solvent are ionic liquids. Among the sugars produced, the polysaccharide represented by the general formula (1) and / or a polysaccharide composed of two or more sugars represented by the general formula (1), the sugar represented by the general formula (2) and / or. Alternatively, a sugar α in which a polysaccharide composed of a polysaccharide represented by two or more general formulas (2) is α-bonded, a sugar represented by the general formula (1) and / or two or more general formulas (1). The total amount of sugar β in which the polysaccharide composed of the sugar represented by the above formula (2) and / or the polysaccharide composed of two or more general formulas (2) are β-bonded. One of claims 1 to 4 , wherein [amount of sugar β / (amount of sugar α + amount of sugar β)] × 100, which is the mass ratio of the sugar β to the mass, is 85% or more. The method for producing a sugar according to. Any of claims 1 to 5 , wherein the electrolyte represented by the general formula (3-1) and the electrolyte represented by the general formula (3-2) are used in a molar ratio of 1: 0.2 to 5.0. The method for producing sugar according to item 1.