WO2014125967A1 - 3,6-O-CROSSLINKED PYRANOSE COMPOUND, AND PRODUCTION METHOD FOR α-O-PYRANOSIDE - Google Patents

Abstract

The present invention addresses the problem of providing a highly-versatile method for easily producing α-O-pyranosides with a high degree of selectivity without establishing severe reaction conditions, and a pyranose donor used in said method. The 3,6-O-crosslinked pyranose compound according to the present invention is a compound represented by general formula (1) (therein, R¹ represents a -SR⁶ group (R⁶ being an optionally-substituted lower alkyl group or the like) or the like, R² represents a hydrogen atom or the like, R³ represents a hydrogen atom or the like, R⁴ and R⁵ each represent an optionally-halogenated lower alkyl group or the like, n represents an integer of 1-4, and p and q each represent an integer of 0-4), or an enantiomer thereof.

Description

Process for producing 3,6-O-bridged pyranose compound and α-O-pyranoside

The present invention relates to a process for producing 3,6-O-bridged pyranose compounds and α-O-pyranoside.

There are two isomers of α-O-pyranoside and β-O-pyranoside in a compound (pyranoside) in which pyranose (sugar) is glycosyl bonded to an alcohol such as naturally occurring steroid. For pyranosides, important compounds having various physiological activities are known, and methods for selectively producing these isomers are expected. As glucosylation methods, methods using enzymes and methods using general chemical synthesis are known.

However, in the method using an enzyme, only limited sugar chains can be synthesized due to the substrate specificity of the enzyme, which is not suitable as an industrial production method. In addition, it is difficult to produce α-O-pyranoside in a highly selective manner only by obtaining a mixture of α-O-pyranoside and β-O-pyranoside by a method using general chemical synthesis. .

As a glycosylation method by highly alpha selective chemical synthesis, a chemical preparation method using a benzyl group in which adjacent group participation does not occur as a protecting group at the 2-position of pyranose is shown (Non-patent Document 1). However, this method is a method to prevent the occurrence of β-selective adjacent group participation when an acyl group is used as the 2-position protecting group, and therefore, a strict reaction is required to cause the reaction to proceed α-selectively. It is necessary to set conditions.

In addition, chemical production methods have also been proposed that make use of α-selective neighboring group participation (Non-patent Documents 2 and 3). However, in these methods, it is necessary to introduce an alkyl group having a nitrogen atom or a heteroarylalkyl group as a protecting group at the 2-position of pyranose.

Furthermore, a method using a bicyclo compound of pyranose and 1,4-oxathiane ring has also been proposed (Non-patent Document 4). However, this method also has limitations in the 1- and 2-position protecting groups.

Therefore, in view of sufficient high α selectivity and the versatility of the reaction conditions and applicable substrates, it is the present situation that a critical high α selective chemical synthesis method has not been found yet.

The object of the present invention is to provide a method for easily producing α-O-pyranoside with high selectivity and a pyranose donor used for the method, without setting highly versatile and strict reaction conditions. It is to be.

As a result of intensive studies to solve the above problems, the present inventors succeeded in synthesizing a 3,6-O-bridged pyranose compound represented by the following general formula (1). It has been found that the -O-bridged pyranose compound can be the desired α-O-glycosylation agent. The present invention has been completed based on such findings.

The present invention provides a method for producing 3,6-O-bridged pyranose compounds shown in the following items 1 and 2 and α-O-pyranoside shown in the items 3.

Item 1. General formula (1)

[Wherein, R ¹ represents a —SR ⁶ group (R ⁶ represents a lower alkyl group which may have a substituent or an aryl group which may have a substituent on the aromatic ring), —OR ^7] Group (R ⁷ represents a hydrogen atom, a protecting group of a hydroxyl group or a group acting as a leaving group with a bonded oxygen atom) or a halogen atom.
R ² represents a hydrogen atom or a hydroxyl protective group.
R ³ represents a hydrogen atom or a hydroxyl protective group.
R ⁴ and R ⁵ are the same or different and each represents a lower alkyl group which may be substituted by a halogen atom, a lower alkoxy group which may be substituted by a halogen atom, a nitro group or a halogen atom.
n represents an integer of 1 to 4; p and q each represent an integer of 0 to 4;
The p R ^{4 s} may be the same or different, and the q R ^{5 s} may be the same or different.
The p adjacent R ⁴ groups may be bonded to each other to form a benzene ring, and the q adjacent R ⁵ groups may be bonded to each other to form a benzene ring. ]
The 3,6-O-bridged pyranose compound represented by, or its enantiomer.
Item 2. Item 3. The 3,6-O-bridged pyranose compound according to Item 1, or an enantiomer thereof, wherein R ¹ in the general formula (1) is a halogen atom.
Item 3. The 3,6-O-bridged pyranose compound according to item 2 is a compound represented by the general formula (2)
R ⁸ OH (2)
[Wherein, R ⁸ represents a residue of a primary, secondary or tertiary alcohol. ]
By reacting with an alcohol compound represented by the general formula (3)

[Wherein, R ² , R ³ , R ⁴ , R ⁵ , R ⁸ , n, p and q are as defined above. ]
A method of producing α-O-pyranoside represented by or its enantiomer.

3,6-O-Bridged Pyranose Compound The 3,6-O-bridged pyranose compound of the present invention is represented by the following general formula (1).

^{Wherein, R 1, R 2, R} 3, R 4, R 5, n, p and q are as defined above. ]
In the present specification, the lower alkyl group means an alkyl group having 1 to 6 carbon atoms, preferably an alkyl group having 1 to 4 carbon atoms, and examples thereof include methyl, ethyl, n-propyl and iso-propyl. Group, n-butyl group, iso-butyl group, tert-butyl group, sec-butyl group, n-pentyl group, neo-pentyl group, n-hexyl group, iso-hexyl group, 3-methylpentyl group, etc. be able to.

The lower alkoxy group is an alkoxy group having 1 to 6 carbon atoms, preferably an alkoxy group having 1 to 4 carbon atoms, and examples thereof include a methoxy group, an ethoxy group, an n-propoxy group, an iso-propoxy group and an n-butoxy group. Groups, iso-butoxy group, tert-butoxy group, sec-butoxy group, n-pentoxy group, neo-pentoxy group, n-hexyloxy group, iso-hexyloxy group, 3-methylpentoxy group, etc. it can.

The lower alkanoyl group is an alkanoyl group having 1 to 6 carbon atoms, preferably an alkanoyl group having 1 to 4 carbon atoms, and examples thereof include an acetyl group, a propanoyl group, a butanoyl group, a 2-methylpropanoyl group and a pentanoyl group. Examples thereof include 2-methylbutanoyl group, 3-methylbutanoyl group, tert-butylcarbonyl group, hexanoyl group and the like.

As an aryl group, a phenyl group, a naphthyl group, etc. are mentioned, for example.

As an aryloxy group, a phenoxy group, a naphthyloxy group, etc. are mentioned, for example.

The halogen atom includes a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.

The protective group for hydroxyl group may be a conventional protective group for hydroxyl group widely known to date, for example, allyl group; methallyl group; a group comprising a halogen atom as a substituent, a lower alkoxy group and an aryloxy group Or lower alkyl group optionally having 1 to 5 at least one group selected from: at least one group selected from the group consisting of halogen atoms, lower alkyl groups and lower alkoxy groups as substituents, on an aromatic ring 1 to 3 phenyl groups which may be contained; 1 to 3 at least one group selected from the group consisting of halogen atoms, lower alkyl groups, lower alkoxy groups and nitro groups as substituents on aromatic rings Benzyl group which may be substituted; at least one group selected from the group consisting of halogen atoms, lower alkyl groups and lower alkoxy groups as substituents Triphenylmethyl group which may have 1 to 3 on an aromatic ring; formyl group; at least one group selected from the group consisting of halogen atoms, lower alkoxy groups, aryl groups and aryloxy groups as substituents A lower alkanoyl group which may have up to 5; at least one group selected from the group consisting of a halogen atom, a lower alkyl group and a lower alkoxy group as a substituent on the aromatic ring A benzoyl group; a silyl group in which at least one group selected from the group consisting of a lower alkyl group and an aryl group is substituted on the silicon atom by 3 groups, and the like. Specifically, allyl group, methallyl group, methyl group, ethyl group, tert-butyl group, methoxymethyl group, 4-methoxyphenyl group, benzyl group, dimethylbenzyl group, 4-methoxybenzyl group, 2-nitrobenzyl group And triphenylmethyl group, formyl group, acetyl group, propionyl group, tert-butylcarbonyl group, benzoyl group, tri-lower alkylsilyl group, tert-butyldiphenylsilyl group and the like. Among these protecting groups, allyl, benzyl, dimethylbenzyl, 4-methoxybenzyl and tri-lower alkylsilyl are preferable.

When R ⁶ represents a lower alkyl group, examples of the substituent on the alkyl include a lower alkoxy group, an aryl group, a halogen atom and the like, and more specifically, a methoxy group, an ethoxy group, a phenyl group, a halogen atom Etc.

When R ⁶ represents an aryl group, examples of the substituent on the aromatic ring include a lower alkyl group, a lower alkoxy group, a halogen atom and the like, and more specifically, a methyl group, an ethyl group, a methoxy group , An ethoxy group, a halogen atom and the like.

The group represented by R ⁷ which acts as a leaving group together with the oxygen atom to be bound may be an existing group which is widely known to date, and has an imide group; 1 to 5 halogen atoms Lower alkylsulfonyl group which may be substituted; benzene which may have on the aromatic ring at least one group selected from the group consisting of halogen atoms, lower alkyl groups, lower alkoxy groups and nitro groups as substituents A sulfonyl group etc. are mentioned. Specifically, trichloroacetoimido group, 4-trifluoromethylbenzylthio-N- (4-trifluoromethylphenyl) formimido group, methanesulfonyl group, trifluoromethanesulfonyl group, 4-toluenesulfonyl group, 2-nitrobenzene sulfonyl group And the like.

In the general formula (1), p adjacent R ^{4 's} are bonded to each other to form a benzene ring, for example, benzene in which two adjacent R ⁴ ' s are bonded to each other and R ⁴ is bonded The case where a naphthalene ring is formed with a ring is mentioned.

In the general formula (1), when q adjacent R ^{5 's} are bonded to each other to form a benzene ring, for example, benzene in which two adjacent R ⁵ ' s are bonded to each other and R ⁵ is bonded The case where a naphthalene ring is formed with a ring is mentioned.

R ² in the general formula (1) is a hydrogen atom or a hydroxyl protecting group. As the protective group for hydroxyl group, those similar to the protective group for hydroxyl group described above are used.

R ³ in the general formula (1) is a hydrogen atom or a hydroxyl protecting group. As the protective group for hydroxyl group, those similar to the protective group for hydroxyl group described above are used.

The value of n in the general formula (1) is an integer of 1 to 4, preferably an integer of 1 to 3, more preferably an integer of 2 to 3, and particularly preferably 2.

The values of p and q in the general formula (1) are each an integer of 0 to 4, but both p and q are preferably an integer of 0 to 2, and particularly preferably 0 or 1.

The 3,6-O-bridged pyranose compound represented by the general formula (1) has a chemical structure in which two aromatic rings in the bridge portion thereof are linked via an alkylene group. Therefore, since the cross-linked part of the 3,6-O-crosslinked pyranose compound has an appropriate degree of freedom in structure, it has an advantage that the reaction of removing the cross-linked part from pyranose tends to progress.

The enantiomer of the 3,6-O-bridged pyranose compound represented by the general formula (1) means a 3,6-O-bridged pyranose compound represented by the following general formula (1 ').

^{Wherein, R 1, R 2, R} 3, R 4, R 5, n, p and q are as defined above. ]
The 3,6-O-bridged pyranose compound represented by the general formula (1) can also be represented as the following formula in consideration of its conformation.

^{Wherein, R 1, R 2, R} 3, R 4, R 5, n, p and q are as defined above. ]
The 3,6-O-bridged pyranose compounds represented by the general formula (1) include compounds represented by the following general formulas (1A), (1B) and (1C).

[Wherein, X represents a halogen atom. R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , n, p and q are as defined above. ]
These compounds can also be represented as in the following formula in consideration of their conformations.

[Wherein, R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , X, n, p and q are as defined above. ]
Among the 3,6-O-bridged pyranose compounds represented by the general formula (1), preferred compounds are those represented by the following general formulas (1a), (1b), (1c), (1d) and (1e) It is a compound represented.

[Wherein, R ¹ , R ² , R ³ , R ⁴ , R ⁵ and n are as defined above. ]
3,6-O-bridged pyranose compounds of the general formula (1A) (compounds of the general formula (1A-1)) in which R ² and R ³ of the present invention are both hydrogen atoms and R ² and R ³ are both hydroxyl groups The 3,6-O-bridged pyranose compound (compound of the general formula (1A-2)) of the general formula (1A) showing a protective group is produced, for example, as shown in the following reaction formula-1.

[Wherein, R ⁴ , R ⁵ , R ⁶ , n, p and q are as defined above. R ^{2 ′} and R ^{3 ′} each represent a hydroxyl protecting group. X ¹ and X ² each represent a halogen atom. ]
The reaction of the compound (4) with the compound (5) can be carried out, for example, by using a basic compound such as sodium hydride in a suitable solvent such as a mixed solvent of toluene and dimethylformamide (DMF) as shown in Example 1 later. It takes place in the presence. The reaction is preferably carried out by dropping the solution of compound (4) and the solution of compound (5) at a suitable rate, respectively, into the solution or suspension of the basic compound. The reaction should be stirred for 10 to 20 hours at a temperature between 70 ° C. and the boiling point of the solvent.

In this reaction, the compound (4) used as a starting material is a known compound, and the compound (5) is a known compound or a compound which can be easily produced from a known compound. When a mixed solvent of toluene and DMF is used as the solvent, the mixing ratio of toluene and DMF can be, for example, a mixed solvent of 0.1 to 1 DMF with 1 L of toluene. In the reaction, it is preferable to use 1 to 3 moles of the compound (5) per 1 mole of the compound (4). In the reaction, it is preferable to use 2 to 10 moles of the basic compound per 1 mole of the compound (4).

The reaction for converting the compound (6) to the compound (1A-1) is carried out, for example, by two steps as shown in Example 1 described later. In this step, R ⁶ SH (wherein R ⁶ is as defined above) is reacted with compound (6) in the presence of a Lewis acid such as trifluoromethanesulfonic acid trimethylsilyl and molecular sieves in a suitable solvent such as dichloromethane. The step of reacting (step A) and the step of reacting the product obtained in step A with a basic compound such as sodium methoxide in an alcohol solvent such as methanol (step B).

The reaction in step A preferably has a reaction temperature of −78 to 25 ° C. and a reaction time of 1 to 60 minutes. In the first half reaction, it is preferable to use 0.8 to 1.5 mol of R ⁶ SH relative to 1 mol of the compound (6). In the reaction of step A, it is preferable to use 0.8 to 2 moles of a Lewis acid per 1 mole of the compound (6).

The reaction in step B preferably has a reaction temperature of 0 to 65 ° C. (more preferably around room temperature) and a reaction time of 5 to 60 minutes. In the latter reaction, the amount of the basic compound used can be, for example, 0.001 to 10 moles of the basic compound per 1 mole of the compound (6) used in the reaction of step A.

The reaction for converting the compound (1A-1) to the compound (1A-2) can be carried out in the presence of a basic compound under the general conditions for introducing a protecting group to a hydroxyl group. For example, as shown in Example 2 below, it can be carried out in a suitable solvent such as a mixed solvent of toluene and DMF in the presence of a basic compound such as sodium hydride. The reaction is preferably carried out at a reaction temperature of 20 to 100 ° C. and a reaction time of 30 to 120 minutes. When a mixed solvent of toluene and DMF is used as the solvent, the mixing ratio of toluene and DMF can be, for example, a solvent in which 0.2 to 2 L of DMF is mixed with 1 L of toluene in volume ratio. In the reaction, it is preferable to use 2 to 10 moles of the basic compound per 1 mole of the compound (1A-1).

When compound (1A-2) has a different hydroxy protecting group represented by R ^{2 ′} and R ^{3 ′} , the reaction for converting compound (1A-1) to compound (1A-2) proceeds through two steps. (1A-2) can be obtained. First, in the first step, a compound (1A-1) and R ^{2 ′} X ³ (wherein R ^{2 ′} is as defined above, and X ³ is a halogen atom) with an appropriate solvent such as tetrahydrofuran During the reaction in the presence of a basic compound such as sodium hydride and copper (II) chloride, it is possible to obtain a compound in which R ² is a hydroxyl protecting group and R ³ is a hydrogen atom in General Formula (1A). it can. The reaction is preferably carried out by adding copper (II) chloride to a stirred mixture solution of compound (1A-1) and a basic compound, and then adding R ^{2 ′} X ³ . In the second step, the desired compound (1A-2) can be obtained from the compound obtained under the general conditions for introducing a protective group to a hydroxyl group in the presence of a basic compound.

3, 6-O-crosslinked pyranose compound of the general formula (1B) ^{where R 7} of the present invention is a hydrogen atom (the compound of the general formula ^{(1B-1)), R} 7 together with the protecting group or bonded to an oxygen atom of the hydroxyl group 3,6-O-bridged pyranose compounds of the general formula (1B) (compounds of the general formula (1B-2)) exhibiting a group acting as a leaving group and 3,6-O-bridged pyranoses of the general formula (1C) The compound is produced, for example, as shown in the following Reaction formula-2.

[Wherein, R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , X, n, p and q are as defined above. R ^{7 ′} represents a hydroxyl-protecting group or a group which acts as a leaving group together with the bonded oxygen atom. ]
The reaction for converting the compound (1A) to the compound (1B-1) is carried out, for example, as shown in Example 3 below, in a suitable solvent such as a mixed solvent of acetone and water, N-halosuccinimide such as N-bromosuccinimide In the presence of The reaction is preferably carried out at a reaction temperature of −40 to 30 ° C. and a reaction time of 0.1 to 4 hours. When a mixed solvent of acetone and water is used as the solvent, the mixing ratio of acetone and water may be, for example, a solvent in which 0.01 to 0.5 L of water is mixed with 1 L of acetone in volume ratio. In the reaction, it is preferable to use 1 to 3 mol of N-halosuccinimide per 1 mol of compound (1A).

The reaction for introducing the compound (1B-1) into the compound (1B-2) is carried out under the general conditions of introducing a protecting group or a group acting as a leaving group together with an oxygen atom bonded to a hydroxyl group in the presence of a basic compound. To be done.

The reaction for converting the compound (1B-1) to the compound (1C) is carried out, for example, as described in Example 4 below, in a suitable solvent such as tetrahydrofuran, the presence of a halogenating agent such as diethylaminosulfur trifluoride (DAST) It takes place below. The reaction is preferably carried out at a reaction temperature of −20 to 40 ° C. and a reaction time of 1 to 60 minutes. In the reaction, it is preferable to use 1 to 6 moles of a halogenating agent relative to 1 mole of a compound (1B-1).

The compounds represented by the general formula (1 ') can also be produced by carrying out the same reaction except that the corresponding enantiomer is used as the starting material in each of the above reaction formulas.

The compound represented by the general formula (1) obtained by the above reaction is separated from the reaction mixture by a conventional separation means and purified. Such separation and purification means may include, for example, distillation, recrystallization, column chromatography, ion exchange chromatography, gel chromatography, affinity chromatography, preparative thin layer chromatography, solvent extraction, etc. it can.

In the compound represented by the general formula (1), the crosslinking portion can be removed from pyranose depending on the conditions of hydrogenation. The reaction is carried out under a hydrogen atmosphere in the presence of a hydrogenation catalyst. In the reaction, as a hydrogenation catalyst, an existing hydrogenation catalyst widely known to date may be used, and examples thereof include palladium / carbon, palladium hydroxide / carbon and the like.

The compounds represented by the general formula (1) of the present invention are suitable as glycosylation agents as an alpha selective sugar donor. The reason why a glycosidic bond is formed α-selectively is not clear yet, but since the bridge portion has a shape covering one side of the pyranose ring, it is selected from the α-plane by steric repulsion on the β-plane It is presumed that the reaction proceeds in a The compound represented by the general formula (1) of the present invention acts as an α-selective sugar donor, and then the reaction for removing the cross-linked portion as described above is represented by an α-O-pyranoside represented by the general formula (3) By carrying out the compound, it is possible to produce various sugars, glycoproteins, glycolipids and the like having an α-O-glycosyl bond.

Method of Producing α-O-Pyranoside By reacting the 3,6-O-bridged pyranose compound represented by the general formula (1C) with the alcohol represented by the general formula (2), a table of the general formula (3) is obtained. Can be selectively synthesized (the following reaction formula -3).

[Wherein, R ² , R ³ , R ⁴ , R ⁵ , R ⁸ , X, n, p and q are as defined above. ]
In the general formula (2), the residue of the primary, secondary or tertiary alcohol represented by R ⁸ is the remaining group obtained by removing the hydroxyl group from the primary, secondary or tertiary alcohol. Means

The alcohol of the general formula (2) is a known compound and is not particularly limited, but lower alcohol having a cycloalkyl group having 3 to 8 carbon atoms such as cyclohexylmethanol or sugar having a hydroxyl group, glycolipid and Glycoprotein etc. are mentioned.

The reaction of the compound of the general formula (1C) with the alcohol of the general formula (2) is carried out, for example, in a suitable solvent such as diethyl ether. These solvents are preferably anhydrous solvents.

The proportion of the compound (1C) to the alcohol (2) used is usually 0.5 to 2 moles, preferably 1 to 1.2 moles of alcohol (2) per 1 mole of compound (1C). That's good.

In the reaction of compound (1C) with alcohol (2), it is preferable to have an activating agent present in the reaction system. Examples of the activating agent include combinations of dicyclopentadienyl zirconium dichloride (Cp ₂ ZrCl ₂ ) / silver (I) perchlorate (AgClO ₄ ), and the like. The amount of the activating agent used is usually about 1 to 5 moles, preferably about 1 to 3 moles of Cp ₂ ZrCl ₂ and preferably about 1 to 7 moles of AgClO ₄ per 1 mole of the compound (1C). Is about 1 to 5 moles.

Further, in the reaction, the presence of molecular sieves (eg, molecular sieves 4A) further improves the yield of the compound (3) which is the target compound.

This reaction usually proceeds suitably at about -90 to 0 ° C, preferably at -80 to -40 ° C.

The α-O-pyranoside obtained by the above reaction is separated from the reaction mixture by, for example, ordinary separation means and purified. As such separation and purification means, those described above can be mentioned.

The various α-O-pyranosides obtained by the above reaction can be used, for example, in important applications such as the synthesis of saccharides, glycolipids and glycoproteins.

The 3,6-O-bridged pyranose compound represented by the general formula (1) of the present invention or an enantiomer thereof can be suitably used as an α-O-glycosylation agent.

When the 3,6-O-bridged pyranose compound represented by the general formula (1) of the present invention or its enantiomer is used, high selection of α-O-pyranoside is possible without setting severe reaction conditions. It can be manufactured easily at a rate.

The invention will be further clarified by the following examples. In the following, the reaction was carried out under an atmosphere of nitrogen or argon if necessary. Further, purification by silica gel chromatography used silica gel 60 N (granular, neutral, 40-50 μm) or silica gel 60 N (granular, neutral, 63-210 μm) (both manufactured by Kanto Chemical Co., Ltd.).

The following instruments were used to measure the physicochemical properties of the compounds.
IR: JASCO FT / IR-4200 (ATR; total internal reflection method)
Specific rotation: JASCO DIP-370 (100 mm cell, wavelength: 589 nm, solvent: CHCl ₃ )
NMR: JEOL JNM-ECX-400 ( ¹ H: 400 MHz, ¹³ C: 100 MHz)
In addition, in the measurement of ¹³ C-NMR, the number of hydrogen atoms bonded to the carbon is measured by the DEPT method, and is indicated by C (s), CH (d), CH ₂ (t), and CH ₃ (q), respectively. The
HRMS: JEOL JMS-700 (ionization method: ESI).

Example 1

[Wherein, Ph represents a phenyl group. ]
Preparation of phenyl 3,6-O- [bibenzyl-2,2'-bis (methylene)]-1-thio-D-glucopyranoside 60% oily sodium hydride (585 mg, 351 mg as sodium hydride) in toluene (80 mL) 14.6 mmol) was added and stirred. While stirring this suspension at 80 ° C., a solution of 2,2′-bis (bromomethyl) bibenzyl (934 mg, 2.53 mmol) in toluene (40 mL) and 1,2,4-orthoacetyl-α-D -A solution of glucopyranose (500 mg, 2.44 mmol) in dimethylformamide (40 mL) was simultaneously added dropwise. These two solutions were dropped using a syringe pump over 40 minutes at a dropping rate of 1 mL / min each. After the addition was complete, the mixture was further stirred at 80 ° C. for 14 hours. The reaction mixture was then quenched by the addition of water (20 mL) with cooling to 0 ° C. The resulting mixture was extracted with ethyl acetate (50 mL × 2) and the extracts combined, which was washed with water (20 mL × 1). Furthermore, the extract solution was dried over anhydrous magnesium sulfate and filtered through a cotton plug, and then the solvent was distilled off to obtain a crude product of compound 3.

In a mixture of the obtained crude product of compound 3, molecular sieves 5A (7.29 g) and dichloromethane (49 mL), thiophenol (269 mg, 2.44 mmol) and trimethylsilyl trifluoromethanesulfonate (644 mg, 2.90 mmol) Added at -75 ° C. The mixture was stirred at -75 ° C for 15 minutes and then at room temperature for another 5 minutes. The reaction mixture was quenched by addition of saturated aqueous sodium hydrogen carbonate solution (5 mL) and the resulting mixture was filtered through cotton and celite to remove molecular sieves from the mixture. The resulting mixture was then extracted with chloroform (20 mL × 2) and the extracts combined. Further, the extract solution was dried over anhydrous magnesium sulfate and filtered through a cotton plug, and then the solvent was distilled off to obtain a yellow amorphous crude product.

A mixture of the obtained yellow amorphous crude product, sodium methoxide (380 mg, 7.03 mmol) and methanol (48 mL) was stirred at room temperature for 30 minutes. The reaction mixture is then quenched by addition of 1 N hydrochloric acid (5 mL), the resulting mixture is extracted with ethyl acetate (15 mL × 2), the extracts are combined, and this is washed with water (1 × 5 mL) did. Further, the extract solution is dried over anhydrous magnesium sulfate and filtered through a cotton plug, and then the solvent is distilled off, and phenyl 3,6-O- [bibenzyl-2,2'-bis (methylene)]-1-thio-D- A crude product of glucopyranoside was obtained. The obtained crude product is purified by silica gel column chromatography (SiO ₂ : 8 g, ethyl acetate / n-hexane (volume ratio) = 1/5 → 1/2) to obtain phenyl 3,6-O- [bibenzyl- 2,2'-bis (methylene)]-1-thio-D-glucopyranoside (mixture ratio α of anomeric isomers α: β = 1: 1, 419 mg, 0.875 mmol, yield: 36%) as a white amorphous solid Obtained.

In the above process, the crude product of Compound 3 was used as it was in the next step, but by silica gel column chromatography (SiO ₂ : 8 g, ethyl acetate / n-hexane (volume ratio) = 1/5 → 1/2) It was possible to refine. The physicochemical properties of Compound 3 are as follows.
mp: 68-71 ° C
[Α] _D ²⁵ = -24.3 (c = 1.00, CHCl ₃ )
IR (ATR): 2920, 2866, 1740, 1491, 1454, 1405, 1358, 1326, 1307, 1229, 1223, 1181, 1137, 1090, 1057, 1039, 1005, 949, 900, 882, 869 , 847, 749, 670, 657, 634, 616, 603 cm ^-1
1 H-NMR (400 MHz, CDCl ₃ ): δ ppm
7.42-7.19 (m, 6H), 5.77 (d, J = 4.8 Hz, 1 H), 4.69 (d, J = 11.4 Hz, 1 H), 4.69 (m, 2 H), 4.55-4. 49 (m, 2 H), 4.42 -4.34 (m, 2H), 3.97 (s, J = 3.8 Hz, 2H), 3.72 (s, 1H), 3.69 (d, 1H), 3.15-3.00 (m, 4H), 1.61 (s, 3H)
¹³ C-NMR (100 MHz, CDCl ₃ ): δ ppm
141.9 (s), 141.8 (s), 135.3 (s), 134.3 (s), 131.2 (d), 131.0 (d), 129.4 (d), 129.1 (d), 128.9 (d), 128.4 (d), 126.5 (d), 126.3 (d), 119.0 (d), 78.0 (d), 72.7 (d), 72.5 (t), 70.8 (t), 70.6 (d), 70.5 (d), 69.2 (t), 33.6 (t), 33.0 (t), 20.4 (q)
HRMS-ESI (m / z): [M + Na] ⁺
Calculated _{(C 24} ^H 26 23 NaO ₆ as) 433.1627, found 433.1612.

The anomeric isomer mixture of phenyl 3,6-O- [bibenzyl-2,2'-bis (methylene)]-1-thio-D-glucopyranoside was subjected to silica gel column chromatography (ethyl acetate / n-hexane (volume ratio)) It could be purified by = 1/5 → 1/2) and separated into alpha and beta isomers, respectively. The physicochemical properties of each are as follows.

Phenyl 3,6-O- [bibenzyl-2,2'-bis (methylene)]-1-thio-α-D-glucopyranoside mp: 76-80 ° C.
[Α] _D ²⁵ = + 7.9 (c = 0.52, CHCl ₃ )
IR (ATR): 3424, 3060, 3022, 2868, 1584, 1492, 1481, 1452, 1438, 1405, 1373, 1233, 1234, 1074, 1046, 1024, 907, 729, 691, 691, 666 , 647, 621, 609 cm ^-1
1 H-NMR (400 MHz, CDCl ₃ ): δ ppm
7.56-7.48 (m, 3H), 7.40-7.26 (m, 7H), 7.25-7.18 (m, 3H), 5.36 (d, J = 2.1 Hz, 1H), 4.70 (d, J = 10.7 Hz, 1H) , 4.47 (d, J = 10.7 Hz, 1H), 4.40 (s, 2H), 4.22 (ddd, J = 8.6, 4.9, 4.2 Hz, 1H), 4.15 (br s, 1H), 4.07 (br s, 1H) ), 3.99 (t, J = 8.9, 8.6 Hz, 1H), 3.86 (t, J = 3.4, 3.4 Hz, 1 H), 3.70 (dd, J = 8.9, 4.9 Hz, 1 H), 3.16-2.96 (m, 4H)
¹³ C-NMR (100 MHz, CDCl ₃ ): δ ppm
141.9 (s), 141.3 (s), 135.5 (s), 135.1 (s), 134.8 (s), 129.6-126.5 (13 doublets overlap: 10 peaks are observed), 83.8 (d), 77.6 (d), 77.3 (d), 72.8 (t), 70.2 (t), 69.7 (d), 68.0 (t), 64.5 (d), 33.9 (t), 33.4 (t)
HRMS-ESI (m / z): [M + Na] ⁺
Calculated _{(C 28} ^H 30 23 NaO as ₅ S) 501.1712, Found 501.1692.

Phenyl 3,6-O- [bibenzyl-2,2'-bis (methylene)]-1-thio-β-D-glucopyranoside mp: 73-78 ° C.
[Α] _D ²³ = -45 (c = 0.53, CHCl ₃ )
IR (ATR): 3435, 3063, 3011, 2870, 1732, 1604, 1583, 1479, 1439, 1359, 1218, 1042, 809, 747 cm ^-1
1 H-NMR (400 MHz, CDCl ₃ ): δ ppm
7.62-7.58 (m, 1H), 7.47-7.40 (m, 3H), 7.38-7.35 (m, 1H), 7.31-7.27 (m, 4H), 7.25-7.19 (m, 2H), 7.17-7.11 (m , 2H), 4.63 (s, 2H), 4.59 (d, J = 8.6 Hz, 1H), 4.48 (d, J = 9.4 Hz, 1H), 4.40 (d, J = 9.4 Hz, 1H), 4.32 (ddd , J = 8.0, 7.7, 3.2 Hz, 1 H), 3.91 (dd, J = 11, 0, 3.2 Hz, 1 H), 3. 79 (dd, J = 11.0, 3.0 Hz, 1 H), 3.74 (t, J = 8.2 , 8.0 Hz, 1H), 3.60 (ddd, J = 7.7, 3.2, 3.0 Hz, 1H), 3.51 (ddd, J = 8.6, 8.2, 2.9 Hz, 1H), 3.04-28.2 (m, 4H), 2.65 ( d, J = 2.9 Hz, 1 H), 1. 86 (d, J = 3.2 Hz, 1 H)
¹³ C-NMR (100 MHz, CDCl ₃ ): δ ppm
141.3 (s), 138.8 (s), 136.7 (s), 135.7 (s), 133.1 (d, 2 C), 132.0 (s), 131.4 (d), 130.2 (d), 129.3 (d), 129.2 ( d), 129.0 (d, 2 C), 128.9 (d), 128.5 (d), 128.0 (d), 126.9 (d), 126.4 (d), 87.1 (d), 83.1 (d), 79.2 (d) , 73.0 (t), 69.0 (t), 68.3 (d), 64.1 (d), 62.7 (t), 32.8 (t), 32.7 (t)
HRMS-ESI (m / z): [M + Na] ⁺
Calculated _{(C 28} ^H 30 23 NaO as ₅ S) 501.1712, Found 501.1711.

Example 2

[Wherein, Ph is the same as above. Bn represents a benzyl group. ]
Preparation of Phenyl 2,4-di-O-benzyl-3,6-O- [bibenzyl-2,2'-bis (methylene)]-1-thio-D-glucopyranoside Phenyl 3,6-O- [bibenzyl- Mixed solution (volume) of 2,2'-bis (methylene)]-1-thio-D-glucopyranoside (39 mg, 81.5 μmol, α / β isomer mixture) and benzyl bromide (55 mg, 322 μmol) in dimethylformamide and toluene 60% oily sodium hydride (20 mg, 12 mg as sodium hydride, 0.50 mmol) was added while dissolving in a ratio 1: 1, 4 mL) and stirring at room temperature. After this was stirred at 75 ° C. for 1 hour, the reaction mixture was quenched by adding saturated aqueous ammonium chloride solution (5 mL) under cooling at 0 ° C. The resulting mixture was extracted with ethyl acetate (5 mL × 2), the extracts were combined, and this was washed with water (1 × 5 mL) and saturated brine (1 × 5 mL). Further, the extract solution was dried over anhydrous magnesium sulfate and filtered through a cotton plug, and then the solvent was distilled off to obtain a crude product. The obtained crude product is purified by silica gel chromatography (SiO ₂ : 500 mg, ethyl acetate / n-hexane (volume ratio) = 1/30 → 1/10) to obtain phenyl 2,4-di-O-benzyl- 3,6-O- [bibenzyl-2,2'-bis (methylene)]-1-thio-D-glucopyranoside (mixing ratio α of anomeric isomers α: β = about 50: 50, 43.1 mg, 65.3 μmol , Yield: 80%) as a white amorphous solid.

Separately, phenyl 2,4-di-O-benzyl-3,6-O- [bibenzyl-2,2'-bis (methylene)]-1-thio-D-glucopyranoside α-isomer and β-isomer are In Example 2, each separated phenyl 3,6-O- [bibenzyl-2,2'-bis (methylene)]-1-thio-α-D-glucopyranoside or phenyl 3,6-O- [bibenzyl-2 It was obtained by using 2,2'-bis (methylene)]-1-thio-β-D-glucopyranoside as a raw material. The physicochemical properties of each are as follows.

Phenyl 2,4-di-O-benzyl-3,6-O- [bibenzyl-2,2'-bis (methylene)]-1-thio-α-D-glucopyranoside mp: 50-55 ° C.
[Α] _D ²⁵ = + 110 (c = 0.50, CHCl ₃ )
IR (ATR): 3063, 3027, 2867, 2243, 1604, 1494, 1481, 1438, 1392, 1362, 1326, 1250, 1208, 1072, 1026, 908, 820, 728 cm ^-1
1 H-NMR (400 MHz, CDCl ₃ ): δ ppm
7.55-7.29 (m, 13 H), 7.25-7. 13 (m, 10 H), 5. 66 (d, J = 4.9 Hz, 1 H), 4. 85 (d, J = 10.1 Hz, 1 H), 4. 76 (d, J = 11.9 Hz) , 1H), 4.73 (d, J = 11.7 Hz, 1H), 4.50 (d, J = 10.1 Hz, 1H), 4.38 (d, J = 11.7 Hz, 1H), 4.32-4.19 (m, 4H), 4.10 (br d, J = 7.6 Hz, 1 H), 4.04 (ddd, J = 4.9, 3.6, 1.2 Hz, 1 H), 3.92-3.80 (m), 3.20-2.85 (m, 4 H)
¹³ C-NMR (100 MHz, CDCl ₃ ): δ ppm
142.3 (s), 142.0 (s), 138.4 (s), 138.0 (s), 136.4 (s), 136.1 (s), 135.0 (s), 131.5-126.2 (23 doublets overlap: 18 peaks , 86.4 (d), 76.3 (d), 74.6 (d), 73.5 (t), 73.1 (d), 73.1 (1 doublet and 1 triplet: 1 peak observed), 71.5 (t), 70.4 (t), 69.7 (t), 34.1 (t, 2 C)
HRMS-ESI (m / z): [M + Na] ⁺
Calculated _{(C 42} ^H ₄₂ 23 NaO as ₅ S) 681.2651, Found 681.2682.

Phenyl 2,4-di-O-benzyl-3,6-O- [bibenzyl-2,2'-bis (methylene)]-1-thio-β-D-glucopyranoside mp: 35-38 ° C.
[Α] _D ²² =-43 (c = 0.83, CHCl ₃ )
IR (ATR): 3063, 3032, 2907, 2871, 1496, 1449, 1366, 1205, 1095, 1076, 1028, 913, 731 cm ^-1
1 H-NMR (400 MHz, CDCl ₃ ): δ ppm
7.53-7.27 (m, 13H), 7.25-7.08 (m, 10H), 5.17 (d, J = 8.9 Hz, 1 H), 4.78 (d, J = 11.9 Hz, 1 H), 4.74 (d, J = 11.9 Hz) , 1H), 4.49 (d, J = 10.3 Hz, 1H), 4.40 (d, J = 10.3 Hz, 1H), 4.37 (d, J = 11.9 Hz, 1H), 4.31 (d, J = 11.9 Hz, 1H) ), 4.20 (d, J = 10.3 Hz, 1H), 4.16 (d, J = 10.3 Hz, 1H), 4.13 (m, 1H), 3.89 (m, 1H), 3.86 (m, 1H), 3.68 (dd) , J = 8.9, 2.3 Hz, 1 H), 3.64 (dd, J = 9.4, 2.8 Hz, 1 H), 3. 60 (dd, J = 9.4, 8.2 Hz, 1 H), 3.05-2.88 (m, 4 H)
¹³ C-NMR (100 MHz, CDCl ₃ ): δ ppm
141.9 (s), 141.6 (s), 138.4 (s), 137.8 (s), 135.7 (s), 135.0 (s), 134.1 (s), 131.9-126.1 (23 doublets overlap: 18 peaks , 83.8 (d), 80.5 (d), 79.6 (d), 78.1 (d), 73.2 (t), 72.9 (d), 72.5 (t), 71.0 (t), 70.2 (t, 2C) , 33.2 (t), 33.1 (t)
HRMS-ESI (m / z): [M + Na] ⁺
Calculated value (as C ₄₂ H ₄₂ ²³ NaO ₅ S) 681.2651, found 681.2668.

Example 3

[Wherein, Ph and Bn are as defined above. ]
Preparation of 2,4-di-O-benzyl-3,6-O- [bibenzyl-2,2'-bis (methylene)]-D-glucopyranose Phenyl 2,4-di-O-benzyl-3,6 -O- [bibenzyl-2,2'-bis (methylene)]-1-thio-D-glucopyranoside (258 mg, 0.392 mmol) was dissolved in a mixed solvent of acetone (9 mL) and water (1 mL). While stirring the mixture solution at 0 ° C., N-bromosuccinimide (105 mg, 0.587 mmol) was added and stirred at room temperature for 1 hour. Then, saturated sodium hydrogencarbonate aqueous solution (5 mL) was added and quenched to the reaction mixture at 0 degreeC. The resulting mixture was extracted with ethyl acetate (10 mL × 2), the extracts were combined, and this was washed with water (1 × 5 mL) and saturated brine (1 × 5 mL). Further, the extract solution was dried over anhydrous magnesium sulfate and filtered through a cotton plug, and then the solvent was distilled off to obtain a crude product. The obtained crude product is purified by silica gel chromatography (SiO ₂ : 450 mg, ethyl acetate / n-hexane (volume ratio) = 1/10 → 1/3), and 2,4-di-O-benzyl-3 , 6-O- [Bibenzyl-2,2'-bis (methylene)]-D-glucopyranose (mixing ratio of anomers: 1: 1, 185 mg, 0.326 mmol, yield: 83%) as white amorphous solid Got as.

The physicochemical properties of 2,4-di-O-benzyl-3,6-O- [bibenzyl-2,2'-bis (methylene)]-D-glucopyranose are as follows.
IR (ATR): 3397, 3041, 3029, 2868, 1731, 1604, 1494, 1454, 1366, 1252, 1216, 1069, 940, 914, 847, 814, 743 cm- ^1
1 H-NMR (partial data, 400 MHz, CD ₃ OD): δ ppm
4.48, J = 3.9 Hz), 4.37 (d, J = 6.9 Hz)
HRMS-ESI (m / z): [M + Na] ⁺
Calculated _{(C 36} ^H 38 23 NaO ₆ as) 589.2566, found 589.2551.

Example 4

[Wherein, B n is the same as above. ]
Preparation of 2,4-di-O-benzyl-3,6-O- [bibenzyl-2,2'-bis (methylene)] glucosyl fluoride 2,4-di-O-benzyl-3,6-O- [Bibenzyl-2,2'-bis (methylene)]-D-glucopyranose (150 mg, 265 μmol) and diethylaminosulfur trifluoride (DAST, 128 mg, 794 μmol) are dissolved in tetrahydrofuran (5 mL) and stirred at room temperature for 10 minutes did. The reaction mixture was quenched by addition of saturated aqueous sodium hydrogen carbonate solution (1 mL). The resulting mixture was extracted with ethyl acetate (10 mL × 2), the extracts were combined, and this was washed with saturated brine (1 × 5 mL). Further, the extract solution was dried over anhydrous magnesium sulfate and filtered through a cotton plug, and then the solvent was distilled off to obtain a crude product. The resulting crude product is purified by silica gel chromatography (SiO ₂ : 3 g, ethyl acetate / n-hexane (volume ratio) = 1/15 → 1/5) to give 2,4-di-O-benzyl-3 6,6-O- [bibenzyl-2,2'-bis (methylene)] glucosyl fluoride (mixture ratio of anomer: 7: 3, 120 mg, 211 μmol, yield: 80%) was obtained as a colorless syrup.

2,4-di-O-benzyl-3,6-O- [bibenzyl-2,2'-bis (methylene)] glucosyl fluoride is high performance liquid chromatography (column: YMC-Pack R & D SIL, R-SIL -5, 250 x 4.6 m, eluent: ethyl acetate / n-hexane (volume ratio) = 92: 8, flow rate: 1 mL / min, detection: UV, 254 nm), alpha isomer and beta isomer I was able to separate into the body. The physicochemical properties of each of these two isomers are as follows.
2,4-di-O-benzyl-3,6-O- [bibenzyl-2,2'-bis (methylene)] glucosyl fluoride (isomer 1: retention time 12 minutes under the conditions of the above high performance liquid chromatography)
[Α] _D ²² = -47 (c = 0.17, CHCl ₃ )
IR (ATR): 3029, 2869, 1496, 1455, 1368, 1216, 1091, 948, 699, 609 cm ^-1
1 H-NMR (400 MHz, CDCl ₃ ): δ ppm
7.44-7.27 (m, 10H), 7.25-7.09 (m, 8H), 5.76-5.58 (dd, J = 55.2, 3.4 Hz, 1 H), 4.79 (d, J = 12.1 Hz, 1 H), 4.69 (d, J) J = 11.9 Hz, 1H), 4.45 (d, J = 11.9 Hz, 1H), 4.42-4.36 (m, 3H), 4.33 (ddd, J = 11.0, 5.3, 0.9 Hz, 1H), 4.24 (s, 2H) ), 3.87-3.80 (m, 2H), 3.75 (br s, 1H), 3.73-3.65 (m, 2H), 3.10-2.97 (m, 1H), 2.92- 2.81 (m, 3H)
¹³ C-NMR (100 MHz, CDCl ₃ ): δ ppm
141.8 (s), 141.7 (s), 137.8 (s), 137.6 (s), 135.7 (s), 134.7 (s), 131.6-126.2 (d, 18 C, 18 doublets overlap: 13 peaks Observation), 107.3 (d, J _CF = 218 Hz), 76.0 (d), 75.7 (d), 74.3 (d), 73.0 (t), 72.4 (t), 71.2 (t), 70.8 (t), 70.6 (d), 70.0 (t), 33.7 (t), 33.3 (t)
HRMS-ESI (m / z): [M + Na] ⁺
Calculated (as C ₃₆ H ₃₇ ²³ NaFO ₅ ) 591.223, found 591.225.
2,4-di-O-benzyl-3,6-O- [bibenzyl-2,2'-bis (methylene)] glucosyl fluoride (isomer 2: retention time 14 minutes under the conditions of the above high performance liquid chromatography)
[Α] _D ²³ = + 24 (c = 0.050, CHCl ₃ )
IR (ATR): 3025, 2867, 1496, 1455, 1365, 1216, 1094, 754, 700 cm ^-1
1 H-NMR (400 MHz, CDCl ₃ ): δ ppm
7.43-7.27 (m, 12H), 7.25-7.09 (m, 6H), 5.66 (dd, J = 58.2, 3.0 Hz, 1H), 4.76 (d, J = 11.9 Hz, 1H), 4.74-4.66 (m, 5H) 3H), 4.42 (s, 2H), 4.32 (br s, 1H), 4.25 (d, J = 10.0 Hz, 1 H), 4.17 (d, J = 10.0 Hz, 1 H), 4.05 (br d, J = 4.9 Hz, 1H), 4.01 (br d, J = 5.6 Hz, 1H), 3.87 (ddd, J = 14.4, 5.6, 3.0 Hz, 1H), 3.72-3.68 (m, 2H), 3.14-3.03 (m, 1 H), 2.95-2.83 (m, 3H)
¹³ C-NMR (100 MHz, CDCl ₃ ): δ ppm
141.6 (s), 138.2 (s), 137.9 (s), 135.6 (s), 135.2 (s), 131.5-126.3 (d, 18 C, overlapping of 18 doublets: 13 peaks are observed), 105.1 (10 d, ¹ J _CF = 225.0 Hz C-1), 78.5 (d), 75.1 (d, ² J _CF = 21.0 Hz C-2), 74.3 (d), 74.2 (d), 73.2 (t), 72.7 (7 t), 71.3 (t), 69.7 (t), 69.3 (t), 33.7 (t), 33.5 (t)
HRMS-ESI (m / z): [M + Na] ⁺
Calculated _{(C 36} ^H 37 23 as NaFO ₅₎ 591.2523, Found 591.2540.

Example 5

[Wherein, B n is the same as above. ]
Α-Glycosylation reaction of 2,4-di-O-benzyl-3,6-O- [bibenzyl-2,2'-bis (methylene)] glucosyl fluoride Molecular sieves 4A (105 mg), dicyclopentadi A mixture of enyl zirconium dichloride (Cp ₂ ZrCl ₂ ; 26 mg, 88.9 μmol), silver (I) perchlorate (AgClO ₄ ; 36 mg, 174 μmol) and diethyl ether (1.0 mL) was stirred at room temperature for 10 minutes. To this mixture at −50 ° C., a solution of cyclohexylmethanol (4.7 mg, 41.2 μmol) in diethyl ether (0.25 mL) and 2,4-di-O-benzyl-3,6-O- [bibenzyl-2, A solution of 2′-bis (methylene)] glucosyl fluoride (20.0 mg, 35.1 μmol) in diethyl ether (0.25 mL) was added. After that, the reaction mixture was stirred at -50 ° C for 14 hours, and then the reaction mixture was quenched by adding a saturated aqueous solution of sodium hydrogen carbonate (5 mL). The resulting mixture was diluted with diethyl ether (20 mL) and then filtered through cotton and celite to remove molecular sieves from the mixture. After separating the organic layer, the organic layer was washed with saturated brine (5 mL × 1). The organic layer was further dried over anhydrous magnesium sulfate, filtered through a cotton plug, and the solvent was evaporated to give a crude product as a mixture of anomeric isomers. The mixing ratio of the anomeric isomers of the crude product was determined from the ratio of the integrated value of the anomeric hydrogen peak in ¹ H-NMR spectral data (400 MHz, CDCl ₃ ), and it was α: β = 97: 3. The obtained crude product is purified by silica gel chromatography (SiO ₂ : 2 g, diethyl ether / n-hexane (volume ratio) = 1/20 → 1/10), and cyclohexylmethyl 2,4-di-O-benzyl -3,6-O- [Bibenzyl-2,2'-bis (methylene)]-α-D-glucopyranoside (16.1 mg) and cyclohexylmethyl 2,4-di-O-benzyl-3,6-O- [Bibenzyl-2,2′-bis (methylene)]-β-D-glucopyranoside (0.3 mg) was obtained as a white amorphous solid. Therefore, the mixture ratio of cyclohexylmethyl 2,4-di-O-benzyl-3,6-O- [bibenzyl-2,2'-bis (methylene)]-D-glucopyranoside (anomer of anomeric isomers α) as an isomer mixture : .Beta. = 98: 2, 16.4 mg, 24.7 .mu.mol, yield: 70%) were isolated.

The physicochemical properties of cyclohexylmethyl 2,4-di-O-benzyl-3,6-O- [bibenzyl-2,2'-bis (methylene)]-α-D-glucopyranoside are as follows.
mp: 32-35 ° C
[Α] _D ²⁵ = + 53.2 (c = 1.00, CHCl ₃ )
IR (ATR): 3063, 3028, 2921, 2245, 1604, 1452, 1362, 1260, 1270, 1151, 1070, 1043, 908, 845, 832, 808, 729 cm- ^1
1 H-NMR (400 MHz, CDCl ₃ ): δ ppm
7.47-7.35 (m, 5 H), 7.34-7.27 (m, 5 H), 7.25-7.12 (m, 6 H), 7.01-7.08 (m, 2 H), 4.83 (d, J = 3.3 Hz, 1 H), 4.72 (d, J = 12.4 Hz, 1 H), 4.66 (d, J = 12.4 Hz, 1 H), 4.56 (d, J = 9.8 Hz, 1 H), 4.45 (d, J = 11.7 Hz) , 1 H), 4.40 (d, J = 11.5 Hz, 1 H), 4.36 (d, J = 12.0 Hz, 1 H), 4.26 (d, J = 9.8 Hz, 1 H), 4.20 (d, J = 12.1 Hz, 1 H), 4.16 (dd, J = 7.1, 7.1 Hz, 1 H), 4.10 (dd, J = 6.8, 6.8 Hz, 1 H), 3.93 (ddd, J = 6.9, 3.4, 2.5 Hz, 1 H), 3.76 (dd, J = 10.5, 3.4 Hz, 1 H), 3.71 (dd, J = 7.1, 3.4 Hz, 1 H), 3.68 (dd, J = 10.8, 2.3 Hz, 1 H), 3.53 (dd, J = 9.4, 6.6 Hz, 1 H), 3.14 (dd, J = 9.4, 6.4 Hz, 1 H), 3.10-2.90 (m, 4 H), 1.85-1. 73 (m, 2 H), 1.73 -1.65 (m, 2 H), 1.65-1.57 (m, 1 H), 1.32-1.13 (m, 4 H), 1.02-0.88 (m, 2 H)
¹³ C-NMR (100 MHz, CDCl ₃ ): δ ppm
141.7 (s), 140.0 (s), 138.9 (s), 138.7 (s), 136.3 (s), 135.6 (s), 131.5 (18 doublets overlap: 13 peaks observed), 96.6 (d ), 79.0 (d), 75.2 (d), 74.1 (t), 73.0 (d), 73.0 (t), 72.6 (t), 72.0 (d), 71.5 (t), 69.8 (t), 65.6 (t) ), 38.0 (d), 33.5 (t), 33.3 (t), 30.1 (t, 2C), 26.7 (t), 26.0 (t), 25.9 (t)
HRMS-ESI (m / z): [M + Na] ⁺
Calculated _{(C 43} ^H 50 23 NaO ₆ as) 685.3505, found 685.3475.

The physicochemical properties of cyclohexylmethyl 2,4-di-O-benzyl-3,6-O- [bibenzyl-2,2'-bis (methylene)]-β-D-glucopyranoside are as follows.
mp: 30-33 ° C
[Α] _D ²⁵ = -53.0 (c = 1.00, CHCl ₃ )
IR (ATR): 3062, 3027, 2922, 2855, 2605, 1405, 1453, 1311, 1218, 1092, 939, 910, 875, 862, 846, 831, 809, 774 cm ^-1
1 H-NMR (400 MHz, CDCl ₃ ): δ ppm
7.45-7.41 (m, 2H), 7.39-7.27 (m, 8H), 7.25-7.08 (m, 8H), 4.86 (d, J = 12.1 Hz, 1H), 4.79 (d, J = 7.1 Hz, 1H) , 4.71 (d, J = 12.1 Hz, 1 H), 4.44 (d, J = 10.1 Hz, 1 H), 4.38 (d, J = 10.3 Hz, 1 H), 4.36 (d, J = 11.9 Hz, 1 H), 4.29 (br d, J = 10.8 Hz, 2 H), 4.20 (d, J = 10.6 Hz, 1 H), 4.05 (br t, J = 7.9, 4.5 Hz, 1 H), 3.85-3. 78 (m, 2 H), 3.70 ( dd, J = 9.4, 6.2 Hz, 1 H), 3.66-3.56 (m, 3 H and H-6), 3. 28 (dd, J = 9.4, 6.9 Hz, 1 H), 3.06-2.83 (m, 4 H), 1.87- 1.57 (m, 6H), 1.31-1.09 (m, 3H), 1.03-0.87 (m, 2H)
¹³ C-NMR (100 MHz, CDCl ₃ ): δ ppm
141.9 (s), 141.4 (s), 138.9 (s), 138.0 (s), 135.7 (s), 135.3 (s), 131.5-126.1 (18 doublets overlap: 13 peaks observed), 101.4 (d), 81.1 (d), 80.6 (d), 76.1 (d), 75.3 (t), 73.3 (t), 73.2 (d), 72.5 (t), 71.1 (t), 70.3 (t), 69.9 (t), 38.2 (d), 33.2 (t, 2C), 30.3 (t), 30.0 (t), 26.8 (t), 26.0 (t), 26.0 (t)
HRMS-ESI (m / z): [M + Na] ⁺
Calculated _{(C 43} ^H 50 23 NaO ₆ as) 685.3505, found 685.3517.

Examples 6-8
The reaction was carried out in the same manner as in Example 5 except that the reaction temperature and the reaction time were as shown in Table 1 below. The yield and ratio of anomers of the obtained cyclohexylmethyl 2,4-di-O-benzyl-3,6-O- [bibenzyl-2,2'-bis (methylene)]-D-glucopyranoside are shown in the following table. Shown in 1. The yield and ratio of anomeric isomers in Examples 6 to 8 were determined from ¹ H-NMR (solvent: CDCl ₃ , standard substance: acetone, and α / β is the ratio of the integrated value of anomeric hydrogen peak).

Example 9
Except that instead of CpZrCl ₂ to SnCl _2, the same manner as in Example 6, the reaction was carried out. Similarly to Example 6, the collection of cyclohexylmethyl 2,4-di-O-benzyl-3,6-O- [bibenzyl-2,2'-bis (methylene)]-D-glucopyranoside determined by ¹ H-NMR The ratio was 63%, and the ratio of anomeric isomers was α: β = 93: 7.

Examples 10 to 18
The reaction was carried out in the same manner as in Example 5 except that the reaction temperature was 25 ° C., the reaction solvent and the reaction time were as shown in Table 2 below. Yield and anomer of cyclohexylmethyl 2,4-di-O-benzyl-3,6-O- [bibenzyl-2,2'-bis (methylene)]-D-glucopyranoside determined by the same method as in Example 6. The proportions of the isomers are shown in Table 2 below. In Table 2, Et is ethyl, i-Pr is isopropyl, t-Bu is tertiary butyl, THF is tetrahydrofuran, and CPME is cyclopentyl methyl ether.

Example 19

Molecular sieves 4A (52.8 mg), dicyclopentadienyl zirconium dichloride (Cp ₂ ZrCl ₂ ; 12.9 mg, 44.1 μmol), silver perchlorate (AgClO ₄ ; 18.2 mg, 87.8 μmol) A mixture of and diethyl ether (0.5 mL) was stirred at room temperature for 10 minutes. To this mixture at room temperature (+)-dihydrocholesterol (8.2 mg, 21 μmol) and 2,4-di-O-benzyl-3,6-O- [bibenzyl-2,2'-bis (methylene)] A solution of glucosyl fluoride (10.0 mg, 17.6 μmol) in diethyl ether (1.5 mL) was added. Then, after stirring the reaction mixture at room temperature for 10 minutes, the reaction mixture was quenched by adding a saturated aqueous solution of sodium hydrogen carbonate (5 mL). The resulting mixture was diluted with diethyl ether (20 mL) and then filtered through cotton and celite to remove molecular sieves from the mixture. The filtrate was extracted with ethyl acetate (30 mL), the extracts were combined, and this was washed with saturated brine (5 mL). The organic layer was further dried over anhydrous magnesium sulfate, filtered through a cotton plug, and the solvent was evaporated to give a crude product as a mixture of anomeric isomers. The yield of dihydrocholesteryl 2,4-di-O-benzyl-3,6-O- [bibenzylbis-2,2 '-(methylene)]-D-glucopyranoside in crude product is ¹ H-NMR (solvent: CDCl _The yield is 74% as determined using ₃ , standard substance: acetone), and the anomeric isomer ratio determined from the ratio of the integrated value of the anomeric hydrogen peak is α / β = 96/4 The

The physicochemical properties of dihydrocholesteryl 2,4-di-O-benzyl-3,6-O- [bibenzylbis-2,2 '-(methylene)]-α-D-glucopyranoside are as follows.
[Α] _D ²² = + 41.8 (c = 0.15, CHCl ₃ )
IR (ATR): 3062, 3027, 2929, 2864, 1731, 1604, 1495, 1454, 1381, 1259, 1215, 1148, 1070, 1027, 954, 805, 750, 697 cm ^-1
1 H-NMR (400 MHz, CDCl ₃ ): δ ppm
7.49-7.27 (m, 10 H), 7.25-7.02 (m, 8 H), 5.03 (d, J = 3.4 Hz, 1 H), 4.72 (d, J = 12.3 Hz, 1 H), 4.64 (d, J) J = 12.3 Hz, 1 H), 4.52 (d, J = 9.7 Hz, 1 H), 4.45 (s, 2 H), 4.35 (d, J = 12.2 Hz, 1 H), 4.27 (d, J = 9.7) Hz, 1 H), 4.20-4.16 (m, 2 H), 4.05 (dd, J = 6.9, 5.0 Hz, 1 H), 3.95 (br d, J = 6.6 Hz, 1 H), 3.75 (dd, J = 10.8, 3.2 Hz, 1 H), 3.69-3.66 (m, 2 H), 3.48 (dddd, J = 15.6, 9.6, 4.6, 4.6 Hz, 1 H), 3.05-2.96 (m, 4 H), 1.97 -1.17 (m, 25 H), 1.16-0.85 (m, 15 H), 0.79 (s, 3 H), 0.64 (s, 3 H)
¹³ C-NMR (100 MHz, CDCl ₃ ): δ ppm
141.8 (s), 139.7 (s), 138.9 (s), 136.6 (s), 135.7 (s), 131.6 (s), 131.6 (d), 130.9 (d), 129.1 (d), 129.0 (d), 128.8 (d), 129.1-127.9 (9 doublets overlap: 5 peaks are observed), 127.6 (d), 127.4 (d), 126.4 (d), 126.2 (d), 94.6 (d), 79.4 (d), 77.2 (d), 75.3 (d), 73.1 (d), 73.1 (t), 72.3 (t), 71.8 (d), 71.6 (t), 69.9 (t), 64.9 (t), 56.7 (d), 56.5 (d), 54.5 (d), 45.2 (d), 42.8 (s), 40.2 (t), 39.7 (t), 37.1 (t), 36.3 (t), 36.1 (t), 35.9 (d), 35.8 (s), 35.7 (d), 33.5 (t), 33.3 (t), 32.3 (t), 28.9 (t), 28.4 (t), 28.2 (d), 27.9 (t), 24.4 (t), 24.0 (t), 23.0 (q), 22.7 (q), 21.4 (t), 18.8 (q), 12.5 (q), 12.2 (q)
HRMS-ESI (m / z): [M + Na] ⁺
Calculated _{(C 63} ^H 84 23 NaO ₆ as) 959.6166, found 959.6138.
The physicochemical properties of dihydrocholesteryl 2,4-di-O-benzyl-3,6-O- [bibenzylbis-2,2 '-(methylene)]-β-D-glucopyranoside are as follows.
[Α] _D ²³ = +12.3 (c = 0.065, CHCl ₃ ),
IR (ATR): 3036, 3027, 2925, 1729, 1604, 1454, 1377, 1261, 1214, 1151, 1071, 1029, 954, 804, 751, 698 cm ^-1 ,
¹ H NMR (400 MHz, CDCl ₃ ): δ ppm
7.44-7.28 (m, 10 H), 7.23-7.08 (m, 8 H), 4.93 (d, J = 7.1 Hz, 1 H), 4.87 (d, J = 12.1 Hz, 1 H), 4.71 (d, J) J = 12.4 Hz, 1 H), 4.42 (d, J = 10.3 Hz, 1 H), 4.37 (d, J = 10.1 Hz, 1 H), 4.37 (d, J = 12.4 Hz, 1 H), 4.28 ( d, J = 12.1 Hz, 1 H), 4.27 (d, J = 10.8 Hz, 1 H), 4.18 (d, J = 10.5 Hz, 1 H), 4.04 (m, 1 H), 3.82 (dd, J = 2.1, 1.8 Hz, 1 H), 3.79 (dd, J = 2.3, 2.1 Hz, 1 H), 3.65-3.55 (m, 4 H), 3.02-2.86 (m, 4 H), 2.09-1.62 (m , 7 H), 1.51-0.92 (m, 24 H), 0.90 (d, J = 6.6 Hz, 3 H), 0.86 (d, J = 8.2 Hz, 3 H), 0.86 (d, J = 6.6 Hz, 3 H), 0.79 (s, 3 H), 0.64 (s, 3 H),
¹³ C NMR (100 MHz, CDCl ₃ ): δ ppm
141.9 (s), 141.4 (s), 139.1 (s), 138.0 (s), 135.8 (s), 135.4 (s), 131.5 (d), 131.2 (d), 129.2 (d), 128.7 (d), 128.4-128.3 (8 doublets overlap: 4 peaks are observed), 128.1 (d, 2C), 127.6 (d, 2C), 126.3 (d), 126.1 (d), 99.4 (d), 81.4 ( d), 81.0 (d), 78.6 (d), 76.1 (d), 73.5 (t), 73.3 (d), 72.5 (t), 71.1 (t), 70.4 (t), 69.9 (t), 54.6 ( d), 56.4 (d), 54.5 (d), 44.9 (d), 42.7 (s), 40.2 (t), 39.7 (t), 37.2 (t), 36.3 (t), 36.0 (d), 35.8 ( s), 35.6 (d), 34.9 (t), 33.2 (t, 2C), 32.3 (t), 29.8 (t), 29.0 (t), 28.4 (t), 28.2 (d), 24.4 (t), 24.0 (t), 23.0 (q), 22.7 (q), 21.4 (t), 18.8 (q), 12.5 (q), 12.2 (q),
HRMS-ESI (m / z): [M + Na] ⁺
Calculated (C ₆₃ H ₈₄ ²³ NaO ₆ as) 959.6166, found 959.6145.

Examples 20 to 24

The reaction was performed in the same manner as in Example 3 except that the alcohol described in Table 3 below was used instead of cyclohexylmethanol. The yield of the resulting compound and the ratio of anomers are shown in Table 3 below. Examples 20 to 23 are the yields determined using ¹ H-NMR (solvent: CDCl ₃ , standard substance: acetone), and Example 24 is the isolated yield. The resulting compound is subjected to catalytic hydrogenation to deprotect benzyl groups such as 2 and 4 and bibenzyl 2,2'-bismethylene groups at 3 and 6 and then using each alcohol with acetic anhydride and pyridine. Acetylation led to known compounds, and α / β isomers were identified.

The physicochemical properties of the compound obtained in Example 20 are as follows.
Α form [α] _D ²⁴ = + 31.4 (c = 0.615, CHCl ₃ ),
IR (ATR): 3041, 3027, 2922, 2868, 1735, 1540, 1455, 1368, 1216, 1095, 1028, 921, 850, 821 cm ^-1 ,
¹ H NMR (400 MHz, CDCl ₃ ): δ ppm
7.44-7.27 (m, 11 H), 7.24-7.09 (m, 7 H), 5.06 (d, J = 4.1 Hz, 1 H), 4.82 (d, J = 12.1 Hz, 1 H), 4.75 (d, J) J = 10.1 Hz, 1 H), 4.62 (d, J = 12.1 Hz, 1 H), 4.49 (d, J = 10.8 Hz, 1 H), 4.35 (d, J = 11.9, 1 H), 4.3 (d , J = 10.8, 1 H, 4.23 (d, J = 10.1, 1 H), 4.21 (d, J = 11.9 Hz, 1 H), 4.07 (br d, J = 7.3 Hz, 1 H), 4.01 ( m, 6.6 Hz, 2 H), 3.78-3.71 (m 3 H), 3.49 (dt, J = 10.5, 4.1 Hz, 1 H), 4.19-2.89 (m, 4 H), 2.38 (ddt, J = 16.5) , 7.1, 2.5 Hz, 1 H), 2.00 (br d, J = 11.9 Hz, 1 H), 1.67-1.60 (m, 2 H), 1.35-1.26 (m, 3 H), 0.95-0.82 (m, 2 H, overlapping with methyl), 0.88 (d, J = 6.5 Hz, 3 H), 0.85 (d, J = 6.9 Hz, 3 H), 0.78 (d, J = 6.9 Hz, 3 H),
¹³ C NMR (100 MHz, CDCl ₃ ): δ ppm
142.1 (s), 141.3 (s), 139.2 (s), 138.7 (s), 136.0 (s), 135.9 (s), 131.5 (d), 131.3 (d), 129.3 (d, 2C), 128.7 (d) ), 128.6 (d), 128.3-128.2 (d, 4 doublets overlap: 3 peaks are observed), 127.9 (d, 2C), 127.7 (d, 2C), 127.5 (d), 127.4 (d ), 126.3 (d), 126.2 (d), 72.9 (d), 75.6 (d), 75.1 (d), 73.6 (d), 73.4 (t), 73.1 (t), 72.4 (d) ), 71.2 (t), 69.9 (t), 67.8 (t), 48.2 (d), 40.4 (t), 34.6 (t), 33.8 (t), 33.7 (t), 31.5 (d), 25.1 (d) ), 23.2 (t), 22.5 (q), 21.3 (q), 16.1 (q),
HRMS-ESI (m / z): [M + Na] ⁺
Calc. (As C ₄₆ H ₅₆ ²³ NaO ₆ ) 727.3975, found 727.3983.
Β body [α] _D ²⁵ = + 1.3 (c = 0.59, CHCl ₃ ),
IR (ATR): 3029, 2922, 2868, 1731, 1604, 1496, 1455, 1365, 1214, 1093, 849, 822, 752 cm ^-1 ,
¹ H NMR (400 MHz, CDCl ₃ ): δ ppm
7.42-7.28 (m, 11 H), 7.25-7.11 (m, 7 H), 4.88 (d, J = 7.1 Hz, 1 H), 4.81 (d, J = 11.9 Hz, 1 H), 4.7 (d, J) J = 11.7 Hz, 1 H, 4.45 (d, J = 10.3 Hz, 1 H), 4.38 (d, J = 10.3 Hz, 1 H), 4.38 (d, J = 11.9 Hz, 1 H), 4.32 ( d, J = 11.9 Hz, 1 H), 4.23 (d, J = 10.5 Hz, 1 H), 4.19 (d, J = 10.5 Hz, 1 H), 4.08 (br m, 1 H), 3.83 (br s , 1 H), 3.78 (br s, Hz, 1 H), 3.65 (dd, J = 9.4, 6.6 Hz, 1 H), 4.59 (dd, J = 7.1, 3.2 Hz, 1 H), 3.57 (dd, J = 6.6, 3.2 Hz, 1 H, 3.36 (dt, J = 10.6, 4.4 Hz, 1 H), 3.03-2.87 (m, 4 H), 2.37 (ddt, J = 16.0, 6.9, 2.1 Hz, 1 H), 2.16 (br d, J = 12.1 Hz, 1 H), 1.63-1.59 (m, 3 H), 1.47-1.25 (m, 3 H), 1.09-0.93 (m, 1 H), 0.9 (d , J = 6.4 Hz, 3 H), 0.85 (d, J = 7.1 Hz, 3 H), 0.72 (d, J = 7.1 Hz, 3 H),
¹³ C NMR (100 MHz, CDCl ₃ ): δ ppm
141.9 (s), 141.4 (s), 139.0 (s), 138.0 (s), 135.8 (s), 135.3 (s), 131.5 (d), 131.2 (d), 129.3 (d), 128.8 (d, 2C) ), 128.4 (d, 2C), 128.3-128.2 (five doublets overlap: three peaks are observed), 128.1 (d, 2C), 127.7 (d, 2C), 126.3 (d), 126.1 (d ), 101.7 (d), 81.8 (d), 81.5 (d), 81.4 (d), 76.0 (d), 73.5 (t), 73.2 (d), 72.4 (t), 71.0 (t), 70.6 (t) ), 69.9 (t), 48.8 (d), 43.5 (t), 34.5 (t), 33.2 (t, 2 C), 31.9 (d), 25.0 (d), 23.1 (t), 22.5 (q), 21.4 (q), 16.1 (q),
HRMS-ESI (m / z): [M + Na] ⁺
Calculated (as C ₄₆ H ₅₆ ²³ NaO ₆ ) 727.3975, found 727.3986.

The physicochemical properties of the compound obtained in Example 21 are as follows.
Α form [α] _D ²³ = + 14.5 (c = 0.54, CHCl ₃ ),
IR (ATR): 3063, 3026, 2951, 2921, 2867, 1735, 1495, 1495, 1366, 1239, 1216, 1071, 1037, 919, 848, 789 cm ^-1 ,
¹ H NMR (400 MHz, CDCl ₃ ): δ ppm
7.52-7.58 (m, 11 H), 7.23-7.02 (m, 7 H), 5.05 (d, J = 3.43 Hz, 1 H), 4.73 (d, J = 11.9 Hz, 1 H), 4.58 (d, J) J = 11.9 Hz, 1 H), 4.53 (d, J = 9.9 Hz, 1 H), 4.44 (d, J = 11.9 Hz, 1 H), 4.38 (d, J = 11.9 Hz, 1 H), 4.33 ( d, J = 11.7 Hz, 1 H), 4.28 (d, J = 9.9 Hz, 1 H), 4.21 (dd, J = 7.8, 4.4 Hz, 1 H), 4.15 (d, J = 11.9 Hz, 1 H) ), 4.06 (dd, J = 7.1, 4.4 Hz, 1 H), 4.02 (m, 1 H), 3.66 (dd, J = 10.3, 3.0 Hz, 1 H), 3.58 (dd, J = 7.8, 3.4 Hz) , 1 H), 3.54 (dd, J = 10.3, 3.9 Hz, 1 H), 3.45 (dt, J = 10.5, 4.4 Hz, 1 H), 3.06-2.85 (m, 4 H), 2.27 (ddt, J = 13.5, 6.6, 1.6 Hz, 1 H), 2.15 (br d, J = 12.4 Hz, 1 H), 1.69-1.58 (m, 3 H), 1.36-12.23 (m, 3 H), 1.11-0.90 m, 1 H, overlapping with methyl), 0.88 (d, J = 6.6 Hz, 3 H), 0.85 (d, J = 7.1 Hz, 3 H), 0.71 (d, J = 6.9 Hz, 3 H),
¹³ C NMR (100 MHz, CDCl ₃ ): δ ppm
141.7 (s), 139.6 (s), 138.7 (s), 138.6 (s), 135.7 (s), 135.7 (s), 131.6 (d), 130.1 (d), 129.0 (d), 129.0 (d), 128.8 (d), 128.4 (d, 2C), 128.2-128.1 (3 doublets overlap: 2 peaks are observed), 127.9-127.8 (4 doublets overlap: 2 peaks are observed), 127.6 (d), 127.4 (d), 126.4 (d), 126.2 (d), 98.0 (d), 81.6 (d), 79.4 (d), 75.4 (d), 73.2 (d), 73.1 (t), 72.4 (t), 71.8 (d), 71.7 (t), 70.0 (t), 64.6 (t), 48.6 (d), 43.1 (t), 34.5 (t), 33.5 (t), 33.2 (t), 31.8 (d), 25.0 (d), 23.2 (t), 22.5 (q), 21.3 (q), 16.3 (q),
HRMS-ESI (m / z): [M + Na] ⁺
Calc. (As C ₄₆ H ₅₆ ²³ NaO ₆ ) 727.3975, found 727.3987.
Β body [α] _D ²² = −26.3 (c = 0.76, CHCl ₃ ),
IR (ATR): 3058, 3028, 2949, 2921, 2867, 1731, 1604, 1454, 1364, 1244, 1216, 1089, 1048, 991, 941, 846, 752 cm ^-1 ,
¹ H NMR (400 MHz, CDCl ₃ ): δ ppm
7.44-7.28 (m, 11 H), 7.25-7.10 (m, 7 H), 4.87 (d, J = 7.1 Hz, 1 H), 4.85 (d, J = 12.2 Hz, 1 H), 4.68 (d, J) J = 12.2 Hz, 1 H), 4.52 (d, J = 10.8 Hz, 1 H), 4.38 (d, J = 11.9 Hz, 1 H), 4.35 (d, J = 10.8 Hz, 1 H), 4.32 ( d, J = 11.9 Hz, 1 H), 4.26 (d, J = 10.5 Hz, 1 H), 4.2 (d, J = 10.5 Hz, 1 H), 3.99 (m, 1 H), 3.88 (dd, J = 2.7, 2.3 Hz, 1 H), 3.81 (dd, J = 2.8, 2.7 Hz, 1 H), 3.66 (dd, J = 9.6, 4.8 Hz, 1 H), 3.58 (dd, J = 9.6, 8.2 Hz , 1 H), 3.54 (dd, J = 7.1, 2.8 Hz, 1 H), 3.45 (dt, J = 10.6, 4.4 Hz, 1 H), 3.06-2.85 (m, 4 H), 2.27 (ddt, J = 13.7, 6.6, 2.5 Hz, 1 H), 2.15 (br d, J = 12.2 Hz, 1 H), 1.67-1.61 (m, 2 H), 1.38-1.18 (m, 3 H), 1.03-0.83 ( m, 2 H, overlapping with methyl), 0.90 (d, J = 6.6 Hz, 3 H), 0.86 (d, J = 7.1 Hz, 3 H), 0.75 (d, J = 6.9 Hz, 3 H),
¹³ C NMR (100 MHz, CDCl ₃ ): δ ppm
141.9 (s), 141.3 (s), 139.2 (s), 136.0 (s), 135.6 (s), 131.4 (s), 131.4 (d), 131.2 (d), 129.4 (d), 128.7 (d), 128.7 (d), 128.4-128.3 (9 doublets overlap: 3 peaks are observed), 128.1 (d, 2C), 127.7 (d), 127.6 (d), 98.4 (d), 81.8 (d) , 80.9 (d), 77.3 (d), 76.3 (d), 73.4 (t), 73.2 (d), 72.5 (t), 71.2 (t), 70.6 (t), 69.6 (t), 48.2 (d) , 41.0 (t), 34.7 (t), 33.4 (t, 2C), 31.7 (d), 25.3 (d), 23.4 (t), 22.5 (q), 21.2 (q), 16.1 (q),
HRMS-ESI (m / z): [M + Na] ⁺
Calc. (As C ₄₆ H ₅₆ ²³ NaO ₆ ) 727.3975, found 727.3975.

The physicochemical properties of the compound obtained in Example 22 are as follows.
Α form [α] _D ²¹ = + 17.3 (c = 0.5, CHCl ₃ ),
IR (ATR): 3062, 3022, 2906, 285, 1730, 1604, 1454, 1354, 1304, 1216, 1150, 1070, 1043, 982, 941, 909, 812, 754 cm- ¹ ,
¹ H NMR (400 MHz, CDCl ₃ ): δ ppm
7.51-7.27 (m, 10 H), 7.24-7.02 (m, 8 H), 5.34 (d, J = 3.7 Hz, 1 H), 4. 76 (d, J = 12.4 Hz, 1 H), 4.58 (d, J) J = 12.4 Hz, 1 H), 4.54 (d, J = 9.9 Hz, 1 H), 4.45 (d, J = 11.9 Hz, 1 H), 4.42 (d, J = 11.9 Hz, 1 H), 4.38 ( d, J = 11.9 Hz, 1 H), 4.26 (d, J = 9.9 Hz, 1 H), 4.23 (dd, J = 7.8, 4.8 Hz, 1 H), 4.20 (d, J = 11.9 Hz, 1 H) ), 4.08-4.03 (m, 2 H), 3. 76 (dd, J = 10.8, 2.8 Hz, 1 H), 3.71 (dd, J = 10.8, 2.0 Hz, 1 H), 3.64 (dd, J = 7.8, 3.7 Hz, 1 H), 3.06-2.94 (m, 4 H), 2.12 (br s, 3 H), 1. 84 (br d, J = 11.7 Hz, 3 H), 1.79 (br d, J = 11.5 Hz, 3 H), 1.61 (s, 6 H),
¹³ C NMR (100 MHz, CDCl ₃ ): δ ppm
141.7 (s), 139.6 (s), 138.9 (s), 136.8 (s), 135.7 (s), 131.7 (s), 131.7 (d), 130.8 (d), 129.1 (d), 120.0 (d), 128.8 (d), 128.4 (d, 2C), 128.2 (d, 2C), 128.1 (d), 127.9 (d, 2C), 127.8 (d, 2C), 127.6 (d), 127.4 (d), 126.4 ( d), 123.2 (d), 89.2 (d), 79.5 (d), 75.2 (d), 74.4 (s), 73.2 (t), 72.9 (d), 72.2 (t), 71.6 (t), 71.5 ( d), 69.9 (t), 64.4 (t), 42.6 (t, 3C), 36.4 (t, 3C), 33.6 (t), 33.4 (t),
HRMS-ESI (m / z): [M + Na] ⁺
Calculated (C ₄₆ H ₅₂ ²³ NaO ₆ as) 723.3662, found 723.3652.
Β body [α] _D ²¹ = −6.41 (c = 0.245, CHCl ₃ ),
IR (ATR): 3062, 3027, 2905, 2951, 1728, 1604, 1454, 1354, 1305, 1215, 1071, 1048, 941, 844, 813, 749 cm ^-1 ,
¹ H NMR (400 MHz, CDCl ₃ ): δ ppm
7.45-7.27 (m, 10 H), 7.23-7.08 (m, 8 H), 5.10 (d, J = 7.6 Hz, 1 H), 4.89 (d, J = 12.1 Hz, 1 H), 4.72 (d, J) J = 12.4 Hz, 1 H), 4.42 (d, J = 10.3 Hz, 1 H), 4.37 (d, J = 12.1 Hz, 1 H), 4.36 (d, J = 10.3 Hz, 1 H), 4.29 ( d, J = 12.1 Hz, 1 H), 4.26 (d, J = 10.5 Hz, 1 H), 4.14 (d, J = 10.5 Hz, 1 H), 4.01 (m, 1 H), 3.82 (dd, J = 2.4, 2.1 Hz, 1 H), 3. 78 (dd, J = 2.8, 2.4 Hz, 1 H), 3.62 (dd, J = 9.4, 5.0 Hz, 1 H), 3.56 (dd, J = 9.4, 6.0 Hz , 1 H), 3.55 (dd, J = 7.6, 2.4 Hz, 1 H), 3.04-2.84 (m, 4 H), 2.14 (br s, 3 H), 1.91 (br d, J = 11.7 Hz, 3 H), 1.8 (br d, J = 11.7 Hz, 3 H), 1.62 (br s, 6 H),
¹³ C NMR (100 MHz, CDCl ₃ ): δ ppm
141.9 (s), 141.3 (s), 139.2 (s), 135.8 (s), 135.5 (s), 131.4 (s), 131.4 (d), 131.2 (d), 129.2 (d), 128.7 (d), 128.6 (d), 128.4 (d, 2C), 128.3 (d, 3C), 128.2 (d, 4C), 127.6 (d), 127.5 (d), 126.3 (d), 126.1 (d), 93.7 (d) , 81.9 (d), 81.0 (d), 75.9 (d), 74.9 (s), 73.5 (t), 73.3 (d), 72.5 (t), 71.0 (t), 70.5 (t), 69.6 (t) , 42.9 (t, 3C), 36.5 (t, 3C), 33.1 (t, 2C), 30.8 (d, 3C),
HRMS-ESI (m / z): [M + Na] ⁺
Calculated (C ₄₆ H ₅₂ ²³ NaO ₆ as) 723.3662, found 723.3652.

The physicochemical properties of the compound obtained in Example 23 are as follows.
Α form [α] _D ²⁴ = +29.6 (c = 0.48, CHCl ₃ ),
IR (ATR): 3062, 3029, 2905, 2859, 1604, 1496, 1362, 1215, 1159, 1072, 912, 753, 698, 667, 630, 610 cm ^-1 ,
¹ H NMR (400 MHz, CDCl ₃ ): δ ppm
7.41-7.27 (m, 21 H), 7.24-7.00 (m, 12 H), 5.01 (d, J = 3.2 Hz, 1 H), 4.94 (d, J = 11.0 Hz, 1 H), 4.82 (d, J) J = 11.0 Hz, 1 H), 4.81 (d, J = 11.0 Hz, 1 H), 4.75 (d, J = 11.7 Hz, 1 H), 4.72 (d, J = 11.7 Hz, 1 H), 4.68 ( d, J = 11.0 Hz, 1 H), 4.6 (d, J = 12.4 Hz, 1 H), 4.59 (d, J = 12.4 Hz, 1 H), 4.56 (d, J = 11.2 Hz, 1 H), 4.55 (d, J = 3.4 Hz, 1 H H-1), 4.42 (d, J = 11.2 Hz, 1 H), 4.36 (d, J = 11.2 Hz, 1 H), 4.32 (d, J = 11.9 Hz) , 1 H), 4.2 (d, J = 11.2 Hz, 1 H), 4. 13 (d, J = 11.9 Hz, 1 H), 4. 13 (dd, J = 7.0, 3.8 Hz, 1 H), 4.02 (dd, J J = 3.8, 1.8 Hz, 1 H, 4 (dd, J = 3.2, 1.8 Hz, 1 H), 3.98-3.94 (m, 2 H), 3.76 (dd, J = 7.0, 3.2 Hz, 1 H) , 3.76-3.73 (m, 1 H), 3.90-3.57 (m, 4 H), 3.43 (dd, J = 3.4, 9.6 Hz, 1 H), 3.32 (s, 3 H), 3.10-2.91 (m, 4 H),
¹³ C NMR (100 MHz, CDCl ₃ ): δ ppm
141.8 (s), 140.3 (s), 139.1 (s), 138.9 (s), 138.7 (s), 138.7 (s), 138.4 (s), 136.2 (s), 135.7 (s), 131.5 (d), 131.0 (d), 129.2 (d), 129.1 (d), 128.8 (d), 128.5-128.4 (10 doublets overlap: 3 peaks are observed), 128.2 (d, 2C), 128.2 (d, 2C), 127.9 (d, 2C), 127.9 (d, 2C), 127.8 (d, 2C), 127.7-127.6 (5 doublets overlap: 3 peaks are observed), 127.4 (d), 126.4 (12 d), 126.2 (d), 98.2 (d), 96.8 (d), 82.2 (d), 80.1 (d), 78.5 (d), 78.0 (d), 75.7 (t), 75.1 (t), 74.8 ( d), 73.5 (t), 73.0 (one doublet and one triplet), 72.5 (t), 72.4 (d), 71.6 (t), 70.4 (d), 69.6 (t), 66.4 (t) , 66.1 (t), 55.2 (q), 33.6 (t), 33.5 (t),
HRMS-ESI (m / z): [M + Na] ⁺
Calculated value (as C ₆₄ H ₆₈ ²³ NaO ₁₁ ) 1035.4659, found 1035.4659.

The physicochemical properties of the compound obtained in Example 24 are as follows.
Α form [α] _D ²³ = −0.752 (c = 0.355, CHCl ₃ ),
IR (ATR): 3055, 3020, 2980, 2936, 2901, 1495, 1454, 1381, 1256, 1212, 1167, 1071, 998, 910, 863, 734 cm ^-1 ,
¹ H NMR (400 MHz, CDCl ₃ ): δ ppm
7.44-7.15 (m, 16 H), 7.06-7.04 (m, 2 H), 5.5 (d, J = 4.8 Hz, 1 H), 4. 98 (d, J = 3.6 Hz, 1 H), 4.77 (d, J) J = 12.4 Hz, 1 H), 4.63 (d, J = 12.4 Hz, 1 H), 4.57-4.55 (m, 2 H), 4.41 (d, J = 11.6 Hz, 1 H), 4.37 (d, J = 11.6 Hz, 1 H), 4.34 (d, J = 12.0 Hz, 1 H), 4.32 (dd, J = 8.0, 2.0 Hz, 1 H), 4.31 (d, J = 11.6 Hz, 1 H), 4.28 (dd, J = 4.8, 2.8 Hz, 1 H), 4.28 (d, J = 12.0 Hz, 1 H), 4.14 (dd, J = 6.8, 3.6 Hz, 1 H), 4.07-4.01 (m, 3 H ), 3.83 (dd, J = 10.8, 6.0 Hz, 1 H), 3.77 (dd, J = 10.8, 3.2 Hz, 1 H), 3.73-3.67 (m, 3 H), 3.09-2.91 (m, 4 H) ), 1.49 (s, 3 H), 1.43 (s, 3 H), 1.31 (s, 3 H), 1.28 (s, 3 H),
¹³ C NMR (100 MHz, CDCl ₃ ): δ ppm
141.7 (s), 140.1 (s), 138.8 (s), 138.7 (s), 136.3 (s), 135.7 (s), 131.6 (d), 131.0 (d), 129.2 (d), 129.0 (d), 128.8 (d), 128.4 (d, 2C), 128.4 (d), 128.2 (d, 2C), 127.8 (d, 2C), 127.8 (d, 2C), 127.6 (d), 127.4 (d), 126.4 ( d), 126.3 (d), 109.2 (s), 108.7 (s), 96.8 (d), 96.4 (d), 78.8 (d), 74.9 (d), 73.0 (t), 72.8 (d), 72.4 ( t), 72.1 (d), 71.4 (t), 70.9 (d), 70.8 (d), 70.7 (d), 69.7 (t), 66.7 (t), 66.2 (d), 65.7 (t), 33.5 ( t), 33.3 (t), 26.3 (q), 26.2 (q), 25.1 (q), 24.6 (q),
HRMS-ESI (m / z): [M + Na] ⁺
Calculated value (as C ₄₈ H ₅₆ ²³ NaO ₁₁ ) 831 .372, found 831.3733.

Example 25

Α-Glycosylation reaction of phenyl 2,4-di-O-benzyl-3,6-O- [bibenzyl-2,2'-bis (methylene)]-1-thio-β-D-glucopyranoside Molecular sieves 4A (82.8 mg), phenyl 2,4-di-O-benzyl-3,6-O- [bibenzyl-2,2'-bis (methylene)]-1-thio-β-D-glucopyranoside (17.9 mg A mixture of 27.2 μmol) and ethyl acetate (1.4 mL) was stirred at 0 ° C. for 5 minutes. To this mixture was added N-bromosuccinimide (NBS; 5.1 mg, 29 μmol) and cyclohexylmethanol (3.7 mg, 33 μmol) at 0 ° C. and stirred at 0 ° C. for 2 hours. The reaction mixture was then quenched with 10% aqueous sodium sulfite solution (10 mL) and filtered through cotton and celite to remove molecular sieves 4A. The filtrate was extracted with ethyl acetate (20 mL × 2), the extracts were combined, and this was washed with 10% aqueous sodium sulfite solution (20 mL) and saturated brine (20 mL). The washed extract was dried over anhydrous magnesium sulfate, filtered through a cotton plug, and the solvent was evaporated to give a crude product. The yield and ratio of anomeric isomers of cyclohexylmethyl 2,4-di-O-benzyl-3,6-O- [bibenzyl-2,2'-bis (methylene)]-D-glucopyranoside in the crude product are ^The yield is 71% as determined from ¹ H-NMR (solvent: CDCl ₃ , standard substance: acetone, α / β is the ratio of the integrated value of the OCH ₂ hydrogen peaks of the cyclohexylmethoxy group), and the yield is 71%. The isomer ratio was α / β = 96/4.

Example 26
Α-Glycosylation reaction of phenyl 2,4-di-O-benzyl-3,6-O- [bibenzyl-2,2'-bis (methylene)]-1-thio-α-D-glucopyranoside Molecular sieves 4A (33.1 mg), phenyl 2,4-di-O-benzyl-3,6-O- [bibenzyl-2,2'-bis (methylene)]-1-thio-α-D-glucopyranoside (7.4 mg) A mixture of 11 μmol) and ethyl acetate (0.6 mL) was stirred at 0 ° C. for 5 minutes. To this mixture was added N-bromosuccinimide (NBS; 2.4 mg, 13 μmol) and cyclohexylmethanol (1.5 mg, 13 μmol) at 0 ° C. and stirred at 0 ° C. for 1 hour. The reaction mixture was then quenched with 10% aqueous sodium sulfite solution (10 mL) and filtered through cotton and celite to remove molecular sieves 4A. The filtrate was extracted with ethyl acetate (10 mL × 3), the extracts were combined, and this was washed with 10% aqueous sodium sulfite solution (10 mL) and saturated brine (10 mL). The washed extract was dried over anhydrous magnesium sulfate, filtered through a cotton plug, and the solvent was evaporated to give a crude product. The yield and ratio of anomeric isomers of cyclohexylmethyl 2,4-di-O-benzyl-3,6-O- [bibenzyl-2,2'-bis (methylene)]-D-glucopyranoside in the crude product are ^The yield is 67% as determined from ¹ H-NMR (solvent: CDCl ₃ , standard substance: acetone, and α / β is the ratio of the integrated value of OCH ₂ hydrogen peaks of cyclohexylmethoxy group), and the yield is 67%. The isomer ratio was α / β = 95/5.

Example 27

Activated molecular sieves 4A (85.3 mg), phenyl 2,4-di-O-benzyl-3,6-O- [bibenzyl-2,2'-bis (methylene)]-1-thio-β-D- Glucopyranoside (18.4 mg, 27.9 μmol) and (+)-dihydrocholesterol (13.5 mg, 34.7 μmol) were added to ethyl acetate (1.4 mL) and stirred at 0 ° C. for 5 minutes. While cooling to 0 ° C., N-bromosuccinimide (NBS, 5.8 mg, 33 μmol) was added to the reaction solution, and the mixture was stirred for 2 hours while maintaining the temperature. The reaction was quenched by addition of 10% aqueous sodium sulfite solution. The resulting reaction mixture was filtered through cotton and celite to remove molecular sieves 4A. The filtrate was extracted with ethyl acetate (20 mL × 2), and the extracts were combined and washed with 10% aqueous sodium sulfite solution (20 mL) and saturated brine (20 mL). Further, the extract solution was dried over anhydrous magnesium sulfate and filtered through a cotton plug, and then the solvent was distilled off to obtain a crude product. The mixing ratio of the anomeric isomers of the crude product was determined from the ratio of the integrated value of the anomeric hydrogen peak in the ¹ H-NMR spectral data (400 MHz, CDCl ₃ ) to be α: β = 98: 2. The obtained crude product is purified by silica gel chromatography (SiO ₂ : 1 g, n-hexane / ethyl acetate (volume ratio) = 1/0 → 14/1) to obtain dihydrocholesteryl 2,4-di-isomer as a mixture of isomers. -O-benzyl-3,6-O- [bibenzylbis-2,2 '-(methylene)]-D-glucopyranoside (23.6 mg, 25.2 μmol, yield: 90%) was isolated as a colorless syrup .

Example 28

Preparation of 2,4-di-O- [bibenzylbis- 2,2 '-(methylene)]-D-glucopyranosyl-trichloroacetimidate 2,4-di-O-benzyl-3,6-O- [bibenzyl- 2,2′-bis (methylene)]-D-glucopyranose (100 mg, 0.177 mmol), cesium carbonate (Cs ₂ CO ₃ ; 58.0 μg, 0.177 mmol), and trichloroacetonitrile (0.16 mL, 59 mmol) was stirred in dry diethyl ether (1 mL) at room temperature for 2 hours. The reaction mixture was filtered through cotton, Celite, SiO ₂ and Celite to remove Cs ₂ CO ₃ from the reaction mixture. The filtrate is concentrated to give 2,4-di-O- [bibenzylbis-2,2 '-(methylene)]-D-glucopyranosyl-trichloroacetimidate (128 mg, quantitative, 45: 55) as a crude product A mixture of diastereomers was obtained. The resulting crude product was used in Example 29 without further purification.

The physicochemical properties of 2,4-di-O- [bibenzylbis-2,2 '-(methylene)]-D-glucopyranosyl-trichloroacetimidate are as follows.
IR (ATR): 3333, 3064, 3029, 2941, 2869, 1732, 1726, 1496, 1456, 1289, 1217, 1075, 1030, 971, 834, 796, 755, 699, 648 cm- ¹ ,
¹ H NMR (partial data, 400 MHz in CDCl ₃ , a mixture of α and β isomers): δ ppm
8.43 (s), 8.37 (s), 6.23 (d, J = 1.8 Hz), 6.18 (d, J = 4.7 Hz),
¹³ C NMR (partial data, 100 MHz in CDCl ₃ , a mixture of α and β isomers): δ ppm
161.5 (s), 161.1 (s), 97.0 (d), 95.1 (d), 91.6 (s), 91.3 (s).

Example 29

Α-Glycosylation reaction of 2,4-di-O- [bibenzylbis-2,2 '-(methylene)]-D-glucopyranosyl-trichloroacetimidate Molecular sieves 4A (150 mg), 2,4-di-O -[Bibenzylbis-2,2 '-(methylene)]-D-glucopyranosyl-trichloroacetimidate (20.1 mg, 44.1 μmol), and cyclohexylmethanol (6.50 μL, 53.0 μmol) in dry diethyl ether (1 mL) The mixture was stirred at room temperature for 15 minutes. The mixture was cooled to −40 ° C., then TiCl ₄ (5.80 μL, 53.0 μmol) was added to the mixture and stirred at −40 ° C. for 1 hour. The reaction mixture was then quenched by the addition of saturated aqueous NaHCO ₃ (1 mL). The quenched reaction mixture was filtered through cotton and celite to remove molecular sieves 4A. The filtrate was extracted with diethyl ether, and the organic layer was washed successively with saturated aqueous NaHCO ₃ solution, water and saturated brine. Further, the extract solution was dried over anhydrous magnesium sulfate and filtered through a cotton plug, and then the solvent was distilled off to obtain a crude product. The yield and ratio of anomeric isomers of cyclohexylmethyl 2,4-di-O-benzyl-3,6-O- [bibenzyl-2,2'-bis (methylene)]-D-glucopyranoside in the crude product are ^The yield is 62% as determined from ¹ H-NMR (solvent: CDCl ₃ , standard substance: acetone, and α / β is the ratio of the integrated value of the OCH ₂ hydrogen peaks of the cyclohexylmethoxy group). The isomer ratio was α / β = 94/6.

Examples 30 to 39
A reaction was carried out in the same manner as in Example 29 except that TiCl ₄ and molecular sieves 4A were replaced by the activators listed in Table 4 below, and the reaction temperature and reaction time were replaced by the ones listed in the following table. . The yield of the obtained cyclohexylmethyl 2,4-di-O-benzyl-3,6-O- [bibenzyl-2,2'-bis (methylene)]-D-glucopyranoside and the ratio of anomers to the examples It is determined in the same manner as 29 and is shown in Table 4 below. In Table 4, TMS is trimethylsilyl, TES is triethylsilyl, TBS is tributylsilyl, TIPS is triisopropylsilyl, Tf is trifluoromethylsulfonyl, Si-gel is silica gel 60 (pH = 6.8; manufactured by Merck) MS stands for molecular sieves, and other abbreviations are as defined above. In Example 39, only molecular sieves 4A was used as an activating agent.

Examples 40 to 44
A reaction was carried out in the same manner as in Example 29 except that the reaction temperature was -10 ° C, TiCl ₄ was TBSOTf, the reaction solvent and the reaction time were as described in Table 5 below. The yield of the obtained cyclohexylmethyl 2,4-di-O-benzyl-3,6-O- [bibenzyl-2,2'-bis (methylene)]-D-glucopyranoside and the ratio of anomers to the examples It is determined in the same manner as 29 and is shown in Table 5 below. The abbreviations used in Table 5 are the same as above.

Example 45

2,4-di-O-benzyl-3,6-O- [bibenzyl-2,2'-bis (methylene)]-D-glucopyranose (10.0 mg, 17.6 μmol) in CH ₂ Cl ₂ (0 Oxalyl chloride (2.5 mg, 20 μmol) was added to a mixed solvent solution of .5 mL) and DMF (50 μL) and the mixture was stirred at room temperature. The reaction mixture was concentrated to give a crude product. The resulting crude product and cyclohexylmethanol (2.4 mg, 21 μm) and activated molecular sieve 4A (17.6 mg) were stirred in diethyl ether (0.5 mL) at room temperature for 1 day. The reaction was quenched by the addition of saturated aqueous NaHCO ₃ (5 mL) to the reaction mixture. After further addition of diethyl ether (20 mL), the mixture was filtered through cotton and celite to remove molecular sieves 4A. Ethyl acetate (30 mL) was added to the filtrate, extraction was performed, and the organic layer was washed successively with water (5 mL) and saturated brine (5 mL). The organic layer was further dried over anhydrous magnesium sulfate, filtered through a cotton plug, and the solvent was evaporated to give a crude product as a mixture of anomeric isomers. The obtained crude product is purified by silica gel chromatography (SiO ₂ : 200 mg, ethyl acetate / n-hexane (volume ratio) = 1/10 → 1/1) to obtain cyclohexylmethyl 2,4-di as an isomer mixture. -O-benzyl-3,6-O- [bibenzyl-2,2'-bis (methylene)]-D-glucopyranoside (mixture ratio of anomers of α: β = 92: 8, 3.1 mg, 4.7 μmol , Yield: 27%) and unreacted starting material (5.5 mg, 9.7 μmol, recovery: 55%) were isolated. Further, the mixing ratio of the anomeric isomers was determined from the ratio of the integrated value of the hydrogen peak of OCH ₂ of the cyclohexylmethoxy group in the ¹ H-NMR spectrum.

Claims (3)

1. General formula (1)
   

   

   [Wherein, R ¹ represents a —SR ⁶ group (R ⁶ represents a lower alkyl group which may have a substituent or an aryl group which may have a substituent on the aromatic ring), —OR ^7] Group (R ⁷ represents a hydrogen atom, a protecting group of a hydroxyl group or a group acting as a leaving group with a bonded oxygen atom) or a halogen atom.
   R ² represents a hydrogen atom or a hydroxyl protective group.
   R ³ represents a hydrogen atom or a hydroxyl protective group.
   R ⁴ and R ⁵ are the same or different and each represents a lower alkyl group which may be substituted by a halogen atom, a lower alkoxy group which may be substituted by a halogen atom, a nitro group or a halogen atom.
   n represents an integer of 1 to 4; p and q each represent an integer of 0 to 4;
   The p R ^{4 s} may be the same or different, and the q R ^{5 s} may be the same or different.
   The p adjacent R ⁴ groups may be bonded to each other to form a benzene ring, and the q adjacent R ⁵ groups may be bonded to each other to form a benzene ring. ]
   The 3,6-O-bridged pyranose compound represented by, or its enantiomer.
2. The 3,6-O-bridged pyranose compound or the enantiomer thereof according to claim 1, wherein R ¹ in the general formula (1) is a halogen atom.
3. The 3,6-O-bridged pyranose compound according to claim 2 is a compound represented by the general formula (2)
   R ⁸ OH (2)
   [Wherein, R ⁸ represents a residue of a primary, secondary or tertiary alcohol. ]
   By reacting with an alcohol compound represented by the general formula (3)
   

   

   [Wherein, R ² , R ³ , R ⁴ , R ⁵ , R ⁸ , n, p and q are as defined above. ]
   A method of producing α-O-pyranoside represented by or its enantiomer.