JP2013166740A - 2,4-o-bridged pyranose inversion compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a pyranose compound to be used in a method for producing β-O-pyranoside with high selectivity and simply.SOLUTION: A 2,4-O-bridged pyranose inversion compound is a compound represented by general formula (1) or its enantiomer.

Description

  The present invention relates to 2,4-O-bridged inverted pyranose compounds.

  A compound in which pyranose (sugar) is glycosylated with a naturally occurring alcohol such as steroid (pyranoside) has two isomers, α-O-pyranoside and β-O-pyranoside. Among these, β-O-pyranoside is an important compound having various physiological activities.

  When pyranoside is produced by a general chemical synthesis, a mixture of α-O-pyranoside and β-O-pyranoside is obtained, and it is impossible to selectively produce β-O-pyranoside. is there.

  Β-O-pyranoside can be selectively produced by using a sugar donor in which the 2-position of the sugar is protected with an acyl group and applying a method involving a neighboring group (Non-Patent Document 1 to Non-Patent Document 5). However, there is a problem that the rate of glycosylation reaction is lowered due to the electron withdrawing property of the acyl group, and this method cannot be used when the acyl group cannot be introduced at the 2-position of the sugar.

  As a result of repeated studies to develop a method for β-O-glycosylation that does not have the above-mentioned drawbacks, the present inventors have found that β-O— by introduction of a bulky silyl group as shown in Non-Patent Document 6. A method of glycosylation was found. However, when the method is applied to β-O-glycosylation with a hydroxyl group having a large steric hindrance in subsequent studies, the target β-O-pyranoside cannot be produced with high yield and high selectivity. found.

  In the subsequent research process, the present inventors have made an epoch-making method capable of producing the target β-O-pyranoside with high yield and high selectivity even when applied to an alcohol having a hydroxyl group having a large steric hindrance. Succeeded in the development of a 3,6-O-bridged inverted pyranose compound, which is a pyranose donor (β-O-glycosylating agent) used in the invention (Patent Document 1).

  β-O-glycosylating agents are important compounds in the field of glycochemistry, and therefore, the development of numerous β-O-glycosylating agents having various chemical structures is desired in the field of glycochemistry.

International Publication No. 2009/102022

Love, K. R .; Andrade, R. B .; Seeberger, H. P. J. Org. Chem., 2001, 66, 8165-8176 Boons, G. -J. Contemp. Org. Synth., 1996, 3. 173-200 Kunz, H .; Harreus, A. Liebigs Ann. Chem., 1982, 41-48 Garegg. J. P .; Norberg, T. Acta. Chem. Scand. B., 1979, 33, 116-118 Koenigs. W .; Knorr, E. Chem. Ber., 1901, 957-981 Okada, Y .; Mukae, T .; Okajima, K .; Taira, M .; Fujita, M .; Yamada, H. Organic Letters, 2007, Vol. 9, No. 8, 1573-1576

  An object of the present invention is to provide a novel pyranose donor which is used in a method for easily producing β-O-pyranoside with high selectivity and has a completely different chemical structure from a known β-O-glycosylating agent. Is to provide.

  In order to solve such problems, the present inventors have conducted further intensive research, and as a result, have succeeded in developing a pyranose donor having a completely different chemical structure from the pyranose donors known to date. . That is, the present inventors succeeded in synthesizing a 2,4-O-bridged inverted pyranose compound represented by the following general formula (1), and the 2,4-O-bridged inverted pyranose compound has a desired β It has been found that it can be an -O-glycosylating agent or a precursor thereof. In particular, the 2,4-O-bridged inverted pyranose compound successfully synthesized for the first time by the present inventor is a general-purpose β for easily producing β-O-pyranoside with high selectivity for various sugar receptors. It has been found that it can be an -O-glycosylating agent. The present invention has been completed based on such findings.

  The present invention provides 2,4-O-bridged inverted pyranose compounds represented by items 1 to 5 below.

  Item 1. General formula (1)

[Wherein, R ¹ represents an —OR ⁶ group (R ⁶ represents a hydrogen atom or a hydroxyl-protecting group).
R ² represents an —OR ⁷ group (R ⁷ represents a hydrogen atom, a protecting group for a hydroxyl group, or a group that acts as a leaving group together with a bonding oxygen atom), and —SR ⁸ group (R ⁸ has a substituent). A lower alkyl group which may be substituted or an aryl group which may have a substituent on the aromatic ring) or a halogen atom.
R ¹ and R ² may combine to form —O—.
R ³ represents a hydrogen atom; a lower alkyl group which may have a substituent; —N (R ⁹ ) ₂ groups (R ⁹ represents a hydrogen atom or an amino group-protecting group, and two R ^9s are the same. Or they may be bonded to each other to form a ring) or -OR ¹⁰ group (R ¹⁰ represents a hydrogen atom or a hydroxyl-protecting group).
R ⁴ represents a lower alkyl group which may be substituted with a halogen atom, a lower alkoxy group which may be substituted with a halogen atom, a nitro group or a halogen atom.
R ⁵ represents a lower alkyl group which may be substituted with a halogen atom, a lower alkoxy group which may be substituted with a halogen atom, a nitro group or a halogen atom.
m and n each represent an integer of 0 to 4, and p represents an integer of 1 to 4.
Further, m R ^{4 s} may be the same or different, and n R ^{5 s} may be the same or different.
m number of R ⁴ adjacent to each other may form a benzene ring bonded to each other, R ⁵ may form a benzene ring bonded to each other adjacent the n mutually. ]
A 2,4-O-bridged inverted pyranose compound represented by the formula:

  Item 2. The 2,4-O-bridged inverted pyranose compound according to Item 1, wherein p represents an integer of 1 to 3, or an enantiomer thereof.

  Item 3. The 2,4-O-bridged inverted pyranose compound according to Item 1, wherein p is 2, or an enantiomer thereof.

Item 4. The 2,4-O-bridged inverted pyranose compound or the enantiomer thereof according to any one of Items 1 to 3, wherein R ¹ and R ² are bonded to each other to form —O—.

Item 5. R ¹ is an —OR ⁶ group (R ⁶ is the same as above), R ² is an —OR ⁷ group (R ⁷ is the same as above), —SR ⁸ group (R ⁸ is the same as above) or halogen The 2,4-O-bridged inverted pyranose compound or the enantiomer thereof according to any one of Items 1 to 3, which is an atom.

2,4-O-Bridged Inverted Pyranose Compound The 2,4-O-bridged inverted 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 , m, n and p are the same as described 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, such as a methyl group, an ethyl group, an n-propyl group, an 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. Can do.

  The lower alkoxy group refers to an alkoxy group having 1 to 6 carbon atoms, preferably an alkoxy group having 1 to 4 carbon atoms, such as a methoxy group, an ethoxy group, an n-propoxy group, an iso-propoxy group, and an n-butoxy group. , 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. .

  The lower alkanoyl group means an alkanoyl group having 1 to 6 carbon atoms. For example, acetyl group, propanoyl group, butanoyl group, 2-methylpropanoyl group, pentanoyl group, 2-methylbutanoyl group, 3-methylbutanoyl group Group, tert-butylcarbonyl group, hexanoyl group and the like.

  Examples of the aryl group include a phenyl group and a naphthyl group.

  Examples of the aryloxy group include a phenoxy group and a naphthyloxy group.

  Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.

  The hydroxyl-protecting group may be any existing hydroxyl-protecting group that has been widely known to date. For example, an allyl group; a methallyl group; a halogen atom, a lower alkoxy group, or an aryloxy group as a substituent group. A lower alkyl group which may have 5; a phenyl group which may have 1 to 3 halogen atoms, lower alkyl groups and lower alkoxy groups on the aromatic ring as a substituent; a halogen atom and lower as a substituent; Benzyl group optionally having 1 to 3 alkyl groups, lower alkoxy groups and nitro groups on the aromatic ring; having 1 to 3 halogen atoms, lower alkyl groups and lower alkoxy groups as substituents on the aromatic ring An optionally substituted triphenylmethyl group; a formyl group; a substituent optionally having 1 to 5 halogen atoms, lower alkoxy groups, aryl groups, and aryloxy groups An alkanoyl group; a benzoyl group optionally having 1 to 3 halogen atoms, lower alkyl groups and lower alkoxy groups on the aromatic ring as a substituent; selected from the group consisting of a lower alkyl group and an aryl group on a silicon atom Examples thereof include a silyl group in which at least one group is substituted by three. 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 , A triphenylmethyl group, a formyl group, an acetyl group, a propionyl group, a tert-butylcarbonyl group, a benzoyl group, a tri-lower alkylsilyl group, a tert-butyldiphenylsilyl group, and the like, more preferably an allyl group, a benzyl group, and a dimethyl group. Examples include benzyl group, 4-methoxybenzyl group, and tri-lower alkylsilyl group.

The group represented by R ⁷ that acts as a leaving group together with the bonded oxygen atom may be an existing group that has been widely known to date, and includes an imide group; 1 to 5 halogen atoms. A lower alkylsulfonyl group which may be substituted; a halogen atom, a lower alkyl group, a lower alkoxy group, a benzenesulfonyl group which may have 1 to 3 nitro groups on the aromatic ring, and the like. Specifically, trichloroacetimide group, 4-trifluoromethylbenzylthio-N- (4-trifluoromethylphenyl) formimide group, methanesulfonyl group, trifluoromethanesulfonyl group, 4-toluenesulfonyl group, 2-nitrobenzenesulfonyl Groups and the like are preferred.

When R ⁸ is a lower alkyl group, examples of the substituent that may be included include a lower alkoxy group, an aryl group, a halogen atom, and the like, and more specifically, a methoxy group, an ethoxy group, and a phenyl group. And halogen atoms.

When R ⁸ 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. Group, halogen atom and the like.

R ³ in the general formula (1) is a hydrogen atom, an optionally substituted lower alkyl group, —N (R ⁹ ) ₂ group (R ⁹ is the same as above) or —OR ¹⁰ group (R ¹⁰ is the same as above, but is preferably a hydrogen atom, a lower alkyl group which may have a substituent, or —OR ¹⁰ group (where R ¹⁰ is the same as above), and more preferably —OR ¹⁰ group. (R ¹⁰ is the same as above).

When R ³ represents a lower alkyl group, examples of the substituent on the lower alkyl group include a lower alkoxy group, an aryl group, and a halogen atom. Specific examples include a methoxy group, an ethoxy group, a phenyl group, and a halogen atom.

The amino-protecting group represented by R ⁹ may be an existing amino-protecting group that has been widely known to date. For example, a halogen atom, a lower alkoxy group, or an aryl group represented by 1 to Lower alkyl group optionally having 5; lower alkanoyl group optionally having 1 to 5 halogen atoms, lower alkoxy groups and aryl groups; halogen atom, lower alkoxy group and biphenylene as substituents Lower alkoxycarbonyl group optionally having 1 to 5 groups; benzyloxy optionally having 1 to 3 halogen atoms, lower alkyl groups, lower alkoxy groups and nitro groups on the aromatic ring as substituents Carbonyl group; triphenyl which may have 1 to 3 halogen atoms, lower alkyl groups, lower alkoxy groups and nitro groups as substituents on the aromatic ring A methoxycarbonyl group; an allyloxycarbonyl group or a methallyloxycarbonyl group; a benzenesulfonyl group optionally having 1 to 3 halogen atoms, lower alkyl groups, lower alkoxy groups, and nitro groups on the aromatic ring; A phthaloyl group etc. are mentioned. Specifically, benzyl group, acetyl group, propionyl group, trichloroacetyl group, trifluoroacetyl group, 2,2,2-trichloroethoxycarbonyl group, 9-fluorenylmethyloxycarbonyl group, tert-butyloxycarbonyl group Benzyloxycarbonyl group, o-nitrobenzyloxycarbonyl group, triphenylmethoxycarbonyl group, allyloxycarbonyl group, methallyloxycarbonyl group, 4-toluenesulfonyl group, 2-nitrobenzenesulfonyl group, phthaloyl group and the like are preferable.

  Although the value of p in General formula (1) is an integer of 1-4, the integer of 1-3 is preferable, the integer of 2-3 is more preferable, and 2 is especially preferable.

  Although the value of m and n in General formula (1) is an integer of 0-4, respectively, the integer of 0-2 is preferable and the integer of 0-1 is especially preferable.

  The 2,4-O-bridged inverted pyranose compound represented by the general formula (1) has a chemical bond in which two aromatic rings in the bridge portion are bonded via an alkylene group. Therefore, the structure has an appropriate degree of freedom and has an advantage that the reaction of removing the cross-linked portion from the pyranose easily proceeds.

  The enantiomer of the 2,4-O-bridged inverted pyranose compound represented by the general formula (1) means a 2,4-O-bridged inverted pyranose compound represented by the following general formula (1 ′). .

[Wherein, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , m, n and p are the same as described above. ]
The 2,4-O-bridged inverted pyranose compound represented by the general formula (1) includes compounds represented by the following general formulas (1-1) and (1-2).

[Wherein, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , m, n and p are the same as described above. ]
In the present invention, the compound represented by the general formula (1) may be any isomer of the above general formula (1-1) and general formula (1-2), but the general formula ( The compound represented by 1) is preferably an isomer of the above general formula (1-1).

  The 2,4-O-bridged inverted pyranose compound represented by the general formula (1) includes compounds represented by the following general formulas (1A), (1B), (1C) and (1D).

[Wherein X represents a halogen atom. R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , m, n and p are the same as above. ]
These compounds can also be represented by the following formulas in consideration of their conformation.

[Wherein, R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , X, m, n and p are the same as above. ]
Among the 2,4-O-bridged inverted pyranose compounds represented by the general formula (1), preferred compounds are the following general formulas (1a), (1b), (1c), (1d) and (1e). It is a compound represented by these.

[Wherein, R ¹ , R ² , R ³ , R ⁴ , R ⁵ and p are the same as above. ]
The 2,4-O-bridged inverted pyranose compound represented by the general formula (1A) of the present invention is produced, for example, as shown in the following reaction formula-1.

[Wherein R ¹¹ represents a leaving group. R ³ , R ⁴ , R ⁵ , m, n and p are the same as above. ]
The leaving group represented by R ¹¹ includes a halogen atom; a lower alkyl sulfonate group optionally having 1 to 5 halogen atoms; a halogen atom, a lower alkyl group, or a lower alkoxy group as a substituent on the aromatic ring. Benzenesulfonate group etc. which 1 to 3 may have. Specific examples include a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a methanesulfonate group, a trifluoromethanesulfonate group, and a 4-toluenesulfonate group.

  The reaction between the compound represented by the general formula (2) and the compound represented by the general formula (3) is carried out in a solvent such as dimethylformamide in a solvent such as dimethylformamide, as shown in Example 1 below. In the presence of the active compound. In the reaction, a solution of the compound represented by the general formula (2) and a solution of the compound represented by the general formula (3) are preferably added dropwise to the basic compound solution or suspension at an appropriate rate. Is done. The reaction temperature is preferably 60 to 100 ° C., and the reaction time is preferably 30 minutes to 3 hours. It is preferable to use 0.9 to 1.3 equivalents of the compound represented by the general formula (3) with respect to 1 equivalent of the compound represented by the general formula (2), and use 2 to 10 equivalents of the basic compound. It is preferable to do this.

  The compound represented by the general formula (2) and the compound represented by the general formula (3) used as starting materials in the above reaction are both known compounds that are easily available, or are easily obtained from known compounds. It is a compound that can be produced. In particular, the compound represented by the general formula (2) is synthesized from the corresponding pyranose compound as shown in Reference Examples 1 and 2 described later. That is, after reacting the corresponding pyranose compound with a sulfonyl halide such as 4-toluenesulfonyl chloride and methanesulfonyl chloride in the presence of a basic compound (specifically, pyridine or the like), the obtained compound is reacted with ethanol or the like. By reacting in the presence of a basic compound such as 1,8-diazabicyclo [5.4.0] -7-undecene in an alcohol solvent, a compound represented by the general formula (2) is obtained.

  The compounds represented by the general formulas (1B), (1C) and (1D) are produced from the compounds represented by the general formula (1A) as described in detail below.

  The 2,4-O-bridged inverted pyranose compound represented by the general formula (1B) of the present invention is produced, for example, as shown in the following reaction formula-2.

[Wherein, R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , m, n, and p are the same as above. ]
The ring-opening reaction of the compound represented by the general formula (1A) is performed, for example, in the presence of an acid anhydride of a lower alkyl carboxylic acid and a Lewis acid. More specifically, as shown in Example 3 or 5 below, the reaction is carried out in acetic anhydride in the presence of trimethylsilyl trifluoromethanesulfonate. The reaction is preferably performed by adding an acetic anhydride solution of trimethylsilyl trifluoromethanesulfonate to an acetic anhydride suspension of the compound represented by the general formula (1A). The reaction temperature of the reaction is preferably −20 to 10 ° C., more preferably about 0 ° C. The reaction time is preferably 1 to 30 minutes. The amount of the Lewis acid used may be a catalytic amount, and is preferably 0.0001 to 1 equivalent based on 1 equivalent of the compound represented by the general formula (1A). The acid anhydride is sufficient if it is present in an amount necessary for the reaction, but it is preferably used in an excess amount relative to the compound represented by the general formula (1A), and more preferably in an amount of solvent. The acid anhydride may be used by mixing with another organic solvent, but it is preferable to use the acid anhydride alone.

  The 2,4-O-bridged inverted pyranose compound represented by the general formula (1C) of the present invention is produced, for example, as shown in the following reaction formula-3.

[Wherein, R ¹² represents a lower alkyl group. R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁸ , m, n and p are the same as above. ]
The reaction of the compound represented by the general formula (1Ba) (the compound in which R ⁷ represents a lower alkanoyl group in the general formula (1B)) and the compound represented by the general formula (4) is, for example, Example 4 or As shown in FIG. 6, the reaction is performed in a solvent such as dichloromethane in the presence of a Lewis acid such as BF ₃ .O (C ₂ H ₅ ) ₂ . The reaction is preferably performed by adding BF ₃ .O (C ₂ H ₅ ) ₂ to a dichloromethane solution of the compound represented by the general formula (1Ba) and the compound represented by the general formula (4). The reaction is preferably performed at −20 to 5 ° C. for 10 to 30 minutes and then at 20 to 30 ° C. for 30 to 100 minutes. It is preferable to use 0.9 to 1.5 equivalents of the compound represented by the general formula (4) with respect to 1 equivalent of the compound represented by the general formula (1Ba). The Lewis acid may be used at least in a catalytic amount. For example, it is preferably used in an amount of 0.001 to 1.6 equivalents relative to 1 equivalent of the compound represented by the general formula (1Ba).

  The 2,4-O-bridged inverted pyranose compound represented by the general formula (1D) of the present invention is produced, for example, as shown in the following reaction formula-4.

[Wherein, R ³ , R ⁴ , R ⁵ , R ⁶ , X, m, n and p are the same as above. ]
The halogenation reaction of the compound represented by the general formula (1Bb) (the compound in which R ⁷ represents a hydrogen atom in the compound of the general formula (1B)) is performed when halogenating the anomeric position of a pyranose compound known to date. Any reaction may be used. For example, the reaction can be carried out in a solvent such as tetrahydrofuran in the presence of a halogenating agent at 0 to 30 ° C. for about 20 minutes to 6 hours. Examples of the halogenating agent used include (dimethylamino) sulfur trifluoride, (diethylamino) sulfur trifluoride, [bis (2-methoxyethyl) amino] sulfur trifluoride and the like.

  The compound represented by the general formula (1 ') can also be produced by performing the same reaction except that the corresponding enantiomer is used as a 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 normal separation means and purified. Examples of such separation and purification means include distillation, recrystallization, column chromatography, ion exchange chromatography, gel chromatography, affinity chromatography, preparative thin layer chromatography, solvent extraction, and the like. it can.

  The compound represented by the general formula (1) has an advantage that the reaction for removing the cross-linked portion from the pyranose easily proceeds. The reaction for removing the cross-linked portion from the pyranose is performed, for example, in the presence of a hydrogenation catalyst in a hydrogen atmosphere as shown in Reference Example 3 described later. In the reaction, as the hydrogenation catalyst, an existing hydrogenation catalyst widely known until now may be used, and examples thereof include palladium / carbon, palladium hydroxide / carbon and the like.

  The glycosylating agent of the present invention can produce various sugars having a β-O-glycosyl bond by acting as a β-selective sugar donor and then performing a reaction for removing the cross-linking moiety as described above. It is.

  Since the compounds represented by the general formulas (1B), (1C) and (1D) have a structure in which the α-face of the tetrahydropyran ring of pyranose is covered with a bridging portion, a compound having a partial structure that is easily isomerized is used. It acts as a universal β-selective sugar donor applicable to a wide range of sugar acceptors. The compound represented by the general formula (1A) is a precursor of the compound represented by the general formulas (1B), (1C), and (1D).

  The 2,4-O-bridged inverted glucose compound represented by the general formula (1) of the present invention or an enantiomer thereof can be suitably used as a β-O-glucosylating agent or a precursor thereof.

  The following reference examples and examples will further clarify the present invention.

  Reference example 1

[Wherein Allyl represents an allyl group, and Ts represents a 4-toluenesulfonyl group. ]
Preparation of 3-O -allyl-6-O-toluenesulfonyl-D-glucopyranose A solution of 3-O-allyl-D-glucopyranose (14.6 g, 60.1 mmol) in pyridine (60 mL) was stirred at 0 ° C. 4-toluenesulfonyl chloride (TsCl, 13.8 g, 72.1 mmol) was added. The mixture was stirred at 0 ° C. for 1.5 hours and further stirred at room temperature (20-30 ° C.) for 2 hours, and then water (10 mL) was added to the reaction mixture and concentrated. Water (10 mL) was further added to the concentrate, and the resulting mixture was extracted with chloroform (100 mL × 2). The extracts were combined and washed successively with a saturated aqueous sodium hydrogen carbonate solution (100 mL × 1) and brine (100 mL × 1). This was dried using anhydrous magnesium sulfate, and the remaining pyridine was removed by azeotropy with toluene. The obtained residue was purified using silica gel column chromatography (SiO ₂ : 300 g, ethyl acetate / n-hexane (volume ratio) = 2/3 → 1/0) to give 3-O-allyl-6-O—. Toluenesulfonyl-D-glucopyranose (16.0 g, 42.8 mmol, yield: 71%) was obtained as a colorless syrup.

The physicochemical properties of 3-O-allyl-6-O-toluenesulfonyl-D-glucopyranose are as follows.
IR (neat): 3403, 2925, 1599, 1356, 1190, 1175, 1067, 1023, 979, 931, 836, 820, 769 cm ^−1
1 H-NMR (partial data, 400 MHz, CDCl ₃ ): δ ppm
7.77 (d, J = 8.2 Hz, 2H), 7.32 (d, J = 8.2 Hz, 2H), 5.93 (m, 1H), 5.26 (m, 1H,), 2.41 (s, 3H)
HRMS-ESI (m / z): [M + Na] ⁺
Calculated (as C ₁₆ H ₂₂ ²³ Na ₁ O ₈ S ₁ ) 397.0933, measured 397.0927.

  Reference example 2

[Wherein Allyl and Ts are the same as above. ]
Preparation of 3-O -allyl-1,6-anhydro-β-D-glucopyranose 3-O-allyl-6-O-toluenesulfonyl-D-glucopyranose (1.25 g, 3.35 mmol) in ethanol (45 mL) ) While stirring the solution at room temperature, 1,8-diazabicyclo [5.4.0] -7-undecene (1.0 mL, 6.70 mmol) was added. After the mixture was stirred at room temperature for 16.5 hours, ethanol was removed under reduced pressure, and the reaction mixture was concentrated. The obtained concentrate was dissolved in chloroform (20 mL), SiO ₂ (5 g) was added, the solvent was distilled off with an evaporator, and the obtained reaction product was adsorbed on silica gel. The silica gel powder adsorbed with the product was used and purified by silica gel column chromatography (SiO ₂ : 25 g, ethyl acetate / n-hexane (volume ratio) = 1/1 → 1/0), and 3-O— Allyl-1,6-anhydro-β-D-glucopyranose (576.4 mg, 2.85 mmol, yield: 85%) was obtained as a colorless syrup.

The physicochemical properties of 3-O-allyl-1,6-anhydro-β-D-glucopyranose are as follows.
IR (neat): 3376, 2963, 2905, 1426, 1337, 1140, 1069, 1003, 928 cm ^−1
1 H-NMR (300 MHz, CDCl ₃ ): δ ppm
5.85 (dddd, J = 17.1, 10.8, 5.4, 5.4 Hz), 5.39 (br, 1H), 5.25 (dddd, J = 17.4, 3.3, 1.5, 1.5 Hz, 1H), 5.16 (dddd, J = 10.2, 3.0 , 1.2, 1.2 Hz), 4.49 (m, 1H), 4.15 (dd, J = 7.2, 0.9 Hz, 1H), 4.04 (ddd, J = 5.4, 1.5, 1.5 Hz, 1H), 4.03 (ddd, J = 5.4, 1.5, 1.5 Hz, 1H), 3.72 (dd, J = 6.6, 5.7 Hz), 3.65 (d, J = 1.8 Hz, 1H), 3.58 (d, J = 1.5 Hz, 1H), 3.44 (ddd, (J = 3.0, 1.5, 1.5 Hz, 1H)
¹³ C-NMR (75 MHz, CDCl ₃ ): δ ppm
64.7, 68.0, 68.8, 71.0, 76.1, 79.3, 101.5, 117.2, 134.1.

  Example 1

[Wherein Allyl is the same as above. ]
Preparation of 3-O-allyl-2,4-O- [bibenzylbis-2,2 ′-(methylene)]-1,6-anhydro-β-D-glucopyranose 2,2′-bis (bromomethyl) bibenzyl ( 426.3 mg, 1.16 mmol) in toluene (21.0 mL) and 3-O-allyl-1,6-anhydro-β-D-glucopyranose (212.8 mg, 1.05 mmol) in DMF (21.0 mL) ) Each solution was prepared. A suspension of 60% oily sodium hydride (252.5 mg, 151.5 mg as sodium hydride, 6.31 mmol) suspended in toluene (40.9 mL) was stirred at 82 ° C. The solution was simultaneously added dropwise using a syringe pump at a rate of 1 mL / min for 21 minutes. After the addition of the solution was complete, the mixture was further stirred at 82 ° C. for 1 hour. The reaction was then quenched by adding water (10 mL). After the reaction mixture was cooled to room temperature, the reaction mixture was extracted with ethyl acetate (50 mL × 3 times), and the extracts were combined, which were sequentially washed with water (50 mL × 1 time) and brine (50 mL × 1 time). did. The solution was further dried over anhydrous magnesium sulfate, the solvent was distilled off, and the obtained residue was subjected to silica gel column chromatography (SiO ₂ : 25 g, ethyl acetate / n-hexane (volume ratio) = 0/1 → 1/1). 3) -O-allyl-2,4-O- [bibenzylbis-2,2 '-(methylene)]-1,6-anhydro-β-D-glucopyranose (397.7 mg, 0.974 mmol) Yield: 93%) was obtained as a colorless syrup.

The physicochemical properties of 3-O-allyl-2,4-O- [bibenzylbis-2,2 ′-(methylene)]-1,6-anhydro-β-D-glucopyranose are as follows.
[Α] _D ²² = −32.8 (c = 0.55, CHCl ₃ )
IR (neat): 3063, 3018, 2962, 2891, 2880, 2867, 2359, 2342, 2249, 1646, 1604, 1494, 1476, 1453, 1388, 1335, 1298, 1261, 1218, 1190, 1146, 1102, 1023 , 921, 876, 809, 759, 733 cm ^−1
1 H-NMR (400 MHz, CDCl ₃ ): δ ppm
7.41-7.30 (m, 4H), 7.28-7.24 (m, 2H), 7.22-7.16 (m, 2H), 5.83 (dddd, J = 17.2, 10.5, 5.5, 5.5 Hz, 1H), 5.55 (br s, 1H), 5.24 (dddd, J = 17.2, 1.6, 1.6, 1.6 Hz, 1H), 5.17 (dddd, J = 10.5, 1.4, 1.4, 1.4 Hz, 1H), 4.76 (d, J = 9.6 Hz, 1H) , 4.71 (br d, J = 5.2 Hz, 1H), 4.67 (d, J = 9.6 Hz, 1H), 4.64 (d, J = 9.6 Hz, 1H), 4.46 (d, J = 9.6 Hz, 1H), 4.15 (dd, J = 7.0, 0.8 Hz, 1H), 4.00-3.91 (m, 2H), 3.80 (br s, 1H), 3.75 (dd, J = 6.9, 5.2 Hz, 1H), 3.50 (br s, 1H), 3.45 (br s, 1H), 3.31 (ddd, J = 12.4, 12.1, 4.4 Hz, 1H), 3.14 (ddd, J = 12.8, 12.4, 3.8 Hz, 1H), 2.96 (ddd, J = 12.8 , 12.4, 4.4 Hz, 1H), 2.87 (ddd, J = 12.4, 12.1, 3.8 Hz, 1H)
¹³ C-NMR (100 MHz, CDCl ₃ ): δ ppm
143.1, 143.0, 135.2, 135.1, 134.6, 131.0, 130.7, 130.6, 130.4, 129.1, 129.0, 126.2, 126.2, 117.7, 100.5, 75.8, 75.2, 74.0, 72.1, 71.8, 71.1, 71.0, 64.8, 35.9, 35.9
HRMS-ESI (m / z): [M + Na] ⁺
Calculated ^{_{(C 25 H 28 23 Na 1}} O 5 as) 431.1834, measured 431.1834.

  Example 2

[Wherein Allyl is the same as above. ]
Preparation of 2,4-O- [bibenzylbis-2,2 ′-(methylene)]-1,6-anhydro-β-D-glucopyranose 3-O-allyl-2,4-O- [bibenzylbis-2, 2 ′-(methylene)]-1,6-anhydro-β-D-glucopyranose (593.0 mg, 1.45 mmol) and 1,3-dimethylbarbituric acid (1.132 g, 7.25 mmol) in methanol ( Tetrakis (triphenylphosphine) palladium (83.8 mg, 0.0725 mmol) was added to the refluxing solution (14.5 mL). After the mixture was stirred for 19 hours, a saturated aqueous sodium carbonate solution (20 mL) was added to the reaction mixture. Extraction from the reaction mixture was performed using ethyl acetate (50 mL × 3 times). The extracts were combined and washed successively with a saturated aqueous sodium carbonate solution (30 mL × 1), water (30 mL × 1) and brine (30 mL × 1). The washings were combined and further extracted with ethyl acetate (50 mL × 2). Next, the extracts were combined, dried using anhydrous magnesium sulfate, and the solvent was distilled off to obtain a concentrate. The obtained concentrate was purified by silica gel column chromatography (SiO ₂ : 18 g, chloroform only → ethyl acetate only) to obtain an orange mixture having the target product as a main product as a solid. Diethyl ether (10 mL) was added to this solid, and the solid was washed by dispersing with ultrasonic waves. The resulting precipitate was collected by filtration and washed with diethyl ether (2 mL) and n-hexane (2 mL), whereby 2,4-O- [bibenzylbis-2,2 ′-(methylene)]-1, 6-Anhydro-β-D-glucopyranose (409.2 mg, 1.11 mmol, yield: 77%) was obtained as a light brown solid.

The physicochemical properties of 2,4-O- [bibenzylbis-2,2 ′-(methylene)]-1,6-anhydro-β-D-glucopyranose are as follows.
mp: 251-252 ° C
[Α] _D ²² = −31.9 (c = 0.18, CHCl ₃ )
IR (neat): 3415, 3059, 3021, 3015, 2976, 2925, 2899, 2871, 2867, 2844, 1105, 754 cm ^−1
1 H-NMR (400 MHz, CDCl ₃ ): δ ppm
7.41-7.36 (m, 2H), 7.36-7.30 (m, 2H), 7.28-7.24 (m, 2H), 7.22-7.17 (m, 2H), 5.63 (br dd, J = 1.8, 1.8 Hz, 1H) , 4.86 (d, J = 9.4 Hz, 1H), 4.77-4.73 (m, 2H), 4.60 (d, J = 9.6 Hz, 1H), 4.44 (d, J = 9.4 Hz, 1H), 4.24 (br d , J = 8.2 Hz, 1H), 4.18 (br d, J = 7.6 Hz, 1H), 3.78 (dd, J = 7.6, 5.5 Hz, 1H), 3.59 (br s, 1H), 3.47 (br s, 1H ), 3.25 (ddd, J = 12.6, 11.2, 3.2 Hz, 1H), 3.16 (ddd, J = 12.6, 11.2, 2.8 Hz, 1H), 2.95 (ddd, J = 12.6, 12.4, 3.2 Hz, 1H), 2.88 (ddd, J = 12.6, 12.4, 2.8 Hz, 1H), 2.46 (d, J = 8.2 Hz, 1H)
¹³ C-NMR (100 MHz, CDCl ₃ ): δ ppm
134.0, 135.3, 135.0, 131.0, 130.8, 130.7, 130.6, 129.2, 129.1, 126.2, 101.1, 77.6, 77.2, 74.5, 71.9, 71.3, 65.4, 65.4, 36.4, 36.4
HRMS-ESI (m / z): [M + Na] ⁺
Calculated ^{_{(C 22 H 24 23 Na 1}} O 5 as) 391.1521, measured 391.1523.

  Example 3

[In the formula, Ac represents an acetyl group, and TMSOTf represents trimethylsilyl trifluoromethanesulfonate. ]
Preparation of 1,3,6-tri-O-acetyl-2,4-O- [bibenzylbis-2,2 '-(methylene)]-D-glucopyranose 2,4-O- [bibenzylbis-2,2' -(Methylene)]-1,6-anhydro-β-D-glucopyranose (20.3 mg, 0.0551 mmol) suspended in acetic anhydride (0.9 mL) under stirring at 0 ° C. A solution of trimethylsilyl trifluoromethanesulfonate (0.10 μL, 0.55 μmol) in acetic anhydride (0.1 mL) was added. After stirring for 15 minutes, a saturated aqueous sodium hydrogen carbonate solution (5 mL) was added to the reaction mixture. The mixture was extracted with ethyl acetate (30 mL x 2). The extracts were combined and washed sequentially with saturated aqueous sodium hydrogen carbonate solution (20 mL × 2 times), water (20 mL × 1 time) and brine (20 mL × 1 time). The washed extract was dried using anhydrous magnesium sulfate, and the solvent was distilled off with an evaporator. The obtained residue was purified by silica gel column chromatography (SiO ₂ : 18 g, ethyl acetate / n-hexane (volume ratio) = 1/3 → 1/1), and 1,3,6-tri-O-acetyl- 2,4-O- [bibenzylbis-2,2 ′-(methylene)]-D-glucopyranose (anomer isomer mixing ratio 65:35, 28.0 mg, 0.0546 mmol, yield: 99%) was colorless. As an amorphous solid.

The physicochemical properties of 1,3,6-tri-O-acetyl-2,4-O- [bibenzylbis-2,2 ′-(methylene)]-D-glucopyranose are as follows.
mp: 52-57 ° C
IR (neat): 3063, 3021, 2936, 2897, 2876, 1740, 1494, 1473, 1455, 1436, 1371, 1220, 1169, 1107, 1084, 1040, 949, 756 cm ^−1
1 H-NMR (partial data, 400 MHz, CDCl ₃ ): δ ppm
5.98 (d, J = 3.9 Hz, 1H), 4.97 (d, J = 9.8 Hz, 1H), 4.89 (d, J = 10.1 Hz, 1H), 4.49 (d, J = 10.1 Hz, 1H), 2.13 ( s, 3H), 2.12 (s, 3H), 2.09 (s, 3H)
HRMS-ESI (m / z): [M + Na] ⁺
Calculated (as C ₂₈ H ₃₂ ²³ Na ₁ O ₉ ) 535.1944, measured 535.1946.

Example 4
Process A:

[Wherein Et represents an ethyl group. Ac is the same as above. ]
Preparation of ethyl 3,6-di-O-acetyl-2,4-O- [bibenzylbis-2,2 ′-(methylene)]-1-thio-D-glucopyranoside 1,3,6-tri-O-acetyl -2,4-O- [bibenzylbis-2,2 '-(methylene)]-D-glucopyranose (45.1 mg, 0.0880 mmol) and ethanethiol (7.8 μL, 0.106 mmol) in dichloromethane (7. 94 mL) Boron trifluoride · diethyl ether (14.3 μL, 0.114 μmol) was added to the solution with stirring at 0 ° C. This was stirred at 0 ° C. for 15 minutes, and further stirred at room temperature for 45 minutes, and then a saturated aqueous sodium hydrogen carbonate solution (1 mL) was added thereto. Extraction from the reaction mixture was performed using ethyl acetate (30 mL × twice). The extracts were combined and washed successively with water (30 mL × 1) and brine (30 mL × 1). The extract after washing was dried over anhydrous magnesium sulfate, the solvent was distilled off, and the remaining ethanethiol was removed by azeotropy with diethyl ether. The obtained residue was purified by silica gel column chromatography (SiO ₂ : 2 g, ethyl acetate / n-hexane (volume ratio) = 0/1 → 1/0), and ethyl 3,6-di-O-acetyl-2 , 4-O- [bibenzylbis-2,2 ′-(methylene)]-1-thio-D-glucopyranoside (mixing ratio of anomeric isomers 83:17, 45.8 mg, 0.0890 mmol, yield: quantitative) Was obtained as a syrup.

Process B:

[Wherein, NIS represents N-iodosuccinimide, and Tf represents a trifluoromethanesulfonyl group. Ac and Et are the same as described above. ]
Production of 3,6-di-O-acetyl-2,4-O- [bibenzylbis-2,2 ′-(methylene)]-D-glucopyranose
A solution of N-iodosuccinimide (234 mg, 1.04 mmol) in a mixed solvent of tetrahydrofuran (12.0 mL) and dichloromethane (0.3 mL) is stirred at room temperature, and trifluoromethanesulfonic acid (6. 2 μL, 70.5 μmol) was added and the mixture was stirred for 5 minutes at room temperature. Ethyl 3,6-di-O-acetyl-2,4-O- [bibenzylbis-2,2 ′-(methylene)]-1-thio-D-glucopyranoside (14.5 mg, 0. 0282 mmol) in a mixed solvent of dichloromethane (1.2 mL) and water (0.12 mL) is stirred at room temperature, and the above solution of N-iodosuccinimide and trifluoromethanesulfonic acid (1.2 mL) is stirred. ) Was added under dark conditions. After stirring at room temperature for 20 minutes, a 10% by mass aqueous sodium thiosulfate solution was added to the mixture. The resulting reaction mixture was extracted with ethyl acetate (20 mL × 1). The extract was washed successively with water (20 mL × 1 time) and brine (20 mL × 1 time). The extract after washing was dried using anhydrous magnesium sulfate, and the solvent was distilled off. The obtained residue was purified by silica gel column chromatography (SiO ₂ : 2 g, ethyl acetate / n-hexane (volume ratio) = 1/1), and 3,6-di-O-acetyl-2,4-O— [Bibenzylbis-2,2 ′-(methylene)]-D-glucopyranose (10.6 mg, 0.0225 mmol, yield: 80%) was obtained as a colorless syrup.

The physicochemical properties of 3,6-di-O-acetyl-2,4-O- [bibenzylbis-2,2 ′-(methylene)]-D-glucopyranose are as follows.
IR (neat): 3463, 3068, 3019, 2925, 2876, 1736, 1494, 1456, 1371, 892, 753 cm ^−1
1 H-NMR (partial data, 400 MHz, CDCl ₃ ): δ ppm
5.40 (d, J = 3.2 Hz, 1H), 5.27 (d, J = 5.0 Hz, 1H), 5.14 (d, J = 9.9 Hz, 1H), 4.93 (d, J = 10.3 Hz, 1H), 4.56 ( d, J = 10.3 Hz, 1H), 4.26 (d, J = 9.9 Hz, 1H), 3.62 (m, 1H), 3.12 (m, 1H), 3.00 (m, 1H), 2.76 (m, 1H), 2.11 (s, 3H), 2.05 (s, 3H)
HRMS-ESI (m / z): [M + Na] ⁺
Calculated (as C ₂₆ H ₃₀ ²³ Na ₁ O ₈ ) 493.1838, measured 493.1831.

  Example 5

[Wherein, Allyl, Ac and TMSOTf are the same as above. ]
Preparation of 1,6-di-O-acetyl-3-O-allyl-2,4-O- [bibenzylbis-2,2 ′-(methylene)]-D-glucopyranose 3-O-allyl-2,4 A suspension of —O- [bibenzylbis-2,2 ′-(methylene)]-1,6-anhydro-β-D-glucopyranose (397.7 mg, 0.974 mmol) in acetic anhydride (7.94 mL) While stirring at ° C., a solution of trimethylsilyl trifluoromethanesulfonate (1.76 μL, 9.74 μmol) in acetic anhydride (1.76 mL) was added. After stirring for 10 minutes, a saturated aqueous sodium bicarbonate solution (20 mL) was added to the reaction mixture. The mixture was extracted with ethyl acetate (50 mL × 3 times). The extracts were combined and washed successively with saturated aqueous sodium hydrogen carbonate solution (50 mL × 2 times), water (50 mL × 1 time) and brine (50 mL × 1 time). The extract after washing was dried using anhydrous magnesium sulfate, and the solvent was distilled off to obtain a residue (mixing ratio of anomeric isomers α: β = 69: 31). The obtained residue was purified by silica gel column chromatography (SiO ₂ : 5 g, ethyl acetate / n-hexane (volume ratio) = 0/1 → 1/1), and 1,6-di-O-acetyl-3- O-allyl-2,4-O- [bibenzylbis-2,2 ′-(methylene)]-D-glucopyranose (mixing ratio of anomeric isomers α: β = 69: 31, 475.8 mg, 0.932 mmol, Yield: 96%) was obtained as a pale yellow amorphous syrup. This mixture of anomeric isomers was separated by HPLC (column: Phenomenex Luna 3μ silica (2), 150 × 4.60 mm; eluent: ethyl acetate / hexane (volume ratio) = 3/17; flow rate: 2.0 mL / min) Both α-form (retention time = 10.0 min) and β-form (retention time = 11.6 min) were obtained as colorless syrup.

The physicochemical properties of 1,6-di-O-acetyl-3-O-allyl-2,4-O- [bibenzylbis-2,2 ′-(methylene)]-α-D-glucopyranose are as follows: It is.
[Α] _D ²² = + 133.8 (c = 0.055, CHCl ₃ )
IR (neat): 3067, 3019, 2925, 2871, 1734, 1604, 1491, 1456, 1373, 1243, 1218, 1165, 1147, 1086, 1044, 1014, 964, 768 cm ^−1
1 H-NMR (400 MHz, CDCl ₃ ): δ ppm
7.48-7.44 (br d, J = 7.8 Hz, 1H), 7.42-7.28 (m, 4H), 7.25-7.19 (m, 3H), 6.06 (d, J = 4.6 Hz, 1H), 5.67 (dddd, J = 17.2, 10.3, 6.0, 5.5 Hz, 1H), 5.07 (br dd, J = 10.3, 1.1 Hz, 1H), 4.99 (br dd, J = 17.2, 1.4 Hz, 1H), 4.73 (d, J = 8.9 Hz, 1H), 4.70 (d, J = 11.5 Hz, 1H), 4.40 (d, J = 11.5 Hz, 1H), 4.34-4.18 (m, 4H), 4.14 (ddd, J = 4.6, 3.7, 0.9 Hz , 1H), 3.87 (dd, J = 13.1, 5.5 Hz, 1H), 3.73 (dd, J = 13.1, 6.0 Hz, 1H), 3.62 (d, J = 3.7 Hz, 1H), 3.56 (ddd, J = 14.0, 13.0, 3.7 Hz, 1H), 3.44 (dd, J = 8.0, 0.9 Hz, 1H), 3.13 (ddd, J = 13.0, 12.8, 5.5 Hz, 1H), 2.97 (ddd, J = 13.0, 12.8, 3.7 Hz, 1H), 2.80 (ddd, J = 14.0, 13.0, 5.5 Hz, 1H), 2.13 (s, 3H), 2.09 (s, 3H)
¹³ C-NMR (100 MHz, CDCl ₃ ): δ ppm
171.3, 170.4, 142.9, 142.1, 135.1, 134.3, 134.0, 131.9, 131.5, 130.2, 129.3, 129.2, 128.8, 126.6, 126.0, 118.6, 92.9, 76.7, 73.3, 73.2, 72.2, 70.8, 70.8, 70.7, 64.7, 33.7, 33.4, 21.4, 21.1
HRMS-ESI (m / z): [M + Na] ⁺
Calculated (as C ₂₉ H ₃₄ ²³ Na ₁ O ₈ ) 533.2151, found 533.2149.

The physicochemical properties of 1,6-di-O-acetyl-3-O-allyl-2,4-O- [bibenzylbis-2,2 ′-(methylene)]-β-D-glucopyranose are as follows: It is.
[Α] _D ²² = + 28.6 (c = 0.20, CHCl ₃ )
IR (neat): 3064, 3020, 2924, 2871, 1740, 1604, 1492, 1456, 1371, 1307, 1237, 1168, 1146, 1100, 1045, 962, 844, 757 cm ^−1
1 H-NMR (400 MHz, CDCl ₃ ): δ ppm
7.42-7.32 (m, 4H), 7.30-7.17 (m, 4H), 6.05 (d, J = 3.4 Hz, 1H), 5.78 (dddd, J = 17.2, 10.5, 5.7, 5.5 Hz, 1H), 5.20- 5.10 (m, 2H), 4.71 (d, J = 9.6 Hz, 1H), 4.62 (d, J = 10.3 Hz, 1H), 4.56 (d, J = 10.3 Hz, 1H), 4.37 (d, J = 9.6 Hz, 1H), 4.34 (dd, J = 11.5, 7.3 Hz, 1H), 4.31 (dd, J = 11.5, 5.5 Hz, 1H), 4.21 (ddd, J = 7.3, 5.5, 2.8 Hz, 1H), 3.97 (dddd, J = 13.1, 5.5, 1.4, 1.4 Hz, 1H), 3.87 (dddd, J = 13.1, 5.7, 1.4, 1.4 Hz, 1H), 3.80 (br s, J = 1.4, 1.4 Hz, 1H), 3.76 (ddd, J = 3.4, 1.4, 1.1 Hz, 1H), 3.61 (br s, J = 2.8, 1.4, 1.1 Hz, 1H), 3.26-3.10 (m, 2H), 3.01-2.80 (m, 2H) , 2.11 (s, 3H), 2.09 (s, 3H)
¹³ C-NMR (100 MHz, CDCl ₃ ): δ ppm
171.0, 169.4, 142.8, 142.5, 134.9, 134.8, 134.1, 131.5, 130.9, 130.0, 129.2, 126.3, 126.2, 117.9, 94.2, 76.1, 75.5, 74.7, 73.1, 72.3, 71.8, 70.8, 65.1, 34.9, 34.9, 21.4, 21.1
HRMS-ESI (m / z): [M + Na] ⁺
Calculated _{(as ^{C 29 H 34 23 Na 1 O}} 8) 533.2151, measured 533.2139.

  Example 6

[Wherein, Allyl, Ac and Et are the same as above. ]
Ethyl 6-O-acetyl-3-O-allyl-2,4-O- [bibenzylbis-2,2 ′-(methylene)]-1-thio-D-glucopyranoside and ethyl 3-O-allyl-2,4 Preparation of —O- [bibenzylbis-2,2 ′-(methylene)]-1-thio-D-glucopyranoside 1,6-di-O-acetyl-3-O-allyl-2,4-O- [bibenzylbis- 2,2 ′-(methylene)]-D-glucopyranose (704.0 mg, 1.38 mmol) and ethanethiol (123 μL, 1.66 mmol) in dichloromethane (7.94 mL) were stirred at 0 ° C. Boron fluoride / diethyl ether (225 μL, 1.79 μmol) was added. This was stirred for 1 hour and saturated aqueous sodium hydrogen carbonate (15 mL) was added to the reaction mixture. The mixture was extracted with dichloromethane (50 mL × 3 times). The extracts were combined and washed with saturated aqueous sodium hydrogen carbonate solution (20 mL × 1). The washed extract was dried using anhydrous magnesium sulfate, and the remaining ethanethiol was removed by azeotroping with diethyl ether to obtain a residue. The obtained residue was purified by silica gel column chromatography (SiO ₂ : 20 g, ethyl acetate / n-hexane (volume ratio) = 0/1 → 1/0), and the main component was ethyl 6-O-acetyl-3- A compound which is O-allyl-2,4-O- [bibenzylbis-2,2 ′-(methylene)]-1-thio-D-glucopyranoside (mixing ratio of anomeric isomers 92: 8) is obtained as a yellow syrup. It was. The crude ethyl 6-O-acetyl-3-O-allyl-2,4-O- [bibenzylbis-2,2 ′-(methylene)]-1-thio-D-glucopyranoside and potassium carbonate (357 .4 mg, 2.59 mmol) in methanol (12.9 mL) was stirred at room temperature for 19 hours. To this was added a saturated aqueous ammonium chloride solution (10 mL), and the mixture was extracted with chloroform (30 mL × 3 times). The obtained extract was dried using anhydrous magnesium sulfate, and the solvent was distilled off to obtain a residue. The obtained residue was purified by silica gel column chromatography (SiO ₂ : 20 g, ethyl acetate / n-hexane (volume ratio) = 1/3 → 1/1), and ethyl 3-O-allyl-2,4-O -[Bibenzylbis-2,2 '-(methylene)]-1-thio-D-glucopyranoside (mixing ratio of anomeric isomers 92: 8, 528 mg, 1.12 mmol, yield: 87%) was obtained as a colorless syrup It was.

The physicochemical properties of ethyl 6-O-acetyl-3-O-allyl-2,4-O- [bibenzylbis-2,2 ′-(methylene)]-1-thio-D-glucopyranoside are as follows: .
IR (neat): 3010, 2989, 2947, 2930, 2896, 2885, 2874, 2828, 1739, 1456, 1368, 1237, 1096, 1344, 920, 772 cm ⁻¹
HRMS-ESI (m / z): [M + Na] ⁺
Calculated (as C ₂₉ H ₃₆ ²³ Na ₁ O ₆ S ₁ ) 535.2130, measured 535.221.

The physicochemical properties of ethyl 3-O-allyl-2,4-O- [bibenzylbis-2,2 ′-(methylene)]-1-thio-α-D-glucopyranoside are as follows.
[Α] _D ²¹ = + 345.6 (c = 0.10, CHCl ₃ )
IR (neat): 3486, 3062, 3015, 2926, 2868, 1455, 1216, 1089, 1076, 1057, 991, 933, 827, 807, 755 cm ^−1
1 H-NMR (400 MHz, CDCl ₃ ): δ ppm
7.47 (br d, J = 7.6 Hz, 1H), 7.41-7.18 (m, 7H), 5.61 (dddd, J = 17.2, 10.3, 5.7, 5.7 Hz, 1H), 5.40 (d, J = 5.0 Hz, 1H ), 5.03 (br dd, J = 10.3, 1.4 Hz, 1H), 4.93 (br dd, J = 17.2, 1.4 Hz, 1H), 4.77 (d, J = 11.8 Hz, 1H), 4.70 (d, J = 9.2 Hz, 1H), 4.48 (d, J = 11.8 Hz, 1H), 4.30 (d, J = 9.2 Hz, 1H), 4.02 (ddd, J = 8.2, 4.8, 3.2 Hz, 1H), 3.89 (ddd, J = 5.0, 1.6 Hz, 1H), 3.87-3.79 (m, 2H), 3.75-3.66 (m, 2H), 3.65-3.59 (m, 1H), 3.62 (ddd, J = 14.7, 12.8, 3.4 Hz, 1H), 3.45 (d, J = 3.6 Hz, 1H), 3.16 (ddd, J = 12.8, 12.6, 6.0 Hz, 1H), 2.98 (ddd, J = 12.6, 12.6, 3.4 Hz, 1H), 2.81 (ddd , J = 14.7, 12.6, 6.0 Hz, 1H), 2.68 (m, 2H), 1.82 (br s, 1H), 1.31 (t, J = 7.3 Hz, 3H)
¹³ C-NMR (100 MHz, CDCl ₃ ): δ ppm
143.1, 142.0, 135.4, 134.4, 134.2, 132.0, 131.5, 130.2, 129.2, 129.1, 128.3, 126.6, 125.9, 118.5, 84.7, 76.8, 74.3, 73.9, 73.7, 72.0, 70.7, 70.7, 63.4, 33.4, 32.8, 24.8, 15.6
HRMS-ESI (m / z): [M + Na] ⁺
Calculated ^{_{(C 27 H 34 23 Na 1}} O 5 as _{S 1)} 493.2025, measured 493.2028.

  Reference example 3

[Wherein, n-Pr represents an n-propyl group. Allyl and Ac are the same as above. ]
Preparation of 1,6-di -O-acetyl-3-On-propyl-D-glucopyranose 1,6-di-O-acetyl-3-O-allyl-2,4-O- [bibenzylbis-2 , 2 ′-(methylene)]-D-glucopyranose (mixing ratio of anomeric isomers α: β = 69: 31, 6.3 mg, 0.0123 mmol) in methanol (0.7 mL) and tetrahydrofuran (0.7 mL) While the solution dissolved in the mixed solution was stirred at room temperature, palladium hydroxide / carbon (6.3 mg, 20% by mass, 9.0 μmol as palladium hydroxide) was added, and the mixture was heated to a hydrogen gas atmosphere at room temperature. The bottom (70 atm) was stirred for 19 hours. The obtained mixture was filtered with cotton and celite, and the used cotton and celite were washed with ethyl acetate. The solvent of the obtained filtrate was distilled off, and the obtained residue was purified by silica gel column chromatography (SiO ₂ : 2 g, ethyl acetate / n-hexane (volume ratio) = 2/3 → 1/0). , 6-Di-O-acetyl-3-On-propyl-D-glucopyranose (mixing ratio of anomeric isomers α: β = 65: 35, 2.7 mg, 8.82 μmol, yield: 71%) Was obtained as a colorless syrup.

The physicochemical properties of 1,6-di-O-acetyl-3-On-propyl-D-glucopyranose are as follows.
IR (neat): 3414, 2983, 2959, 2930, 2922, 2868, 1744, 1684, 1270, 1229, 1035, 772 cm ^−1
1 H-NMR (partial data, 400 MHz, CDCl ₃ ): δ ppm
6.21 (d, J = 3.9 Hz, 1H), 4.53 (dd, J = 3.9, 4.6 Hz, 1H), 4.17 (dd, J = 12.4, 2.3 Hz, 1H), 2.17 (s, 3H), 2.12 (s , 3H), 0.95 (t, J = 7.3 Hz, 3H)
HRMS-ESI (m / z): [M + Na] ⁺
Calculated _{(as ^{C 13 H 22 23 Na 1 O}} 8) 329.1212, measured 329.1218.

Claims (5)

General formula (1)

[Wherein, R ¹ represents an —OR ⁶ group (R ⁶ represents a hydrogen atom or a hydroxyl-protecting group).
R ² represents an —OR ⁷ group (R ⁷ represents a hydrogen atom, a protecting group for a hydroxyl group, or a group that acts as a leaving group together with a bonding oxygen atom), and —SR ⁸ group (R ⁸ has a substituent). A lower alkyl group which may be substituted or an aryl group which may have a substituent on the aromatic ring) or a halogen atom.
R ¹ and R ² may combine to form —O—.
R ³ represents a hydrogen atom; a lower alkyl group which may have a substituent; —N (R ⁹ ) ₂ groups (R ⁹ represents a hydrogen atom or an amino group-protecting group, and two R ^9s are the same. Or they may be bonded to each other to form a ring) or -OR ¹⁰ group (R ¹⁰ represents a hydrogen atom or a hydroxyl-protecting group).
R ⁴ represents a lower alkyl group which may be substituted with a halogen atom, a lower alkoxy group which may be substituted with a halogen atom, a nitro group or a halogen atom.
R ⁵ represents a lower alkyl group which may be substituted with a halogen atom, a lower alkoxy group which may be substituted with a halogen atom, a nitro group or a halogen atom.
m and n each represent an integer of 0 to 4, and p represents an integer of 1 to 4.
Further, m R ^{4 s} may be the same or different, and n R ^{5 s} may be the same or different.
m number of R ⁴ adjacent to each other may form a benzene ring bonded to each other, R ⁵ may form a benzene ring bonded to each other adjacent the n mutually. ]
A 2,4-O-bridged inverted pyranose compound represented by the formula:   The 2,4-O-bridged inverted pyranose compound according to claim 1, wherein p represents an integer of 1 to 3, or an enantiomer thereof.   The 2,4-O-bridged inverted pyranose compound according to claim 1, wherein p is 2, or an enantiomer thereof. The 2,4-O-bridged inverted pyranose compound according to any one of claims 1 to 3, wherein R ¹ and R ² are bonded to each other, or an enantiomer thereof. R ¹ is an —OR ⁶ group (R ⁶ is the same as above), R ² is an —OR ⁷ group (R ⁷ is the same as above), —SR ⁸ group (R ⁸ is the same as above) or halogen The 2,4-O-bridged inverted pyranose compound according to any one of claims 1 to 3, which is an atom, or an enantiomer thereof.