JPH10296089A - Method for forming stereoselective glycosidic linkage - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for forming a glycosidic linkage which enables a control or three-dimensional control of a side reaction under mild conditions and is highly diastereoselective. SOLUTION: In the method for forming a glycosidic linkage, a reaction is effected in the presence of a glycosidic linkage forming catalyst containing azo compounds represented by the formula (R shows a lower alkyl group). And sugar halide may be allowed to react with unsaturated compounds in the presence of the catalyst.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a novel catalyst for forming a glycoside bond, and a method for producing a glycoside using the catalyst.

[0002]

2. Description of the Related Art C-glycoside exists as a subunit of various natural products and as an enzyme inhibitor, and has an interesting value as a chiral building block. In particular, C-glycosides having an axial carbon-carbon bond include interesting natural products such as Palytoxin, and in their synthesis, precise control of diastereoselectivity at the anomeric position is important. It becomes a problem. To date, there have been many reports on the control of the anomeric position, and among them, the most effective α-linked C-glycopyranoside (α-linked C-glycopyranosi
As a method for synthesizing des), a method is known in which an anomer-position radical is reacted with an activated olefin by Gies et al. (B. Gies., Org. Synth. 65 , 236 (1987).
etc). The selectivity in this photoradical reaction is α: β =
Although the ratio is 10: 1, it cannot be said that the selectivity is still sufficiently satisfactory, and it is desired to establish stereocontrol with better selectivity.

[0003]

DISCLOSURE OF THE INVENTION The present invention has been made in view of the above-mentioned circumstances, and is capable of controlling side reactions and steric control under mild conditions, and has a highly diastereoselective glycosidic bond. It is an object of the present invention to provide a method for forming a film.

[0004]

The present invention comprises the following arrangement. "(1) General formula [1]

[0005]

Embedded image

(Wherein, R ¹ represents a lower alkyl group)
A glycoside bond-forming catalyst comprising an azo compound represented by the formula:

(2) A method for forming a glycosidic bond, wherein the reaction is carried out in the presence of the catalyst according to (1).

(3) A method for forming a glycosidic bond, comprising reacting a sugar halide with an unsaturated compound in the presence of the catalyst according to (1).

(4) A glycosylation method using the catalyst according to (1).

(5) A method for adding a sugar halide to an unsaturated compound, comprising using the catalyst according to (1).

(6) A process for producing glycosides, comprising reacting a sugar halide with an unsaturated compound in the presence of the catalyst according to (1).

(7) In the presence of the catalyst described in (1), a compound of the general formula [2]

[0013]

Embedded image (Wherein, R represents a hydrogen atom or a protecting group, and X represents a halogen atom), and a sugar halide represented by the general formula [3]:

[0014]

Embedded image

(Wherein R ² represents a hydrogen atom, an alkyl group, a haloalkyl group, an aryl group which may have a substituent,
Optionally substituted aralkyl groups, aliphatic heterocyclic groups, aromatic heterocyclic groups, alkyloxycarbonyl groups, hydroxyalkyloxycarbonyl groups, aralkyloxycarbonyl groups, aryloxycarbonyl groups,
It represents an acyloxy group, an acyl group, an alkoxy group, an aralkyloxy group, an aryloxy group, a cyano group, an amino group, a carbamoyl group, a sulfonic acid group, and a carboxyl group. Wherein the alkene is represented by the general formula [4]:

[0016]

Embedded image

(Wherein R and R ² are the same as described above). "

That is, the present inventors have conducted intensive studies on the control and steric control of side reactions and the glycosylation reaction capable of complete steric control under mild conditions. Paying attention to the fact that the azo compound represented by the above general formula [1] effectively generates a radical species at a low temperature, and using the azo compound as a catalyst for forming a glycosidic bond, can solve all of the above problems. And arrived at the present invention.

In the general formula [1], examples of the lower alkyl group represented by R ¹ include an alkyl group having 1 to 4 carbon atoms, and specific examples include a methyl group, an ethyl group and a butyl group. Among them, a methyl group is preferable.

In the general formula [2], examples of the halogen atom represented by X include fluorine, chlorine, bromine and iodine, and among them, bromine is preferable. The protecting group represented by R is generally used as a protecting group for a hydroxyl group (hydroxyl group) (for example, “PROTECTIVE GROUPS IN ORG”).
ANIC SYNTHESIS second edition ”and the like are not particularly limited, and examples thereof include an acyl group, an alkyloxycarbonyl group, and an alkyloxycarbonyl group having a substituent. The acyl group may be linear or branched, and is preferably an acyl group having 2 to 21 carbon atoms, such as an acetyl group, a propionyl group, a butyryl group, and a pentanoyl group. Hexanoyl group, heptanoyl group, octanoyl group, nonanoyl group, decanoyl group, benzoyl group and the like. The alkyloxycarbonyl group may be linear or branched, and may have 2 to 2 carbon atoms.
21 alkyloxycarbonyl groups, specifically, methyloxycarbonyl, ethyloxycarbonyl, propyloxycarbonyl, butyloxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl, heptyloxycarbonyl, octyl Examples include an oxycarbonyl group, a nonyloxycarbonyl group, a decyloxycarbonyl group, a dodecyloxycarbonyl group, an octadecyloxycarbonyl group, a tert-butyloxycarbonyl group, a 2-ethylhexyloxycarbonyl group, and the like. Examples of the substituent of the alkyloxycarbonyl group having a substituent include phenyl, naphthyl, anthryl, 4-methylphenyl, 4-methoxyphenyl, 3,5-dimethoxyphenyl, 4-chlorophenyl, and 4 -Nitrophenyl group, fluorenyl group, and the like. Examples of the alkyloxycarbonyl group having the substituent include those in which one or more hydrogen atoms of the above-described alkyloxycarbonyl group have been substituted with the substituent. Specific examples of the alkyloxycarbonyl group having a substituent include, for example, a benzyloxycarbonyl group, a phenethyloxycarbonyl group, a fluorenylmethyloxycarbonyl group, a 3,5-dimethoxyphenylmethyloxycarbonyl group, and a 4-methoxyphenylmethyloxy Examples include a carbonyl group and a 4-nitrophenylmethyloxycarbonyl group.

In the general formulas [3] and [4], the alkyl group represented by R ² may be linear, branched, or cyclic. Examples of the alkyl group include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a tert-butyl group, a sec-butyl group, a pentyl group, an isopentyl group, and a neopentyl group. Tert-pentyl group, 3,3-dimethylbutyl group, 1,1-dimethylbutyl group, 1-
Methylpentyl group, n-hexyl group, isohexyl group,
Examples include heptyl, octyl, nonyl, decyl, undecyl, dodecyl, hexadecyl, octadecyl, cyclopropyl, cyclopentyl, cyclohexyl and the like. Examples of the haloalkyl group include a haloalkyl group having 1 to 20 carbon atoms in which the above alkyl group is halogenated (for example, fluorinated, chlorinated, brominated, iodinated, etc.), and specifically, a chloromethyl group, Bromomethyl group, trifluoromethyl group, 2-chloroethyl group, 3-chloropropyl group, 3-bromopropyl group, 3,3,3-
Trifluoropropyl group, 2-perfluorooctylethyl group, perfluorooctyl group, 1-chlorodecyl group, 1-
Examples thereof include a chlorooctadecyl group and an 8-iodooctyl group. The aryl group which may have a substituent includes
For example, phenyl, tolyl, xylyl, naphthyl, anthryl, 4-methylphenyl, 4-ethylphenyl, 4-methoxyphenyl, 4-chlorophenyl,
Examples include an aminophenyl group, a hydroxyphenyl group, and a carboxyphenyl group. Examples of the aralkyl group which may have a substituent include, for example, an aralkyl group having 7 to 20 carbon atoms and a nuclear substituent thereof, and specifically, a benzyl group, a phenethyl group, a 3-phenylpropyl group, And a (4-methyloxycarbonylphenyl) propyl group. As the aliphatic heterocyclic group, for example, a 5- or 6-membered aliphatic heterocyclic group is preferable, and
For example, those containing a hetero atom such as a nitrogen atom, an oxygen atom, and a sulfur atom, and specific examples thereof include:
Examples include a pyrrolidyl-2-one group, a piperidino group, a piperazinyl group, a morpholino group and the like. As the aromatic heterocyclic group, for example, a 5- or 6-membered aromatic heterocyclic group is preferable, and as an isomer atom, 1 to 3 nitrogen atoms,
Examples thereof include those containing a hetero atom such as an oxygen atom and a sulfur atom, and specific examples thereof include a pyridyl group, an imidazolyl group, a thiazolyl group, a furanyl group, and a pyranyl group. The alkyloxycarbonyl group may be linear or branched, and may be, for example, an alkyloxycarbonyl group having 2 to 21 carbon atoms.
Specifically, a methyloxycarbonyl group, an ethyloxycarbonyl group, a propyloxycarbonyl group, a butyloxycarbonyl group, a pentyloxycarbonyl group, a hexyloxycarbonyl group, a heptyloxycarbonyl group,
Examples include an octyloxycarbonyl group, a nonyloxycarbonyl group, a decyloxycarbonyl group, a dodecyloxycarbonyl group, an octadecyloxycarbonyl group, a tert-butyloxycarbonyl group, a 2-ethylhexyloxycarbonyl group, and the like. Examples of the hydroxyalkyloxycarbonyl group include a hydroxyalkyloxycarbonyl group having 2 to 20 carbon atoms in which a hydrogen atom of the alkyl group of the alkyloxycarbonyl group is substituted with a hydroxyl group as described above. Carbonyl group, hydroxyethyloxycarbonyl group, hydroxypropyloxycarbonyl group, hydroxybutyloxycarbonyl group, hydroxypentyloxycarbonyl group, hydroxyhexyloxycarbonyl group, hydroxyheptyloxycarbonyl group, hydroxyoctyloxycarbonyl group, hydroxynonyloxycarbonyl group , Hydroxydecyloxycarbonyl, hydroxydodecyloxycarbonyl, hydroxyoctadecyloxycarbonyl and the like. That. Examples of the aralkyloxycarbonyl group include those having 8 carbon atoms.
To 20 aralkyloxycarbonyl groups, specifically, benzyloxycarbonyl group, phenethyloxycarbonyl group and the like. As the aryloxycarbonyl group, for example, an aryloxycarbonyl group having 7 to 20 carbon atoms is preferable, and specific examples include a phenyloxycarbonyl group and a naphthyloxycarbonyl group. As the acyloxy group, for example, an acyloxy group having 2 to 21 carbon atoms derived from a carboxylic acid is preferred. , Octanoyloxy group,
Examples include a nonanoyloxy group, a decanoyloxy group, and a benzoyloxy group. As the acyl group, for example, an acyl group having 1 to 21 carbon atoms derived from a carboxylic acid is preferable,
Specifically, formyl group, acetyl group, propionyl group,
Butyryl, pentanoyl, hexanoyl, heptanoyl, octanoyl, nonanoyl, decanoyl, benzoyl and the like. The alkoxy group may be linear or branched, and may be, for example, an alkoxy group having 1 to 20 carbon atoms. Specific examples include a methoxy group, an ethoxy group, a propoxy group, a butoxy group, and a pentyloxy group. Group, hexyloxy group, heptyloxy group,
Octyloxy group, nonyloxy group, decyloxy group,
A dodecyloxy group, an octadecyloxy group, a 2-propoxy group, a tert-butoxy group, a 2-ethylhexyloxy group, and the like. Examples of the aralkyloxy group include an aralkyloxy group having 7 to 20 carbon atoms, and specific examples include a benzyloxy group and a phenethyloxy group. Examples of the aryloxy group include, for example, those having 7 to 2 carbon atoms.
An aryloxy group of 0 is preferable, and specific examples include a phenoxy group and a naphthyloxy group.

Specific examples of the alkene represented by the above general formula [3] according to the present invention include, for example, ethylenic aliphatic hydrocarbons having 2 to 20 carbon atoms such as ethylene, propylene, butylene and isobutylene, for example, styrene, Α-ethylenic aromatic hydrocarbons having 8 to 20 carbon atoms, such as 4-methylstyrene, 4-ethylstyrene, and 4-methoxystyrene, for example, the carbon number of vinyl formate, vinyl acetate, vinyl propionate, and isopropenyl acetate 3-20 vinyl esters, for example, ethylenic carboxylic acids having 3-20 carbon atoms such as acrylic acid and vinylbenzoic acid (these acids are, for example, alkali metal salts such as sodium and potassium, ammonium salts, etc.
It may be in the form of salt. ), For example, methyl acrylate, ethyl acrylate, butyl acrylate, 2-ethylhexyl acrylate, lauryl acrylate, stearyl acrylate, vinyl acrylate, 2-hydroxyethyl acrylate, 3-hydroxypropyl acrylate, acrylic acid 2 C4 to C20 ethylenic carboxylic acid esters such as -hydroxypropyl; for example, C3 to C20 containing cyanovinyl compounds such as acrylonitrile; for example, C3 to C20 vinyl amide compounds such as acrylamide; C3 to C20 ethylenic aldehydes such as acrolein, for example, C2 to C20 vinyl sulfonic acids such as vinylsulfonic acid and 4-vinylbenzenesulfonic acid (these acids are, for example, alkali metal salts such as sodium and potassium) Etc., which may be in the form of salt.),
For example, vinyl aliphatic amines having 2 to 20 carbon atoms such as vinylamine, for example, vinyl aromatic amines having 8 to 20 carbon atoms such as vinylaniline, for example, N-vinylpyrrolidone,
Vinyl aliphatic heterocyclic amines having 5 to 20 carbon atoms such as vinylpiperidine, for example, vinyl aromatic heterocyclic amines having 5 to 20 carbon atoms such as vinylpyridine and 1-vinylimidazole, for example, 4-vinylphenol Has 8 or more carbon atoms
And 20 ethylenic phenols.

The present invention will be described below by taking as an example the case where the sugar halide represented by the above general formula [2] and the alkene represented by the above general formula [3] are used as the unsaturated compound.

That is, the sugar halide as described above and the alkene as described above are mixed in a suitable solvent in the presence of the catalyst for forming a glycosidic bond and tin hydride, if necessary, in an inert gas atmosphere according to a conventional method. By reacting
For example, the general formula [4]

[0025]

Embedded image

(Wherein, X, R and R ² are as defined above)
(Adduct) can be obtained.

The post-treatment after the reaction may be carried out in accordance with a usual post-treatment method, and the produced compound may be purified by a method known per se, that is, by performing various chromatography, recrystallization and the like. Good.

Examples of the reaction solvent include hydrocarbons such as toluene, xylene, benzene, cyclohexane, n-hexane and n-octane; halogenated hydrocarbons such as methylene chloride, dichloroethane and trichloroethane;
For example, methyl acetate, ethyl acetate, n-butyl acetate, esters such as methyl propionate, for example, acetone, methyl ethyl ketone, methyl isobutyl ketone, tert-butyl methyl ketone, ketones such as cyclohexanone, for example, dimethyl ether, diethyl ether, diisopropyl ether, Dimethoxyethane, tetrahydrofuran,
Ethers such as dioxane and tert-butyl methyl ether; These may be used alone or in combination of two or more.

The inert gas used as required includes, for example, nitrogen gas, argon gas and the like.

Examples of the tin hydride according to the present invention include tributyltin hydride and triphenyltin hydride.

The amount of tin hydride used is not particularly limited and is determined as appropriate, but is usually selected from the range of 1.0 to 10.0% by weight, preferably 1.0 to 2.0% by weight.

The amounts of the sugar halide and the alkene are not particularly limited, but it is preferable to use the alkene in excess of the sugar halide.

The amount of the glycosidic bond-forming catalyst used is not particularly limited and may be determined as appropriate. The amount is usually selected from the range of 0.1 to 10 equivalents, preferably 0.5 to 2 equivalents, based on the sugar halide. .

The reaction temperature is not particularly limited. If the reaction temperature is too low, the progress of the reaction is slowed down due to little decomposition of the azo group, and if it is too high, the selective addition reaction hardly occurs.
Less than 70 ° C, preferably -30 to 60 ° C, more preferably -10
It is appropriately selected from the range of ~ 30 ° C.

The reaction time varies depending on the reaction conditions such as the reaction temperature, the type and concentration of the sugar halide to be reacted, the alkene, the catalyst for forming the glycosidic bond, and the like. Therefore, thin-layer chromatography (TLC) or high-performance liquid chromatography (HPLC) ), Etc., may be monitored to monitor the progress and may be determined as appropriate, but is usually selected as appropriate from the range of 10 minutes to 170 hours.

The sugar halide and alkene may be either commercially available products or those appropriately produced by a conventional method. Also, the azo compound represented by the general formula [1] may be a commercially available product or US Pat.
Any of those manufactured according to the manufacturing methods described in JP-A-995 and JP-A-50-13328 can be used.

The thus obtained general formula [4]
Is obtained by using a sugar halide represented by the general formula [2] and, for example, an alkene represented by the general formula [3], using the azo compound represented by the general formula [1] of the present invention as a catalyst. The α-isomer can be obtained in high yield and with almost complete stereocontrol.

Further, the glycoside represented by the general formula [4] is obtained by converting the carbon to which the halogen atom of the sugar halide represented by the general formula [2] is bonded to the alkene represented by the general formula [3]. It is obtained by bonding with the carbon to which R ² is bonded to form a new glycosidic bond.

The present invention is characterized in that the azo compound represented by the above general formula [1] used as a radical initiator is used as a catalyst for forming a glycosidic bond. Since the azo compound generates a radical species at around room temperature, it does not require heating or the like to generate a radical species such as azobisisobutyronitrile, which is generally used as a radical initiator, so that a side reaction occurs. Control and three-dimensional control have become possible. That is,
By using the catalyst for forming a glycosidic bond comprising the azo compound represented by the general formula [1] of the present invention, for example, the sugar halide represented by the general formula [2] can be converted to, for example, the general formula [3] A regioselective addition reaction to an unsaturated compound such as an alkene represented by the formula (1), that is, a diastereoselective addition reaction becomes possible, and the desired glycoside represented by the above general formula [4] (adduct ) Can be obtained with high yield and almost complete stereocontrol.

Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples, but the present invention is not limited thereto.

[0041]

The formal names of the abbreviations used in the following Examples, Comparative Examples and Tables are as follows. V-70: 2,2'-azobis (4-methoxy-2,4-dimethylvaleronitrile) AIBN: azobisisobutyronitrile BPO: benzoyl peroxide Et ₃ B: triethylborane hv: irradiation IPE: diisopropyl ether TBME: tert-butyl methyl ether

Example 1. 2,3,4,6-Tetra-O-acetyl-
To a solution of α-D-glucopyranosyl bromide (568 mg, 1.3 mmol) in anhydrous ether (60 ml), under a nitrogen atmosphere, V-70 (511 mg)
(1.66 mmol) and acrylonitrile 733 mg (1.3 mmol)
, And tributyltin hydride 4
After 10 ml of an ether solution of 83 mg (1.66 mmol) was slowly added dropwise at room temperature, the mixture was stirred and reacted for 12 hours. After the reaction,
10 ml of a 10% aqueous solution of potassium fluoride was added to the reaction solution, followed by vigorous stirring. The organic layer is concentrated, and the obtained residue is subjected to silica gel column chromatography [filler; Wakogel C-200]
(Trade name of Wako Pure Chemical Industries, Ltd.), Eluent: ethyl acetate / n-
Hexane = 1/1] to give the desired 1-deoxy-
2,3,4,6-tetra-O-acetyl-1- (2-cyanoethyl) -α-
363 mg (68.3% yield) of D-glucopyranose was obtained. Table 1 shows the results. ¹ H-NMR δ ppm (CDCl ₃ , 200 MHz): 1.84-1.95 (m, 1
H, CC H ₂ ), 2.05 (s, 6H, 2OAc), 2.09 (s, 3H, OA
c), 2.11 (s, 3H, OAc), 2.05-2.22 (m, 1H, CC
_{H 2), 2.46 (m,} 2H, C H 2 CN), 3.88 (ddd, 1H, H 5, J 5.6 = 5.8
0Hz, J _{5.6 '} = 2.88Hz, J _4.5 = 8.30Hz., 4.12 (dd, 1H, H _6' , J
_{6.6 '= 12.24Hz), 4.23 (} m, 1H, H 1), 4.32 (dd, 1H,
_{H 6), 4.98 (t,} 1H, H 4, J 3.4 = 8.30Hz), 5.09 (dd, 1H, H 2,
J _1.2 = 5.23 Hz, J _2.3 = 8.30 Hz), 5.23 (t, 1H, H ₃ ). IR (KBr) cm ^-1 : 2240 (C≡N), 1745 (C = O).

Embodiments 2-4. In Example 1, the objective 1-deoxy-2,3,4,4 was obtained in the same manner as in Example 1 except that the type of the solvent used, the reaction temperature and the reaction time were changed as shown in Table 1. 6-Tetra-O-acetyl-1- (2-cyanoethyl) -α-D-glucopyranose was obtained. Table 1 shows the results.

Comparative Examples 1 and 2. In Example 1, except that the radical initiator used, the type of solvent, the reaction temperature and the reaction time were as shown in Table 1, the desired 1-deoxy-2, 3,4,6-Tetra-O-acetyl-1- (2-cyanoethyl) -α-D-glucopyranose was obtained. Table 1 shows the results.

Comparative Example 3. 2,3,4,6-Tetra-O-acetyl-
To a solution of 568 mg (1.3 mmol) of α-D-glucopyranosyl bromide in 60 ml of anhydrous ether, 733 mg (1.3 mmol) of acrylonitrile was added under a nitrogen atmosphere, and 483 mg (1.66 mmol) of tributyltin hydride in ether was added using a syringe pump.
After slowly adding 10 ml dropwise at room temperature, to this under stirring,
Irradiated with high pressure mercury lamp at 0 ° C. for 1 hour. After the reaction,
Post-treatment was performed in the same manner as in Example 1 to obtain the desired 1-deoxy-2,3,
4,6-Tetra-O-acetyl-1- (2-cyanoethyl) -α-D-glucopyranose was obtained. The results are shown in Table 1.

The reaction formulas of Examples 1 to 4 and Comparative Examples 1 to 3 are shown below.

[0047]

(Equation 1)

[0048]

[Table 1] α-form (target) β-form By-product (1-deoxy-2,3,4,6-tetra-O-acetyl-
α-D-glucopyranose) Raw material (2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide) 1) Isolation yield. The production ratio was determined by high performance liquid chromatography (HPLC). *: -78 ° C to room temperature a) β-isomer was not detected by thin-layer chromatography. In ¹ H-NMR, α: β> 20: 1. b) β-isomer was not detected by thin layer chromatography. c) 53-55%

From the above results, it can be seen that in the addition reaction of 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide to acrylonitrile, V-70 was used as a catalyst. Gives the desired α-isomer in a high yield and with almost complete stereocontrol by a reaction at room temperature, but is free from other radical initiators AIB
In the case of using N (Comparative Example 1) or in the case of a radical addition reaction by light irradiation (Comparative Example 3), although the desired α-isomer is obtained, a considerable amount of by-product β-isomer and debrominated product are produced. In addition, when Et ₃ B was used (Comparative Example 2), it was found that the reaction required an extremely low temperature, and the yield was extremely lower than when V-70 was used.

Embodiment 5 FIG. Example 1 Example 1 was repeated except that acrolein was used in place of acrylonitrile.
The reaction and post-treatment were carried out in exactly the same manner as described above, and the desired 1-deoxy-2,3,4,6-tetra-O-acetyl-1- (2-formylethyl) -α-D-glucopyranosyl bromide was obtained. (30% yield)
I got Table 2 shows the results. ¹ H-NMR δppm (CDC
_{l 3, 200MHz): 1.82-1.95 (} m, 1H, CC H 2), 2.02 (s, 3H,
OAc), 2.03 (s, 3H, OAc), 2.08 (s, 3H, OA)
c), 2.10 (s, 3H, OAc), 2.05-2.22 (m, 1H, CC
_{H 2), 2.58 (t,} 2H, C H 2 CHO), 3.85 (ddd, 1H, H 5, J 5.6 = 5.
80Hz, J _{5.6 '} = 2.88Hz, J _4.5 = 8.30Hz.), 4.05 (dd, 1H, H _6' ,
_{J 6.6 '= 12.24Hz), 4.15} (m, 1H, H 1), 4.25 (dd, 1H,
_{H 6), 4.98 (t,} 1H, H 4, J 3.4 = 8.30Hz), 5.09 (dd, 1H, H 2,
_{J 1 .2 = 5.23Hz, J 2.3} = 8.30Hz), 5.31 (t, 1H, H 3). IR
(KBr) cm ^-1 : 1745,1750 (C = O).

Embodiment 6 FIG. The reaction and post-treatment were carried out in the same manner as in Example 1 except that methyl acrylate was used in place of acrylonitrile.
Deoxy-2,3,4,6-tetra-O-acetyl-1- (2-methoxycarbonylethyl) -α-D-glucopyranosyl bromide (yield 59%) was obtained. The results are shown in Table 2. ¹ H-NMR δ ppm (CDCl ₃ , 270 MHz): 1.82-1.93 (m, 1
H, CC H ₂ ), 2.03 (s, 3H, OAc), 2.05 (s, 3H, OA
c), 2.09 (s, 3H, OAc), 2.11 (s, 3H, OAc), 2.
04-2.21 (m, 1H, CC H 2), 2.41 (m, 2H, C H 2 OMe), 3.69
(S, 3H, OMe), 3.83 (ddd, 1H, H 5, J 5.6 = 5.80Hz, J 5.6 '= 2.
88Hz, J _4.5 = 8.30Hz., 4.05 (dd, 1H, H _{6 '} , J _6.6' = 12.2H
z), 4.18 (m, 1H , H 1), 4.21 (dd, 1H, H 6), 4.99 (t, 1
H, H ₄ , J _3.4 = 8.30Hz), 5.09 (dd, 1H, H ₂ , J _1.2 = 5.23Hz, J
_{2.3 = 8.30Hz), 5.26 (t} , 1H, H 3). IR (KBr) cm ^-1 : 1745 (C = O).

[0052]

(Equation 2)

[0053]

[Table 2] d) Isolation yield of α form by column chromatography.
β-isomer could not be confirmed by thin-layer chromatography.

From the above results, it can be seen that even in the addition reaction to alkenes other than acrylonitrile (Examples 1 to 4), the α-isomer can be obtained with high yield and almost complete stereocontrol.

[0055]

As described above, the present invention provides a novel catalyst for forming a glycosidic bond and a highly diastereoselective C-
The present invention provides a method for producing a glycoside, and the use of the catalyst makes it possible to produce a stereoselective glycoside compound, which has been conventionally difficult, whereby the α-isomer, which is the desired adduct, can be produced in high yield. In addition, it has a remarkable effect in that it can be given by complete stereoscopic control.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification code FI C07M 9:00

Claims (15)

[Claims] 1. A compound of the general formula [1] (In the formula, R ¹ represents a lower alkyl group.) A catalyst for forming a glycosidic bond comprising an azo compound represented by the formula: 2. A method for forming a glycosidic bond, wherein the reaction is carried out in the presence of the catalyst according to claim 1. 3. A method for forming a glycosidic bond, comprising reacting a sugar halide with an unsaturated compound in the presence of the catalyst according to claim 1. 4. The method according to claim 3, wherein the unsaturated compound is an alkene.
The method for forming a glycosidic bond according to the above. 5. The method for forming a glycosidic bond according to claim 2, wherein the glycosidic bond formation is diastereoselective bond formation. 6. A glycosylation method using the catalyst according to claim 1. 7. The glycosylation method according to claim 6, wherein the glycosylation method is a diastereoselective glycosylation method. 8. A method for adding a sugar halide to an unsaturated compound, comprising using the catalyst according to claim 1. 9. The unsaturated compound is an alkene.
The addition method described in 1. 10. The addition method according to claim 8, wherein the addition method is a diastereoselective addition method. 11. A process for producing a glycoside, comprising reacting a sugar halide with an unsaturated compound in the presence of the catalyst according to claim 1. 12. The method according to claim 11, wherein the unsaturated compound is an alkene. 13. The sugar halide is represented by the general formula [2]: (Wherein, R represents a hydrogen atom or a protecting group, and X represents a halogen atom). 14. An alkene having the general formula [3] (Wherein, R ² represents a hydrogen atom, an alkyl group, a haloalkyl group, an aryl group which may have a substituent, an aralkyl group which may have a substituent, an aliphatic heterocyclic group, an aromatic heterocyclic group. Group, alkyloxycarbonyl group, hydroxyalkyloxycarbonyl group, aralkyloxycarbonyl group, aryloxycarbonyl group, acyloxy group, acyl group, alkoxy group, aralkyloxy group, aryloxy group, cyano group, amino group, carbamoyl group, sulfone 14. The production method according to claim 12, wherein the compound is an acid group or a carboxyl group. 15. A compound of the general formula [2] in the presence of the catalyst according to claim 1. (Wherein, R represents a hydrogen atom or a protecting group, and X represents a halogen atom), and a sugar halide represented by the general formula [3]: (Wherein, R ² represents a hydrogen atom, an alkyl group, a haloalkyl group, an aryl group which may have a substituent, an aralkyl group which may have a substituent, an aliphatic heterocyclic group, an aromatic heterocyclic group. Group, alkyloxycarbonyl group, hydroxyalkyloxycarbonyl group, aralkyloxycarbonyl group, aryloxycarbonyl group, acyloxy group, acyl group, alkoxy group, aralkyloxy group, aryloxy group, cyano group, amino group, carbamoyl group, sulfone (Representing an acid group and a carboxyl group)), characterized by reacting with an alkene represented by the general formula [4]: (Wherein, R and R ² are the same as described above).