JPH08843B2 - Cyclic heterooligosaccharide and method for synthesizing the same - Google Patents

Description

TECHNICAL FIELD The present invention relates to a novel cyclic heterooligosaccharide and a method for synthesizing the same.

[Background of the Invention]

Cyclodextrins are widely used as deterioration inhibitors, solubilizers, and emulsifiers for pharmaceuticals, foods, cosmetics, etc., because they have the property of incorporating various organic compounds into their molecular cavities. Further, various chemical conversions have been carried out for the purpose of improving and modifying its physicochemical properties, but since cyclodextrin has many hydroxyl groups, conventional methods have problems in yield, selectivity, etc. .

On the other hand, the present inventor has succeeded in selectively synthesizing a linear maltooligosaccharide at a high yield by decomposing cyclodextrin with acetic acid (Japanese Patent Application No. 1-57235).
See the specification). The present inventors have found that a novel cyclic oligosaccharide can be synthesized by using a linear maltooligosaccharide obtained by this method as a starting material, binding an arbitrary sugar chain to this as a starting material, and then subjecting it to recirculation. The invention was completed.

[Problems to be Solved by the Invention]

It is an object of the present invention to provide new cyclic heterooligosaccharides.

Another object of the present invention is to provide a method for synthesizing cyclic oligosaccharides.

[Means for solving the problem]

The novel cyclic heterooligosaccharide of the present invention is represented by the following general formula.

In the formula, R ¹ represents hydrogen or a benzyl group, R ² represents hydrogen or an acetyl group, and R ³ represents an amino group or an azido group.

The above-mentioned cyclic heterooligosaccharides and other cyclic oligosaccharides of the present invention include, for example, a linear maltooligosaccharide obtained by decomposing acetic acid of a complete acetyl derivative of cyclodextrin as a starting material, and linking an arbitrary sugar chain thereto. Then, it can be synthesized by reclosing the ring.

More ingredients other manner, peracetyl malto oligosaccharide represented by the formula (11) (1
1 ) is thioglycosidated to give thiomaltooligosaccharide ( 1
2 ) is obtained, and the compound ( 12 ) is deacetylated, then treated with α, α-dimethoxytoluene in the presence of an acid catalyst to give benzylidene, and then benzylated to give the compound ( 13 ) represented by the formula ( 13 ). Then, the compound ( 13 ) is treated with BH ₃ · NMe ₃ —AlCl ₃ to obtain a sugar acceptor ( 14 ). The compound ( 14 ) is treated with a sugar donor ( 19 ) in the presence of a glycosylation catalyst. The compound ( 15 ) is reacted to obtain a compound ( 16 ) by selectively deprotecting the compound ( 16 ), and the compound ( 16 ) is treated with a glycosylation catalyst to ring-close the compound ( 15 ). The cyclic heterooligosaccharide represented by 17 ) can be synthesized.

Furthermore, by deprotecting the compound represented by the formula (17) and (17) by a conventional method, it is possible to synthesize cyclic hetero-saccharide represented by the formula (18).

In the above formula, R ⁴ represents an alkyl group, an aryl group or a pyridyl group, R ⁵ represents a functional group capable of undergoing a glycosylation reaction, R ⁶ represents a protective group other than a benzyl group, Y represents a protected glucose group. Represents a sugar donor residue other than, Y ′ represents a sugar donor residue other than glucose, and n represents an integer of 3 to 6.

In the step, compound ( 11 ) was added to a solvent such as methanol,
Deacetylation with sodium methoxide, acetic anhydride-
After treatment with sodium acetate, it is reacted with phenylthiotrimethylsilane, methylthiotrimethylsilane, ethylthiotrimethylsilane, 2-pyridylthiotrimethylsilane, etc. in the presence of zinc iodide, etc. to obtain thioglycoside ( 12 ).

Suitable solvents are aprotic solvents such as 1,2-dichloroethane, chloroform and dichloromethane, and the reaction temperature and time are 0 to 100 ° C. and 1 to 24 hours.

In the step, the compound ( 12 ) was treated with sodium methoxide-
After deacetylation by treatment with methanol or the like, a protecting group-forming compound such as α, α-dimethoxytoluene is reacted in the presence of an acid catalyst such as toluenesulfonic acid to selectively select the sugar-increasing site of the 4-terminal sugar. To protect. Then, this is treated with a conventional method, for example, sodium borohydride-benzyl bromide and benzylated to obtain a compound ( 13 ).

Suitable solvents are N, N-dimethylformamide, dimethylsulfoxide and the like, and the reaction temperature and time are 0 to 80 ° C,
1 to 24 hours.

In the step, the compound ( 13 ) is treated with borane trimethylamine complex, molecular sieve 4A, aluminum chloride or the like to selectively deprotect the sugar-reducing site of the sugar at the non-reducing end to obtain the sugar acceptor ( 14 ).

Suitable solvents are aprotic solvents such as terrahydrofuran, diethyl ether, toluene, reaction temperature,
The time is 0 to 100 ° C. and 12 to 96 hours.

In the step, the sugar acceptor ( 14 ) is reacted with the sugar donor ( 19 ) in the presence of an acid catalyst such as trimethylsilyltrifluoromethanesulfonate or boron trifluoride-diethyl ether complex to increase the sugar, and a compound ( 15 ) is obtained. Examples of the sugar donor ( 19 ) include a compound ( 9 ) shown below, a hexasaccharide such as glucose and mannose, a pentasaccharide such as xylose, a disaccharide such as maltose and gentiobiose, and derivatives thereof. If a compound other than glucose is used as the sugar donor, a cyclic heterooligosaccharide can be obtained. Further, a branched cyclodextrin can be synthesized by using a disaccharide or trisaccharide as the sugar donor ( 19 ). As the functional group R ⁵ capable of performing a glycosylation reaction, a halogen atom such as bromine, chlorine and fluorine, an alkylthio group, an allylthio group, an acetyloxy group and the like can be used in addition to those shown in the compound ( 9 ).

As R ⁶ , any protecting group capable of selectively deprotecting the sugar-increasing site can be used.

Suitable solvents include diethyl ether, acetonitrile,
Such as nitromethane, dichloromethane, toluene,
The reaction temperature and time are -40 to 50 ° C and 1 to 24 hours.

In the step, the ring closure site of compound ( 15 ) is selectively deprotected to obtain compound ( 16 ). As shown in Examples below, when the protecting group R ⁶ of the selective deprotection site is a p-methoxybenzyl group, it is 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ). It can be deprotected by treatment or by oxidation with cerium ammonium nitrate. When protected with an acyl group such as an acetyl group, a base, with an acid when protected with an acetal group such as a tetrahydropyranyl group, and with a fluorine ion when protected with a silyl group such as t-butyldimethylsilyl group. Each can be deprotected.

Suitable solvents are dichloromethane, methanol, ethanol, tetrahydrofuran, acetonitrile and the like,
The reaction temperature and time are 0 to 100 ° C. and 1 to 24 hours.

In the step, the compound ( 16 ) is treated with a glycosylation catalyst such as trimethylsilyltrifluoromethanesulfonate, N-bromosuccinimide, phenylselenenyltrifluoromethanesulfonate or the like to undergo ring closure to obtain a cyclic cyclodextrin ( 17 ).

Suitable solvents are diethyl ether, tetrahydrofuran, acetonitrile, dichloromethane, nitromethane, etc., and the reaction temperature and time are -40 to 50 ° C and 1 to 96 hours.

In the step, the compound ( 17 ) is treated and deprotected to obtain a cyclic heterooligosaccharide ( 18 ) by a conventional method.

 More specific examples of the synthesis method of the present invention are shown below.

First, phenyl thioglycoside the peracetylated maltohexaose (1) represented by the formula (1), phenyl thio maltohexaoside (2), which was deacetylated and then α in the presence of an acid catalyst , obtained after benzylidene by treatment with α- dimethoxy toluene, to give the compound benzylated (3), the compound (3) was treated with BH ₃ · NMe ₃ -AlCl ₃ sugar receptor (4) , This is reacted with a sugar donor ( 9 ) in the presence of a glycosylation catalyst to obtain a compound ( 5 ) with increased sugar.

Further, the compound ( 5 ) is selectively deprotected to obtain the compound ( 6 )
To give a cyclic heterooligosaccharide represented by the formula ( 7 ), and by deprotecting the compound ( 7 ), a cyclic heterooligosaccharide ( 8 ) is obtained.

〔The invention's effect〕

The compound ( 8 ) of the present invention has a ring structure similar to that of β-cyclodextrin, and therefore exhibits an inclusion action similar to that of β-cyclodextrin. Further, 10 to 20-fold improvement in solubility and pH dependency of β-cyclodextrin, which is poorly soluble in water, are observed, and it can be expected to be used as an inclusion agent different from β-cyclodextrin. It can be used as a drug delivery system by encapsulating a drug, but since it contains sugars other than glucose, improvement in organ specificity can be expected. Further, it can be used as a heparinoid after being converted into a sulfuric ester, and in that case, it can be expected that the toxicity is lower than that of cyclodextrin.

 Hereinafter, the present invention will be described in more detail with reference to Examples.

Reference example Icosa acetyl hexaose ( 1 ) α-Cyclodextrin octadecaacetate (3.5
g) in acetic anhydride-concentrated sulfuric acid (50: 1,25 ml)
Stir at 36 ° C. for 36 hours.

The reaction mixture was poured into ice water, stirred for 3 hours and then extracted with chloroform. The organic layer was washed successively with saturated brine, saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting syrup was separated by silica gel column chromatography (chloroform-ethyl acetate; 6: 4) to give white amorphous icosaacetylmaltohexaose (1).
(2.1 g, 58%) was obtained. ¹ H-NMR (400 MHz, CDCl ₃ standard substance TMS) 6.25 (0.84H, d, J3.7Hz, H-1α) 5.75 (0.16H, d, J8.1Hz, H-1β) 5.51 (1H, t , J10.0Hz, H-3) 5.07 (1H, t, J10.0Hz, H-4 5) 4.85 (1H, dd, J3.9,10.3Hz, H-2) 2.23,2.21,2.20,2.19,2.18 , 2.15,2.10, 2.06,2.05,2.03,2.02,2.01,2.00,1.99, 1.98, (60H, each s, CH ₃ CO × 20) Elemental analysis: Calculated as C ₇₆ H ₁₀₂ O ₅₁・ H ₂ O ( %):. C, 49.35; H, 5.67 measured values (%):. C, 49.35 ; H, 5.56 example 1 phenyl 2 ^1, 2 ^2, 2 ^3, 2 ^4, 2 ^5, 2 ^6, 3 ^1, 3 ² , 3 ³ , 3 ⁴ , 3 ⁵ , 3 ⁶ ,
4 ^6, 6 ^1, 6 ^2, 6 ^3, 6 ^4, 6 ^5, 6 ⁶ - nonadeca -O- acetyl -1 ¹ -
Thio -β- maltohexaoside (2) 1 ^1, 2 ^1, 2 ^2, 2 ^3, 5 ^4, 2 ^5, 2 ^6, 3 ^1, 3 ^2, 3 ^3, 3 ^4, 3 ^5, 3 ^6, 4 ⁶ , 6 ¹ , 6 ² ,
6 ^3, 6 ^4, 6 ^5, 6 ⁶ - icosa -O- acetyl maltohexaose (1) (50 g, 27.3 mmol) in methanol (1) and 2
8% Sodium methoxide (5 ml) was added, the mixture was stirred at room temperature for 5 hr, neutralized with acetic acid, and the solvent was evaporated. Sodium acetate (25g) was added to the residue, and acetic anhydride (500ml) was added at 130 ° C.
Was added little by little, and the mixture was stirred at the same temperature for 1 hour. The reaction mixture was poured into ice water and extracted with chloroform. Water organic layer,
The extract was washed successively with aqueous sodium hydrogen carbonate solution and brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained syrup was dissolved in 1,2-dichloroethane (400 ml), and zinc iodide (25 g) and phenylthiotrimethylsilane (20 ml) were added.
g) was added and the mixture was stirred at room temperature overnight. The insoluble matter was filtered off, the filtrate was washed with aqueous sodium hydrogen carbonate solution and brine,
It was dried (Na ₂ SO ₄ ) and concentrated under reduced pressure. The obtained syrup was purified by silica gel column chromatography (toluene-ethyl acetate 1: 1) to obtain the compound ( 2 ) on amorphous (43 g, 84%).

▲ [α] ²³ _D ▼ + 112 ° (C 0.21, chloroform) Elemental analysis: Calculated as C ₈₀ H ₁₀₄ O ₄₉ S ・ H ₂ O (%): C, 50.56; H, 5.62; S, 1.69. Measured value (%): C, 50.52; H, 5.54; S, 1.90. NMR (C ₆ D ₆ ) δ: 1.54, 1.65, 1.66, 1.74, 1.75, 1.78, 1.79,
1.82,1.83,1.85,1.86,1.88,1.89,1.94,1.95,1.99,2.07,
2.15, 2.20 (19 x s, 19 x 3H), 2.78-2.81 (m, 1H), 3.62,
−3.64 (m, 2H), 3.86 − 4.06 (m, 5H), 4.19 − 4.49 (m, 14
H), 4.69 (d, 1H, J9.3Hz), 4.80-4.94 (m, 6H), 5.05 (d
d, 1H, J3.9Hz, 10.5Hz), 5.23 (d, 1H, J3.9Hz), 5.31 (t, 1
H, J9.0Hz), 5.40 (t, 1H, J9.8Hz) 5.46 (d, 1H, J3.9Hz)
5.48 (d, 1H, J4.1Hz), 5.49 (d, 1H, J3.9Hz), 5.65 (d, 1
H, J3.9Hz), 5.74-5.82 (m, 5H). Example 2 Phenyl 2 ¹ , 2 ² , 2 ³ , 2 ⁴ , 2 ⁵ , 2 ⁶ , 3 ¹ , 3 ² , 3 ³ , 3 ⁴ , 3 ⁵ , 3 ⁶ ,
6 ^1, 6 ^2, 6 ^3, 6 ^4, 6 ⁵ - heptadeca -O- ^benzyl-6, 6 ⁶ -
O-benzylidene- ¹¹ -thio-β-maltohexaside ( 3 ) Compound ( 2 ) (31.3 g, 16.6 mmol) was added to methanol (500 m
1) Sodium methoxide (5 ml) was added and the mixture was stirred at room temperature for 5 hours. Water was added to dissolve the insoluble matter, and the mixture was neutralized with an ion exchange resin (Dowex 50w × 8 (H ⁺ )), and the solvent was evaporated under reduced pressure. The residue was dissolved in N, N-dimethylformamide (300 ml), and α, α-dimethoxytoluene (6
g) and p-toluenesulfonic acid hydrate were added to adjust the pH to 2, and the mixture was stirred at 60 ° C. under reduced pressure for 15 hours. The reaction mixture is N, N-
Dilute with dimethylformamide (200ml) and cool with ice 60%
Sodium borohydride (23 g) was added and after stirring for 1 hour, benzyl bromide (69 ml) was added. The mixture was stirred at 0 ° C. to room temperature overnight. Methanol and water were added little by little and extracted with chloroform. The organic layer is 2M hydrochloric acid,
The extract was washed successively with aqueous sodium hydrogen carbonate solution and brine, dried (Na ₂ SO ₄ ), and concentrated under reduced pressure. The obtained syrup was purified by silica gel column chromatography (toluene-ethyl acetate 39: 1 → 19: 1) to obtain the compound ( 3 ) (33.2 g, 74%).

▲ [α] ²³ _D ▼ + 52 ° (C 0.24, chloroform) Elemental analysis: Calculated as C ₁₆₈ H ₁₇₂ O ₃₀ S ・ 2H ₂ O (%): C, 73.66; H, 6.48; S, 1.17 Measured value ( %): C, 73.72; H, 6.36; S, 1.24 NMR (CDCl ₃ ) δ: 5.50 (d, 1H, J4.0Hz) 5.52 (s, 1H), 5.5
6 (d, 1H, J3.8Hz), 5.60 (d, 1H, J4.0Hz), 5.67 (d, 1H, J
4.0Hz), 5.69 (d, 1H, J4.0Hz). Example 3 Phenyl 2 ¹ , 2 ² , 2 ³ , 2 ⁴ , 2 ⁵ , 2 ⁶ , 3 ¹ , 3 ² , 3 ³ , 3 ⁴ , 3 ⁵ , 3 ⁶ ,
6 ^1, 6 ^2, 6 ^3, 6 ^4, 6 ^5, 6 ⁶ - octadeca -O- ^Benzyl-1 -
Thio-β-maltohexaside ( 4 ) Compound ( 3 ) (30 g, 11.1 mmol) was dissolved in tetrahydrofuran (400 ml), and borane trimethylamine complex (9.5
g, 130 mmol), molecular sieves 4A (30 g) and aluminum chloride (17 g, 127 mmol) were added, and the mixture was stirred at room temperature for 2 days. The insoluble material was filtered off, the filtrate was diluted with diethyl ether, washed successively with 1M hydrochloric acid, aqueous sodium hydrogen carbonate solution and brine, dried (MgSO ₄ ) and concentrated. The obtained syrup was separated by silica gel column chromatography (toluene-ethyl acetate 97: 3) to find unreacted compound ( 3 ) (8.6g, 29%) and compound ( 4 ) (20.2g, 67%).
was gotten.

▲ [α] ²³ _D ▼ + 77 ° (C 0.24, chloroform) Elemental analysis: Calculated as C ₁₆₈ H ₁₇₄ O ₃₀ S ・ H ₂ O (%): C, 74.10; H, 6.51; S, 1.18 Measured value ( %): C, 73.95; H, 6.45; S, 1.23 NMR (CDCl ₃ ) δ: 5.49 (d, 1H, J3.7Hz), 5.55 (d, 1H, J3.7)
Hz), 5.60 (d, 1H, 3.4Hz), 5.66 (d, 1H, J4.4Hz), 5.69
(D, 1H, J3.4Hz). Example 4 phenyl 6 ⁷ -O- acetyl -2 ⁷ - azido-2 ^1, 2 ^2,
2 ³ , 2 ⁴ , 2 ⁵ , 2 ⁶ , 3 ¹ , 3 ² , 3 ³ , 3 ⁴ , 3 ⁵ , 3 ⁶ , 3 ⁷ , 6 ¹ , 6 ² , 6 ³ , 6 ⁴ , 6 ⁵ , 6 ⁶
-Nonadeca-O-benzyl-2 ⁷ -deoxy-4 ⁷ -O-
(P- methoxybenzyl) -1 ¹ - thio -β- maltoheptaose oxide (5) 6-O-acetyl-2-azido--3-O-benzyl -
2-deoxy-4-O- (p-methoxybenzyl) -D
-Glucopyranose (107mg, 0.37mmol) was dissolved in dichloromethane (5ml) and trichloroacetonitrile (0.2m
l) and anhydrous potassium carbonate (50 mg) were added, and the mixture was stirred at room temperature for 3
Stir for hours. Hexane (15 ml) was added, the insoluble material was filtered off, and the solvent was evaporated under reduced pressure. Compound ( 4 ) (500 mg, 0.185 mmol), Molecular Sieves AW-300 (dried at 160 ° C. under reduced pressure, 5 hours) on the obtained syrup (500 m
g) and diethyl ether (2 ml) were added, and the mixture was cooled to -15 ° C under an argon atmosphere. Trimethylsilyl trifluoromethanesulfonate (10 μl) was added, and the mixture was stirred at the same temperature for 3 hours. After adding an aqueous sodium hydrogen carbonate solution and dichloromethane, the insoluble matter was filtered off. The filtrate was washed with brine, dried (Na ₂ SO ₄ ) and concentrated under reduced pressure. The obtained syrup was separated by silica gel column chromatography (toluene-ethyl acetate 19: 1) to obtain a compound ( 5 ) (230 mg, 39%).

▲ [α] ²³ _D ▼ + 74 ° (C 0.14, chloroform) Elemental analysis: Calculated as C ₁₉₁ H ₁₉₉ O ₃₆ N ₃ S ・ 3H ₂ O (%): C, 71.72; H, 6.45; N, 1.31 S , 1.00 Measurement (%): C, 71.58; H, 6.29; S, 1.22 S, 1.21 NMR (CDCl ₃ ) δ: 1.94 (s, 3H), 3.80 (s, 3H) 5.48 (d, 1
H, J3.4Hz), 5.54 (d, 1H, J3.7Hz), 5.64 (d, 1H, J3.4H
z), 5.66 (d, 1H, J3.4Hz), 5.68 (d, 1H, J2.9Hz), 5.73
(D, 1H, J3.7Hz). Example 5 phenyl 6 ⁷ -O- acetyl -2 ⁷ - azido-2 ^1, 2 ^2,
2 ³ , 2 ⁴ , 2 ⁵ , 2 ⁶ , 3 ¹ , 3 ² , 3 ³ , 3 ⁴ , 3 ⁵ , 3 ⁶ , 3 ⁷ , 6 ¹ , 6 ² , 6 ³ , 6 ⁴ , 6 ⁵ , 6 ⁶
- nonadec -O- benzyl-2 ⁷ - deoxy ¹ - thio -
β-maltoheptaoxide ( 6 ) Compound ( 5 ) (200 mg, 0.064 mmol) was dissolved in 2% water-containing dichloromethane to give 2,3-dichloro-5,6-dicyano-p-
Benzoquinone (75 mg) was added, and the mixture was stirred at 0 ° C for 5 hr. After adding a sodium thiosulfate aqueous solution, the mixture was extracted with dichloromethane. The organic layer was washed with aqueous sodium thiosulfate solution, dried (MgSO ₄ ) and concentrated under reduced pressure. Silica gel column chromatography (toluene-ethyl acetate 93:
The compound ( 6 ) (106 mg, 56%) was obtained by purification with 7).

▲ [α] ²³ _D ▼ + 62 ° (C 0.19, chloroform) Elemental analysis: Calculated as C ₁₈₃ H ₁₉₁ O ₃₅ N ₃ S (%): C, 72.67; H, 6.37; N, 1.39; S, 1.06. Measured value (%): C, 72.33; H, 6.49; N, 1.25; S, 0.99. NMR (CDCl ₃ ) δ: 2.03 (s, 3H), 5.54 (d, 1H, J3.7Hz), 5.
64 (d, 1H, J3.4Hz), 5.67 (d, 1H, J2.9Hz), 5.68 (d, 1H, J
3.7Hz), 5.71 (d, 1H, J3.6Hz), 5.76 (d, 1H, J3.8Hz). Example 6 6-O-acetyl-2-azido-3-O-benzyl-
2-Deoxy-hexakis (2,3,6-tri-O-benzyl) cyclomaltoheptaose ( 7 ) Compound ( 6 ) (150 mg, 50 μmol) and molecular sieves 4A (170 ° C, 5 hours vacuum drying: 2 g A suspension of diethyl ether (5 ml) was cooled to 0 ° C., methyltrifluoromethanesulfonate (150 μl) was added, and the mixture was stirred at room temperature for 2 days. After adding methanol (0.5 ml) and triethylamine (0.5 ml), the insoluble matter was filtered off and diluted with chloroform. The organic layer was washed with 1M hydrochloric acid, an aqueous solution of sodium hydrogencarbonate, brine, dried (Na ₂ SO ₄ ) and concentrated under reduced pressure, and the resulting syrup was subjected to silica gel column chromatography (toluene-ethyl acetate 20: 1). Compound ( 7 )
(60 mg, 41%) was obtained.

▲ [α] ²³ _D ▼ + 55 ° (C 0.21, chloroform) Elemental analysis: Calculated as C ₁₇₇ H ₁₈₅ N ₃ O ₃₅ (%): C, 72.95; H, 6.40; N, 1.44 Measured value (%): C, 73.11; H, 6.25; N, 1.31 NMR (CDCl ₃ ) δ: 1.88 (s, 3H), 4.70 (d, 1H, J3.5Hz), 4.
96 (d, 1H, J3Hz), 4.98 (d, 1H, J3Hz), 5.06 (d, 1H, J3.5H)
z), 5.41 (d, 1H, J3.9Hz), 5.48 (d, 1H, J3.7Hz). Example 7 2-Azido-2-deoxycyclomaltoheptaose ( 8 ) The compound ( 7 ) was dissolved in tetrahydrofuran (2 ml) -methanol (0.5 ml), and 1M sodium methoxide (0.05 m) was added.
l) was added, and the mixture was stirred at room temperature for 3 hours. Dowex 50w ×
It was neutralized with 8 (H ⁺ type) and the solvent was distilled off under reduced pressure. Dissolve the residue in methyl cellosolve (10 ml) and add 0.1 M hydrochloric acid (0.5 m
l) and 10% palladium carbon (30 mg) were added, and the mixture was shaken at room temperature for 5 hours in a hydrogen atmosphere. The catalyst was filtered off, the solvent was distilled off under reduced pressure, and the residue was dissolved in 0.01M hydrochloric acid (8 ml).
% Palladium on carbon (30 mg) was added, and hydrogenolysis was carried out again for 7 hours. The catalyst was filtered off, the solvent was distilled off, and the resulting residue was purified by CM-Sephadex C-25 (water → eluted with 0.2M aqueous ammonia) and Sephadex G-15 (eluted with water) to give a compound. ( 8 ) (2.2 mg, 70%) was obtained.

▲ [α] ²³ _D ▼ + 146 ° (C 0.18, water) Elemental analysis: Calculated as C ₄₂ H ₇₁ O ₃₄ N ・ 2H ₂ O (%): C, 43.12; H, 6.46; N, 1.20 Measured value ( %): C, 42.97; H, 6.35; N, 1.28 NMR (D ₂ O) δ: 2.80 (dd, 1H, J4.0,9.6Hz), 4.93 (d, 1H, J
4.0Hz), 4.98-5.04 (m, 6H). Solubility of compound ( 8 ) ^* (22 ℃) Dilute hydrochloric acid (pH1) 22g Water 11g * For 100ml solvent

Claims (6)

[Claims] 1. A cyclic heterooligosaccharide represented by the following general formula: In the formula, R ¹ represents hydrogen or a benzyl group, R ² represents hydrogen or an acetyl group, and R ³ represents an amino group or an azido group. 2. A cyclic oligo characterized by using, as a starting material, a linear maltooligosaccharide obtained by decomposing a complete acetyl derivative of a cyclodextrin with acetic acid, and linking an arbitrary sugar chain thereto and then reclosing the oligosaccharide. Sugar synthesis method. 3. A formula (11) with peracetylated malto oligosaccharide represented (11) with thioglycoside of, resulting thio malto oligosaccharide (12), compound (12) was deacetylated and then in the presence of an acid catalyst The compound represented by the formula ( 13 ) ( 1 ) is treated with α, α-dimethoxytoluene to form benzylidene, and then benzylated.
3) to give the compound (13) was treated with BH ₃ · NMe ₃ -AlCl ₃ obtained sugar receptor (14), compound (14), in the presence of glycosylation catalyst, glycosyl donor (19 ) was reacted to give compound (15), characterized the compound (15), selectively obtained deprotected compound (16), compound (16), to ring closure by treatment with glycosylated catalyst And a method for synthesizing a cyclic heterooligosaccharide represented by the formula ( 17 ). In the above formula, R ⁴ represents an alkyl group, an alur group or a pyridyl group, R ⁵ represents a functional group capable of a glycosylation reaction,
R ⁶ represents a protective group other than a benzyl group, Y represents a protected sugar donor residue other than glucose, and n represents an integer of 3 to 6. A compound represented by wherein (17) (17), wherein the deprotecting method of synthesizing cyclic hetero-saccharide represented by the formula (18). In the formula, Y ′ represents a sugar donor residue other than glucose, and n
Represents an integer of 3 to 6. 5. Peracetylmaltohexaose ( 1 ) represented by the formula ( 1 ) is thioglycosidated to obtain thiomaltohexaside ( 2 ), and the compound ( 2 ) is deacetylated and then acidified. It was treated with α, α-dimethoxytoluene in the presence of a catalyst to benzylidene, and then benzylated to obtain the compound ( 3 ) represented by the formula ( 3 ). The compound ( 3 ) was converted into BH ₃ · NMe ₃ -AlCl ₃ in the process to yield a glycosyl acceptor (4), the compound (4), in the presence of glycosylation catalyst, glycosyl donor (9) and the compound is reacted to give the (5), compound (5), selectively obtained deprotected compound (6), the compound (6), was treated with glycosylated catalyst characterized by ring closure, the synthesis of cyclic hetero-saccharide represented by the formula (7). A compound represented by wherein formula (7) (7), wherein the deprotecting method of synthesizing cyclic hetero-saccharide represented by the formula (8).