JPH0489801A - Cyclic heterooligosaccharide and its synthesis - Google Patents

Abstract

PURPOSE:To prepare a new cyclic heterooligosaccharide by bonding an arbitrarily selected saccharide chain to a linear maltooligo-saccharide obtd. by the acetolysis of a fully acetylated cyclodextrine and recyclizing the product. CONSTITUTION:A cyclic heterooligosaccharide of formula I (wherein R<1> is H or benzyl; R<2> is H or acetyl; and R<3> is amino or azido), which is synthesized by, e.g. converting a peracetylated maltooligo-saccharide of formula II into a thiomaltosaccharide, deacetylating it, treating the product with alpha,alpha- dimethoxytoluene,in the presence of an acid catalyst to give a benzylidene derivative, then benzylating it, treating the resulting compd. with BH3.NMe3- AlCl3 to give a saccharide acceptor, selectively deblocking it, treating the product with a glycosylation catalyst to thereby cyclize it into a cyclic heterooligosaccharide, and deblocking the product, thus giving a cyclic heterooligosaccharide of formula III.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a novel cyclic hetero-oligosaccharide and a method for synthesizing the same.

[Background of the Invention] Cyclodextrins have the property of incorporating various organic compounds into their molecular cavities, and are therefore widely used as deterioration inhibitors, solubilizers, and emulsifiers in pharmaceuticals, foods, cosmetics, and the like. In addition, various chemical transformations have been carried out to improve or modify its physicochemical properties, but because cyclodextrin has many hydroxyl groups, conventional methods have had problems with yield, selectivity, etc. .

On the other hand, the present inventor has succeeded in synthesizing linear malto-oligosaccharides selectively and in high yield by subjecting cyclodextrin to modified acid decomposition (Japanese Patent Application No. 1-572
(See specification No. 35). The present inventor discovered that a new cyclic oligosaccharide can be synthesized by using the linear malto-oligosaccharide obtained by this method as a starting material, bonding an arbitrary sugar chain thereto, and then re-closing the oligosaccharide. I was able to complete it.

1. Problems to be Solved by the Invention] An object of the present invention is to provide a novel cyclic hetero-oligosaccharide.

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

[Means for Solving the Problem] The novel cyclic hetero-oligosaccharide of the present invention is represented by the following general formula.

R2 In the formula, R1 represents hydrogen or a Hensyl group, R2 represents hydrogen or an acetyl group, and R3 represents an amino group or an and group.

The above-mentioned cyclic hetero-oligosaccharides and other cyclic oligosaccharides of the present invention are produced by using, for example, a linear malto-oligosaccharide obtained by modified acid decomposition of a complete acetyl derivative of cyclodextrins as a starting material, and adding any sugar chain to this. can be synthesized by bonding and then ring-closing again.

More specifically, ■ peracetylmaltooligosaccharide represented by formula (II) (IO is thioglycosidated to form thiomaltooligosaccharide Q
2) is obtained, (1) Compound (+2) is deacetylated, then treated with α,α-dimethoxytoluene in the presence of an acid catalyst to benzylidene, and then hensylated to obtain compound (13) represented by 2θ3). ■ Compound (13) was obtained by BH3・NMe:+-AICI
:+ to obtain the sugar acceptor side; ■ The compound side is treated with the sugar ■ Compound 0ω in the presence of a glycosylation catalyst to close the ring, resulting in the compound represented by 207). Cyclic hetero-oligosaccharides can be synthesized.

By deprotecting the compound, a cyclic hetero-oligosaccharide represented by formula (18) can be synthesized.

〇C obtained, Ac υBn Bn nU υbn In the above formula, R4 represents an alkyl group, an aryl group or a pyridyl group, R5 represents a functional group capable of glycosylation reaction, R6 represents a protective group other than a Hensyl group, Y represents a protected sugar donor residue other than glucose, Y' represents a sugar donor residue other than glucose, and n represents an integer from 3 to 6.

In step (2), compound (11) is mixed in a solvent such as methanol,
After deacetylation with sodium methoxy F etc., 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 Q2).

Appropriate? The medium is an aprotic solvent such as 1,2-dichloroethane, chloroform, dichloromethane, etc., and the reaction temperature and time are 0 to 100°C for 11 to 24 hours.

In step (2), compound (12) is treated with sodium methoxide methanol or the like to deacetylate it, and then reacted with a protecting group-forming compound such as α,α-dimethoxytoluene in the presence of an acid catalyst such as toluenesulfonic acid. Selectively protects the 4-terminal sugar hyperglycation site.

Then, this is benzylated by a conventional method, for example, by treatment with sodium borohydride-benzyl bromide to give the compound (
13) is obtained.

Suitable solvents include N,N-dimethylformamide, dimethyl sulfoxide, etc., and the reaction temperature and time range from O to 80
“C11 to 24 hours.

In step (2), compound (13) is treated with poranttrimethylamine complex, Molecular Sheep 4A, aluminum chloride, etc. to selectively deprotect the sugar-proliferating site of the non-reducing terminal sugar to obtain sugar acceptor 04).

Appropriate? The vehicle is an aprotic solvent such as trihydrofuran, diethyl ether, toluene, etc., and the reaction temperature,
The time is 112 to 96 hours at 0 to 100°C.

In step (2), in the presence of an acid catalyst such as trimethylsilyl trifluoromethanesulfonate or boron trifluoride/diethyl ether complex, sugar acceptor properties, six monosaccharides such as glucose and mannose, pentoses such as xylose, and three monosaccharides such as maltose and gentiobiose are processed. Examples include saccharides and their derivatives. If a compound other than glucose is used as a sugar donor, a cyclic hetero-oligodose can be obtained. Furthermore, if a trisaccharide or a trisaccharide is used as the sugar donor 09),
Branched cyclodextrins can be synthesized.

As the functional group R5 capable of glycosylation reaction, the compound (
In addition to those shown in 9), halogen atoms such as bromine, chlorine, and fluorine, alkylthio groups, allylthio groups, acetyloxy groups, and the like can be used.

Any protecting group that can selectively deprotect the sugar increasing site can be used as R6.

Suitable solvents include diethyl ether, acetonitrile, nitromethane, dichloromethane, toluene, etc., and the reaction temperature and time are -40 to 50°C for 11 to 24 hours.

In step (2), the ring-closing site of compound 05) is selectively deprotected to obtain compound 0ω. As shown in the Examples below, when the protecting group R6 of the selective deprotection site is p-methoxybenzyl group, 2,3-dichloro5,6-dicyano-
Deprotection can be achieved by treatment with p-benzoquinone (DDΩ) or oxidation with cerium ammonium nitrate. In addition, when protected with an acyl group such as an acetyl group, it is a base,
When protected with an acetal group such as a tetrahydropyranyl group, it can be deprotected with an acid, and when protected with a silyl group such as t-butyldimethylsilyl group, it can be deprotected with a fluorine ion.

Suitable solvents are dichloromethane, methanol, ethanol, tetrahydrofuran, acetonitrile, etc., and the reaction temperature and time are 0 to 100'' C11 to 24 hours.

In step (2), compound θO is treated in the presence of a glycosylation catalyst such as trimethylsilyltrifluoromethanesulfonate, N-bromosuccinimide, phenylcerephnyltrifluoromethanesulfonate, etc. to undergo ring closure to obtain cyclic cyclodextrin G'7).

Suitable solvents include diethyl ether, tetrahydrofuran, acetonitrile, dichloromethane, nitromethane, etc., and the reaction temperature and time are -40 to 50°C, 11 to 9
It is 6 hours.

In step (2), the compound surface is treated and deprotected by a conventional method to obtain a cyclic hetero-oligo 11Q8).

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

First, peracetylmaltohexaose (1) represented by formula (1) is converted into phenylthioglycosidation to obtain phenylthiomaltohexaoside (2), which is deacetylated and then α , treated with α-dimethoxytoluene to benzylidene, resulting in BH3・NMe:+
- treatment with AlCl3 to obtain the sugar receptor (4), which
Compound (5) is obtained by reacting with sugar donor (9) in the presence of a glycosylation catalyst to increase the sugar content.

Furthermore, compound (5) is selectively deprotected to form compound (6).
), which is treated with a glycosylation catalyst to undergo ring closure,
A cyclic hetero-oligosaccharide represented by formula (7) is obtained, and the compound (7) is further deprotected to obtain a cyclic hetero-oligosaccharide (8).

〔Effect of the invention〕

Since the compound (8) of the present invention has a ring structure similar to that of β-cyclodextrin, it exhibits the same clathration effect as β-cyclodextrin. In addition, it is observed that the solubility is 10 to 20 times higher than that of β-cyclodextrin, which is poorly soluble in water, and pH dependence is observed, so 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 including drugs, but since it contains substances other than glucose, it is expected to improve organ specificity. Furthermore, it can be converted into a sulfate ester and used as a heparinoid, but in this case, it is expected to be less toxic than cyclodextrin.

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

Reference example Icosaacetylhexaose (1) α-cyclodextrin octadecaacetate (3,5
g) was dissolved in acetic anhydride-concentrated sulfuric acid (50:1, 25d) and stirred at 50-60°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 hydrogen carbonate solution, and saturated brine, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure.

The resulting syrup was separated by silica gel column chromatography (chloroform ethyl acetate; 6:4) to obtain white amorphous icosacetylmaltohexaose (
1) (2.1 g, 58%) was obtained.

'H'NMR (400MHz, CDCl 3 standard material TMS) 6.25 (0,84H,d, J 3.7H
z, H-1cy)5.75(0,16H,d J
8. I Hz, )I-1β) 5.5HL H,t,
J10. OHz, H-3) 5.07 (I H,t,
J10. OHz, H-4') 4.85 (I H,
dd, J 3.9.10.3 Hz, H-2)2.
23.2.21.2.20.2.19.2.1B, 2
．． 15.2.10゜2.06.2.05.2. (13.
2. (12.2.OL 2.00. 1.99゜1.9
B, (601(, each s, CH3COX20)
Elemental analysis: Calculated value (χ) as CwJ+ozOs+・H2O: C, 49,35; l(,5,6
7゜Measurement value (χ): C, 49, 35, H, 5,
56゜Example 1 Phenyl 2'2'',23.2',25,263'
323'3'35.36,466'
6",63.6',65.6' -nonadeca-○-acetyl-II-1,000 β-maltohexaoside (2) 1 Summer 2', 2", 2
3, 2', 2 5, 2'3'
32333', 3'36,466' 62
63.6', 65.6''-icosa0-acetylmaltohexaose (1) (50 g27, 3 mmol) in methanol (1 l) and 28% sodium methoxide (5
A11 was added, stirred at room temperature for 5 hours, neutralized with acetic acid, and then the solvent was distilled off. Anhydrous sodium acetate (25 g) was added to the residue, and acetic anhydride (500 d) was added little by little at 130°C, followed by stirring at the same temperature for 1 hour. The reaction mixture was poured into ice water and extracted with chloroform. The organic layer was washed successively with water, an aqueous sodium bicarbonate solution, and brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. 1 or 2 pieces of the obtained Shirabu
-Dissolved in dichloroethane (400d), zinc iodide (
25g) and phenylthiotrimethylsilane (20g
) and stirred at room temperature overnight. Insoluble matter was filtered off, and the filtrate was washed with an aqueous sodium bicarbonate solution and brine, dried (tJazso4), and concentrated under reduced pressure. The obtained silica was purified by silica gel column chromatography (toluene-ethyl acetate 1:1) to obtain amorphous compound (2) (43 g, 84%).

Elemental analysis: C11OH30-0-9S, calculated value (χ) as HzO: C, 50, 56, H, 5,
62; S, 1.69° Measured value (χ): C, 50
,52; H,5,54; S, 1.90°NMR
(C6D6) δ: 1.54. 1.65. '
1.66, 1.74. 1.75°1.7B,
1.79. 1.82. 1.83. 1.85. 1
．． 86. 1.8B.

1.89 1.94. 1.95. 1.99. 2.
07. 2.15. 2.20 (19X s, 1
9X3H), 2.78-2.81(m, IH)
, 3.623.64(+++, 28), 3
．． 86-4.06 (m, 5H), 4.19-4
．． 49 (m, 1414), 4.69 (d,
IH, J 9.3 Hz), 4.80-4.94 (
m, 6Fl), 5.05(dd, IH, J
3.9 Hz, 10.5 Hz) 5.23 (d
IHJ 3.9Hz), 5.3Ht, LH
, J 9.0Hz), 5.40(t, IH, J
9.8 Hz), 5.46(d, IH, J3
．． 9 Hz) 5.48 (d, IH, J 4.I
Hz), 5.49(d, IHJ 3.9
Hz), 5.65 (d, IH, J 3.9 H
z), 5.745.82 (m, 5H).

Example 2 Phenyl 2', 22.2', 2', 25,263'
323'3',35.3',6'6"6'
6' 65-hebutadeca-〇-benzyru 46
56 Q-Benzylidene-1'-thio-β-maltohexaoside (3) Compound (2) (31.3g, 16.6 +no+
ol) was suspended in methanol (500d), 1M sodium methoxide (5d) was added, and the mixture was stirred at room temperature for 5 hours.

Add water to dissolve insoluble matter, and add ion exchange resin (Dowe
After neutralization with x 50 w Add acid hydrate and p
H2 and stirred at 60°C under reduced pressure for 15 hours. The reaction mixture was diluted with N,N-dimethylformamide (200d) and added with 60% sodium borohydride (23g) under water cooling.
was added, and after stirring for 1 hour, benzyl bromide (69d) was added.

The mixture was stirred at 0°C to room temperature overnight. Methanol and water were successively added little by little, and the mixture was extracted with chloroform.

The organic layer was washed successively with 2M hydrochloric acid, an aqueous sodium bicarbonate solution, and brine, dried (Na2SO4), and concentrated under reduced pressure. The obtained Sila Nobu was purified by silica gel column chromatography (toluene-ethyl acetate 39:1→19:1) to obtain compound (3) (33.2 g, 74%).

[α] + 52° (CO, 24, chloroform) elemental analysis' C + bsH +, zOzoS Calculated value (χ) as -2820: C, 73, 66; C 6, 4
8; S, 1.17 Measured value (χ): C, 73
,72; II, 6.36; S, 1.24N
MR (CDCE 3) δ: 5.50 (d, IH,
J4. OHz), 5.52 (s, IH), 5.
56 (d, IH, J 3.8) 12), 5.60
(d, IH.

J4. Ofiz), 5.67 (d, 18. J
4. OHz), 5.69 (d.

IHJ 4. (OHz).

Example 3 Phenyl 2'2223.2',25,263'
32333' 3S 36,6'6" 63
6'6'6'-Octadeca-〇Hensyl-11-thioh β-maltohexaoside (4) Compound (3) (30 g, 11.1 mmol)
was dissolved in tetrahydrofuran (400d), and borane trimethylamine complex (9.5g, 130 mmol
), Molecular Raj ~ Bus 4A (30 g) and aluminum chloride (17 g, 127 +n+nol
) and stirred at room temperature for 2 days. Insoluble matter was filtered off, the filtrate was diluted with diethyl ether, washed successively with 1M hydrochloric acid, aqueous sodium bicarbonate solution, and brine, and dried (MgSO
After a), it was concentrated. The obtained silica was subjected to silica gel column chromatography (toluene-ethyl acetate 97:3).
), unreacted compound (3) (8.6 g, 2
9%) and compound (4) (20.2g, 67%
)was gotten.

[α]fi+77° (CO, 24, chloroform) Elemental analysis: C+6sL740z. Calculated value (χ) as S-H2O: C, 74,10; H, 6,5
1; S, 1.18 Measured value (χ): C, 73,
95; H, 6,45; S, 1.23 NMR (C
DCf δ: 5.49 (d, 18. J 3.7
Hz), 5.55 (d, IH, J 3.7 Hz)
, 5.60 (d, 18 3.4 Hz).

5.66 (+j, IH, J 4.4 Hz),
5.69 (d, IH, J 3.4Hz).

Example 4 Phenyl 67-0-acetyl-27-azido 2',2
2.2', 2'2',26332333' 35
3"'3'6'6",63.6',6'
6rononadekar Ohensyl-27-dioxy-47-
○-(p-methoxyhensyl)-1'-thio-β-maltoheptaoxide (5) 6-○-acetyl-2-azido 3-0-benzyl-2
-deoxy-4-0-(p-methoxybenzyl)-D-
Glucobilanose (170■.

0.37+nmo2) was dissolved in dichloromethane (5%), trichloroacetonitrile (0.2d) and anhydrous potassium carbonate (50 ml) were added, and the mixture was stirred at room temperature for 3 hours. After adding hexane (15 m) and filtering off insoluble matter, the solvent was distilled off under reduced pressure. Compound (4) (500 mmol, 0.185 mmol), Molecular Sieves AW-300 (dried under 160" C1 vacuum for 5 hours) (500 mmol), and diethyl ether (211 mmol) were added to the obtained silica. The mixture was cooled to −15° C. under an argon atmosphere. Trimethylsilyltrifluoromethanesulfonate (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, insoluble materials were filtered off. The filtrate was washed with saline and dried (
Na2SO4) and concentrated under reduced pressure. The obtained silica was separated by silica gel column chromatography (toluene-ethyl acetate 19:1) to obtain compound (5) (230 μl, 39%).

~23 [α]D+74° (CO, 14, chloroform) Elemental analysis: Calculated value (χ) as C+qIH+qqOibN3S・3H20: C,71,72; H,6
,45i N, 1.31S, 1.00 Measurement accuracy (χ): C,71,5B.

S, 1.21 NMR (CDC13) δ: 1.94 (s, 3
H), 3.80 (s, 3B).

5.48 (d, DI, J 3.4 Hz),
5.54 (d, II (, J 3.7H2),
5.64(d, 1)1. J 3.4 Hz)
, 5.66 (d, LH, JH, 6, 29;
N, 1.22 3.4) 1z), 5.68 (d, 1) 1.
J 2.9)1z), 5.73(d, ])I
HJ 3.7Hz).

Example 5 Phenyl 67-0-acetyl 2', 2"232' 25 3", 33.3'3' 36 6"6"6'656' Benzyl-27-dioxy-11 Luthebutaoxide (6) Compound ( 5) (200mg, 0.064 tnm
ol) in 2% dichloromethane, 2,3-
Dichloro-5,6-dicyate-P-benzoquinone (75
(2) was added and stirred at 0°C for 5 hours. After adding an aqueous sodium thiosulfate solution, extraction was performed with dichloromethane. The organic layer was washed with an aqueous sodium thiosulfate solution and dried (
MgSOa) and concentrated under reduced pressure. Purification by silica gel column chromatography (toluene-ethyl acetate 93 nia) yielded compound (6) (106 ■).

56%) was obtained.

27-Azidononadeca-0 Thio β-ma [α Co2: l + 62° (CO, 19, Chlorophor L) Elemental analysis: C + a: + H + q + 0: + 5 Calculated value as N3S (χ): C, 72, 67; H, 6, 37
; N, 1.39iS, 1.06° Measured value (χ): C, 72, 33; H, 6,
49; N, 1.25; S, 0.99 NMR (CDCff 3) δ: 2. (13(s,
3H), 5.54(d, 11(, J3.7
Hz), 5.64 (d, ltl, J 3
．． 4 Hz), 5.67 (d, IH, J 2.
9 Hz), 5.68 (d, IH, J 3.7
)1z), 5.71(d, LH,J 3.6
Hz), 5.76 (d, IH, J 3.8
Hz).

Example 6 6-0-acetyl-2-azido-3-〇-benzyl-2
-deoxy-hexakis(2,3,6-tri-benzyl)cyclomaltoheptaose compound (6) (15
0■, 5Qμmol) and molecular sieves 4
A suspension of A (170°C, 5 hours vacuum drying: 2g) in diethyl ether (5d) was cooled to O°C, 150 μl of methyl trifluoromethanesulfonate was added and stirred at room temperature for 2 days. Methanol ( After adding triethylamine (0.5m) and triethylamine (0.5d), insoluble matter was filtered off and diluted with chloroform.The organic layer was washed with 1M hydrochloric acid, hydrogen carbonate), IJum aqueous solution, and brine, and dried (Na2
SO4), and the silamp obtained by concentration under reduced pressure was subjected to silica gel column chromatography (toluene-ethyl acetate 20
: When subjected to 1), compound (7) (60■, 41%)
was gotten.

[α]D+55° (CO, 21, chloroform) Elemental analysis: C+tJ+s5N+O:+s Calculated value (χ
): C, 72,95; H, 6,40;
N, 1.44 Measured value (χ): C, 73, 11;
H, 6,25; N, 1.31 NMR (CDCE
3) δ: 1.88 (s, 3H), 4.70 (
d, 18 J3.5 Hz), 4.96(d, I
H, J 3 Hz), 4.98 (d, IHJ 3
Hz), 5.06 (d, IH, J 3; 5 Hz)
, 5.41 (d, IH, J 3.9 Hz), 5
．． 48 (d, IH, J 3.7Hz).

Example 7 2-azido-2-deoxycyclomaltoheptaose (
8) Dissolve compound (7) in tetrahydrofuran (2-)-methanol (0.5d) and add 1M sodium methoxide (
0.05m) was added and stirred at room temperature for 3 hours. Neutralized with Dowenx 50wX3 (type), and the solvent was distilled off under reduced pressure. The residue was dissolved in methyl cellosolve (10 relatives).
0.1M hydrochloric acid (0.5d), 10% palladium on carbon (3
0■) was added thereto, and the mixture was shaken at room temperature for 5 hours under a hydrogen atmosphere. After the catalyst was filtered off and the solvent was distilled off under reduced pressure, the residue was reduced to 0.
The mixture was dissolved in OIM hydrochloric acid (8d), 10% palladium on carbon (30μ) was added, and hydrogenolysis was again carried out for 7 hours.

The catalyst was filtered off, the solvent was distilled off, and the resulting residue was purified with CM-Sephadex C-25 (eluted with water → 0.2M aqueous ammonia) and Sephadex G-15 (eluted with water). Compound (8) (22 mg 70%) was obtained.

[α] D+ 146° (CO, 18, water) elemental analysis:
Calculated value (χ
): C, 43, 12i H, 6, 46, N,
1.20 Measured value (χ'): C, 42,97i
1(,6,35,N,1.28NMR((120)δ
: 2.80 (dd, LH, J 4.0.9.6
Hz).

4.93 (d, 1B, J 4.OHz), 4.9
8-5.04 (a+, 6B).

Solubility of compound (8) 1 (22°C) Dilute hydrochloric acid (pH 1
) 22g Water 11g* 100M
For the solvent of Il

Claims (6)

[Claims] (1) A cyclic hetero-oligosaccharide represented by the following general formula. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ 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) Using a linear malto-oligosaccharide obtained by acetolytic decomposition of a complete acetyl derivative of a cyclodextrin as a starting material, a cyclic oligosaccharide is produced by bonding an arbitrary sugar chain to this and then re-circulating it. Synthesis method. (3) The peracetylmaltooligosaccharide (11) represented by formula (11) is thioglycosidated to obtain the thiomaltooligosaccharide (12), the compound (12) is deacetylated, and then α, After treatment with α-dimethoxytoluene to benzylidene, benzylation was performed to obtain compound (13) represented by formula (13), and compound (13) was converted into BH_3・NMe_3-AlCl_
3 to obtain a sugar acceptor (14), Compound (14) was reacted with a sugar donor (19) in the presence of a glycosylation catalyst to obtain a compound (15), and a compound (15) was obtained.
15) is selectively deprotected to obtain a compound (16), and the compound (16) is treated with a glycosylation catalyst to undergo ring closure, a cyclic hetero-oligosaccharide represented by the formula (17). synthesis method. ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (11) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (12) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (13) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ( 14) R^6O-Y-R^5 (19) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (15) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (16) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (17) In the above formula, R^4 represents an alkyl group, aryl group, or pyridyl group, R^5 represents a functional group capable of glycosylation reaction, R^6 represents a protective group other than benzyl group, and Y represents a protected sugar donor residue other than glucose, and n represents an integer from 3 to 6. (4) A method for synthesizing a cyclic hetero-oligosaccharide represented by formula (18), which comprises deprotecting compound (17) represented by formula (17). ▲There are mathematical formulas, chemical formulas, tables, etc.▼(18) In the formula, Y' represents a sugar donor residue other than glucose, and n
represents an integer from 3 to 6. (5) Peracetylmaltohexaose (1) represented by formula (1) is thioglycosidated to obtain thiomaltohexaoside (2), compound (2) is deacetylated, and then in the presence of an acid catalyst. was treated with α,α-dimethoxytoluene to benzylidene, and then benzylated to form the compound (3) represented by formula (3).
), and compound (3) was obtained as BH_3・NMe_3-AlCl_3
to obtain the sugar acceptor (4), react the compound (4) with the sugar donor (9) in the presence of a glycosylation catalyst to obtain the compound (5), and select the compound (5). A method for synthesizing a cyclic hetero-oligosaccharide represented by formula (7), which is characterized in that compound (6) is obtained by deprotecting the compound (6), and compound (6) is ring-closed by treatment with a glycosylation catalyst. ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (2) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (3) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (4) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ( 5) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(6) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(7) (6) A method for synthesizing a cyclic hetero-oligosaccharide represented by formula (8), which comprises deprotecting compound (7) represented by formula (7). ▲There are mathematical formulas, chemical formulas, tables, etc.▼(8)