JPH0278694A - Novel sialic acid donor, preparation thereof and preparation of stereoselective glycoside using the same sialic acid donor - Google Patents

Abstract

NEW MATERIAL:An alpha type sialic acid donor compound of formula I (R is lower alkyl; Bn is benzyl; Ac is acetyl; Ph is phenyl). USE:For the preparation of alpha-glycosides. The alpha-glycosides can be obtained selectively in high yields. PREPARATION:A compound of formula II is deacetylated and subsequently benzylated to prepare a compound of formula III, which is esterified with a lower alkyl and reacted with a halogenating agent to give a compound of formula IV [R<1> is COOR or OH; R<2> is OH or COOR; R<3> is X (X is halogen) or H; R<4> is H or X]. The compound of formula IV is reacted with thiophenol in the presence of a base and further treated with the base to give a compound of formula V, followed by halogenating the compound of formula V.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a novel sialic acid derivative, a method for producing the same, and a method for stereoselectively glycosylating sialic acid using the sialic acid derivative.

[Background of the invention]

The sugar chains contained in complex carbohydrates have a high degree of diversity.
Many problems still remain in its synthesis. To solve this problem, approaches from both the development of rational synthetic strategies and the development of new glycosylation reactions are required.

In this glycosylation reaction, the glycosylation reaction using sialic acid as a sugar donor has been regarded as an important subject, but the yield has conventionally been low and stereochemical control has been extremely difficult.

[Purpose of the invention]

The object of the present invention is to provide α
- To provide a method for stereoselectively producing glycosides with good yield.

Another object of the present invention is to provide a novel sialic acid donor useful in the above-mentioned glycosylation reaction.

[Structure of the invention]

The present invention relates to an α-type sialic acid donor compound (8a) represented by the following formula.

(8a) (R is a lower alkyl group, Bn is a benzyl group, AC is an acetyl group, and Ph is a phenyl group.) The present invention also provides a β-type sialic acid donor compound (8b) represented by the following formula.
Regarding.

μdan (R is a lower alkyl group, Bn is a benzyl group, AC is an acetyl group, ph is a phenyl group, and X is a halogen group such as F, Cj!, or Br). )'' (R is a lower alkyl group, AC is an acetyl group) is deacetylated to produce compound (2) Haruka (Bn is a benzyl group), and compound (3) is converted into a lower alkyl ester. Compound (4)'' (R represents a lower alkyl group) is produced, and a halogenating agent is reacted with the compound to form a compound U H' (5a): R'=C0OR, R'=XR '=DH,R
'=H (5b): R'=OH, R3=)I R''=C0OR, R'=X (Ph is a phenyl group, X is a halogen group such as IJ, Sr, or r.) Compound ( By reacting 5a) with thiophenol in the presence of a base, or by reacting compound (5b) with thiophenol in the presence of a base to produce compound (6), the compound (6) can be produced by further treatment with a base.
7) and halogenating (7),
α-type sialic acid donor (U) or β-type sialic acid donor (8b
).

Furthermore, the present invention provides an α-type sialic acid donor (8aL or α
After reacting the sugar acceptor with a mixture of a type sialic acid donor (8a) and a β type sialic acid acceptor (8b) in which X is F,
The present invention relates to a method for producing an α-glycoside compound (A) represented by the following formula, which is characterized by removing a PhS group by a reduction reaction.

(A> (However, in the formula, R is a lower alkyl group, R1 is a sugar residue, R
2 represents a benzyl group, an acetyl group, or a hydrogen atom. The present invention further relates to a method for producing an α-glycoside compound (A), which comprises reacting a β-type sialic acid donor with a sugar acceptor and then removing a PhS group by a reduction reaction.

The present invention will be explained in more detail below.

■Explanation of abbreviations and symbols The meanings of the abbreviations and symbols used in this specification are as follows.

AC Niacetyl group Me: Methyl group Et: Ethyl group Bu Nibutyl group Ph: Phenyl group Bn: Benzyl group THF: Tetrahydrofuran DBU: Diazibicycloundecene DBN
Nidiazobicyclononene DMF Nidimethylformamide DMAP Nidimethylaminopyridine DMSO Nidimethylsulfoxide TMSOTf: ) Lyntylsilyl triflate DA
ST: Diethylaminosulfur trifluoride ■, Example of Embodiment One example of a preferred embodiment of the present invention is shown in the following schemes 1 to 1.
4.

(2) Reaction conditions for each step Next, regarding the reaction conditions for each step in the method for producing α-type sialic acid donor (8a), β-type sialic acid donor (8b), and α-glycoside compound A of the present invention. , schemes 1-7
This will be explained using the example shown in .

i) Reaction conditions for producing compound (2) from compound (1) Compound (2) can be produced by deacetylating compound (1). Preferred reaction conditions that can be used in this reaction are as follows.

Temperature knee 20℃~50℃.

Reagent: Nal]? Je, K2C[]3, Na2
CO3, εt, N, KCN.

NaCN et al.

Solvent: THF-11eOH, dioxane-MeOHS
MeO) 1st class.

ii) Reaction conditions for producing compound (3) from compound (2) Compound (3) can be produced by benzylating compound (2). Preferred reaction conditions that can be used in this reaction are as follows.

Temperature: 0°C to 50°C.

Reagent: [Bu<N) = DoKOH-BaO-PhC
)1. Br.

Ba(leaf)2-BaO-PhCH, Br5NaH-Ph
CH2Br.

Ba(Owl) 2-Ba0-PhC)l*c It
, NaH-PhCtl, Ci.

Ag2OPhC)lJr et al.

Solvent: DMFSTHF, DMSo, 1,2-dimethoxyethane, etc.

iii) Reaction conditions for producing compound physics from the amount of compound Compound (4) can be produced by converting compound (3) into a lower alkyl ester. Preferred reaction conditions that can be used in this reaction are as follows.

Temperature knee 40℃~30℃.

Reagent: Mel-2CD1, Mel-Na) ISC82
N2 etc.

Solvent: DMFSTHF, x-chill, MeOH, etc.

iv) Reaction conditions for producing compound (5a) and...U from compound physics Compound (4) is N-bromosuccinimide (NBS),
By reacting with N-chlorosuccinimide (NC3), N-iodosuccinimide (NIS), preferably NBS, a mixture of halohydrin bodies and bodies can be produced. Preferred reaction conditions are as follows.

Temperature: 0°C to 80°C.

Reagent: NBS, NC35NIS 0 Solvent: C)
lzCN HJ et al.

Compounds (5a) and (5b) can be separated from the resulting mixture by a conventional method such as silica gel column chromatography.

(2) Reaction conditions for producing compound 2 from above or from a compound plate via compound physics Compound (7) can be obtained by reacting thiophenol with a compound plate in the presence of a base. Preferred reaction conditions are as follows.

Temperature: 0°C to 50°C.

Reagents: 0t8u, HSNaH, etc.

Solvent: tBuOH-T)IF5THF, DMF
etc.

Further, after compound (6) is obtained by reacting compound (5b) with thiophenol in the presence of a base, compound (7) can be obtained by further treating with a base such as DBU. The reaction conditions for obtaining compound (6) from compound (5b) are the same as those for obtaining (7) from (5a).

Further, the following reaction conditions are preferable for converting compound (6) to compound (7).

Temperature: 0°C to 50°C.

Reagents: Ku80, Kuchi BN, NaOMe, etc.

Solvent: toluene, MeOH, T) IP, etc.

vi) Reaction conditions for producing compound [compound] or compound [mu] from compound [compound] By reacting compound (7) with HF-pyridine or DAST and fluorinating it, the α-type sialic acid donor compound (8a) of the present invention can be obtained. and a mixture of compound (8b) in which X is F can be produced.

Preferred reaction conditions that can be used in this reaction are as follows.

Temperature knee 40℃~50℃.

Solvent: THFSCH, Cj! , , anhydrous solvents such as ether and toluene.

Compound 1 and the compound (8t+) in which X is F can be separated by a conventional method using silica gel column chromatography or the like.

Compound (8b) in which X is C1 can be obtained by a method such as reacting compound m with CC14-(L(ezN) aP in toluene. Preferred reaction conditions are as follows.

Temperature knee 70℃~50℃.

Reaction reagent and solvent: CC1, -(Me,M) 3P/
) Luene, SOCIt z-Me2NCHD/CH2
CR, Ph5P-CC1, /THF, etc.

A compound μ in which
You can get tricks. Preferred reaction conditions are as follows.

Temperature knee 70℃~50℃.

Reaction reagent and solvent: CBr, -(Me2N)3P
/THF %CBr, -Ph, P/THF, (OBr
) z-MezNCHO/CLC12 etc.

Compounds in which X is Cβ2 and Or are produced from the compound layer under the above reaction conditions while maintaining their steric structure, so there is usually no need to separate them from the α-type compound.

vii) Compound “U” or “U” or compound (8a)
Reaction conditions for producing α-glycoside compound A from a mixture of compound (8b) in which X is F In order to produce α-glycoside compound A, first compound (8a) or (8
b), or compound (8a) and compound (8
After reacting the mixture of b) with an arbitrary sugar acceptor to produce the compound pA A (in the formula, R represents a lower alkyl group and R1 represents a sugar residue), the PhS group is eliminated by a reduction reaction. do it.

Here, examples of sugar receptors include compound (9) shown in the scheme, 0υ, surface, and 00.

Further, as specific examples of compound pA, compounds αG, Q31S (ISl, 0 mouth and (21)
etc. can be mentioned.

b) First, react compound (8a) with an arbitrary sugar receptor,
Preferred reaction conditions for producing compound pA are as follows.

Reaction example: (8a) + (14) - (15)
+ (16) Temperature: 0°C to 50°C.

Reagent: AgC104SnC12, Ag5o, cf',
-3nC1x, TMSOTf, 5iFa, BFs・
0) It2.5n(OTf)t, n-Bu, 5nOT
f etc.

Solvent: toluene, benzene, CH2Cj! ,,(CI
ICH*)*, CCβ24, etc.

) Next, react compound (8b) with an arbitrary sugar receptor,
Preferred reaction conditions for producing compound pA are as follows.

Mamedan + Diagram - Ton + Ton Temperature: 0°C to 50°C.

Reagent: AgCj! 04, Ag5OsCF*, )Ig
(CN)2-HgBr2, ^hcOs, etc.

Solvent: toluene, benzene, CH, Cβ2, CC1,
etc.

c) Next, preferred reaction conditions for reacting the mixture on the compound and on the compound in which X is F with any sugar acceptor to produce compound pA are as follows.

Reaction example: [Blood + Danbon (X:F)] Temperature: 0°C ~
50℃.

Reagent: ^gsO3cP3 SnCj! 2.AgCj!
04 SnCj! 2, TMSOTfS 5IFa,
BFs-oBt2, Sn (mouth Tf),, n-Bu
3SnOTf etc.

Solvent: ether, (CjICH*)z, CCI! 4
etc.

2) Further, the PhS group is removed by a reduction reaction to form compound 9
Preferred reaction conditions for producing compound A from A are as follows. As specific examples on the compound, compound layer, amount, plate, plate, μ■, (27)R plate are shown in the scheme.

Example reaction:! g - amount Temperature = 80°C to 140°C.

Reagents: Ph, 5nH-α, α'-azobis-isobutyronitrile (AIBN), Raney nickel pen n-
Bu, SnH, etc.

Solvent: toluene, benzene, xylene, BtOH.

Me Kano et al.

It is also possible to oxidize the PhS group to a phso□ group using metachloroperbenzoic acid or the like prior to reduction, and then reduce it with ^β-Hg or the like to eliminate it.

Reaction example Niton - μ average Temperature = 80°C to 140°C.

Reagents: n-Bu, 5ntl-AION, Raney nickel, n-Ph3SnH-AIBN, etc.

Solvent: toluene, benzene, xylene, BtOH.

After hydrogenating each of the above compounds (23) such as MeOH, acetylation can be performed to obtain the amount of the compound. Preferred reaction conditions at that time are as follows.

Reaction example = (2) - One (to) (23)→ →(24) Reaction conditions for hydrogenation Temperature = 20°C to 80°C.

Reagents: Pd(OH)2, PtO2, Raney Nickel, Pd-C, etc.

Solvent: [,tO)1. Dioxa? /-8,0, AcO)
ISMeOH et al.

Reaction conditions for acetylation Temperature 20℃~100℃.

Reagent: Ac20-εt, N-D1. IAP, AcC
I! -Et3N.

Ac, 0-ro? , lAP et al.

Solvent: 'rttp, dioxane, pyridine, etc.

After hydrolyzing the above compound (25), hydrogenation can be performed to obtain compound (26). Preferred reaction conditions at that time are as follows.

Reaction example: Dan- Hydrolysis reaction conditions Temperature 20℃~50℃.

Reagent = OH, NaOH, CO, Na, CO, etc.

Solvent: THF-H2O, MeOHHzO1Bt H-
H2O, dioxane-HtOll, 2-dimethoxyethane-H2O, etc.

Reaction conditions for hydrogenation Temperature = 20°C to 80°C.

Reagents: Pd(Of()*, pto□, Raney nickel, etc.

Solvent: εtoll, dioxane-8,0, AcOH, etc.

After hydrolyzing the above compound (27), hydrogenation can be performed to obtain compound μ. Preferred reaction conditions at that time are as follows.

Reaction example: (27) → Hydrolysis reaction conditions Temperature: 0°C to 50°C.

Reagents: LiOH, OH5NaOH, K2COs, etc.

Solvent: T) IP-H2O, MeOH-1f, 0, BtO
H-H,0, dioxane-820,1,2-dimethoxyethane-H2O, etc.

Reaction conditions for hydrogenation Temperature: 20°C to 80°C.

Reagent: Raney nickel etc.

Solvent: MeOH, ethyl acetate, etc.

〔Effect of the invention〕

By using the novel sialic acid donor of the present invention, α
- Glycosides can be selectively produced in high yields.

〔Example〕

Hereinafter, the present invention will be explained in more detail using Examples.

Example 1 Synthesis of (2)===Yu(1) (291.2 mg, 0.616 mmol) was dissolved in 10 ml of methanol and O,l M sodium methoxide methanol solution (1 ml, 0.1 ma+o1)
．． ) and stirred at room temperature for 3 hours. The reaction solution was mixed with ion exchange resin [Product name: Amberlyst A-15 (AMBE)
RLYST A-15) ) neutralized water (10 ml)
), filtered, and concentrated.
99%) was obtained as a white powder.

Example 2 Synthesis of (3) ===- (2) (1,050 g, 3.44 mmol) and hensyl bromide (4.8rd, 40 mmol) were dissolved in 20 ml of dimethyl sulfoxide and heated at 0°C under a nitrogen stream. Stir.

Add barium oxide (3.05g, 19.9m) to this solution.
mol), tetrabutylammonium iodide (70 mg
.

0.19 mmol) and potassium hydroxide (2.23 g.

39.7 mmol) was added and the mixture was stirred at room temperature for 18 hours. After adding methanol (4 ml) under water cooling, the mixture was stirred at room temperature for 30 minutes, followed by ether (100 ml) and water (1 ml).
00rnl>. It was made acidic by adding 2N aqueous hydrochloric acid solution and extracted twice with ether (150ml).The organic layer was washed with water (200ml) and saturated brine (100rnl), dried over anhydrous magnesium sulfate, and concentrated. Purified by Kagel ram chromatography (n-
Hexane:ethyl acetate:acetic acid=15:10:1) L, 1
．． 770 g (79%) of (3) was obtained.

(Physical and chemical properties of (3)) Rf = 0.42 (n-hexane: ethyl acetate: acetic acid = 10:10:1) m, P, 126-128°C [α] -7,7@(C1,0 , CHCj2.) Elemental analysis calculated value (CasH4+N, 0s) C71,87 H6,34 N 2.15 Actual value C71,58 H6,31 N 2.14' H-NMR (CDC/s, 90M) lz) 6. 19(d, 3.5Hz, H-3), 5.24
(d, 7.2Hz, NH)1.72(S, Ac
) Example 3 Synthesis of (4) (3) (3,272 g 15.02 mmol) was dissolved in ether (30 mj) and methanol (10 ml),
The mixture was treated with excess diazomethane (ether solution) under water cooling. Excess diazomethane was decomposed with 1rnl of acetic acid, concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography (
Purified with n-hexane: ethyl acetate = 3 = 2), 3.1
98 g (96%) of (4) was obtained.

(Physical and chemical properties of C4)) Rf = 0.27 (n-hexane: ethyl acetate = 3
:2) [α] -3,3° (C1,0, CHCj!,) Elemental analysis calculation value C1°H43NI011 (0,5820)C
72,16 (71,19) H6,51 (6,72) N 2.10 (2,08) Actual value C71,33 H6,48 N 2.09')l-NMR (CDC1s, 400MHz) 6, +35 (d, 4.2) 1z, H-3), 5.1
64(d, 7.6Hz, N)l), 4.152(d
d, 5.6.4.6Hz, H-7), 3.979
(ddd.

5.4.4.6.4.4Hz, )l-8), 3.9
05 (dd, 10.0.5.4Hz, H-9), 3
,770(S, CD2Me) ,3. '705 (dd
,'10.0.4.4Hz,)l-9'),1
．． 736 (S, Ac) Example 4 (4) (7,077 g, 10.63 mmoi) was dissolved in acetonitrile-water (12:1:130rn1), and to this solution was added 2.27 g of N-bromosuccinimide;
2,8 mmoj! ) was added. The mixture was stirred at 60°C for 30 minutes and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane: ethyl acetate = 1: l) to give (5b) (6,28621
78%) and a dish (1,546 g, 19%) were obtained.

(Physical and chemical properties of (5b)) Rf = 0.20 (n-hexane: ethyl acetate = 1:
1) [α]+35.1° (co, 8, C) lcj! a) Elemental analysis calculated value (CsoL4N10Jr1) C62,99 85,81 N 1.84 Actual value C62,65 H5,81 N 1.84' H-NMR (CDCj!a, 500MHz) 4.633 (IH, d, J 3.7) 1z, H=3
), 4.437 (IH, dd.

J 10.0, 3.7Hz, H-4), 3.849
(IH, ddd, J 10.7°10.0, 8.3H
z, H-5>, 3.769 (3H, s, CO,
1,te), 1,643 (3H,s, Ac).

(Physical and chemical properties of (5a)) [α] 51.8” (co, 8, CtlCj!
s) m, p, 148-150°C (crystallized from ether)
Rf O,36 (n-hexane:ethyl acetate l:1) Elemental analysis calculated value C4oH44N10JrI C62,99 H5,81 N 1.84 Actual value C62,85 H5,76 N 1.87' H-NMR (CDCj!s , 500MHz) 4.497 (E, d, J 11.OHz, H-3
), 3.847 (3H.

s, CO, 1Je), 1.715 (3H, s,
AC).

Example 5 Synthesis of (7) ===- Thiophenol (1,0rnl, 9.7 mmoj7
) to t-butanol-TI(F (1: 1.30 mt
') and stirred under cooling with water, a solution of potassium t-butoxide in t-butanol (0.76M; 10mj!,
Added 7.8 mm. 10 minutes later (5b) (3
, 876 g, 5.082 mmol) in THF solution (2
0mj) was added thereto, and the mixture was stirred for 2 hours under water cooling and further stirred for 1 hour at room temperature. The reaction solution was diluted with ether (200ml) and washed with water (100ml). The aqueous layer is ether (10
0-), and the organic layers were combined and diluted with 0.2N NaO.
After washing with H aqueous solution (100 mf) and saturated brine (100 mj), it was dried over anhydrous magnesium sulfate. Concentrated under reduced pressure, the residue (4.23 g) was dissolved in toluene (50 rnl), and 1,8-diadibicyclo was dissolved with stirring under water cooling. [:5
．． 4.0]-7-undecene (DBU, 75μ!10,
Added 50 mm. Cool the mixture in water for 2 hours,
The mixture was stirred at room temperature for 30 minutes and diluted with ethyl acetate (100ml).Washed with 0.1N HCj' aqueous solution, and the aqueous layer was extracted with ethyl acetate (500rd).The organic layers were combined, washed with saturated brine, and anhydrous. After drying over magnesium sulfate, the residue was filtered under reduced pressure. The residue was crystallized from ether (50-) to obtain 2.660 g of a product.

After further concentrating the mother liquor, it was purified by silica gel column chromatography (n-hexane:ethyl acetate = 2:1) to obtain a total of 3.300 g (82%).

(Physical and chemical properties of (7)) [α] +9.4@ (co, 9, [') Ic 1 s
) m, p, 97-99°C Rf = 0.47 (n-hexane: ethyl acetate = 1:
1) Elemental analysis calculation value C4J4 autoNtOsS+ C69,76 H6,24 N 1.7? Actual value C69,62 H6,18 N 1.74' H-NMR (CDC1's, 400MHz) 4°875 (IH, d, J 9.7H2, N)l)
, 4.396 (IH, d.

J 10.8Hz, )l-6), 4.205(ill
, ddd, J 10.8.9.7°9.5Hz,
)I-5), 3.943(1)1. dd, J 1
0.8.9.5Hz.

H-4), 3. ．． 645 (1B, d, J 10.8
)1z, H-3), 3.559(3)1. S,
C0Je), 1.772 (3H,s, Ac).

Also, (5a) (1,277g, 1.674 mm
oi2) versus thiophenol (0.35rnl, 3
．． 4 mmoj and potassium t-butoxide (2,5
The same treatment as in (5b) was performed using > mmol. It was purified by silica gel column chromatography (n-hexane:ethyl acetate = 2:1) and purified with silica gel (593 mg, 4
5%).

Example 6 (7) (53.7 mg, 0.0678 mmol)
1,2-dichloroethane-toluene (1:2.1.5
rIf,) and stirred at -40°C. Add d to this solution
iethylaminosulfur trifluo
ride (3Q p 1.

Q. Add i35 mmoi and heat at -40℃ for 30 minutes.
The mixture was stirred at 0°C for 30 minutes. The reaction solution was diluted with ethyl acetate (30mj
dilute with water and add saturated NaHCOs aqueous solution (5r) with stirring.
Add the ingredients carefully. The aqueous layer was extracted with ethyl acetate (30 Wdl). The organic layers were combined, washed with saturated brine (30 rnl), dried over anhydrous magnesium intelate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography. Graphic (n-hexane:ethyl acetate = 2
: Purified by 1) and (8b) (51.4 mg, 9
6%) into a mixture ((8a): (8b) = 2=1
) was obtained.

(Physicochemical properties of μU and (8b)) Rf = 0.45.0.40 (n-hexane: ethyl acetate = 3: 1)') I-NMR (CDC1's, 400MH2) 4.354 (2/ 3H, dd, J 9.5. 9.
3) 1z, H-4α), 4.005 (1/3H
, dd, J 10.3. 9.5Hz, H-4
β) , 3.674 (2H,s, CO2Me α)
, 3.647 (2/3) 1. dd.

J 11.0. 3.2Hz, H-9α), 3
．． 586 (IH, s.

CO, Meβ), 3.379 (2/3H, dd, J
13.7. 9.5Hz.

H-3α), 1.695 (IH,s, Acα).

Example 7 Synthetic thickness of (8b) (469.9 mg, 0.593 open OR) and carbon tetrachloride (0.23 mj!, 2.4 mmoj of THF)
Hexamethylphosphite triamide (0.32 mj!, 1.8
mmo! , ) was added. The mixture was stirred at -70°C to room temperature for 3 hours and diluted with ether (5Q-).

Ice water (3(1-)-saturated NaHCOs aqueous solution (20-)
The aqueous layer was extracted with ether (50ml).

The organic layers were combined, washed with saturated brine (30 mJ), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane: ethyl acetate = 3:2) (8b) (X = Cjri
(475.0 mg, 99%) was obtained.

((8b) (Physical and chemical properties of X=Cj) Rf =0
．． 30 (n-hexane: ethyl acetate = 2:1) 'H-NMR (CDC1's, 400M11z) 4.756 (I
H, d, J 8. IHz, NH), 4.635 (
1)1. d.

J lo, 7Hz, H-6), 4.129 (IH, d
d, J 10.0.9.3) 1z.

H-4), 3.854 (ltl, d, J 10.O
Hz, )l-3), 3.792(LH,d, J
9. OHz, H(), 3.624(3H,s, CO
=Me), 1,674 (3H,s,AC).

(7) (168,81ng, 0.213 mmoj
and carbon tetrabromide (220 mg, 0.663 mo+
Hexamethylphosphite triamide (120μ
j! , 0.660 mmo 1 ) was added. The mixture was stirred at -70°C to room temperature for 3 hours, and ether (50ml
) was diluted with

ice water (20 mj monosaturated NaHCO3 aqueous solution (10 mj)
The aqueous layer was extracted with ether (1 portion of 30 rr).

The organic layers were combined, washed with saturated brine (30 ml), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.

The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate = 2:1).
X=Br) (170.9 mg, 94%) was obtained.

((8b) Physical and chemical properties of (X=Br)) Rf =0
．． 30 (n-hexane: ethyl acetate = 2:1)' H-NMR (CDCfa, 500MHz) 4.585 (IH, dd, J 10.5.1.5Hz
, H-6), 4.157(1)1. dd, J
9.8.9.5Hz, H-4), 4.103 (I
I(.

ddd, J 10.5.9.8.9.0)1z, H
-5), 3.811 (ill.

dd, J 8.0.1.5Hz, )l-7), 3.
713 (LH, d, J 9.8, Hz, H-3),
3.669 (3)1. s, CD2Me), 1.6
75 (3) 1°s, Ac).

Example 8 Synthesis of C1 Method A Silver trifluoromethanesulfonate (20 mg.

0.078 mmol), stannous chloride (15 mg).

0.079 mmol) and powdered molequinyl sieve 4
A (0.25 g) was suspended in carbon tetrachloride (lit') and stirred under ice cooling.

A mixture of (8a) and (8b) (X=F) ((8a)
: (8b)=2:1) (31.5mg, 0
．． 0397 aunojiri and (9) (17mg,
o, 065 mmol) in carbon tetrachloride solution (2-)
was added and the mixture was stirred at 0°C to room temperature overnight. The mixture was diluted with ethyl acetate (30mj?), added with saturated NaHCO3 aqueous solution (5mf), and stirred. Extracted.

The organic layers were combined, washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain αQ (19.7 mg,
(48%) and 10.4 mg (33%) of (8b)
was recovered.

(Physical and chemical properties of αQ) [α] −4,5° (cl, 0, CHCj!s)R
f = 0.35 (n-hexane: ethyl acetate = 3:2
) Elemental analysis calculated value Cs@HsJ+0+<5t C67,36 86,53 N 1.35 Actual value C67,29 H6,53 N 1.30 'H-NMR (CDC1's, 500MHz) 5.460 (IH, d , J 4.9Hz, H-1a
), 4.466 (LH, dd.

J 7.9.2.1Hz, H-3a), 4.337
(IH, dd, J 10.7°1.5Hz, H-6
b), 4.256 (IH, t, 10.1Hz, )l
-4b), 4.229 (LH, dd, J 4.9.2
．． 4Hz, H-2a), 4,059.

(1M, dd, J 7.9. 1.8) 1z,
tl-4a), 3.975 (IH, dd.

J 9.5. 6.7Hz, H-6a), 3.
658(3)1. s, CO, Me), 3.
274 (IH, d, J 10.IHz, If-
3b), 1.639(3)1. s.

AC) Method B Silver trifluoromethanesulfonate (34 mg.

Q, l 3 mmojri and powder molekin two-sieve 4
A suspension of carbon tetrachloride (1 mf) of -20
(8b) (X= CI) (53
,5mg.

0,660a+moi) and gl(2?+gs o,
10 mmol 1 ) of carbon tetrachloride solution (2-) was added. The mixture was stirred at -20°C to room temperature overnight. The reaction solution was diluted with ethyl acetate (30-), saturated NaHCOs aqueous solution (5rd) was added and stirred, and then insoluble matter was filtered off through Celite. The filtrate was washed with water (30ml), and the aqueous layer was extracted with ethyl acetate (30rn1).The organic layers were combined, washed with saturated brine (30nj'), dried over anhydrous magnesium sulfate, and concentrated.The residue was purified using a silica gel column. Purified by chromatography to obtain 1.4 (35.8 mg, 52%
) was obtained.

Method C Mercury cyanide (25 mg, Q, l Q mmoj,
Mercury bromide (12 mg, 0.30 mmol) and powdered mol L/kg.

Larshiep 4A (0.2 g) was suspended in carbon tetrachloride (lrm) and cooled with water (8b) (X= Cfl> (5
3.0mg.

0.0654mmof) and 'fpj (27
mg5o, 10mmo1) of carbon tetrachloride solution (
2-) was added. The mixture was stirred at 30° C. for 72 hours and diluted with chloroform (30 rnl). Filter the insoluble matter through Celite and reduce the filtrate to 10%! Washed with aqueous solution (21) tl. The aqueous layer was extracted with chloroform (30 mf), and the organic layers were combined, washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. It was concentrated under reduced pressure and the residue was purified by silica gel column chromatography to obtain C1 (3
1.2 mg, 46%) was obtained.

Method D Mercury cyanide (30 mg, 0.12 mmof), mercury bromide (13% g, 0.036 mmof') and powdered molequinyl sieve 4A (0.2 g) were dissolved in carbon tetrachloride (
lrnl) and while stirring under water cooling (8b).
(X=Br) (62.5 mg, 0.0731 mmo
Jiri and Kaki (30mg.

0.12 mmoi) of carbon tetrachloride solution (2rn1) was added. The mixture was stirred at 0° C. to room temperature for 18 hours, diluted with chloroform (30 mf), and then insoluble matter was filtered off through Celite. Add the filtrate to 10% KI aqueous solution (30ml)
The aqueous layer was extracted with chloroform (30-).

The organic layers were combined, washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated.

The residue was purified by silica gel column chromatography (n-hexane:ether = 2:3) and αQ (54,7m
g, 72%).

Example 9 Synthesis of αJ ==: 111111- Mercury cyanide (54 mg, 0.21 mmof),
Mercury bromide (24 mg, 0.067 mmol) and powdered molecular sieve 4A (0.3 g) were dissolved in carbon tetrachloride (2
ml) and stirred while stirring (8b) (X=C
i') (107,9fl1g, 0.133 mm
ol) and history (99 mg.

0.21 mmol of carbon tetrachloride solution (3 ml) was added. The mixture was stirred at 40°C for 40 hours and chloroform (3
0-). Insoluble matter was filtered off through Celite, and the filtrate was washed with a 10% Kl aqueous solution (30ml).The aqueous layer was extracted with chloroform (30ml), and the organic layers were combined, washed with saturated brine, and dried over anhydrous magnesium sulfate. It was condensed under reduced pressure and the residue was subjected to silica gel column chromatography (
Purified with toluene:ethyl acetate = 4:1) and purified with Kabuto (
117.0mg.

71%>.

(Physical and chemical properties of C31) [α] +19.5° (co, 9, CHCl*)R
f = 0.49 () Luene: Ethyl acetate = 2: 1
)') l-NMR (CDCj!, , 500MHz) 4.307 (IH, dd, J 11.3.1.otl
z, H-6b), 4.196(1)1. dd, J
7.2.8.2Hz, H-4b), 4.027(i
ll, dd.

J 10.7.2.0) 1z, H-6a), 3.98
6(1)1. dd, J 10.7°4.9Hz H
-6a'), 3.623 (3H,s, C0Je)
, 3.329 (LH, d, J 8.2Hz, H-3
b) , 3.270 (3H, s.

0λie), 1.613(3)1. s, Ac)
Example 10 Synthetic mercury cyanide (21) (3Qmg, o, 12mm)
, mercury bromide (14 mg, 0.039 +nmoj7)
and powdered molequinylar sieve 4A (0.2 g) in carbon tetrachloride suspension (1 ml) while stirring under water cooling (8b).
(X=Br) (60.3mg, 0.0705
mmol and QD (61 mg, 0, 11 mmoj
A carbon tetrachloride solution (2 ml) was added. Mixture at 0℃
The mixture was stirred for 2 hours at room temperature, then overnight at room temperature, and chloroform (30
-) diluted with Insoluble matter was filtered through Celite, and the filtrate was
Washed with 0% KI aqueous solution. The aqueous layer was filtered with chloroform (30
The organic layers were combined, washed with saturated brine, and dried over anhydrous magnesium sulfate. Concentrate under reduced pressure and subject the residue to silica gel column chromatography (toluene:
Purification by ethyl acetate = 5:1) and preparative thin layer chromatography gave a plate (22.2 mg, 24%).

((21) (Physical and chemical properties) [α]-9,2° (C1,O,C)I(J,)Rf
=0.31 () Luene: Ethyl acetate = 3:1) Elemental analysis calculated value C8゜) 1113N+0l-3L・H,0C7
2,10 H6,43 N 1.05 Actual value C72,13 H6,4O N 1.02' H-NMR (CDC1s, 500M)1z) 4.184(1)1. d, J 7.3Hz, H-
1a), 3.728 (IH, dd.

J 9.8.7.3) 1z, H-2a), 3.69
6 (LH, dd, J 5.5゜1.8Hz, H-7
b), 3.626 (3H,s, C0Je), 3J8
1 (IH, d, J 10.7) 1z, H-3b)
, 1.522 (s, 3H, Ac) Example 11 α$ Synthesis Method A Silver trifluoromethanesulfonate (40 mg).

0.16 mmojri, stannous chloride (30 mg,
0.16 mmo j! ) and powdered molecular sieve 4A (0.3 g) were suspended in carbon tetrachloride (1-), and while stirring under cooling with water,
Ages 01) and 0.4) (139 mg, 0.157
mmof) in carbon tetrachloride (3rnl) was added. The mixture was stirred at room temperature overnight and diluted with ethyl acetate (30 ml). A saturated Na HCOs aqueous solution (5 mj) was added and stirred, and insoluble materials were filtered off through Celite. The filtrate was washed with water (30 ml), and the aqueous layer was extracted with ethyl acetate (30 ml).

The organic layers were combined, washed with saturated brine (30 tl), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.

The residue was purified by silica gel column chromatography (toluene: ethyl acetate = 3:1) and preparative thin layer chromatography (n-hexane: ether = 1:2) to obtain Tonto (56.6 mg, 35%). Ta.

(Q31 (Physical and chemical properties) [α) +12.3@ (cl, 8, CI (CI 3
>Rf = 0.46 () Toluene: Ethyl acetate = 2:
1) Elemental analysis calculated value C1°. Hl. sN+o+ss+C72,49 H6,39 NO185 Actual value C72,24 H6,42 NO,88 Goose)! -NMR (CDCji!s, 500MHz) 4.760 (IH, d, J 9.2) 1z, NH)
, 4.161 (IH, d.

J 7.6Hz, H-1a), 3.865 (IH, d
d, J 9.5.3.1Hz.

) 1-3b) , -3,831 (1B, d, J 3
．． IHz, H-4b), 3.619 (3H,s, C
OzMe), 3.390 (1)! , d, J 9.
5Hz.

) 1-3c) , 1.668 (3H, s, AC) Method B Mercury cyanide (28 mg, o, 11 mmoj7)
, mercury bromide (20 mg, 0.055 mmoi) and powdered molecular sieve 4A (0.2 g) were suspended in carbon tetrachloride (lrnl) and mixed with stirring (8b) (X
= C1>57, 1 mg, 0.0705 mmol and % (10 omg.

0.113 mmol) of carbon tetrachloride solution (2-) was added. The mixture was stirred at 40° C. for 40 hours, the reaction mixture was diluted with chloroform (30 ml), and insoluble matter was filtered off through Celite.

The filtrate was washed with 10% KI aqueous solution, and the aqueous layer was extracted with chloroform (30 ml'). The organic layers were combined, washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography and preparative thin layer chromatography.
g, 62%).

Method C Mercury cyanide (35 mg, 0.14 mmoi')
, mercury bromide (16 mg, 0.044 mmol) and powdered molecular sieve 4A (0.2 g) were suspended in carbon tetrachloride (1 mj) and stirred under water cooling (8b).
(X=Br) (74.3 mg, 0.0869 mmo
l) and C4) (122 mg, o, 138 m
mol) of carbon tetrachloride solution (3-) was added. Stirred overnight at 0°C to room temperature and diluted with chloroform (30 mi'). Insoluble matter was filtered off through Celite, and the filtrate was diluted with 10% Kl.
Washed with aqueous solution.

The aqueous layer was extracted with chloroform (30 rn!), and the organic layers were combined, washed with saturated brine (30-ml), and dried over anhydrous magnesium sulfate. Concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography (toluene; ethyl acetate). =5
: Purified in 1) to obtain a quantity (113 mg, 78%).

Example 12 Q! Synthesis of D! (1 (27.2 mg, 0.0263 mmol)
,) Riphenylstannane (27mg, 0.076
mmof) and α,α′-azobis-isobutyronitrile (1 mg.

A toluene solution (1,2-) of 0,005 mmol was heated to reflux while blowing nitrogen gas. After 1 hour, trifylstannane (27 mg, o, 076 mmo
A toluene solution (0.2 mi') of 1) was added, and the mixture was further heated under reflux for 1 hour. The reaction solution was concentrated under reduced pressure and subjected to silica gel column chromatography (toluene: ethyl acetate = 2:1).
) to refine α! I) (18.9 mg, 77%) was obtained. In addition, 5.6 ag (21%) of unreacted 01 was recovered.

(α physical and chemical properties) Rf = 0.32 (n-hexane: ethyl acetate = 2:
1) [α] -29,8@ (C1,2, CHCf,) Elemental analysis calculated value Cs*HiJ1014 C67,44, H6,86, N1.51 Actual value C67,50, H7,06, N1.461 H -NMR (CDCj!s 1400MHz) 5.479 (d, 4.9flz, )l-1a),
4.560 (dd, ?, 8.2.4Hz, H-3a
), 4.273(dd, 4.9.2,4H2,H-2
a), 4.239 (dd, 7, 8.1, 5) 12.
H-4a), 4.122 (dd.

10.7.1.7Hz, H-6b), 3.955(
ddd, 7.0.4, 3.1.7Hz, H-8
b), 3.803(ddd, 10.5.10.0.
8.8Hz, tl-5b), 3.642(S
, CD, Me), 2.790 (dd.

12.5.4.3Hz, tl-3b eq),
1.760 (S, Ac), 1.745 (dd,
12.5.11.9 tlz, H-3ba ax) Synthesis of Example 13 (1) as (11.2 mg, 0.0121 mmol) was dissolved in methanol (1 ml) and heated at normal pressure in the presence of 10% palladium-carbon (18+ng). Hydrogenation was performed at

After reacting at 50° C. for 4 hours, the catalyst was filtered off, and the filtrate was concentrated and dried. The residue was treated with pyridine (0.3ml), acetic anhydride (0.1rn1) and 4-dimethylaminopyridine (lll1g). After 3 hours, it was concentrated under vacuum and purified by silica gel column chromatography (toluene:
Acetone=2:1) L■ (8.0 mg, 92%) was obtained.

@ Rf = 0.29 () Luene: Acetone = 2:
1)') l-NHR (C, D,, 400MHz) 5.760 (ddd, 7.1.6.0.2.5Hz,
H-8b), 5.480 (dd, 7.1.2.
4) 1z, )l-7b), 5.463(d, 5
．． 1Hz.

H-1a), 4.828 (ddd, 12.1.1
0.3.4.5Hz.

H-4b), 4.594 (dd, 12.5.2.
5) 1z, H-9b), 4.517 (dd, ?
, 9.2JHz, )I-3a), 3.430(S.

CD, 'le), 2,745 (dd, 12.6.4
．． 6Hz, H-3b eq), 2.015(dd,
12.6.12.1Hz, H-3b ax) Synthesis of Example 14 (23) C3 (60.3ag, 0.0487 mmoi),
) Riphenylstannan (70mg, 0.02001
), and α, α′-azobisisobutyronitrile (1
23) (48.4 mg, 88%) was purified using silica gel column chromatography (n-hexane: ethyl acetate = 3:2). Ta.

(Physical and chemical properties of (23)) Rf = 0.19 (n-hexane: ethyl acetate = 3:
2) [α] +2.2@(C1,01C)lcj! s) Elemental analysis calculated value C1H7sN+Ou C72,26, H6,69, N1.24 Actual value C72,11, H6,79, N1.24') I-NMR (CDCj!s, 400M)lz) 4.565(d , 3.1Hz, H-1a), 4.
074 (10,5,1,5Hz, H-6b), 3.
642 (S, CD2Me), 3.500 (dd.

9.3, 3.7Hz, H"-2a), 3.336
(S, OMe) , 2.835 (dd, 12
．． 5.4.2Hz, )l-3b eq), 1.77
1 (S, AC), 1.758 (dd, 12.5.12
．． 0Hz, H-3b ax) Example 15 Synthesis of (24) (23) (19.5mg, 0.017311111
101) with 10% palladium on charcoal,! (15 mg), methanol (1 ml) was hydrogenated at 50° C. under normal pressure.

After 5 hours, the catalyst was filtered off and the filtrate was concentrated. The residue was dissolved in 0.5 mj of viridi 7 (0.5 mj) and acetic anhydride (0.3 mj), 4-dimethylaminopyridine (1 mg) was added, and the mixture was stirred at room temperature for 18 hours. The reaction solution was concentrated under vacuum and subjected to silica gel column chromatography. (24) (13.4 mg, 98
%) was obtained.

(24) Rf = 0.51 () Luene: Acetone = 1 = 1) 'H-NL(R (('[lC1,,400M)fz) 5.436 (10,0,9,8Hz, )l- 3a)
, 5.346 (ddd, 9,0°5.6.2.4Hz
, H-8b), 5.297 (dd, 9,0.1.7
Hz.

)1-7b), 5.166(dd, 9.8.9.3
Hz, H-4a), 4.937(d, 3.7Hz,
H-1a), 4.882 (dd, 10.0.3.
7Hz, H-2a), 4.876(ddd, 12.
2.10.0.4.8Hz, )I-4b), 4.2
60 (dd, 12.5.2.4Hz, tl-9b)
, 4.049 (12,5,5,6Hz: H-9b'
), 3.807 (S.

C0Je), 3.384 (S, OMe), 2.62
4(dd, 12.8.4.8Hz, )l-3b e
q), 1.978(dd, 12.8.12.2Hz
.

H-3b ax) Synthesis of Example 16 (25) C51 (41.6 mg, 0.0251 mmoi+)
,)su7znylstannan (46mg, O,L 3
mmol) and α,α′-azobisisobutyronitrile (1 mg).

A toluene solution of 0.006 mmol was heated under reflux for 3 hours while blowing nitrogen gas.

The reaction solution was concentrated under reduced pressure and purified by silica gel column chromatography (n-hexane:ether = 1:4) to obtain a product (25.8+g, 68%).

(Physical and chemical properties of (25)) Rf = 0.44 () Luene: Ethyl acetate = 3:
1) [α] +2.3° (C0,7L (1'l(
i,) Elemental analysis calculation value Cs3) 1sJ+0. .・H20C72,78
, H6,37, NO,91 Actual value C72,74, H6,46, NO,91' H-NMR (CDC1s, 400MHz) 5.139 (d, 3.9)1z, H-4b)
, 4.804(d, 9.1llHz.

NH), 4.492.4.353 (2d, 7.
8Hz, H-1a,)1-1b), 2.285
(dd, 13.4.5.4Hz, H-3be
q), 1.780 (dd, 13.4.10.9Hz
, H-3ba ax), 1.771 (S, AC) Example 17 Synthesis of (26) (25) (14.5 mg, 0.00956 mmol
) was dissolved in dioxane (lrd) and water (0.3ml), and lithium hydroxide aqueous solution (1.25N, 0.3rrI
1) was added and stirred at room temperature for 20 hours. The reaction solution was diluted with ethyl acetate (20 mi') and water (10 mi'), and the
．． The mixture was made acidic with a 5N aqueous hydrochloric acid solution. Ethyl acetate (20rn
The organic layers were combined and extracted twice with saturated brine (20
The residue (14,5a+g>) was dissolved in methanol (lWd) and the mixture was heated to normal pressure in the presence of 10% palladium-carbon (12+g). Hydrogenation was carried out at 50°C. After 3 hours, the catalyst was filtered off and the filtrate was concentrated. The residue was dissolved in water (0,2-) and diluted with a 0.05N aqueous sodium hydroxide solution (basic with 0.3mJ). After purification with Cephadex G-25 (water) to 6.0
mg (98%) of 26) was obtained.

(Physical and chemical properties of double ■) 'H-NIJR (020,4Q 034)1z) 5.228(d, 3.8Hz, )I-1aα),
4.670(d, 8.0Hz.

H-1aβ), 4.543(d, 7.8Hz, H
-1b), 3.290 (dd, 8.8.8.0)1
z, H-2aβ), 2.765 (dd, 12.6
．． 4.4Hz, H-3c eq), 2.039(S
, Ac), 1.808 (dd12.2.12.0H
z, H-3c ax) Synthesis of Example 18 (28) (21) (16.2 mg, 0.0123 mmoA)
) Riphenylstannane (25mg, 0.072
mmof) and α,α'-azobis-isobutyronitrile (1 mg, 0.006 mmof), a reaction was carried out in the same manner as in the synthesis procedure, and preparative thin layer chromatography (toluene:ethyl acetate = 2: 1), and (
27) (8.3 mg, 56%) Rf O, 41D: ethyl acetate = 2:1) was obtained. Also, 5.8mg
(36%) of (21) was recovered.

(27) (8.3mg, 0.OO69mmo 1
) in a mixed solvent of 1,2-dimethoxyethane-water (10
:1;1.1rnl) and stirred under water cooling.
．． 4N lithium hydroxide aqueous solution (10μi', 0.04
mmoi> was added. After stirring the mixture at room temperature overnight, water (
Diluted with ethyl acetate (20-), acidified with 2N HCβ
20rn1) twice. The organic layers were combined, washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Dissolve the residue in methanol (lrrll) and add 1
Normal pressure, 40°C in the presence of 0% palladium-carbon (12 mg)
Hydrogenation was carried out for 48 hours.

Insoluble matter was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by gel filtration (Sephadex G-25; H2O) to obtain 28) (3.0 mg, 94%).

Claims (6)

[Claims] (1) α-type sialic acid donor compound ¥(8a)¥ represented by the following formula. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ ￥(8a)￥ (R is a lower alkyl group, Bn is a benzyl group, Ac is an acetyl group, and Ph is a phenyl group.) (2) β-type sialic acid donor compound ¥(8b)¥ represented by the following formula. ▲Contains mathematical formulas, chemical formulas, tables, etc.▼ ￥(8b)￥ (R is a lower alkyl group, Bn is a benzyl group, Ac is an acetyl group, Ph is a phenyl group, X is a halogen group of F, Cl, or Br) ) (3) Compound ￥(1)￥ ▲There are mathematical formulas, chemical formulas, tables, etc.▼ ￥(1)￥ (R is a lower alkyl group, Ac indicates an acetyl group) is deacetylated to form a compound ￥(2)￥ ▲There are mathematical formulas, chemical formulas, tables, etc.▼ ￥(2)￥ is manufactured, compound ￥(2)￥ is benzylated, and compound ￥
(3) ￥▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ￥(3) ￥ (Bn represents a benzyl group). Compound ￥(3) ￥ is converted into a lower alkyl ester to form compound ￥(4) ￥. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ ￥(4)￥ (R represents a lower alkyl group) is produced, and the compound ￥(4)￥ is reacted with a halogenating agent to form the compound ￥(5a)￥, Producing the compound ￥(5b)￥,
▲There are mathematical formulas, chemical formulas, tables, etc.▼ ¥(5a)¥:R^1=COOR, R^3=XR^2=
OH, R^4=H ¥(5b)¥: R^1=OH, R^3=H R^2=COOR, R^4=X (Ph is a phenyl group, X is any of Cl, Br, I By reacting compound ¥(5a)¥ with thiophenol in the presence of a base, or by reacting compound ¥(5b)¥ with thiophenol in the presence of a base, compound ¥(6)¥▲formula, There are chemical formulas, tables, etc. ▼ After manufacturing ￥(6)￥, the compound ￥ is further treated with a base.
(7)￥ ▲There are mathematical formulas, chemical formulas, tables, etc.▼￥(7)￥ The α-type sialic acid donor according to claim (1), characterized in that ￥(7)￥ is produced and ￥(7)￥ is halogenated. Body ¥ (8a)
￥ or β-type sialic acid donor ￥ (8b) according to claim (2)
) Production method of ¥. (4) The α-type sialic acid donor according to claim (1) (8a
) After reacting with the sugar receptor, Ph
α- represented by the following formula, characterized by eliminating the S group
Method for producing glycoside compound ￥A￥. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ ￥(A)￥ (However, in the formula, R is a lower alkyl group, R_1 is a sugar residue,
R_2 represents a benzyl group, an acetyl group, or a hydrogen atom. ) (5) β-type sialic acid donor ¥ (8b) according to claim (2)
) After reacting with the sugar receptor, Ph
A method for producing an α-glycoside compound (A), which comprises eliminating an S group. (6) The α-type sialic acid donor according to claim (1) (8a
) ¥ and X are F, the mixture of β-type sialic acid donor ¥(8b)¥ according to claim (2) is reacted with a sugar acceptor, and then the PhS group is removed by a reduction reaction. A method for producing an α-glycoside compound (A).