JPS60190787A - Sialic acid derivative and its preparation - Google Patents

Abstract

NEW MATERIAL:A compound shown by the formula I (R1 is H, or CH3; R2 is acyl, or n-propyl; R3 and R4 are H, D-glucopyranosyl, 2,3,4-tri-O-benzyl-D-glycopyranosyl, 2,3,4-tri-O-benzyl-6-O-monochloroacetyl-D-glucopyranosyl, benzoyl, or benzyl; R5 and R6 are linked to form isopropylidene, or benzylidene; Ac is acetyl). USE:A remedy for meningitis. PREPARATION:A compound shown by the formula II is deacetylated, reacted with 2,2-dimethoxypropane to give a novel compound shown by formula III, which is reacted with a compound shown by the formula IV (X is halogen, Br is benzyl; MCA is monochloroacetyl) in a solvent such as 1,2-dichloroethane, etc. in the presence of glycosidation catalyst such as Hg(CH)2, etc. at -20-150 deg.C for 1-120hr, and if necessary, the protecting group is removed, or reduced, to give a compound shown by the formula I .

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel sialic acid derivative and a method for producing the same.

It is known that sugar chains containing sialic acid form partial structures such as glycoproteins, glycolipids, and polysaccharide sugar chains. Their biological functions include determining the lifespan of glycoproteins and cells, and acting as receptor sites for various biological functions.
Various things are being clarified. However, it is extremely difficult to isolate and purify oligosaccharide chains containing sialic acid from living organisms and to chemically identify them. Therefore, the precise synthesis of such sialic acid-containing oligosaccharide chains is
This is essential for elucidating the correlation between accurate biological IPr%i and molecular structure of these sugar chains.

The present inventors have so far succeeded in synthesizing a model glycolipid a with a repeating structure of glue 7°C Meningokotsukal polysaccharide (Sugimoto, Ogawa, Japanese Agricultural Chemistry Society Showa Sg Annual Meeting (79g 3) il /i Abstracts), and further conducted research on the synthesis of saccharides belonging to Group YK, leading to the completion of the present invention.

The present invention provides a novel sialic acid derivative represented by the following general formula I and a method for producing the same.

In the formula, R1 represents a hydrogen atom or a methyl group, R2 represents an allyl group or an n-propyl group, R5 and R4 each independently represent one hydrogen atom, a D-glucohyranosyl group,
2. ．． 1lI-to1)-〇-benzyruo-ylucobyranosyl group, 3. Gutley〇-benzyl-6-〇-
It represents a monochloroacetyl-glucopyranosyl group, a benzoyl group or a benzyl group, R5 and R6 each represent a hydrogen atom or jointly represent an inpropylidene group or a benzylidene group, and Ac represents an acetyl group.

The above compound can be synthesized, for example, as follows.

Formula (1): %Formula% (In the formula, Ac represents an acetyl group) When deacetylating the compound (], ), the formula (
2) Compound (2) represented by 2OOH OOH is obtained. Compound (3) represented by formula (3) is obtained by reacting this with a,2-dimethoxypropane.

Further, the compounds represented by the above general formula I include compounds represented by the following general formulas If, III and ■.

＼ORe In the formula, s R2 represents an allyl group or an n-pyruyl group,
R5 and R6 each represent a hydrogen atom or together form an impropylidene group, AC represents an acetyl group, R7 represents a hydrogen atom or a benzyl group, and R8 represents a hydrogen atom or a monochloroacetyl group.

The above compound is a compound represented by formula (3): (wherein, Ac represents an acetyl group) and a compound represented by formula (4): (wherein, X is a halogen atom, Bn is a benzyl group, and MC
A represents a monochloroacetyl group)
It can be synthesized by reacting 4) and, if necessary, reducing or eliminating the anchor group.

Furthermore, the compound represented by the above general formula I includes a compound represented by the following general formula V.

In the formula, R7 represents a hydrogen atom or a methyl group, R3 and R4 each independently represent a Mizuya atom, a benzyl group or a benzoyl group, and R5 and R6 jointly represent an isozolopylidene group or a benzylidene group.

Compound (3) is compound m [Carbohydrat
e Re5ea-rch, 7. ! r(/9gO＞/90
-/911. v.

Eschenfelder & R. Brosmer]
is deacetylated using a base such as sodium methoxide in a solvent such as alcohol to obtain compound (2),
This was mixed in a solvent supposed to be DMF in the presence of p-)luenesulfonic acid.

It can be synthesized by adding kodimethoxyprone and reacting.

Compound (4) can be synthesized, for example, as follows. First of all, Allyl-Ω...? , 1I-) When rho-0-benzyl-β-D-glucopyranoside is reacted with monochloroacetic anhydride in pyridine, a 6-0-monochloroacetyl compound is obtained. This was dissolved in 95% acetic acid with PdCl2.
After deallylation by treatment with Na0Ac, 5OC12
The desired chloride (4) can be obtained by treatment with .

The general formula 0. The metal compound represented by lI[, IV can be obtained by reacting compound (3) with compound (3) as a sugar acceptor and compound (4) as a sugar donor, and removing or reducing the protecting group if necessary.

This reaction is carried out using Hf(CN), HfBr2, molecular sieves, At2GO6-ArClO41A in a solvent such as dichloromethane or 12-dichloroethane.
rO5O2CF3°(CH3)3CO3O2CF3 and other glycosidation catalysts at -20°C-is
It may be carried out at 0° C. for about 2θ hours. The desired compound can be obtained by removing or removing the preservation group of the disaccharide (5) or (6) or the trisaccharide (7) obtained by For example, in an acetic acid aqueous solution,
The reaction is carried out at 30° C. for λ time using the button.

The monochloroacetyl group can be removed in a solvent such as methanol, etc.
A ring moiety such as IJ methoxide is added and removed by, for example, a softening treatment at room temperature for an hour.

Reduction and debenzylation of the allyl group can be carried out, for example, by catalytic reduction in the presence of Pd/c in a solvent such as acetic acid.
proceed at the same time.

The compound represented by the general formula V of the present invention is a compound (
Compound 06) is obtained by treating 3) with benzoyl chloride in gyridine, and compound (17) is obtained by treating with benzoyl chloride and N,N-dimethylaminopyridine in pyridine. Also, compound (2)
For example, DMF -OH! By treating with benzaldehyde dimethyl acetal in the presence of para-toluenesulfonic acid in lCN, benzylidene compound a81 can be obtained. Furthermore, treatment of compound (181) with pyridine/benzoyl chloride provides dibenzoyl chloride.

On the other hand, compound (3) was added to [3aO/Ba(O
H) Compound f2i1 upon treatment with benzyl bromide in the presence of 2.

(221 was obtained, which was esterified with diazomethane etc. in methanol to give the compounds (20 and (
2: U) is obtained.

An example of the synthetic route for the compound of the present invention is shown below.

The compound of the present invention belongs to Glue fY, which is a 14-molecule capsular polysaccharide of Neisseria meningitidis, and is extremely useful as a therapeutic agent for meningitis.

Compounds (2), (31, (5) obtained in the present invention)
, (6), (7), C8), (9), (0), (f
l! , αri, ([3, αΦ, u5J, C6), (17)
, f181, μgong, (201, I2's, ga and □
□□ are all new compounds 9.

Hereinafter, the present invention will be explained in more detail by showing examples.

Example/ Compound (11,?, θf (5,4O-1) is dissolved in methanol 3θ-, 2g% CH3ONa #solution θ, 2g is added and stirred at room temperature for 2 hours. The reaction solution is mixed with Amberlyst^-75 After neutralizing with
/1f (91A6%) + ml) I2-410 (absorptive)
[α connection 5-3θ (c=lθveoH) Elemental analysis Calculated value C, 1, 3g, Hr & 7g, N,
3. gt (as 015825NO9) 枳11fix f1业C, gg,! ;/ , H, MU71RI, N, J, '77R/ 0. k t (suoh−εt
oh-H2o, 2: /: /) Example co-compound (2136,3W9 (/, θmmol))
MF g, θ, ff7! P-toluenesulfone Nf (/hydrate) was added to the solution, and while stirring at 8 temperature, the mixture was dissolved in P-toluenesulfone Nf (Mw10!).
/j, /, 7mmo I) and stirred for 1 hour.

Add 0.0% triethylamine to the reaction solution. /me is added, dried under reduced pressure, and the residue is purified by flash chromatography using 810□C-30θ tiot. EtOA containing s% MeOH
Compound 43) is obtained by e.

Needle-shaped crystals 33/mycg2%) mp/g3-4" Elemental analysis Calculated value C1 left 3.3g, H, 7,, 23xN
*'3. Gua (C48829NO9 Toshite) Measured value C1 left 3. Left 7H, 7-, 2g x + 3
1Lt3[α)C3-2,30(C=i0MaOH
)R/0.32<! ;% MeOH-containing EtOAc) Example 3 To the activated molecular sheep, 37 grams of mercury cyanide (/, 2 darrnol), 41 grams of mercury bromide
'l g m? (/, 2 II rrrnol), compound (3), 507~(/, 211 rrrnol), and dichloroethane 5- were added, and under stirring with water cooling, compound (4
) /, 0 / OtsuV (Yazaotsu nyno l ) dissolved in dichloroethane/θ- is added dropwise under an argon atmosphere. After completion of the dropwise addition, the reaction solution was heated and stirred at θ0 for 27 hours. The reaction solution is filtered, and the filtrate is washed with NaHCO3 solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure (crude yield/7 lI/f).

The residue is purified by flash chromatography using 5ho2c-300CIθ1). Compound (5), 229■(/3.
g%), Compound (6) g6M? (7,4%), compound (7), 279 Tn9 (/k, g%) wo4
? ,=.

[Compound (5)] Elemental analysis Calculated value CA; 9. ,! ;2. H,1,39
,N,il1g (as C47H58NO15'2H20) Measured value C9ta9! '73. H, Mu/9. N, 13
4t[α'], +'13.3° (C=lθ/c+c/,
)R/C33(Toluene-ethyl acetate/:/) [Compound (
6)] Elemental analysis Calculated value C2 θ1s7rH, MU 0. N,
l! r/(as C47HssNO+ 5Cl-H2O) Measured value C2 θg51H1k3g, N, 14 [
αH3+Otsuθ0 (C=θ/3CHCIJ3)R/ 0.
/3C toluene-ethyl acetate /:/) [Compound (force)] Elemental analysis Calculated value C+A Hiroshi,,l+++mu/7.N,
C9ri (as C76H87No2.C7!!2) Measured value C2 Otsuhiro 07. Hrm/g, N, C99 [α] Otsu 3
+, l direct C = 10 cHclx,) R/ θg (toluene-acetic acid ethyl alcohol /:/) Example compound (5) / 07 W (0, / / 7 rr
mol) was dissolved in a mixed solvent of AcOH:H2O1I:/, and heated and stirred at SO0C for 2 hours. After the reaction is completed, the solvent is distilled off under reduced pressure, and the residue is purified by column chromatography. Compound (8) & 7ki (5, t, A%) was obtained using a mixed solvent of toluene-ethyl acetate/:2.

Elemental analysis Calculated value C2 Oko/2. H, L37. N,l
Left 3 (as C44H54NO4501-3AC7H8) Measured value C2 Otoko, 3! ;*H*'7. /A;,N,
13 Otsu [α connection” II da (c = θ left θ CHCl3) Rf
O, Shio 4t (Chloroform: Ethanol 10:/) Example 5 Compound (8) Ta7ki (0,013 mmol) was dissolved in methanol 1I, and N-NaOCH3 solution 0.
/ of the mixture and stirred at room temperature for 7 hours. After the reaction solution is neutralized with Amberlyst A-/& to remove the resin, it is concentrated under reduced pressure, and the residue is separated and purified by column chromatography.

5I02 /Q f 1 Rioroform: Ethanol (2
θ2/) gives compound (9), ? g q (73,7%
) and compound 00)q■ (/7.3%) were obtained.

[Compound (9)] Elemental analysis Calculated values C16/def, H, Mu7/, Nri
ri6 (as C42H53N 014/H20) Measured value C16/6/, H1'7. θ2. N, 177 [α] Otsu 4 + λ core (C = 0.mu CHCA'5) Fl/ o
, l/loc eyebrow loform: ethanol/θ:/) [Compound (10)) R/=a11. S-(chloroform:ethanol/θ:
/) Example 6 Compound (9134q(θ, θ41 j ryynol
) was added with AcOHjml and 10% pd-C3gIn
g and catalytic reduction at SO 0°C for 30 minutes. After the reaction
Remove d-C and dry under reduced pressure. Compound α1) 2'
1 mg (Ube) was obtained.

[Compound α9] Example 7 Compound GO) Dissolve 9.0~(θ, θ/ / mmol) in acetic acid, add 70% pd-CI3~ and go
Catalytic reduction was carried out at ℃ for 3θ minutes. Filter to remove pd-C, and dry the mother liquor under reduced pressure. Compound (121 Otsu, θ~ (depository)
was gotten.

[Compound (121) Example g Compound (7) 9 otsu, 9 my (0.06 g rrrn
ol>gO% AcOH solution 107! was added, and the mixture was heated and stirred at 30°C for 2 hours. After the reaction is completed, the solvent is distilled off and the product is purified by column chromatography. Toluene-ethyl acetate =/:
Compound a3) 7 O + + v (g O, 7
%) obtained 0 Elemental analysis Measurement value C1 Oko, 6 Otsu HH+mu/, 21N
, lθ0 (as C73H8, No21C12/H20) Measured value C1 Oko, 30 t H, Mu07. N, θ tag [α connection 4 + lIm ff (c = θ, 75.CHC ~) R
/ C32 (toluene-ethyl acetate =/:, 5-) Example De Compound Q31 7 A 17g", (0,0!; 5
mmol) in 1 Irnl of methanol. I
Add N-NaOCH30,/me to 77% at room temperature.
Stir for an hour. After neutralizing with Amberlis) A-/left, filter and concentrate under reduced pressure. The residue is purified by Silica/1/column chromatography. Compound I is 37 rn9 (!;
l/L, g%) was obtained.

Elemental analysis Calculated value C, Otsu 5gl Hl Otsu 7za, N,
l//(as C/19H81N019/YH20) Measured value C2 Otsusa Otsu7. H1 otsu j, 2. N, z4/4' [
α connection 1 + G, L, t (C-θ, Koza 5 cHcd3) R
f θ Otsu 0 (Chloroform: Ethanol 10: /
) Example 10 To the compound (14127 m? (0,022 mmol), add 5 m/l of acetic acid, add 27 m/l of 10% Pd-C, and add g
Contact was carried out for 3θ minutes at 0°C. The reaction solution was filtered and Pd-C
The mother liquor is dried under reduced pressure. Compound 05) is / '1.
g■ (quantitative) obtained.

R/ 0.113 (BuOH:EtOH:H2O2:
/ : / )Example// Compound (3) OtsulI left key (7, 1st side Ql) with pyridine/
Dissolve the mixture in a pot, add 673 cm of benzoyl chloride, and stir at room temperature overnight. After the reaction solution was concentrated under reduced pressure, ethyl acetate and H2O were added and shaken. After drying the ethyl acetate layer over magnesium sulfate, it was concentrated under reduced pressure, and the residue was purified with silica gel C-3θθ 7θ? Purify using. Compound σ61'7/9 (73,!;%) was obtained using a toluene-ethyl acetate/:/ mixed solvent.

Needle tool mpgO~g-〇Elemental analysis Calculated value C1 Otsu 7011, H, Mu Akebono'
r N+ -2, -22 (03□H57NO71・H2
O) Measured value C1 Oi27, H, Mu Otsu6. N
, 2. AOcα)P' -119,110(C==i
00, cHc6a)R/θl,,/(EtOA
c) Example/, 2 Compound f3) 'f' 0 "9 (0,/ mmol
) was dissolved in pyridine/, θ, N,N-dimethylaminopyridine/2rmi and benzoyl chloride 5
6) and stirred at room temperature overnight. The reaction solution was concentrated under reduced pressure, the residue was dissolved in ethyl acetate, and saturated deuterated water,
Wash with saturated saline. After drying over anhydrous magnesium sulfate, it was concentrated under reduced pressure, and the residue was purified with silica gel C-30010t.
Purify using. Compound tn) 3s~ is obtained using a mixed solvent of toluene-ethyl acetate/:/ (37.7%)
.

Elemental analysis! f calculation value C, A2. gll, H, mu/(7
, N, code (as 052H57No11) Measured value C1 Otsu 2.93. H, Mu/3. N,,2.15
[α]♂''+'72° (C-θSdaCHCl3) Example/3 Compound (2) 3OJTng (/, θrrmol) was dissolved in DMF-CH5CN (/:/), tml, and para-toluenesulfone was added. Add acid/hydrate 2θ~ and benzaldehyde dimethyl acetal/67μ and stir at room temperature for g hours. Add triethylamine θ,/- to the reaction solution and concentrate under reduced pressure. Add silica/l/C-3θθ lθ to the residue.
Purify using 9. Elution with ethyl acetate containing 3% methanol yields compound θ(he)236■ (2.3% on the left).

R/ C3 Hiro (ethyl acetate containing 5% methanol) Example/q Compound α8) g! ; m? (θ, / g g m
Dissolve mol) in 0:3 pyridine, add 79rrv of benzoyl chloride, and stir at room temperature overnight. Dissolve the reaction solution in ethyl acetate and wash with water. After drying over anhydrous magnesium sulfate, it was concentrated under reduced pressure, and the residue was purified using a silica/r' column. Compound α97/fflF
(5g, 4%) was observed.

Example/5 BaQ, 2.621 and Ba(OH)2・gH207
11.9 mv in 5 ml of DMF! Dissolve compound (3) in
20/rvy (0.0 jmmol), benzyl bromide/g 3 f were added and stirred overnight. Add 10θml of chloroform to the reaction solution and wash with water. The chloroform layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is dissolved in ether and extracted with NaHCO3 solution. The NaHCO3 layer is slightly acidified with dilute HCl solution and extracted with chloroform. Wash with saturated saline. Dry over anhydrous magnesium sulfate and concentrate under reduced pressure. Compound (company)/
911trng is obtained. Add this to 3 methanol
mlV and add an ethereal solution of diazomethane. The reaction solution was concentrated under reduced pressure, and the residue was transferred to a silica gel column C-
Purify using 300/θt. Compound (21)/7 with toluene-ethyl acetate =/:/ mixed solvent ↓
Furu (40.3%).

mp /37-9゜ [α酩6-/θke0 (C=12yu c) lc6g) Elemental analysis Calculated value C2 otori gk, H, 7, θ&, N,, 2
0 (as C32H, 1No9) World 11 constant value C1 Otori Otugu, H, 7, 0g 2 countries, λ Shiogu Rf O, 11, :l (Toluene-ethyl acetate/:/)
The aqueous layer is neutralized with dilute HC4 to make it slightly acidic and extracted with chloroform/50ml. After sweating with saturated saline solution, dry with anhydrous magnesium sulfate. Concentrate under reduced pressure, and the residue [Compound (22+1) is dissolved in 5 portions of methanol, and an ethereal solution of diazomethane is added. The reaction solution is concentrated under reduced pressure, and the residue is purified using a silica gel column C-300/θV.Toluene- A compound (23i 3 !r~ is obtained from ethyl acetate=/:/mixed solvent (/ll-%).

mp /, 2 goo 6゜[α]δ6/lAg'CHc#6c =0.7 g Elemental analysis Calculated value C2 θg gr Hr 7/shio, N,
2g (as C25835NO9) Measured value C,61O/, H,7/Gl N 12g4t
R/ 0.33<Toluene-ethyl acetate/:/) Showa
Year, month, day 1, case display 11i, i Japanese 59 year patent application No. 449t
No. 15 No. 2 Name of the invention Alkaline acid derivatives and their manufacturing method 3 Relationship with the case of person who tampered with the issue Name of person (67!) RIKEN Kanto Ishiba Pharmaceutical Co., Ltd. 4 Representative (1 Hoseki) History 7)

Claims (1)

[Claims] (1) A sialic acid derivative represented by the following general formula 1. In the formula, R4 represents a hydrogen atom or a methyl group, R2 represents an allyl group or an n-globyl group, and R and R4 each independently represent a hydrogen atom, a D-glucobylanosyl group, 2
．． 3. 'l-tri-O-benzy-D-glucopyranosyl a, 2.3. ? -tri-0-benzy-6-0-monochloroacetyl-D-glucopyranosyl group, benzoyl group or benzyl group, R5 and R6 each represent a hydrogen atom or jointly represent an inpropylidene group or benzylidene group, Ac indicates an acetyl group. T2) R is a methyl group, R2 is an allyl group, R3, R4
The sialic acid derivative according to claim 7, wherein tR and R6 are hydrogen atoms. (The sialic acid derivative according to claim 1, wherein R1 is a methyl group, R2 is an allyl group, R3 and R4 are hydrogen atoms, and R5 and R6 are jointly an isopropylidene group. (4) R is methyl group, R2 is an allyl group, R3 is λ; 3,4t-tri-benzyl-)monochloroacetyl-D-glucopyranosyl;, R4 is a hydrogen atom, R
The sialic acid derivative according to claim 1, wherein R6 and R6 together represent an isopropylidene group. (5) R is a methyl group, R2 is an allyl group, R3 is a hydrogen atom, and R4 is 2.3. 2. The sialic acid derivative according to claim 1, wherein the ll-tri-benzyl-o-monochloroacetyl-o-glucopyranosyl group, R5 and R6 are jointly an inpropylidene group. (6) R4 is a methyl group, R2 is an allyl group, R6 and R4 are each 2, 3. The sialic acid derivative according to claim 1, wherein the 'l-tri-benzyl-6-o-monochloroacetyl-α-D-glucopyranosyl group, R5 and R6 are jointly an isopropylidene group. (7) R1 is a methyl group, R2 is an allyl group, R3 is 2゜3, 'I-tri〇-benzyl-〇-monochloroacetyl-〇-glucopyranosyl group, R4゜R and R
The sialic acid derivative according to claim 1, wherein 6 is a hydrogen atom. (8) R is a methyl group, R2 is an allyl group, and R5 is a
, 'l-tri-O-benzyl-α-D-glucopyranosyl group, and % R4' R5 and R6 are hydrogen atoms, the sialic acid derivative according to claim 1. (91R, is a methyl group, R2 is an allyl group, R3 is a co. The sialic acid derivative according to item 1. α[1] R4 is a methyl group, R2 is an n-propyl group, R3
are α-D-glucopyranosyl groups, R4, R5 and R6
sial according to claim 1, wherein is a hydrogen atom.
Acid derivatives. +it+ R4 is a methyl group, R2 is n-propylidene,
The sialic acid derivative according to claim 1, wherein R3 is a β-0-glucopyranosyl group, and R4+ R5 and R6 are hydrogen atoms. 02R4 is a methyl group, R2 is an allyl group, R3 and R4
are respectively 2,3,4'-)di-0-benzyl-6-
The sialic acid derivative according to claim 1, wherein 0-monochloroacetyl-α-D-glucopyranosyl, R and R6 are hydrogen atoms. (131R1 is a methyl group, R2 is an allyl group, R3 and R4 are each a co, ?, 1I-) Lee O-benzyl-α-D-glucopyranosyl group, and R5 and R6 are hydrogen atoms Claim 1 Sialic acid derivatives described in Section. R41R, is a methyl group, R2 is an n-propyl group, R3 and R4 are α-D-glucopyranosyl groups, R
The sialic acid derivative according to claim 1, wherein 5 and R6 are hydrogen atoms. α5) The sialic acid derivative according to claim 1, wherein R is a methyl group, R2 is an allyl group, [(6 is a benzoyl group, R is a hydrogen atom, and R5 and R6 are jointly an isopropylidene group). (+6) The sialic acid derivative according to claim 1, wherein R is a methyl group, R2 is an allyl group, R3 and R are a benzoyl group, and R5 and R6 are jointly an isopropylidene group. 0η R1 is methyl The group %R2 is an allyl group, R3 and R
4. The sialic acid derivative according to claim 1, wherein 4 is a hydrogen atom, and R5 and R6 jointly represent a benzylidene group. (181R is a methyl group, R2 is an allyl group, R3 and R
The sialic acid derivative according to claim 1, wherein is a benzoyl group, and R5 and R6 are jointly a benzylidene group. α! 1R5 is a hydrogen atom, R2 is an allyl group, R3 and R
4. The sialic acid derivative according to claim 1, wherein 4 is a benzyl group, and R5 and R6 are jointly an inpropylidene group. (2υ The sialic acid derivative according to claim 1, wherein R1 is a methyl group, R2 is an allyl group, R3 and R4 are a benzyl group, and R5 and R6 are jointly an inzolobylidene group. (21) R is hydrogen The sialic acid derivative according to claim 1, wherein R2 is an allyl group, R6 is a benzyl group, R4 is a hydrogen atom, and R5 and R6 are jointly an inpropylidene group. (23R is a methyl group, The sialic acid derivative according to claim 1, wherein R2 is an allyl group, R3 is a benzyl group, R4 is a hydrogen atom, and R5 and R6 are jointly an inpropylidene group. (c) Formula (1): In the formula, AC represents an acetyl group) Compound (1) represented by the following is deacetylated to obtain the formula (2):
A method for producing a sialic acid derivative represented by the formula (3), which comprises obtaining a compound (2) represented by the formula and reacting the compound with 2,2-dimethoxyptetrapane. A compound represented by the formula (3): (wherein, Ac represents an acetyl group) and a compound represented by the formula (4): (wherein, X is a halogen atom, and Bn is a benzyl group)
A represents a monochloroacetyl group)
4) and, if necessary, reducing or eliminating the protective group, a method for producing a sialic acid derivative represented by the following general formula. In the formula, R4 is a methyl group, R2 is an allyl group or n-propyl group, R3 and R4 are each independently a hydrogen atom,
D-glucopyranosyl group, 223, 'I-tree〇-
Benzyl-D-glucopyranofur group, or co, 3. Gootry〇-benzyl-9-0-monochloroacetyl-
represents a D-glucopyranosyl group, where R3 and R4
does not represent a dihydrogen atom, and R5 and R
6 each represents a hydrogen atom, or together represent an inzolobylidene group.