JPH0273093A - 3-deoxy-d-glycero-d-galacto-2-nonulopyranosonic acid derivative - Google Patents

Abstract

NEW MATERIAL:A compound expressed by formula I (R<1> is H or acetyl; R<2> is 1-6C alkoxy, cholestenyl, cholestanyl or halogen; R<3> is H, 1-6C alkyl, aryl, aralkyl, alkali metal or NH<+>4). USE:The compound expressed by formula I has nerve activation action, immune reguating action, antiphlogistic action, etc. PREPARATION:N-Acetyl-D-neuramic acid is subjected to methanol treatment and then acetic anhydride-pyridine treatment to give a compound expressed by formula II, which is then reacted with dinitrogen tetraoxide in the presence of sodium acetate in acetic acid and further refluxed in carbon tetrachloride while heating to afford a compound expressed by formula III. The compound expressed by formula III is further subjected to K2CO3-methanol treatment and then 0.1N-NaOH treatment and heated in an aqueous solution of CF3OOH and subjected to demethylation to provide the aimed compound.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to novel 3-deoxy-D-glycero-D-galacto-2-nonuroviranosonic acid derivatives.

[Background of the invention]

N-acetyl-D-neuraminic acid is widely distributed in deglycosylated proteins and glycolipids. And N-acetyl-
Synthesis examples of 2-0-glycodyl and 2-N-substituted derivatives of D-neuraminic acid and cholesterol glycoside have been reported (Chew, Pharm, Bull
, 35 (10) 4043-4048 (1987)
). Furthermore, it has been reported that sialosylcholesterol is useful as a therapeutic agent for neurological disorders [JP-A-62-265229].

Therefore, an object of the present invention is to provide a novel derivative of nonulopyranosonic acid that is expected to have nerve activation, immunomodulation, anti-inflammatory effects, and the like.

[Disclosure of the invention]

The present invention provides 3-deoxy-D-
This invention relates to glycero-D-galacto-2 nonulopyranosonic acid derivatives.

Examples include chlorine and bromine, examples of the alkyl group of Ct ``'' Cb include methyl, ethyl, propyl, butyl, pentyl, and hexyl, and examples of the aralkyl group include m = 0 to 3).

Specific examples of the compounds of the present invention are shown below.

(In the formula, R1 represents hydrogen or an acetyl group, and R2 is C1
~Ch represents an alkoxy group, cholestenyl group, cholestanyl group, or halogen; R3 represents hydrogen, a CI-Cb alkyl group, an aryol group, an aralkyl group, an alkali metal, or NHa"c) The present invention will be described below. .

In the general formula representing the compound of the present invention, examples of the alkoxy group of CI''Cb include methoxy, ethoxy, propoxy, etc., and examples of the halogen include the method for producing the compound of the present invention according to the scheme.

Jin Kaiyeon↓ (Schemes 1-1 to l-3) From N-acetyl-D-neuraminic acid (2) to compound (3
), (4), (5) and (7) can be synthesized sequentially.

N-acetyl-D-neuraminic acid (2) is commercially available and is methyl esterified by a known method [for example, treated with methanol in the presence of DOWEX-50 (H''), then methyl esterified with A
Compound (3) can be obtained by a method of hexaacetylation by treatment with ctOPy (acetic anhydride-pyridine).

When compound (3) is reacted with dinitrogen tetroxide in acetic acid in the presence of sodium acetate, a yellow N-acetyl-N-nitrosoneuraminic acid derivative (4) is obtained. Further, when compound (4) is heated and refluxed in carbon tetrachloride, the yellow color disappears and compound (5) and by-product (6) are obtained. Compound(
7) can be obtained by deprotecting compound (5) by K z CO3-methanol treatment. In addition, compound (7) was further treated with 0.1N NaOH and CF
Compound (1) can be obtained by demethylation by heating in a 3COOH aqueous solution.

Alternatively, compound (7) was treated with IN NaOH and then C! Benzyl ester (14) can be obtained by treatment with 3zCO3, BnBr (benzyl bromide).

Scheme p 115-118°C wp 59-61°C Synthesis method 2 (Schemes 2-1 to 2-2) D-mannose to 3-deoxy-D-glycero-D-
Compounds (8), (9), (10), (11), (12), via galacto-2-nonuroviranosonic acid (1),
(13), (15), (16), (17) and (1
8) can be synthesized.

Compound (1) is a type of chum salmon (
) Ion-exchange chromatography (Dowex-1 (formate ester),
It can also be obtained using 2M formic acid elution). Also, D-
Compound (1) can be synthesized from mannose by aldol condensation of oxaloacetic acid and D-mannose in an aqueous solution under basic conditions (sodium carbonate and sodium hydroxide, ρB11), followed by decarboxylation.

Compound (1) is, for example, treated with methanol in the presence of DOWEX-50 (H'') to give methyl ester (8), and then (8) is further treated with AC!0-PV to give hexaacetylated compound (9). can be obtained.

Compound (1) can be converted into compound (10) by treating with AczO-Py, and then reacting the product with Cs, CO, and then with BnBr. Compound(
1O) is brominated with TiBr, to form the compound (1
1).

Methyl ester (12) can be obtained by treating compound (11) with methanol in the presence of AgzCOi.

Methyl ester (12) is subjected to Ac removal treatment (e.g. 0.01
(NNaOH treatment), compound (13) can be obtained.

Also, compound (11) is A g OS O! Compound (15) by reacting with cholesterol in the presence of CF
(α-isomer) and (16) (β-isomer) can be obtained, and compounds (15) and (16) can be deprotected (for example, INNaO
H treatment), compound (17) (α form) and (
1B) (β form) is obtained.

〔Usefulness〕

The novel 3-deoxy-D-glycero-D-galacto-2-nonulopyranosonic acid derivatives of the present invention have neurostimulatory effects,
It is expected to have immunomodulatory effects, anti-inflammatory effects, etc.
It is expected to be used as a variety of medicines.

〔Example〕

The present invention will be further explained below with reference to Examples.

Reference Example 1 (D-Mannose-(1)) 27.03 g (150 mmol) of D-mannose and 6.36 g (60 mmol) of anhydrous sodium carbonate were mixed with 3211 g of water.
1 and 6.61 g of oxaloacetic acid (50 mm
ol) was added little by little. The reaction solution was then adjusted to pH 11 using 10M sodium hydroxide solution and stirred at room temperature for 2 hours. After the reaction, Dowex-50 (H" type) was added to adjust the reaction solution to pH 1-2, and stirring was continued at room temperature. After 30 minutes, stirring was stopped and Dowex-50 was removed by filtration, and the filtrate was diluted with aqueous ammonia. Neutralize using Dow
It was subjected to ion exchange chromatography using ex-1 (formic acid type) and eluted with a 0.3M aqueous formic acid solution. After distilling off the solvent under slight pressure, the eluate was neutralized and dissolved using aqueous ammonia, and the solvent was distilled off again under slight pressure to obtain a colorless oil.

Yield: 5.6 g Yield: 39% Example 1 ((1)-(10)) In a mixed solution of 54 ml of pyridine and 54 all of acetic anhydride, 3.9 g (13.7 mmol) of compound (1) and N,
67 mg of N-dimethylaminopyridine was added and stirred at room temperature. After 24 hours, stop stirring and add 390 ml of chloroform.
ml, cooled to 5°C, and diluted with 140 tan of IN hydrochloric acid.
Washed twice. The organic layer was dried over anhydrous magnesium sulfate;
The solvent was distilled off under slight pressure. Next, the residue was treated with 5 mj of N,N-dimethylformamide. 1.53 g (4.7 mmol) of cesium carbonate was added thereto and stirred. When foaming stopped, the solvent was distilled off under slight pressure. The residue was dissolved in 20 ral of N,N-dimethylformamide, and 1.9 g (1.1 mmol) of benzyl bromide was added thereto.
was added and stirred at room temperature. After 2 hours, add 100% water to the reaction solution.
The mixture was extracted with 30 ml of ethyl acetate three times, and the organic layers were combined and washed with an aqueous sodium bicarbonate solution and brine. The organic layer was dried using anhydrous magnesium sulfate, and after distilling off the solvent under slight pressure, it was subjected to column chromatography using silica gel as an adsorbent to obtain the desired product as a colorless oil.

Yield 4.05g Yield 47% "αJ 25-17.4° (cm1.C)IC1i)
.

Mass spectrometry (El) mm 550 (M''-59).

Elemental analysis (Cz.H3401S): C; 55.
08. H; 5.61° Measured value: C; 55.29
．． H; 5.78゜IRI/to Br cva-' 2
960.1745゜'HNMR(300M)lz, C
DCJa) 1.99.2.01.2.02゜2.02
．． 2.09.2.11 (18H, 5x6), 2.0
8 (IH, dd.

J = 13.5 and 11.4 Hz, 3-Hax),
2.62 (IH, dd.

J=13.5 and 5.2 Hz, 3-Heq), 4
．． 15 (IH, dd.

J=12.5 and 5.9 Hz, 9-H), 4.1
9 (18, dd.

J=10.2 and 2.2 Hz, 6-H), 4.4
0 (18, dd.

J=12.5 and 2.6 Hz, 9'-H), 4
．． 96 (IH, t.

J=10.2 and 9.8 Hz, 5-H), 5.1
6 (IH, m, 8-H), 5.15.5.23
(2H, dx2. J=r2.OHz, CHtPh)
.

5.26 (1)1. m, 4-H), 5.39
(1B, dd, J=6.1 and 2.2 Hz, 7
H), 7.35 (5H,m, aromatic H).

Example 2 ((10)-(11)) 2.0 g (3.3 mmol) of compound (10) was added to 103 ml of anhydrous dichloromethane. 8, 2.0 g of Molecular Sieves 4A was added thereto, and the mixture was stirred at room temperature.

- hours later, it was cooled to 5°C and 4.85g of titanium bromide was added.
(13 mmol) was added and stirred at room temperature for 16 hours.

After the reaction, 8.9 g of anhydrous sodium acetate and 5711 l of acetonitrile were added and stirred at room temperature for 30 minutes to decompose excess titanium bromide. Further, 268 all of toluene was added and stirred while cooling in ice water. After stirring for 30 minutes, insoluble matter was removed by filtration, and the solvent was distilled off from the filtrate under slight pressure to obtain the desired product as a colorless oil.

Yield 2.07 g Yield 100% rα”25 5
9.0” (cm0.6. CHCl!ri.

Mass spectrometry (El) +a Muro 31.633 (M”)
.

IRν to Br cm-' 34B0. 2970.
1750°'H-NMR (300MHz, CDCj
! 3) 2.02.2.05゜2.06.2.08.
2.09 C3Hx5. sx5. C0CH1),
2.23<IN.

dd, J=14.2 and 11.2 tlz, 3-8
ax), 2.99 (IH.

dd, J=14.2 and 5.0 Hz, 3-11e
q), 4.12 (LH.

dd, J=12.8 and 4.9 Hz, 9-H),
4.36 (IH, dd.

J=12.8 and 2.4 Hz, 9'-H), 4
．． 44 (IH, dd.

J=10.4 and 2.1 Hz, 6-H), 4.9
9 (IH, t, J=10.0 Hz, 5 H
), 5.23 (IH, m, 8 H),
5.26°5.38 (2H, dx2. J=1
2.0 Hz, CHzPh), 5.50 (
IH.

m, 4-)1), 5.51 (IH, dd, J=
8.4 and 2.1 Hz.

? -H), 7.40 (5H, m, aromatic 11).

Example 3 ((11) → (12)) Compound (II) 1.03g (1
, 63 mmol) and molecular sieves 4A1.03
g and 903 mg of silver carbonate were added thereto, and the mixture was stirred at room temperature for 30 minutes.

After the reaction, the insoluble matter was removed by filtration, and the filtrate was distilled off under slight pressure to remove the solvent, followed by column chromatography using silica gel as an adsorbent to obtain the desired product as a colorless oil.

Yield 712 mg Yield 75% [αJ 25-24.0° (cm1. C11(1,)
.

Mass spectrometry (El) m/z 582 (M”).

Elemental analysis (CzJ340+4): C; 55.6
7, )l; 5.8B.

Actual value: C; 55.90. H, 5, 93°IR
vKBr cm-' 2980, 2950, 1750
゜'HNMR (300MHz, CDCj!s)
1.89. (1)1. t, J=12.5
Hz, 3=Hax), 1.99. 1.99.
2.02. 2.09゜2.16 (15H, sx
5. C0Cth), 2.70 (1)1.
dd, J=12.7 and 4.2 Hz, 3-1
1eq), 3.23 (3H,s, CHz).

4.12 (IH, dd, J=12.5 and 4.6
Hz, 9-H).

4.18 (IH, dd, J=10.0 and 2.2
Hz, 6-H).

4.26 (IH, dd, J=12.5 and 2.4
tlz, 9′-H).

4.86 (IH, t, J=9.511z,
5-tl), 4.89 (III, m.

4-H), 5.20. 5.25 (211,d
x2. J = 12.0 Hz.

CHgPh), 5.34 (LH, dd, J=9.
1 and 2.2 Hz.

7-H), 5.42 (IH, m, 8-H)
.

Example 4 ((12)-(13)) 300 mg of compound (12) (0,
515 mmol) was dissolved therein, 15 mj2 of a 0.01N aqueous sodium hydroxide solution was added thereto, and the mixture was stirred at room temperature for 2 hours. After the reaction, 30 ml of water was added and Dowex-50 (
Dowex-50 was removed by filtration. After distilling off the solvent under slight pressure, the filtrate was recrystallized to obtain the desired product as colorless needle-like crystals.

Yield 11it130mg Yield 67%mp97-99
℃.

[αJ 27-38.4° (cm0.17. MeOH
).

Mass spectrometry (El) rn/z 341 (M” 31
).

Elemental analysis (C+JzaOq・LO): C; 52.
30. H; 6.7L Actual value: C; 52.42.
) 1.6.49°IR1 (Br cm-' 3510.
3330.2950.2900°1720°' H-NMR data are shown in Table 1.

Example 5 ((7)-(14)) 55 mg of compound (7) was dissolved in IN aqueous sodium hydroxide solution and stirred at room temperature for 2 hours. Next, Dowex-50 (
After neutralizing the reaction solution using a diluted solution (H" type) and filtering, the solvent was distilled off under slight pressure. The residue was dissolved in 5 ml of N,N-dimethylformamide, and 57 mg of benzyl bromide was added thereto, and the mixture was stirred at room temperature. Stirred for 2 hours.

After the reaction, insoluble matter was removed by filtration, the solvent was distilled off from the filtrate under slight pressure, and the residue was subjected to column chromatography using silica gel as an adsorbent to obtain the desired product as a colorless oil.

Yield: 40 mg Yield: 58% "αJ 26-37.9" (cm0.33.Me
O)I).

Mass spectrometry (El) m/z 340 (M” 32)
Elemental analysis (C+, HzaOq・HzO): C: 5
2.30. H; 6,71°Actual measurement: C; 52
．． 71. H; 6.58゜IRvKBr cm-'
3300.2925.1725°' H-NMR data are shown in Table 1.

Example 6 ((11)-(15), (16)) 770 tags of cholesterol in 30 ml of dichloromethane (2
mmol) in which hemolecular sieves 4
770 mg of A was added and stirred at room temperature for 1 hour. Next, 1.5 g (2.4 mmol) of compound (11) was added into this.
) and 0.51 g of silver trifluoromethanesulfonate were added, and the mixture was stirred for one day at room temperature while shielded from light. After the reaction, insoluble materials were removed by filtration, the solvent was distilled off from the filtrate under slight pressure, and the residue was subjected to chromatography using silica gel as an adsorbent to obtain the desired product as a colorless oil.

By-product 490mg By-product 43% α form (1
5): r αJ 25-37.4° (cm1.C
HCj! :l).

Mass spectrometry (El) mm859 (M”80), elemental analysis (CsJtaO+4): C; 67.78.H;
8.37. Actual value: C; 67.82. H; 8
．． 28゜IRvKBr cm-' 2940.174
5. 'H-NMR data is shown in Table 2.

β body (16): rαJ 25 35.6” (c
m1. CHCl3).

Mass spectrometry (El) m/z 937 (M”) Elemental analysis (CsJ, aO□): c; 67.78. H;
8.37° Actual measurement: C; 67.67, H; 8.
17°IRvKBr cm-” 1940.1750.
'H-NMR data is shown in Table 2.

Compound -Wax -Heq -H -H -H -H -H -H -H CR3 nzph Aromatic H Table 1 1.59 2.49 3.75 3.37 3.71 3.61 3.69-3. 73 3.53 3.70 3.71 5.22 7.29-7.39 'H=NMR (DZO) t, J=12.0Hz dd, J=12.4. 4.0Hz ■ t, J=9.5Hz ■ bro-d, J=10.0)1z sodd, J=12.0.4.9Hz Steel nd 1.61 2.23 3.85 3.45 3 .75 3.69 3.75 3.58 3.74 3.10 5.18.5.25 7.32-7.39 MHz, δPPM) IH, t, J=12.1Hz IH, dd, J= 13.0.5.0HzLH,dd
d, J=11.4. 9.5. 5.0Hz1B,
t, J=9.5Hz IH, dd, J=9.5. 1.0Hz1B, dd
, J=10.0. 1.0Hz1B, m LH, dd, J=12.0.5.4Hz18,
m 3H,5 IHX2. dX2 50, ra Compound KDN group 3-8ax 1.90 3-Heq 2.72 4-8 4.89 5-H4,84 6-H4,13 ? -85,31 8-H5,35 9-H4,1B 9-H4,30 (COCH3) s 1.98 1.99 2.01 2.09 2.14 CHzPh 5.17.5.24 Aromatic 8 7 .30-7.40 Cholesterol group 3-H3,46-3,57 18-CH0,65 19-CH0,95 Table 1 'NMR (CDCj!3) (300?IHz,
δPPM)dd, J=13.0. 11.6Hzdd
, J=13.0.4.5Hz ddd, J-11,6,9,5,4,5Hzt, J
=10.0Hz dd, J=10.0. 1.9Hz dd, J=8.0.1.9Hz ddd, J=8.0.4.6.2.2Hzdd, J
=12.5.4.6) 12 dd, J=12.5.2.2Hz 3uxs, 5X5 1) IX2. dX2. J=12.0Hz5H, r
a 18, ra IH,s lH+ s 1.79 2.59 5.30 4.86 4.24 4.21 1.79 1.98 1.99 2.09 5.15. 5.26 7.30-7.40 dd, J=13.0. 11.6Hzdd, J=1
3.0.5.2Hz ddd, J=11.6.9.5.5.2Hzt,
J=lO,0Hz dd, J=10.0.2.2Hz dd, J=3.5.2.2Hz ddd, J=7.4.3.5.2. IHzdd, J
=12.5.7.4Hz dd, J=12.5.2.1Hz 3HX5,5X5 1HX2. dX2. J=12.1Hz5H, cm 3.46-3.58 18. m O,663B, s O,963H,s Example? ((15), (16) → (17), (18)
) Compounds (15), (16) in 10 val of methanol
50 mg was dissolved, 10 ml of IN aqueous sodium hydroxide solution was added thereto, and the mixture was stirred at room temperature for 3 hours. After the reaction, add 1 portion of water
The mixture was neutralized using [)owex-50 (H'' type), filtered to remove Dowex-50, and the filtrate was lyophilized to obtain the desired product as a white powder.

α body (17): rcxJ27-36.7° (cm0
．． 42. MeOH).

Mass spectrometry (FD) m/z 859 (M”).

Elemental analysis (CsJ6+0Ja): C; 65.53.
H; 9.16° Actual measurement: C; 65.42. H
;9.21゜IRνKBr c+w-' 340.0
．． 2940. 1?20゜'H-NMR (300Mn
2. CDzOD) 0.70-2.45 (4
5H, m.

Cholesterol) 2.62 (1)1. dd,
J=12.7.4.2Hz, 3 Heq) 3.45-3.90 (7H, ta, 4-5 6
7-8 9-9' -H) β form (1B): raJ
25-36.7° (c = 0.42.MeOH)
.

Mass spectrometry (FD) ts/z 659 (M”).

Elemental analysis (Cz, l+, 01Na): C; 65.
53. H; 9.16°Actual measurement: C; 65.0
5. H; 9.38゜IRνKBr cm-' 3
400.2940.1720゜'H-NMR (300M
n2. CD30D) 0.70 2.30 (
45H.

steel, cholesterol) 2.37 (IH, dd,
J=12.9°4.8 Hz, 3-11eq) 3.40-3.95 (7H, m, 4-5-6-
7-8-9-9'-II) Example 2 Add ION NaOH to ice water (30 mj!) and adjust the pH.
The pH was adjusted to 10.0 (pH meter), and oxaloacetic acid (5.0 g) and ION NaOH were added under water cooling while stirring well.
Add H10 little by little, then add D-mannose (20.5g) and dilute with 1ON NaOH.
The mixture was adjusted to H11.0 and stirred at room temperature for 2 hours. Dowex
After adjusting the PL to +6.0 using 50W-X8 (H), add (0.05g) as anhydrous nickel chloride,
The mixture was heated and stirred at 0 to 60°C for 1 hour. The pH of the solution is
The pH was maintained at 6.0 by appropriately adding ex 50 W -X 8 (H"). The resin was filtered off, concentrated by freeze-drying, and Dowex 1-X 8 (H")
The product was purified using a column of Z-), sequentially eluted with water and 0.2N HCO□H, and lyophilized to obtain Compound (1) in the form of a colorless foam. Yield: 7.04 g, yield: 69%. 300MH2'H-NMR of the ammonium salt of 1 revealed that 1 was a mixture of 3-deoxy-D-glycero-β-ri-tallow and 2-neuraminic acid (20) at a ratio of about 4.3:1.

300MH2'HNMR (DzO) (1) ・NH, δ: 1.65 (18, dd, J=1
1.5Hz, 13.0Hz) 2.05 (18, dd,
J=5.0Hz, 13.0Hz) (20) ・NH,
δ: 1.91 (IH, dd, J=3.0Hz, 15.
0Hz)2,01 (18,dd, J=3.OH2,
15,0H2) Example 8 ((10)-(11)) Add 1Il11 of acetyl chloride to 30mj of (1 substance) glacial acetic acid,
Hydrogen chloride gas was blown into the water-cooled solution for 30 minutes. Furthermore, compound (10) 3 g (4,91 mm
o 1 ) was added and stirred at room temperature for 6 hours. After the reaction, the solvent was distilled off under slight pressure, and the residue was purified by silica gel column chromatography to obtain the desired product.

Yield 2.7 g Yield 94% Mass spectrometry m/z 386.388 (M IR spectrum 2950, 1?40.1430.1365 cm-''
HNMR (300M) lz, CDCI ri 2.002
．． 0? (3HX5. sX5+ C0CHs)2.
24 (IH, dd, J=14.0. 11.3 H
z, 3-Hax) 2.84 (IH, dd, J-1
4,0,5,0Hz, 3-Heq)4.10 (IH
, dd, J=12.5.5.0 Hz, 9-H)4
．． 34 (18, dd, J=12.5.2.5 Hz
, 9'-II) 4.48 (IH, dd, J=1
0.5.2.3 Hz, 6-H)4.95 (IH,
t, J=10.0 Hz, 5-H)5.22 (I
H, m, 8-)1) 5.22 5.34 (IHx2.sX2.CHz
Ph) 5.44 (III, m, 4-H) 5.4
7 (IH, dd, J=8.0.2.3 Hz, 7
-H) 7.30 7.40 (5H, cm, aromatic H) Reference example 3 ((2) → (3)) Compound (2) (N-acetyl-
25 g (84 mmol) of D-neuraminic acid] and D
Add 50g of ohex-50 (H" type) and heat at 80℃ for 1
The mixture was heated under reflux for 0 hours. Next, Dowex-50 was removed by filtration, and the solvent was distilled off under slight pressure. The residue is pyridine 100
mj! 22II11 of acetic anhydride and 183 mg of dimethylaminopyridine were added thereto, and the mixture was stirred at room temperature for 7 days. After the reaction, 50I111 of methanol was added and the solvent was distilled off under slight pressure. The residue was subjected to column chromatography using silica gel as an adsorbent to obtain the desired product (3).

Yield 8.17 g Yield 19% Example 9 ((3) → (4)) 3.3 g (6.5 mm
ol) and 5.64 g of sodium acetate were added thereto and cooled with water, and 2.1 tal of dinitrogen tetroxide dissolved in acetic acid (2 mJ!) was added thereto and stirred at room temperature for 2 hours. After the reaction, excess dinitrogen tetroxide was decomposed by adding ice water, and then powdered sodium hydrogen carbonate was added to neutralize it.

The aqueous layer was extracted three times with 100 t*l of dichloromethane,
The organic layers were combined, washed with brine, dried over anhydrous magnesium sulfate, filtered, and the solvent was distilled off. The residue was subjected to column chromatography using silica gel as an adsorbent to obtain the desired product (4) as yellow needles.

Yield 3.24 g Yield 93% Melting point 77-80°C (decomposition) Mass spectrometry m/z 534 (M=) Elemental analysis calculation C: 47.19 H: 5.66 N:
5.24 Measured value C: 47.20 H: 5.6
1 N: 5.00'HNMR (400MHz, C
DCj! s) 1,80 2.06 (3tl x5.
s x5. C0C) Is) 1.78 (IH, dd
, J=13.0.11.4 Hz, 3-Hax)2
．． 49 (1)1. dd, J=13.0.5.3
)1z, 3-)leq)4.05 (18,dd,
J=12.5.6.6 Hz, 9-)1)4.59
(if(, dd, J=12.5.2.51(z, 9
'-H)4.74 (IH,t, J=10.0H
z, 5-)1)4.91 (1)1. dd, J=
5.8.2.0 Hz, ? -H) 4.96 (LH,
dd, J=10.0.2.0 Hz, 6-H)5.
20 (ltl, m, 8-H)5.59 (LH
, m, 4-t () Example 10 ((4) → (5)) 3.14 g of compound (4) was added to 125 ml of carbon tetrachloride (
5.9 mmol) was dissolved and heated under reflux at 80° C. for 2 hours. After the reaction, the solvent was distilled off and the residue was subjected to column chromatography using silica gel as an adsorbent to obtain the desired product (5) as colorless needle crystals.

Yield 0.506g Yield 17% Melting point 115-118°C IT analysis m/z 507 (M”+ 1) Elemental analysis calculated value C: 49.80 H: 5.97 measured value
C: 49.90 H: 6.05'HNMR (30
0MHz, CDC1s>1.83 (1M, dd,
J=13.0.11.4 Hz, 3-)tax)1
．． 97-2.12 (3Hx5. SX5.-CD0C
R3) 2.51 (IH, dd, J=13.0.5.
3 Hz, 3-)1eq)3,25 (3H,s,
DC)! 3>3,80 (3H,s, CD0CR
3) 4.05 (IH, dd, J=IO, 0, 2,
2Hz, 6-1)4.14 (1)1. dd,
J=12.5.6.8 Hz, 9-II) 4.7
0 (1)1. dd, J=12.5. 2.
211z, 9'-H)4.88 (IH,t,
J=10.0 Hz, 5-H)5.29 (
1)1. m, 8-H) 5.30 (IH, m
, 4-H) 5.40 (IH, dd, J=5
．． 4. 2.2 fiz, 7-H) Example 11 (
(5)-(7)) 2 ml of methanol! 48 mg (0,0
95 mmol) was dissolved therein, 6 mg of potassium carbonate was added thereto, and the mixture was stirred at room temperature for 30 minutes. After the reaction, the solvent was distilled off,
The residue was subjected to column chromatography using silica gel as an adsorbent to obtain the desired product (7) as colorless needle crystals.

Yield 22 mg Yield 78% Melting point 123-125°C Mass spectrometry ra/z 297 (M”+ 1) Elemental analysis (C1l)l!.o*+ozo) Calculated value C:
42.04 H: 7.06 measured value C: 41.
91H: 6.93'HNMR (300MH2,0
20) 1.65 (18, dd, J=13.5. 11
．． 5 Hz, 3-Hax)2.26 (1)1.
dd, J=13.5. 5.2) 1z, 3
-)1eq)3.19 (3H,s, -0CR,
) 3.49 (IH, t, J=9.5 Hz,
5-H) 3.63 (IH, m, 9-H)3.
73 (1)1. dd, J=10.0. 0
．． 8 Hz, 6-H) 3.76-3.83 (6)
1. m, ? -8-9' -○ and -COOCR,)

Claims (1)

[Claims] 3-deoxy-D-glycero- represented by the following general formula
D-galacto-2-nonulopyranosonic acid derivative. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R^1 represents hydrogen or an acetyl group, R^2 represents a C_1 to C_6 alkoxy group, cholestenyl group, cholestanyl group, or halogen, and R^3 represents hydrogen. , C_
1 to C_6 alkyl group, aryl group, aralkyl group, alkali metal or NH_4^+. )