JP2701035B2 - Novel amino sugar derivative and method for producing the same - Google Patents

Description

Description: FIELD OF THE INVENTION The present invention relates to a novel amino sugar derivative useful as a raw material for pharmaceuticals, immunological drugs, etc., as an intermediate and the like, and a method for producing the same.

[Background of the Invention] Various biological activities (immunomodulation, pyrogenicity, etc.) are present in the peptide glycan portion forming the skeleton of the bacterial cell wall (particularly, peptidoglycan of bacteria parasitic on mammals including humans). It has been known for a long time. The minimum unit of the immunopotentiating activity of peptidoglycan was reported by Lederer et al., France, 1974-1975, and Kotani, Shiba et al., Osaka University, to find that N-acetylmuramyl-L-alanyl-D-isoglutamine (MD
P).

On the other hand, it is also known as a major component of lipopolysaccharide (LPS) endotoxin (endotoxin) located in the outer membrane of the cell wall of Gram-negative bacteria, and also has various physiological activities including antitumor activity. Have been. Regarding lipid A, which is the main body of this lipopolysaccharide, a new structural formula has been proposed by Westphal group in West Germany and Khorana et al. In MIT.

Thus, since it has various biological activities and can be expected to be used as pharmaceuticals and immunological agents, basic research on biopolymers such as peptidoglycan and lipopolysaccharide, and applied research aiming to make effective use of these activities have been conducted. It is currently being actively promoted in the area.

[Object of the Invention] The present invention has been made in view of the above situation,
It is an object of the present invention to provide a novel amino sugar derivative useful as a raw material or an intermediate for pharmaceuticals, immunological drugs, and the like, and a simple and efficient method for producing the same.

[Constitution of the Invention] The present invention relates to a compound of the general formula [I] [In the formula, R ⁰ represents a lower alkyl group, and R represents an acyl group represented by R ⁰ CO- (R ⁰ is as defined above). R ¹ represents -OR (R is the same as described above), and R ² represents a hydrogen atom. Is reacted with 2- (trialkylsilyl) ethanol to give a general formula [II] (Wherein, R, R ¹ and R ² are the same as above, and TAS represents a trialkylsilyl group). The compound is then treated with an alkali in the absence of water to obtain a compound represented by the general formula [ III] (Wherein R and TAS are the same as above. R ³ represents a hydroxyl group and R ⁴ represents a hydrogen atom.) Then, the compound is reacted with an acetone reagent in the presence of an acid catalyst. And the general formula [IV b] (Wherein R and TAS are the same as described above), and then the acyl group is deprotected. (Wherein R and TAS are the same as above.) 1- [2- (trialkylsilyl) ethyl] -2-amino-2-deoxy-4,6-0-isopropylidene-β-D- It is an invention of a method for producing galactopyranoside.

Further, the present invention provides a compound represented by the general formula [VI b]: [Wherein, R ⁵ represents an acyl group represented by R ⁰ CO— (where R ⁰ is the same as described above) or a hydrogen atom, and TAS is the same as described above. ] It is invention of the amino sugar derivative represented by these.

That is, the present inventors have proposed a compound represented by the general formula [I] 2- (trialkylsilyl) ethanol (hereinafter referred to as TASEtO).
Abbreviated as H. ), The 1-position hydroxyl group is 2-
A β-amino sugar derivative represented by the general formula [II] protected with a (trialkylsilyl) ethyl group (TASC ₂ H ₄ group) and selectively represented by the general formula [II] can be obtained. III], that the compounds represented by the general formulas [IVb] and [Vb] can be produced easily and in good yield,
The present invention has been completed.

R ⁰ in the general formula [I] according to the present invention represents a lower alkyl group such as a methyl group, an ethyl group and a propyl group, and is represented by the general formulas [I], [II], [II] and In the general formula [IV b], R represents an acyl group represented by R ⁰ CO— (R ⁰ is as defined above), and examples of the acyl group include an acetyl group, a propionyl group, and a butanoyl group. . Formula [II], Formula [III], Formula [IV
b], TAS in the general formulas [Vb] and [VIb] represent a trialkylsilyl group such as a trimethylsilyl group, a triethylsilyl group, a triisopropylsilyl group, and a dimethyl t-butylsilyl group. Further, in the general formulas [I] and [II], R ¹ represents -OR (R is the same as described above), and R ² represents a hydrogen atom. Further, R ³ in the general formula [III] represents a hydroxyl group, and R ⁴ represents a hydrogen atom. R ⁵ in the general formula [VI b] represents a hydrogen atom or an acyl group represented by R ⁰ CO— (R ⁰ is the same as described above), and examples of the acyl group include an acetyl group, a propionyl group, Butanoyl group and the like.

Examples of the 2- (trialkylsilyl) ethanol used in the present invention include trimethylsilylethanol (hereinafter abbreviated as TMSEtOH), triethylsilylmethanol, triisopropylsilylethanol, dimethyl t-butylsilylethanol, and the like.

Examples of the acetone-forming reagent (isopropylidene-forming reagent) used in the present invention include, for example, 2,2-dimethoxypropane (hereinafter abbreviated as DMP), 2-methoxypropene, acetone and the like.

 Hereinafter, the production method of the present invention will be described.

First, the compound represented by the general formula [II] can be produced as follows. That is, the compound represented by the general formula [I] is dissolved in an appropriate amount of a non-polar solvent (preferably sufficiently dehydrated) such as dichloromethane, dichloroethane, chloroform, carbon tetrachloride and the like, and TASEtOH is added to the general formula [I]. 1 to 5 times the molar amount of the compound represented by the formula [I],
Further molecular sieves 4A (hereinafter, abbreviated as MS-4A.), Was added an appropriate amount of drying agent such as calcium sulfate, after thoroughly dried, concentrated sulfuric acid, p- toluenesulfonic acid (hereinafter, p-T _S OH ), And the mixture is reacted at room temperature to 50 ° C for 1 to 10 hours with stirring.
After the reaction is completed, ion exchange resin (OH ^- type) or, for example, NaHCO ₃
The reaction solution is neutralized with a weak alkali such as, for example, filtered, and the filtrate is concentrated under reduced pressure. If the obtained product is purified by column chromatography or the like, if necessary, the hydroxyl group at the 1-position is 2-
The target compound represented by the general formula [II] protected by the (trialkylsilyl) ethyl group is obtained.

The 2- (trialkylsilyl) ethyl group is not limited to the amino sugar derivative according to the present invention, and can be widely used as a protecting group for the hydroxyl group at position 1 of β-type saccharides.
Unlike conventional protecting groups such as benzyl and aryl groups,
No severe conditions are required for desorption, and mild conditions, that is, fluorine compounds capable of generating fluoride ions (F ⁻ ) such as, for example, BF ₃ -ether, NaBF ₄ , KBF ₄ , and LiBF ₄ , and FeCl ₃ , for example. The compound can be easily eliminated by treating with a Lewis acid such as, for example, and is therefore extremely useful as a protecting group for the hydroxyl group at the 1-position of the β-type sugar derivative.

Next, the compound of the general formula [II] is dissolved in an alcoholic solvent such as methanol or ethanol (preferably sufficiently dehydrated), and an alkali such as a metal alcoholate such as sodium methylate or sodium ethylate is used. The reaction mixture was reacted under stirring at 0 to 50 ° C. for several tens of minutes to several hours to remove the hydroxyl-protected acyl group. The reaction solution was neutralized according to a conventional method, and the filtrate obtained by filtration was concentrated under reduced pressure. If
The compound represented by the general formula [III] is obtained.

Then, the compound of the general formula [III] is dissolved in a solvent such as dimethylformamide (DMF), and the solution is added with an acetone reagent,
Such as 2-methoxypropene, in addition to 5-fold molar amount of the compound of general formula [III] the DMP or the like, in addition further catalytic amount of an acid catalyst, for example p-T _S OH, the H ₂ SO ₄ or the like, The mixture is stirred and reacted for several hours at room temperature or slightly heated, and after the reaction, the reaction solution is neutralized with an ion exchange resin (OH ^- type) or a weak alkali such as NaHCO ₃ and filtered to obtain a filtrate. Is concentrated under reduced pressure. If necessary, the obtained residue may be purified by column chromatography or the like to obtain a compound represented by the general formula [IVb] (general formula [VI
b] wherein R ⁵ is an acyl group represented by R ⁰ CO-).

Further, the compound represented by the general formula [IV b] is treated with an alkali hydroxide in an aqueous solvent, and after the reaction, extracted with a non-polar solvent such as dichloromethane, dichloroethane, chloroform, carbon tetrachloride, etc., and the extracted layer is washed with water and dried. , The solvent is distilled off, and the obtained residue is purified by column chromatography or the like, if necessary. The compound represented by the general formula [Vb] (in the general formula [VIb], R ⁵ is a hydrogen atom) Thing) is obtained.

The compound represented by the general formula [I] is described, for example, in J. Org.
m., 33 , pp. 3585-3588 (1968); Carbohydrate Research, 2
1 , pp. 460-464 (1972) and the like, 2-acetamido-1,3,4,6-tetra-0-acetyl-2-deoxy-β-D-curcopyranose (pentaacetyl β-D
-Glucosamine) as raw material and FeCl ₃ or Z as condensing agent
Those obtained by a method using nCl ₂ or the like may be used, or those obtained by the following method newly found by the present inventors may be used. That is, the general formula [VII] (R, R ¹ and R ² are the same as described above.) Is dissolved in a non-polar solvent (preferably sufficiently dehydrated) such as dichloromethane, dichloroethane, chloroform, carbon tetrachloride and the like. Perfluoroalkanesulfonic acid trialkylsilyl ester,
For example, trifluoromethanesulfonic acid trimethylsilyl ester (hereinafter abbreviated as TMSOTf) is represented by the general formula [VI
1 to 5 times the molar amount of the compound of formula [I], and the mixture is reacted at room temperature to 70 ° C for 1 to 10 hours with stirring. After the reaction, the product is extracted with a non-polar solvent such as dichloromethane, dichloromethane, chloroform, carbon tetrachloride and the like according to a conventional method, and the extracted layer is washed with an alkaline solution and water sequentially, dried, and then the solvent is distilled off. A syrupy compound of the general formula [I] is obtained in high yield. Further, this may be optionally purified by a known purification method such as column chromatography if necessary.

The compound represented by the general formula [VII] is prepared by reacting D-glucosamine or D-galactosamine with an acylating agent such as an acid anhydride such as acetic anhydride or an acid chloride such as acetyl chloride by a conventional method. Since it can be easily obtained in the process, it is sufficient to use the one thus obtained.

In addition, in order to protect the hydroxyl group at the 1-position of the β-type saccharide with a 2- (trialkylsilyl) ethyl group, for example, the following may be performed.

That is, acylated sugars by first such was the conventional method, and then after introduction of a halogen group to the 1-position by hydrogen bromide by a conventional method, Hg (CN) ₂ and HgBr _2, Ag ₂ CO ₃ and AgCl
By reacting TESEtOH in the presence of a condensing agent such as O ₄ , Ag ₂ CO ₃ and I ₂ , AgClO ₄ , Hg (CN) ₂ , the hydroxyl group at the 1-position is protected by a 2- (trialkylsilyl) ethyl group The obtained β-type sugar derivative is obtained.

Hereinafter, the present invention will be described in more detail with reference to Reference Examples and Examples, but the present invention is not limited to these Examples.

[Example] Reference Example 1. 4,5 (3,4,6--O- acetyl-2-deoxy -D- glucopyranose) -2-methyl - [delta ² - Synthesis of oxazoline 2-acetamido-1, 1 g of 3,4,6-tetra-O-acetyl-2-deoxy-D-glucopyranose was dissolved in 10 ml of sufficiently dehydrated dichloromethane, and TMSOTf 0.55 ml was added thereto.
Was added thereto, and the mixture was stirred and reacted under reflux for 5 hours. After completion of the reaction, and extracted by adding dichloromethane to the reaction mixture, after the dichloromethane layer was successively washed with 2N-Na ₂ CO ₃ solution and water,
After drying over Na ₂ SO ₄ and concentration under reduced pressure, the syrupy 4,5-
(3,4,6--O- acetyl-2-deoxy -D- Gurikopirano) -2-methyl - [delta ² - oxazoline 0.70g
Was obtained (83% yield).

IR (neat): 1740-1750 (C = 0), 1670 (C = N) c
m ^-1 .

Reference Example 2. 4,5 (3,4,6--O- acetyl-2-deoxy -D- Garakutopirano) -2-methyl - [delta ² - Synthesis of oxazoline 2-acetamido-1,3,4, 0.39 g of 6-tetra-O-acetyl-2-deoxy-D-galactopyranose was dissolved in 3 ml of sufficiently dehydrated dichloromethane, and TMSOTf was added thereto.
0.22 ml was added, and the mixture was stirred and reacted under reflux for 5 hours. After completion of the reaction, and extracted by adding dichloromethane to the reaction mixture, after the dichloromethane layer was successively washed with 2N-Na ₂ CO ₃ solution and water, dried over Na ₂ SO _4, and concentrated under reduced pressure, syrupy 4, Five
-(3,4,6-tri-O-acetyl-2-deoxy-D-
Garakutopirano) -2-methyl - [delta ² - oxazoline 0.
32 g were obtained (97% yield).

IR (neat): 1740-1750 (C = 0), 1670 (C = N) c
m ^-1 .

Reference Example 3. 4,5 (3,4,6--O- acetyl-2-deoxy -D- glucopyranose) -2-methyl - [delta ² - Synthesis of oxazoline 2-acetamido-1,3,4, 4 g of 6-tetra-O-acetyl-2-deoxy-D-glucopyranose was dissolved in 50 ml of dichloromethane, and 3.2 g of FeCl3 was added thereto.
The mixture was stirred and reacted for 1.5 hours. After the reaction is completed, the reaction solution is NaHCO ₃
After washing with water and drying over Na ₂ SO ₄ , the solvent was distilled off to give syrup-like 4,5- (3,4,6-tri-O-acetyl-
2-deoxy-D-glycopyrano) -2-methyl- [Delta] ²
3.3 g of oxazoline was obtained (yield 97%).

 The physical properties were the same as those obtained in Reference Example 1.

Reference Example 4. 1- [2- (trimethylsilyl) ethyl]-
Synthesis of 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranoside 4,5- (3,4,6-tri-O-acetyl obtained in Reference Example 1 -2-Deoxy-D-glucopyrano) -2-methyl-
Delta ² - was dissolved in dichloromethane 10ml was thoroughly dehydrated oxazoline 0.7 g, was added to TMSEtOH0.5ml and MS-4A1g,
After reacting for 1 hour with stirring, a catalytic amount of concentrated sulfuric acid (1 drop)
Was added and the mixture was further stirred for 5 hours. After completion of the reaction, the reaction solution was neutralized with Amberlite IR-410 (trade name, OH ^- type, manufactured by Organo Corporation), and the filtrate obtained by filtration was concentrated under reduced pressure. The resulting syrup is subjected to column chromatography [filler; Wakogel
C-200 (trade name of Wako Pure Chemical Industries, Ltd.), eluent: CH ₂ C
l ₂ : CH ₃ OH = 150: 1] to give a syrup of 1-
[2- (Trimethylsilim) ethyl] -2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D
0.78 g of glucopyranoside was obtained (81% yield).

 mp: 152-155 ° C.

[Α] _D = -7.7 ° (C = 0.78, CHCl ₃ ).

IR (film): 3280 (NH), 1740 (C = 0), 1650, 1560
(NH), 860,830 (Si-C) cm ^-1 .

¹ H NMR (CDCl ₃ ): δ -0.1 to 0.1 (m, 9H, TMS), 0.87
_{(M, 2H, -C H 2} TMS), 1.88,1.96,1.97,2.03 (4s, 12H, -
_{COC H 3 × 4), 3.50} (m, 1H, C H -CH 2 TMS), 3.64 (m, 1
H, H-5), 3.69 (q-1H, J 1,2 J 2,3 J 2, NH = 8.8
Hz, H-2), 3.90 (m, 1H, C H -CH 2 TMS), 4.06 (bd, 1H,
J = 12Hz, H-6a), 4.21 (dd, 1H, J _gem = _12Hz , J _5,6b = 4.7
Hz, H-6b), 4.67 (d, 1H, J 1,2 = 8.4Hz, H-1), 5.00
(T, 1H, J _3,4 J _4,5 = 10Hz, H-4), 5.27 (t, 1H, J _2,3
= J _3,4 = 10Hz, H-3), 5.48 (d, 1H, J _{2, NH} = 8.8Hz, H-
2).

Example 1. 1- [2- (trimethylsilyl) ethyl]-
Synthesis of 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-galactopyranoside 4,5- (3,4,6-tri- O- acetyl-2-deoxy -D- Garakutopirano) -2-methyl - [delta ² - was dissolved in dichloromethane 3ml was thoroughly dehydrated oxazoline 0.32 g, was added to TMSEtOH0.2ml and MS-4A300mg, under stirring for 1 hour After the reaction, a catalytic amount of concentrated sulfuric acid (1 drop) was added, and the mixture was further stirred for 5 hours. After completion of the reaction, the reaction solution was neutralized with Amberlite IR-410 (trade name, OH ^- type, manufactured by Organo Corporation), and the filtrate obtained by filtration was concentrated under reduced pressure. The obtained syrup is subjected to column chromatography [filler; Wak
ogel C-200 (trade name of Wako Pure Chemical Industries, Ltd.), eluent;
Purified by CH ₂ Cl ₂ : CH ₃ OH = 250: 1 and CH ₂ Cl ₂ : CH ₃ OH = 150: 1], and syrupy 1- [2- (trimethylsilim)
Ethyl] -2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-galactopyranoside 0.39 g
Was obtained (yield 90%).

Elemental analysis values Theoretical value (%): C; 50.99, H; 7.43, N; 3.13.

 Found (%): C; 51.28, H; 7.65, N; 3.12.

_[Α] D = -15.95 ° _{(C = 1.128, CHCl 3)} .

Reference Example 5. 1- [2- (trimethylsilyl) ethyl]-
Synthesis of 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranoside 4,5- (3,4,6-tri-O-acetyl obtained in Reference Example 3 -2-Deoxy-D-glycopyrano) -2-methyl-
Delta ² - was dissolved in dichloromethane 50ml was thoroughly dehydrated oxazoline 3.3 g, was added to p-TsOH in TMSEtOH1.77g and a catalytic amount, and reacted under stirring at room temperature overnight. The reaction solution was NaHC
After neutralization with O ₃ , the mixture was washed with water, dried over Na ₂ SO ₄ , and evaporated. The obtained syrup was purified by column chromatography [filler; Wakogel C-200 (trade name of Wako Pure Chemical Industries, Ltd.), eluent; CH ₂ Cl ₂ : CH ₃ OH = 400: 1] to give a syrup. 1- [2- (trimethylsilyl) ethyl]-
4.26 g of 2-acetamide-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranoside was obtained (yield).
95%).

 The physical properties were the same as those obtained in Reference Example 4.

Reference Example 6. 1- [2- (trimethylsilyl) ethyl]-
Synthesis of 2-acetamide-2-deoxy-β-D-glucopyranoside 1- [2- (trimethylsilyl) obtained in Reference Example 4
Ethyl] -2-acetamide-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranoside (448 mg) was dissolved in sufficiently dehydrated methanol (10 ml), and a catalytic amount of sodium methylate was added. After reacting for 1 hour with stirring, Amberlite IR-120 (trade name of Organo, H ⁺
), The reaction solution was neutralized, and the filtrate obtained by filtration was concentrated under reduced pressure to give 1- [2- (trimethylsilyl) ethyl] -2-.
Acetamide-2-deoxy-β-D-glucopyranoside crystals were obtained quantitatively.

Elemental analysis: Theory (%): C; 48.57; H; 8.47; N; 4.36.

 Measurement values (%): C; 48.66, H; 8.59, N; 4.40.

[Α] _D = -27.41. (C = 0.868, CH ₃ OH).

 mp: 178-182 ° C.

Example 2. 1- [2- (trimethylsilyl) ethyl]-
Synthesis of 2-acetamide-2-deoxy-β-D-galactopyranoside 1- [2- (trimethylsilyl) obtained in Example 1
Ethyl] -2-acetamide-3,4,6-tri-O-acetyl-2-deoxy-β-D-galactopyranoside 390 mg
Was dissolved in 10 ml of sufficiently dehydrated methanol, a catalytic amount of sodium methylate was added, and the mixture was reacted with stirring for 1 hour. After completion of the reaction, the reaction solution was neutralized with Amberlite IR-120 (trade name of Organo, H ⁺ type), and the filtrate obtained by filtration was concentrated under reduced pressure to give 1- [2- (trimethylsilim) ethyl. ] Acetamide-2-deoxy-β-D-galactopyranoside crystals were obtained quantitatively.

Elemental analysis: Theory (%): C; 48.57; H; 8.47; N; 4.36.

 Found (%): C; 48.73, H; 8.53, N; 4.46.

[Α] _D = -9.13 ゜ (C = 0.428, CH ₃ OH).

 mp: 192-193 ° C.

Reference Example 7. 1- [2- (Trimethylsilyl) ethyl]-
Synthesis of 2-acetamide-2-deoxy-4.6.O-isopropylidene-β-D-glucopyranoside 1- [2- (trimethylsilyl) obtained in Reference Example 6
Ethyl] -2-acetamide-2-deoxy-β-D-glucopyranoside (310 mg) was dissolved in DMF (10 ml), DMP (1 ml) and a catalytic amount of p-TsOH were added, and the mixture was reacted at room temperature for 1 hour with stirring. After completion of the reaction, the reaction solution was neutralized with Amberlite IR-410 (trade name, OH ^- type, manufactured by Organo Corporation), and the filtrate obtained by filtration was concentrated under reduced pressure. The obtained residue was purified by column chromatography [filler; Wakogal C-200 (trade name of Wako Pure Chemical Industries, Ltd.), eluent; CH ₂ Cl ₂ : CH ₃ OH = 100: 1], and 1- [2- (Trimethylsilyl) ethyl]-
Crystals of 2-acetamide-2-deoxy-4.6-O-isopropylidene-β-D-glucopyranoside were quantitatively obtained. IR (Film): 1660 (C = 0), 1560 (NH), 850 (Si-
_{C, C (CH 3) 2} ) cm -1.

 mp: 123-124.7 ° C.

[Α] _D = -73.9 ゜ (C = 0.82, CH ₂ Cl ₂ ).

Example 3. 1- [2- (Trimethylsilyl) ethyl]-
Synthesis of 2-acetamide-2-deoxy-4,6-O-isopropylidene-β-D-galactopyranoside In Reference Example 7, 1- [2- (trimethylsilyl)
1- [2] obtained in Example 2 in place of ethyl] -2-acetamide-2-deoxy-β-D-glucopyranoside
-(Trimethylsilyl) ethyl] -2-acetamide-2
In the same manner as in Reference Example 7, except that -deoxy-β-D-galactopyranoside was used, the corresponding 1- [2-
(Trimethylsilyl) ethyl] -2-acetamido-deoxy-4,6-O-isopropylidene-β-D-galactopyranoside was obtained.

Reference Example 8. 1- [2- (trimethylsilyl) ethyl]-
Synthesis of 2-amino-2-deoxy-4.6.O-isopropylidene-β-D-glucopyranoside 1- [2- (trimethylsilyl) obtained in Reference Example 5
Ethyl] -2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranoside (4 g) was dissolved in methanol (100 ml), and a few drops of a 28% methanol solution of sodium methylate were added. The reaction was allowed to proceed with stirring at room temperature for 30 minutes. The reaction solution was neutralized with Amberlite IR-120 (trade name of Organo, H ⁺ type), and the filtrate obtained by filtration was concentrated under reduced pressure. The obtained syrup was dissolved in 100 ml of DMF, and 10 ml of DMP and a catalytic amount of p-TsOH were added thereto.
The reaction was carried out under stirring for hours. The reaction solution was neutralized with a 28% methanol solution of sodium methylate and concentrated under reduced pressure.
Added 80ml and _{Ba (OH) 2 · 8H 2} O6g, was reacted for 2 days under reflux. After confirming the formation of an amino group by ninhydrin coloring, chloroform was added to the reaction solution for extraction. The chloroform layer was washed with water, dried over NaSO ₄ and the solvent was distilled off to obtain a syrup. The obtained syrup was purified by column chromatography [filler; Wakogal C-200 (trade name of Wako Pure Chemical Industries, Ltd.), eluent; CH ₂ Cl ₂ : CH ₃ OH = 100: 1], -[2- (trimethylsilyl) ethyl] -2
2.6 g of -amino-2-deoxy-4.6-O-isopropylidene-β-D-glucopyranoside was obtained (yield 92
%).

 mp: 110-111 ° C.

[Α] _D = -59,0, (C = 0.45, CH ₂ Cl ₂ ).

IR (film): 3400 (OH, NH), 1580 (NH), 850 (Si-
C, (CH ₃ ) ₂ C) cm ⁻¹ .

¹ H NMR (CDCl ₃ ): δ -0.1 to 0.1 (m, 9H, TMS), 1.00
_{(M, 2H, -C H 2} TMS), 1.40,1.48 [2s, 6H, (C H 3) 2 C
=], 1.92 (6s, 3H , O H, N H 2), 2.71 (t, 1H, J = 8Hz, H-
2), 3.23 (m, 1H , H-5), 3.4~3.6 (m, 3H, C H CH 2 TM
S, H-3,4), 3.78 (t, 1H, J = 10Hz, H-6a), 3.89 (dd, 1
H, J _gem = 10Hz, J _5,6b = 5.5Hz, H-6b), 3.95 (m, 1H, C H C
_{H 2 TMS), 4.21 (d} , 1H, J 1,2 = 8Hz, H-1).

Example 4. 1- [2- (Trimethylsilyl) ethyl]-
Synthesis of 2-amino-2-deoxide-4,6-O-isopropylidene-β-D-galactopyranoside In Reference Example 8, 1- [2- (trimethylsilyl)
1- [2- (trimethylsilyl) ethyl]-obtained in Example 1 in place of ethyl] -2-acetamide-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranoside. The corresponding 1 was prepared in the same manner as in Reference Example 8 except that 2-acetamide-3,4,6-tri-O-acetyl-2-deoxy-β-D-galactopyranoside was used.
-[2- (trimethylsilyl) ethyl] -2-amino-
2-deoxy-4,6-O-isopropylidene-β-D-
Galactopyranoside was obtained.

Reference Example 9. 1- [2- (Trimethylsilyl) ethyl]-
Synthesis of 2,3,4,6-tetra-O-acetyl-β-D-galactopyranosideSufficient 5.04 g of 1,2,3,4,6-penta-O-acetyl-D-galactopyranoside Was dissolved in 50 lm of dehydrated dichloromethane, 25 g of a 30% acetic acid solution of hydrogen bromide was added at 0 ° C., and the mixture was reacted at room temperature with stirring for 1.5 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to obtain a syrup, which was dissolved in 25 ml of dichloromethane, added with 5 g of MS-4A, and reacted with stirring for 5 hours (reaction liquid-1). On the other hand, Ag ₂ CO ₃ 7g, AgClO ₄ 2.
7 g, 3.66 ml of TMSEtOH and 5 g of MS-4A were suspended in 25 ml of sufficiently dehydrated dichloromethane, and reacted with stirring for 5 hours (reaction liquid-2). Next, the reaction solution-1 and the reaction solution-2 were mixed and reacted overnight with stirring. After completion of the reaction, the reaction solution was filtered through celite, the filtrate was concentrated under reduced pressure, and the resulting syrup was subjected to column chromatography [filler; Wakogal C-
200 (trade name of Wako Pure Chemical Industries, Ltd.), eluent; CH ₂ Cl ₂ ]
To give 4.2 g of a syrup of 1- [2- (trimethylsilyl) ethyl] -2,3,4,6-tetra-O-acetyl-β-D-galactopyranoside (yield 72.5).
%).

Elemental analysis: Theory (%): C; 50.88, H; 7.19.

 Found (%): C; 50.95, H; 7.30.

[Α] _D = -9.49 ゜ (C = 1.01, CHCl ₃ ).

Reference Example 10. 1- [2- (Trimethylsilyl) ethyl]
Synthesis of -β-D-galactopyranoside 1- [2- (trimethylsilyl) obtained in Reference Example 9
Ethyl] -2,3,4,6-tetra-O-acetyl-β-D-
Methanol 3 sufficiently dehydrated 3.36 g of galactopyranoside
0 ml, add a catalytic amount of sodium methylate and add
Stirred for hours. After completion of the reaction, Amberlite IR-120
The reaction solution was neutralized with an (organo trade name, H ⁺ type), and the filtrate obtained by filtration was concentrated under reduced pressure to give 1- [2- (trimethylsilyl) ethyl] -β-D-galactopyranoside. Crystals were obtained quantitatively.

Elemental analysis: theoretical (%): C; 47.12; H; 8.63.

 Measured value (%): C; 47.35, H; 8.71.

_[Α] D = -22.06 ° _{(C = 1.012, CH 3 OH} ).

[Effects of the Invention] As described above, the present invention provides a novel amino sugar derivative useful as a raw material and an intermediate of a drug, an immunological drug and the like, and a method for producing the same. The derivative is a β-isomer in which the 1-position is protected by a 2- (trialkylsilyl) ethyl group, and the 2- (trialkylsilyl) ethyl group is different from a conventional protecting group and requires severe conditions for its elimination. Since it can be easily desorbed under acidic conditions, it is extremely useful as a synthetic raw material or intermediate for glycolipids and lipid A, etc., and is a great invention that contributes to the industry.

Claims (3)

(57) [Claims] 1. A compound of the general formula [I] [In the formula, R ⁰ represents a lower alkyl group, and R represents an acyl group represented by R ⁰ CO- (R ⁰ is as defined above). R ¹ represents -OR (R is the same as described above), and R ² represents a hydrogen atom. Is reacted with 2- (trialkylsilyl) ethanol to give a general formula [II] (Wherein, R, R ¹ and R ² are the same as above, and TAS represents a trialkylsilyl group). III] (Wherein R and TAS are the same as above. R ³ represents a hydroxyl group, and R ⁴ represents a hydrogen atom). And the general formula [IV b] (Wherein R and TAS are the same as described above), and then the acyl group is deprotected. (Wherein R and TAS are the same as above.) 1- [2- (trialkylsilyl) ethyl] -2-amino-2-deoxy-4,6-0-isopropylidene-β-D- A method for producing galactopyranoside. 2. A compound of the general formula [III] [Wherein, R represents an acyl group represented by R ⁰ CO- (where R ⁰ represents a lower alkyl group), and TAS represents a trialkylsilyl group. R ³ represents a hydroxyl group, and R ⁴ represents a hydrogen atom. Wherein the compound represented by the general formula [IV b] is reacted with an acetone reagent in the presence of an acid catalyst. (Wherein, R and TAS are the same as described above). 3. A compound of the general formula [VI b] [In the formula, R ⁵ represents an acyl group represented by R ⁰ CO— (where R ⁰ represents a lower alkyl group) or a hydrogen atom, and TAS represents a trialkylsilyl group. ] The amino sugar derivative represented by these.