JP2003252891A - Intermediate for synthesizing cytosaminomycin and method for producing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an intermediate for synthesizing Cytosaminomycin having coccidiostat activity, and to provide a method for producing the intermediate. <P>SOLUTION: This method for producing the intermediate for the Cytosaminomycin comprises preparing a disacchride derivative and reacting the prepared derivative with a cytosine derivative. The method is developed and selected, after various routes for synthesizing the intermediate for the Cytosaminomycin are eagerly investigated. <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to cytosaminomycin, which is a nucleoside antibiotic having anticoccidial activity. For details, see Cytosaminomycin (Cyt
The present invention relates to a synthetic intermediate of osaminomycin) and a method for producing the same. Coccidium is a kind of chicken pathogen. Chicken coccidiosis caused by this bacterium is known to cause great damage to the poultry industry. The invention has applications in the field of veterinary medicine.

[0002]

BACKGROUND ART As anticoccidial drugs, monensin and salinomycin (Slinom) are available.
Polyether compounds such as ycin) and lasalocid are used. But 19
In 1983, the emergence of coccidia that showed resistance to the aforementioned polyether compounds was reported. On the other hand, 199
In 6 years, cytosaminomycin (Cytosamine) which is a nucleoside antibiotic contained in the culture solution of actinomycetes
omycin) was reported to exhibit anticoccidial activity. However, cytosaminomycin (Cyto
Since saminomycin) can be obtained only in a small amount from actinomycetes, it is not possible to perform a detailed study on biological activity, and its practical application has not been realized.

[0003]

The present invention is directed to cytosaminomycin (Cytosa) having anticoccidial activity.
It is an object of the present invention to provide a chemical synthesis intermediate which enables quantitative supply of minomycin).

[0004]

Means for Solving the Problems Cytosaminomycin is a disaccharide nucleoside derivative composed of two sugar derivatives and a cytosine derivative. In order to chemically synthesize this compound, it is necessary to synthesize two sugar derivatives and cytosine derivatives, which are the constituents, and further carry out a condensation reaction of these compounds, and the number of reaction steps reaches several tens. Therefore, various synthetic routes can be considered for synthesizing cytosaminomycin. The present inventors have found that cytosaminomycin (Cytosamino)
As a result of intensive studies for the purpose of developing a chemical synthesis method of (mycin), a synthesis via a cytosaminomycin (Cytosaminomycin) synthetic intermediate obtained by first preparing a disaccharide derivative and then reacting this compound with a cytosine derivative. The present inventors have found that the route is effective for the synthesis of cytosaminomycin (Cytosaminomycin), and arrived at the present invention.

That is, the present invention has the general formula [1]

[Chemical 6] (In the formula, R ¹ represents a sugar hydroxyl protecting group, and R ² represents a sugar anomeric protecting group.) A cytosaminomycin synthetic intermediate which is a disaccharide derivative.

General formula [2]

[Chemical 7] (In the formula, R ¹ is a sugar hydroxyl protecting group, R ³ is an alkyl group,
Alternatively, it represents an aryl group. ) 4,6-dideoxy sugar derivative represented by the general formula [3]

[Chemical 8] (Wherein R ¹ represents a sugar hydroxyl protecting group and R ² represents a sugar anomeric protecting group), and is reacted with a 2,6-dideoxy sugar derivative represented by the general formula [ 1] Cytosaminomycin
ycin) A method for producing a synthetic intermediate.

General formula [4]

[Chemical 9] (Wherein R ¹ represents a sugar hydroxyl protecting group and R ⁴ represents an amino protecting group).
tosaminomycin) synthetic intermediate.

Cytosaminomycin (Cytosamycin) represented by the general formula [4] characterized by reacting a cytosaminomycin synthetic intermediate represented by the general formula [1] with a cytosine derivative.
process for producing a synthetic intermediate.

General formula [5]

[Chemical 10] (Wherein R ¹ represents a sugar hydroxyl protecting group and R ⁴ represents an amino protecting group).
tosaminomycin) synthetic intermediate.

Further, a cytosaminomycin (Cytosaminomycin) synthetic intermediate represented by the general formula [4] is purified, and the cytosaminomycin (Cytosaminomyc) represented by the general formula [5] is characterized.
in) A method for producing a synthetic intermediate.

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be described in detail below.

First, the compound of the present invention will be described. Cytosaminomycin represented by general formula [1], general formula [4], or general formula [5]
Synthetic intermediates, 4,6-dideoxy sugar derivative represented by the general formula [2], and 2,6-- represented by the general formula [3]
In the dideoxy sugar derivative, R ¹ may be a commonly used protective group for a hydroxyl group such as an acyl group, an alkyl group or a silyl group. Specific examples include an acetyl group, a benzoyl group, a benzyl group, and a tert-butyldimethylsilyl group. In particular, using a benzyl group
It is preferable from the viewpoint of purification. In addition, cytosaminomycin represented by the general formula [1]
in) In the synthetic intermediate and the 2,6-dideoxy sugar derivative represented by the general formula [3], R ² is a commonly used sugar anomeric protecting group such as an acyl group, an alkyl group, an aryl group or a silyl group. Can be used. Specific examples include an acetyl group, a trimethylsilylethyl group, a 4-methoxyphenyl group, and a tert-butyldimethylsilyl group. It is particularly preferable to use a trimethylsilylethyl group from the viewpoint of purification. Furthermore, the general formula [4],
Cytosaminomycin represented by the general formula [5] (Cyt
osaminomycin) synthetic intermediate, R ⁴
Can be a commonly used amino-protecting group such as an acyl group or an alkyl group. Specific examples thereof include an acetyl group, a benzoyl group and a benzyl group.

Next, a method for producing the compound of the present invention will be described.
Describe in detail.

First, it is represented by the general formula [1] by the reaction between the 4,6-dideoxy sugar derivative represented by the general formula [2] and the 2,6-dideoxy sugar derivative represented by the general formula [3]. Cytosaminomyc
in) Synthesis of synthetic intermediates will be described. This reaction is
Under an atmosphere of an inert gas such as nitrogen or argon, an aprotic solvent such as ether, tetrahydrofuran, dichloromethane, chloroform, toluene or acetonitrile is added to 1 mol of the 2,6-dideoxy sugar derivative represented by the general formula [3]. 1 to 500 ml, preferably 100 ml, and the reaction temperature is -78 to 30 ° C.
It can be preferably carried out at -20 to 0 ° C. Also,
The reaction time is 0.5 to 50 hours, preferably about 1 hour.

As the activator used in this reaction,
Usual activators of thioglycoside such as N-bromosuccinimide, iodonium collidine perchlorate, and dimethylmethylthiosulfonium triflate can be used. Particularly, a combination of N-iodosuccinimide and trimethylsilyl triflate is preferable. The amount used is 4,6 represented by the general formula [2].
1 to 10 mol of dideoxy sugar derivative, 1 to 10 mol of N-iodosuccinimide, preferably 1 to 3 mol,
Trimethylsilyl triflate is 0.01 to 1 mol, preferably 0.01 to 0.3 mol.

Next, the cytosaminomycin (Cytosaminomycin) represented by the general formula [4] is obtained by the reaction of the cytosaminomycin synthetic intermediate represented by the general formula [1] with a cytosine derivative.
ycin) The synthesis of the synthetic intermediate will be described. In this reaction, first, the cytosaminomycin synthetic intermediate represented by the general formula [1] is converted to glycosyl chloride. As a conversion method,
Well-known methods for converting to glycosyl chloride can be used, such as a method using zinc chloride and α, α-dichloromethyl methyl ether. Then, this glycosyl chloride is reacted with a cytosine derivative that can be prepared by a known method to obtain a cytosaminomycin synthetic intermediate represented by the general formula [4]. The cytosine derivative in this synthetic method represents a silylated form of a compound in which the amino group of cytosine is substituted. As the substituent of the amino group, a commonly used protecting group for the amino group such as an acyl group and an alkyl group can be used. Specific examples thereof include an acetyl group, a benzoyl group and a benzyl group.

This reaction is carried out under the atmosphere of an inert gas such as nitrogen or argon, ether, tetrahydrofuran, dichloromethane, chloroform, toluene,
An aprotic solvent such as acetonitrile is treated with cytosaminomycin (Cytosa) represented by the general formula [1].
1 to 1 mol of the synthetic intermediate
500 ml, preferably 100 ml is used, and the reaction temperature is −
It can be carried out at 78 to 30 ° C, preferably at -20 to 0 ° C. The reaction time is 0.5 to 50 hours, preferably about 15 hours.

As the activator used in this reaction,
Commonly used activators of glycosyl chloride such as silver carbonate, silver trifluoromethanesulfonate and silver perchlorate can be used. In particular, a combination of silver carbonate and silver trifluoromethanesulfonate is preferable. The amount used is 1 m of cytosaminomycin synthetic intermediate represented by the general formula [1].
2 to 10 mol of silver carbonate, preferably 2 to ol.
3 mol, silver trifluoromethanesulfonate 1-5 mo
1, preferably 1.5 to 3 mol.

Next, the cytosaminomycin (Cytosaminomycin) synthetic intermediate represented by the general formula [4] is purified, and the cytosaminomycin (Cytosaminomyc) represented by the general formula [5] is characterized.
in) A method for producing a synthetic intermediate will be described. General formula [5]
Cytosamine represented by
The synthetic intermediate of ocycin is represented by the general formula [4], Cytosaminomycin.
n) Obtained by purifying the synthetic intermediate twice using silica gel column chromatography. As a developing solvent, a mixture of hexane and ethyl acetate at a volume ratio of 1 to 7 is used.

The present invention is described in detail below with reference to examples, but these do not limit the scope of the invention.
The NMR spectrum was measured using EX-400 manufactured by JEOL Ltd.

[0021]

EXAMPLE 2- (Trimethylsilyl) ethyl 2-deoxy-D-glucopyranoside (38
1 mg, 1.4 mmol) was dissolved in 15 ml of acetonitrile, benzaldehyde dimethyl acetal (0.5 ml, 3.4 mmol) and (±) -10-camphorsulfonic acid (84 mg, 0.36 mmol) were added, and the mixture was stirred for 1 hour. did. Chloroform was added to the reaction mixture, the layers were separated, and washed with saturated aqueous sodium hydrogen carbonate solution. The chloroform layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 4: 1), and 2-
(Trimethylsilyl) ethyl 4,6-O-benzylidene
-2-Deoxy-D-glucopyranoside (400 mg, 1.
1 mmol, yield 79%) was obtained.

¹ HNMR (CDCl ₃ ): δ = 0.03 (s, 9
H), 0.90-1.05 (m, 2H), 1.73 (ddd, J = 9.8, 10, 13 Hz,
1H), 2.30 (ddd, J = 2.2, 5.0, 13 Hz, 1H), 3.37 (dt, J =
5.0, 10 Hz, 1H), 3.47 (t, J = 10 Hz, 1H), 3.52-3.60
(m, 1H), 3.81 (t, J = 10 Hz, 1H), 3.89-4.30 (m, 2H), 4.
34 (dd, J = 5.0, 10 Hz, 1H), 4.64 (dd, J = 2.2, 9.8 Hz,
1H), 5.56 (s, 1H), 7.20-7.55 (m, 5H).

The obtained 2- (trimethylsilyl) ethyl 4,6-O-benzylidene-2-deoxy-D-glucopyranoside (400 mg, 1.1 mmol) was dissolved in 10 ml of N, N-dimethylformamide, and 55% thereof was added thereto. Sodium hydride (120 mg, 2.8 mmol) was added,
Stir for 1 hour. Benzyl bromide (0.45
ml, 3.8 mmol) was added and stirred for 18 hours. After adding 10 ml of methanol to the reaction solution and stirring for 1 hour,
It was concentrated under reduced pressure. The residue was extracted with ether, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 8: 1), and 2- (trimethylsilyl) ethyl 4,6-O-benzylidene-3-O-benzyl-2-deoxy-D-glucopyranoside (501 mg, 1.1 mmo
1, yield 100%) was obtained.

¹ HNMR (CDCl ₃ ): δ = 0.01 (s, 9
H), 0.85-1.00 (m, 2H), 1.72 (td, J = 10, 13 Hz, 1H),
2.29 (ddd, J = 2.2, 4.9, 13 Hz, 1H), 3.33 (ddd, J = 4.9,
9.8, 10 Hz, 1H), 3.45-3.55 (m, 1H), 3.65-3.80 (m, 1
H), 3.66 (t, J = 10 Hz, 1H), 3.81 (t, J = 10 Hz, 1H), 3.
90-4.00 (m, 1H), 4.31 (dd, J = 4.9, 9.8 Hz, 1H), 4.55
(dd, J = 2.2, 10 Hz, 1H), 4.70 (d, J = 12 Hz, 1H), 4.81
(d, J = 12 Hz, 1H), 5.58 (s, 1H), 7.23-7.52 (m, 10H).

The obtained 2- (trimethylsilyl) ethyl 4,6-O-benzylidene-3-O-benzyl-2-deoxy-D-glucopyranoside (925 mg, 2.1 mmo
l) was dissolved in 20 ml of 80% acetic acid aqueous solution and stirred at 80 ° C. for 5 hours. The reaction solution was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography (hexane: ethyl acetate = 1: 1).
Purified in 1), 2- (trimethylsilyl) ethyl 3-O
-Benzyl-2-deoxy-D-glucopyranoside (352
mg, 0.99 mmol, yield 48%).

¹ HNMR (CDCl ₃ ): δ = 0.01 (s, 9
H), 0.85-1.00 (m, 2H), 1.72 (td, J = 10, 13 Hz, 1H),
2.29 (ddd, J = 2.2, 5.0, 13 Hz, 1H), 3.34 (ddd, J = 5.0,
9.8, 10 Hz, 1H), 3.45-3.55 (m, 1H), 3.66-3.85 (m, 3
H), 3.90-4.10 (, 1H), 4.55 (dd, J = 2.2, 10 Hz, 1H), 4.
70 (d, J = 12 Hz, 1H), 4.81 (d, J = 12 Hz, 1H), 7.23-7.5
2 (m, 5H).

The obtained 2- (trimethylsilyl) ethyl 3-O-benzyl-2-deoxy-D-glucopyranoside (352 mg, 0.99 mmol) was added to 10 ml of pyridine.
Dissolved in p-toluenesulfonyl chloride (406m
g, 2.1 mmol) was added. After stirring for 16 hours,
The reaction solution was extracted with chloroform. The chloroform layer was washed with water, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 3: 1), and 2- (trimethylsilyl) ethyl 3-O-benzyl-2-deoxy was obtained.
-6-O- (p-toluenesulfonyl) -D-glucopyranoside (494 mg, 1.0 mmol, 98%) was obtained.

Subsequently, the obtained 2- (trimethylsilyl) ethyl 3-O-benzyl-2-deoxy-6-O- (p-
Toluenesulfonyl) -D-glucopyranoside (494m
g, 1.0 mmol) was dissolved in 10 ml of tetrahydrofuran and cooled in an ice bath. Lithium aluminum hydride (90 mg, 2.4 mmol) was added to the reaction solution, and the temperature was raised to room temperature. After stirring for 22 hours, the reaction solution was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous sodium hydrogen carbonate solution and dried over anhydrous magnesium sulfate,
It was filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 4: 1), and 2- (trimethylsilyl) ethyl 3-O-benzyl-
2,6-Dideoxy-D-glucopyranoside (226m
g, 0.61 mmol, yield 61%) was obtained.

¹ HNMR (CDCl ₃ ): δ = 0.03 (s, 9
H), 1.90-1.00 (m, 2H), 1.32 (d, J = 6.0 Hz, 1H), 1.55
(dt, J = 9.8, 12 Hz, 1H), 2.30 (ddd, J = 2.0, 4.6, 12 H
z, 1H), 3.19 (t, J = 9.0 Hz, 1H), 3.27 (qd, J = 6.0, 9.0
Hz, 1H), 3.38 (ddd, J = 4.6, 9.0, 12 Hz, 1H), 3.43-3.
52 (m, 1H), 3.92-4.01 (m, 1H), 4.43 (dd, J = 2.0, 9.8,1
H), 4.44 (d, J = 12 Hz, 1H), 4.66 (d, J = 12 Hz, 1H), 7.
25-7.40 (m, 5H).

The resulting 2- (trimethylsilyl) ethyl 3-O-benzyl-2,6-dideoxy-D-glucopyranoside (168 mg, 0.50 mmol) and lauryl 4-azido-2,3 prepared by known methods. -O-benzyl-
4,6-Dideoxy-1-thio-β-D-glucopyranoside (302 mg, 0.55 mmol) was dissolved in 5.4 ml ether under argon atmosphere. After adding 500 mg of molecular sieves 4A, 30 minutes at room temperature, -2
The mixture was stirred at 0 ° C for 30 minutes. N-iodosuccinimide (147 mg, 0.65 mmol) and silver trifluoromethanesulfonate (15 mg, 0.06 mmol) were added to the reaction solution.
Was added, and the mixture was stirred at −20 ° C. for 2 hours. The reaction solution was extracted with ethyl acetate, the organic layer was washed with an aqueous sodium thiosulfate solution and a saturated aqueous sodium hydrogen carbonate solution, and then dried over anhydrous magnesium sulfate. After filtration and concentration under reduced pressure, the residue was purified by silica gel column chromatography (hexane: ethyl acetate = 7: 1), and 2- (trimethylsilyl) ethyl (4-azido-2,3-O-benzyl-4,6-dideoxy).
-D-glucopyranosyl) -3-O-benzyl-2,6-dideoxy-D-glucopyranoside (319 mg, 0.46 m
mol, yield 93%) was obtained.

¹ HNMR (CDCl ₃ ): δ = 0.03 (s, 9
H), 0.93-1.02 (m, 2H), 1.27 (d, J = 6.1 Hz, 3H), 1.37
(d, J = 5.9 Hz, 3H), 1.62 (ddd, J = 9.8, 11.7, 12 Hz, 1
H), 2.41 (ddd, J = 2.0, 4.9, 12 Hz, 1H), 3.07 (t, J = 9.
8 Hz, 1H), 3.34-3.59 (m, 3H), 3.47 (dd, J = 3.8, 9.8 H
z, 1H), 3.69 (dd, J = 6.3, 9.8 Hz, 1H), 3.76 (t, J = 9.8
Hz, 1H), 3.85 (ddd, J = 4.9, 9.8, 11.7 Hz, 1H), 3.90-
4.10 (m, 1H), 4.36 (d, J = 11.7 Hz, 1H), 4.43 (d, J = 12
Hz, 1H), 4.47 (dd, J = 2.0, 9.8 Hz, 1H), 4.59 (d, J = 12
Hz, 1H), 4.67 (d, J = 11.7 Hz, 1H), 4.77 (d, J = 10 Hz,
1H), 4.93 (d, J = 10 Hz, 1H), 5.80 (d, J = 3.8 Hz, 1H),
7.10-7.35 (m, 15H).

The resulting 2- (trimethylsilyl) ethyl (4-azido-2,3-O-benzyl-4,6-dideoxy)
-D-glucopyranosyl) -3-O-benzyl-2,6-dideoxy-D-glucopyranoside (311 mg, 0.45 m
mol) under an argon atmosphere to give 4.6 m of dichloromethane.
It was dissolved in 1. Zinc chloride (8.8m
g, 0.07 mmol) and α, α-dichloromethyl methyl ether (0.1 ml, 1.1 mmol).
After stirring for 1.5 hours under ice cooling, the reaction solution was extracted with dichloromethane. The organic layer was washed with saturated brine and saturated aqueous sodium hydrogen carbonate solution, and dried over anhydrous magnesium sulfate. After filtration and concentration under reduced pressure, the residue was dissolved in 4.6 ml of dichloromethane. Add Molecular Sieves 4A to the reaction mixture and
After stirring for an hour, bis (trimethylsilyl) -N ⁴ -acetylcytosine (1.8 mmol) prepared by a known method
Was dissolved in 6 ml of a dichloromethane solution and added. Furthermore, silver trifluoromethanesulfonate (231 mg,
0.90 mmol) was added and the mixture was stirred for 16 hours. The reaction mixture was filtered through Celite, concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane: ethyl acetate = 1: 7) to give N ⁴ -acetyl-1- [4-azido-
2,3-O-benzyl-4,6-dideoxy-D-glucopyranosyl) -3-O-benzyl-2,6-dideoxy-D-glucopyranosyl] cytosine (48 mg, 0.07 mmo
l, yield 15%) was obtained.

¹ HNMR (CD ₃ OD): δ = 1.2-1.31 (m,
3H), 1.39-1.44 (m, 3H), 1.70-1.83 (m, 1H), 2.23-2.3
0 (m, 3H), 2.50-2.72 (m, 1H), 3.10-3.25 (m, 1H), 3.40
-4.03 (m, 6H), 4.38-4.97 (m, 6H), 5.63-5.90 (m, 2H),
6.85-7.00 (m, 1H), 7.15-7.45 (m, 15H), 8.18-8.27 (m, 1
H).

The obtained N ⁴ -acetyl-1- [4-azido-
2,3-O-benzyl-4,6-dideoxy-D-glucopyranosyl) -3-O-benzyl-2,6-dideoxy-D-glucopyranosyl] cytosine (48 mg, 0.07 mmo
l) was purified twice by silica gel column chromatography (hexane: ethyl acetate = 1: 7), and N ⁴ -acetyl-1- [4-azido-2,3-O-benzyl-4,6-dideoxy was used. -α-D-glucopyranosyl) -3-O-benzyl-2,
6-Dideoxy-β-D-glucopyranosyl] cytosine (4
6 mg, 0.06 mmol, yield 90%) were obtained.

¹ HNMR (CD ₃ OD): δ = 1.27 (d, J =
6.1 Hz, 3H), 1.40 (d, J = 6.1 Hz, 3H), 1.75 (td, J = 11,
12.3 Hz, 1H), 2.25 (s, 3H), 2.66 (ddd, J = 2.2, 4.9,
12.3Hz, 1H), 3.14 (t, J = 9.1 Hz, 1H), 3.50 (dd, J = 3.
9, 9.5 Hz, 1H), 3.52-3.83 (m, 3H), 3.75 (t, J = 9.5 H
z, 1H), 3.98 (ddd, J = 4.9, 9.1, 11 Hz, 1H), 4.41 (d, J
= 12 Hz, 1H), 4.45 (d, J = 11.7 Hz, 1H), 4.57 (d, J = 11.
7 Hz, 1H), 4.67 (d, J = 12 Hz, 1H), 4.75 (d, J = 10.7 H
z, 1H), 4.87 (d, J = 10.7 Hz, 1H), 5.78 (d, J = 3.9 Hz,
1H), 5.86 (dd, J = 2.2, 11 Hz, 1H), 6.91 (d, J = 7.6 Hz,
1H), 7.15-7.45 (m, 15H), 8.23 (d, J = 7.6 Hz, 1H).

Effect of the Invention Cytosaminomycin (Cytosam)
Inomycin) is effective in suppressing the growth of coccidia, which is a pathogen of chickens. Therefore, the compound of the present invention, which is a synthetic intermediate of cytosaminomycin, and its production method have great industrial value as new materials that can contribute to the development of new veterinary drugs.

Claims (6)

[Claims] 1. A general formula [1]: (In the formula, R ¹ represents a sugar hydroxyl protecting group, and R ² represents a sugar anomeric protecting group.) A cytosaminomycin synthetic intermediate which is a disaccharide derivative. 2. A general formula [2]: (In the formula, R ¹ is a sugar hydroxyl protecting group, R ³ is an alkyl group,
Alternatively, it represents an aryl group. ) 4,6-dideoxy sugar derivative represented by the general formula [3] (Wherein R ¹ represents a sugar hydroxyl protecting group and R ² represents a sugar anomeric protecting group), and is reacted with a 2,6-dideoxy sugar derivative represented by the general formula [ 1] Cytosaminomycin
ycin) A method for producing a synthetic intermediate. 3. A general formula [4]: (Wherein R ¹ represents a sugar hydroxyl protecting group and R ⁴ represents an amino protecting group).
tosaminomycin) synthetic intermediate. 4. A cytosaminomycin (Cytosamycin) represented by the general formula [4], which comprises reacting a cytosaminomycin synthetic intermediate represented by the general formula [1] with a cytosine derivative.
process for producing a synthetic intermediate. 5. A general formula [5]: (Wherein R ¹ represents a sugar hydroxyl protecting group and R ⁴ represents an amino protecting group).
tosaminomycin) synthetic intermediate. 6. A cytosaminomycin represented by the general formula [5], characterized in that a synthetic intermediate for the cytosaminomycin represented by the general formula [4] is purified.
Manufacturing method of synthetic intermediate.