JPH07157496A - Production of deoxynucleotide - Google Patents

Abstract

PURPOSE:To efficiently produce a deoxynucleotide compound useful as a medicine, etc., by converting hydroxyl groups of a nucleotide derivative to thiocarbonyl groups, phosphonyl groups, etc., at positions to be deoxidized and reducing the resultant modified nucleotide derivative with a specified organosilane in the presence of a radical initiator. CONSTITUTION:A nucleotide derivative synthesized by converting hydroxyl groups to thiocarbonyl groups or phosphonyl groups at positions to be deoxidized and represented by formula I (B is a nucleic acid base or a nucleic acid base derivative; R1 is H or a hydroxyl-protecting group; R2 is thiocarbonyl or phosphonyl), etc., is used as the raw material compound. This compound is deoxidized through radical reduction with an organosilane (e.g. triphenylsilane) having >=90 deg.C boiling point in the presence of a radical initiator (e.g. azoisobutyronitrile), thus producing the objective deoxynucleotide represented by formula II, etc., and useful as a medicine, a raw material or an intermediate for synthesis of a medicine.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a deoxynucleoside useful as a drug or a raw material and an intermediate for synthesizing a drug, more specifically 2'-deoxynucleoside, 2 ', 3'-dideoxynucleoside and 2'. −
The present invention relates to a novel method for producing a deoxy-2'-substituted nucleoside.

[0002]

2. Description of the Related Art Among deoxynucleosides, 2'-
Deoxynucleosides, 2 ′, 3′-dideoxynucleosides and 2′-deoxy-2′-substituted nucleosides have pharmaceutically useful properties such as anticancer action and antiviral action, and are useful substances as pharmaceuticals, It is also useful as a raw material for other pharmaceuticals. For example, 5-
Fluoro-2'-deoxyuridine, 5-iodo-2 '
It has been reported that 2'-deoxynucleosides such as -deoxyuridine have anticancer activity and antiviral activity, and 2 ', 3'-dideoxyinosine,
2 ', 3'-Dideoxycytidine and other 2', 3'-dideoxynucleosides are used as anti-AIDS virus agents, and further 2'-C-cyano-2'-deoxy-
A 2'-deoxy-2'-substituted nucleoside represented by 1-β-D-arabinofuranosylcytosine is under development as an anticancer agent (J. Med. Chem., 34, 291).
7, (1991)).

Such deoxynucleosides are synthesized by deoxidizing the sugar group hydroxyl groups of the nucleoside raw materials used as the respective raw materials. The deoxygenation reaction of the nucleoside is carried out by converting the deoxygenating hydroxyl group of the sugar portion of the nucleoside into a halogen compound or a thiocarbonate compound,
This is carried out by radical reduction using hydrogenated tributyltin as a hydrogen source in the presence of a radical initiator in an organic solvent such as toluene (J. Am. Chem. Soc., 10
3, 932 (1981)). However, since hydrogenated tributyltin used as a hydrogen source is an environmentally harmful substance, it is important to remove hydrogenated tributyltin from the reaction system after the reaction. The law has not yet been reported. Therefore, it is practically impossible to apply the above method using hydrogenated tributyltin to industrial production.

[0004]

Recently, a deoxidation method by radical reduction using non-toxic diphenylsilane instead of hydrogenated tributyltin has been developed (Tetr
ahedron Lett., 31, 4681 (1990)), an example in which this is applied to deoxidation of 1,6-anhydro-D-glucose (Tetrahedron Lett., 33, 6629 (1992)) and 2 ',
Example applied to production of 3'-didehydro-2 ', 3'-dideoxynucleoside (Tetrahedron Lett., 32, 2569
(1991)) has been reported. However, in the above literature, 2 ′, 3′-, which performs dehydrogenation at the same time as deoxylation,
Only a method for producing a didehydro-2 ′, 3′-dideoxynucleoside is described, but a conventional method for producing a deoxynucleoside without dehydrogenation is not described.

[0005]

Means for Solving the Problems As a result of repeated research on the industrial scale application of the deoxidation method of nucleosides by radical reduction using silanes, the present inventors have found that
The inventors have found that the use of silanes having a boiling point above a certain temperature makes it possible to produce deoxynucleosides extremely efficiently and easily, and completed the present invention. Therefore, the present invention uses a nucleoside derivative in which a hydroxyl group at a site to be deoxylated is converted to a thiocarbonyl group or a phosphonyl group as a raw material compound, and in the presence of a radical initiator, a radical using an organic silane having a boiling point of 90 ° C. or higher is used. The present invention relates to a method for producing a deoxynucleoside, which is characterized by deoxidizing by reduction.

The present invention will be described in detail below. The nucleoside derivative used as the raw material compound is not particularly limited as long as it has a hydroxyl group at the site to be deoxylated converted to a thiocarbonyl group or a phosphonyl group.
Specifically, the following formulas (I), (III) and (V)
What is represented by is illustrated.

[0007]

[Chemical 7]

[Chemical 8]

[Chemical 9]

In the above formula, B is a nucleobase or a nucleobase derivative, R ₁ is a hydrogen atom or a hydroxyl-protecting group, R ₂ is a thiocarbonyl group or a phosphonyl group, R ₃ is a cyano group, a lower alkyl group or a substituted lower alkyl. Indicates a group.
The nucleobase or nucleobase derivative represented by B is not particularly limited, but includes adenine, guanine, hypoxanthine, 6-mercaptopurine, 6-methylthiopurine, 6-chloro-2-aminopurine, 2, Purine bases such as 6-diaminopurine or derivatives thereof, pyrimidine bases such as uracil, cytosine, thymine, 5-fluorouracil, 5-bromouracil, 5-chlorouracil, 5-iodouracil, 5-ethyluracil or derivatives thereof, and Examples thereof include purine bases, pyrimidine bases, and their derivatives into which a protecting group such as an acyl group has been introduced, if necessary.

The protective groups for the hydroxyl group represented by R ₁ may be the same or different, and examples thereof include those usually used as the protective group for the hydroxyl group of a nucleoside. For example,
Acyl-based protecting groups such as acetyl, propionyl, butyryl, pivaloyl and benzoyl, silyl-based protecting groups such as tetraisopropyldisiloxyl (TIPDS) and t-butyldimethylsilyl, trityl-based such as triphenylmethyl (trityl) and dimethoxytrityl. Examples of the protective group include ether-based protective groups such as tetrahydropyranyl and methoxymethyl, and silyl-based protective groups are particularly preferable.

Examples of the thiocarbonyl group represented by R ₂ include xanthyl, phenylthiocarbonyl, thiocarbonylimidazoyl, thioacetyl and thiobenzoyl, and examples of the phosphonyl group include triethylphosphonyl and thiotriethylphosphonyl. Is exemplified. From the viewpoint of reaction yield and the like, it is preferable to use a thiocarbonyl group. The lower alkyl group represented by R ₃ is an alkyl group having about 1 to 5 carbon atoms, and specific examples thereof include methyl, ethyl and propyl. The substituted lower alkyl group is an alkyl group having a substituent and having about 1 to 5 carbon atoms, and specific examples thereof include hydroxymethyl, halogenomethyl (such as fluoromethyl), azidomethyl, cyanomethyl, and nitromethyl.

Such a raw material compound can be prepared by a method of converting a hydroxyl group at a site to be deoxylated in a nucleoside derivative into a thiocarbonyl group or a phosphonyl group. Conversion of a hydroxyl group to a thiocarbonyl group or a phosphonyl group can be performed by a conventional method. For example, the starting compound represented by the formula (I) can be prepared as follows.

That is, in a basic solvent such as triethylamine, tributylamine, pyridine, picoline, diethylaniline, etc., 1 to 5 moles of alkylsilylsilyl halide such as chloroalkylsilane is used per mole of purine ribonucleoside or pyrimidine ribonucleoside. Are used to react these compounds at 0 to 50 ° C. for 1 to 20 hours to obtain a compound in which the hydroxyl groups at the 3′-position and 5′-position of the sugar moiety are protected by a silyl group. Then, a basic catalyst such as N, N-dimethylaminopyridine, pyridine, picoline, diethylaniline, tributylamine or triethylamine in an organic solvent such as methylene chloride, acetonitrile, N, N-dimethylformamide or N, N-dimethylacetamide. In the presence of 1 per mole of the above protected compound
The starting compound represented by the formula (I) can be synthesized by using -5 times mole of phenylchlorothionoformate and reacting them at 0-50 ° C for 1-20 hours. The compound thus obtained can be isolated and purified by ordinary silica gel column chromatography.

The compound represented by the formula (III) can also be prepared according to the above-mentioned synthetic method of the compound represented by the formula (I). Furthermore, the preparation of the compound of formula (V) is carried out by a known method (J. Med. Che).
m., 34, 234-239 (1991)).
The starting compound thus obtained is deoxygenated by radical reduction using an organic silane having a boiling point of 90 ° C. or higher in the presence of a radical initiator to obtain a target deoxynucleoside. Examples of the radical initiator used for radical reduction include azobisisobutyronitrile, di-t-butyl peroxide, benzoyl peroxide anhydride and the like.

The organic silanes used for radical reduction are not particularly limited as long as they have a boiling point of 90 ° C. or higher. Specifically, triphenylsilane, diphenylsilane, dimethylphenylsilane, methylphenylsilane, phenylsilane, diphenylmethylsilane, methylphenylvinylsilane, triethylsilane, tripropylsilane, triethoxysilane, tripentyloxysilane, octylsilane, Examples thereof include tris (trimethylsiloxy) silane. Among such silanes, by using one having a boiling point of 90 to 200 ° C., more preferably 100 to 150 ° C., the reaction yield is not extremely lowered and the reaction is performed simultaneously with or after the reaction. Organosilanes can be removed from the reaction system only by heating.

In the radical reduction of the present invention, it is not necessary to use a reaction solvent in particular, and the above-mentioned organic silane serves as both a hydrogen source and a solvent. The radical reduction reaction is performed in the presence of a catalytic amount of a radical initiator, using 1 to 50 times mol, preferably 2 to 20 times mol, of organic silane, and 90 to 200 ° C., preferably 100 to 150 ° C.
It can be carried out by reacting for about 1 to 10 hours. The reaction is preferably carried out in a stream of an inert gas such as argon or nitrogen.

The deoxynucleosides thus obtained, specifically, the respective target compounds when the compounds represented by the formulas (I), (III) and (V) are used as starting compounds. The following formula (II) and formula (I
V) and the compound of formula (VI)
It can be carried out by a usual isolation and purification method (for example, crystallization or silica gel column chromatography). Further, when further deprotection is required, appropriate treatment for normal deprotection such as tetrabutylammonium fluoride treatment, acidic hydrolysis, alkaline hydrolysis, catalytic reduction, etc. is appropriately performed depending on the protective group used. You can select it.

[0017]

[Chemical 10]

[Chemical 11]

[Chemical 12] (In the formula, B represents a nucleobase or a nucleobase derivative, R ₁ represents a hydrogen atom or a hydroxyl-protecting group, and R ₃ represents a cyano group, a lower alkyl group or a substituted lower alkyl group.)

[0018]

The desired deoxynucleoside can be prepared in good yield by the method of the present invention using an organic silane having a boiling point of 90 ° C. or higher. Also, the boiling point is 90 to
If the one having a temperature range of 200 ° C. is used, the operation of removing the organic silane after the reaction can be extremely simplified.

[0019]

EXAMPLES The present invention will now be described in detail with reference to examples, but the present invention is not limited thereto. Example 1: 1- [2-deoxy-3,5-O-
(1,1,3,3-tetraisopropyldisilox-
Preparation of 1,3-diyl) -β-D-ribofuranosyl] uracil (formula (II), B = uracil, R ₁ = tetraisopropyldisiloxyl (hereinafter abbreviated as TIPDS)).

(1) 1- [2-phenoxythiocarbonyloxy-3,5-O- (1,1,3,3, -tetraisopropyldisilox-1,3-diyl) -β-D-ribofuranosyl] -Uracil (formula (I), B = uracil,
Synthesis of R ₁ = TIPDS, R ₂ = PhO (S) C) 1- [3,5-O- (1,1,3,3, -tetraisopropyldisilox-1,3-diyl) -β-D -Ribofuranosyl] uracil 397 mg was added to anhydrous acetonitrile 1
It was dissolved in 1 ml, 273 mg of dimethylaminopyridine and 0.22 ml of phenoxythiocarbonyl chloride were added at 0 ° C under an argon stream, and the mixture was stirred at room temperature for 5 hours. After completion of the reaction, ethyl acetate was added, and the mixture was washed twice with deionized water. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was purified by silica gel column chromatography (15 g, eluted with hexane: ethyl acetate = 5: 1) to give the title compound as a white foam (437 mg, yield 86%).

¹ H-NMR (CDCl ₃ ) δ: 0.85-
1.11 (28H, m), 4.01 (2H, m), 4.
24-4.27 (1H, m), 4.54-4.57 (1
H, m), 5.72-5.74 (1H, m), 5.93.
(1H, s), 6.01-6.02 (1H, m), 7.
09-7.14 (2H, m), 7.26-7.32 (1
H, m), 7.40-7.44 (2H, m), 7.73
(1H, d, J = 7.8Hz), 8.63 (1H, br
s)

(2) 1- [2-deoxy-3,5-O-
(1,1,3,3-tetraisopropyldisilox-
Synthesis of 1,3-diyl) -β-D-ribofuranosyl] uracil (formula (II), B = uracil, R ₁ = TIPDS) Method 1: Compound 18 obtained in (1) under argon flow.
7 mg, triphenylsilane 361 mg, and azoisobutyronitrile 20 mg were added, and the mixture was stirred at 100 ° C. for 2 hours. The reaction solution was directly purified by 24 g of silica gel column chromatography (6 g, eluted with hexane: ethyl acetate = 4: 1) to give the title compound as a white foam at 107 m.
g (yield 76%) was obtained. Method 2: Using 227 mg of the compound obtained in (1), 0.58 of triethylsilane instead of triphenylsilane
The title compound was obtained as a white foam in an amount of 133 mg (yield 77%) by the same procedure as in Method 1 using ml.

¹ H-NMR (CDCl ₃ ) δ: 0.91-
1.18 (28H, m), 2.23-2.29 (1H,
m), 2.47-2.55 (1H, m), 3.75-
3.78 (1H, m), 4.00-4.05 (1H,
m), 4.12-4.16 (1H, m), 4.41-
4.48 (1H, m), 5.69 (1H, d, J = 8.
3 Hz), 6.03 to 6.05 (1 H, m), 7.77
(1H, d, J = 8.3 Hz), 8.49 (1H, br
s) In addition, a compound in which R ₁ is a hydrogen atom can be synthesized by a method commonly used as a method for removing a silyl group such as an acid or fluorine ion treatment.

Example 2: 1- [2-deoxy-3,5-
O- (1,1,3,3, -tetraisopropyldisilox-1,3-diyl) -β-D-ribofuranosyl] -N
⁴ - benzoyl cytosine (Formula (II), B = N ⁴ over benzoyl cytosine, R ₁ = TIPDS) (1) Preparation of 1- [2-phenoxy-thiocarbonyl-oxy -
3,5-O- (1,1,3,3, -tetraisopropyldisilox-1,3-diyl) -β-D-ribofuranosyl] -N ⁴ -benzoylcytosine (formula (I), B = N ⁴ −
Benzoylcytosine, R ₁ = TIPDS, R ₂ = PhO
Synthesis of (S) C)) 1- [3,5-O- (1,1,3,3, -tetraisopropyldisilox-1,3-diyl) -β-D-ribofuranosyl] -N ⁴ -benzoyl The same procedure as in (1) of Example 1 was performed using 294 mg of cytosine, and the product was purified by silica gel column chromatography (5 g, eluted with hexane: ethyl acetate = 3: 1) to give the title compound as a pale yellow foam (264 mg). Yield 73%).

¹ H-NMR (CDCl ₃ ) δ: 0.88-
1.14 (28H, m), 4.01-4.08 (1H,
m), 4.18-4.21 (1H, m), 4.31-
4.35 (1H, m), 4.51-4.54 (1H,
m), 6.09 (2H, m), 7.13-7.64 (1
0H, m), 7.90 (1H, d, J = 7.3Hz),
8.27 (1H, d, J = 7.3 Hz), 8.72 (1
H, s)

(2) 1- [2-deoxy-3,5-O-
(1,1,3,3-tetraisopropyldisilox-
1,3-diyl)-beta-D-ribofuranosyl] -N ⁴ -
Synthesis of benzoylcytosine (Formula (II), B = N ⁴ -benzoylcytosine, R ₁ = TIPDS) Method 1: The same method as in Method 1 of Example 1 (2) was used using 109 mg of the compound obtained in (1). The mixture was manipulated and purified by silica gel column chromatography (3 g, eluted with hexane: ethyl acetate = 3: 1) to obtain 25 mg (yield 29%) of the title compound as a pale yellow powder. Method 2: Using 109 mg of the compound obtained in (1), the same operation as in Method 2 of Example 1 (2) was performed, and the product was subjected to silica gel column chromatography (3 g, eluting with hexane: ethyl acetate = 3: 1). Purification yielded 30 mg (35% yield) of the title compound as a pale yellow powder.

¹ H-NMR (CDCl ₃ ) δ: 0.88-
1.26 (28H, m), 2.36-2.41 (1H,
m), 2.58-2.66 (1H, m), 3.83-
3.85 (1H, m), 4.03-4.07 (1H,
m), 4.20-4.23 (1H, m), 4.38-
4.44 (1H, m), 6.09-6.11 (1H,
m), 7.46-7.63 (4H, m), 7.88-
7.90 (2H, m), 8.32 (1H, d, J = 6.
8 Hz), 8.65 (1 H, brs) Further, a compound in which R ₁ is a hydrogen atom can be synthesized by a method commonly used as a method for removing a silyl group, such as an acid or fluorine ion treatment.

Example 3: 1- [2-deoxy-3,5-
O- (1,1,3,3, -tetraisopropyldisilox-1,3-diyl) -β-D-ribofuranosyl] -adenine (formula (II), B = adenine, R ₁ = TIPD
Production of S) (1) 1- [2-phenoxythiocarbonyloxy-
3,5-O- (1,1,3,3, -tetraisopropyldisilox-1,3-diyl) -β-D-ribofuranosyl] -adenine (formula (I), B = adenine, R ₁ = TI)
Synthesis of PDS, R ₂ = PhO (S) C 1- [3,5-O- (1,1,3,3, -tetraisopropyldisilox-1,3-diyl) -β-D-ribofuranosyl] The same procedure as in (1) of Example 1 was performed using 255 mg of adenine and purified by silica gel column chromatography (9 g, eluted with hexane: ethyl acetate = 3: 1) to give 263 mg of the title compound as a white foam.
(Yield 82%) was obtained.

¹ H-NMR (CDCl ₃ ) δ: 0.98-
1.13 (28H, m), 4.04-4.20 (3H,
m), 5.35-5.39 (1H, m), 5.59 (2
H, brs), 6.16 (1H, d, J = 1.0H
z), 6.38 (1H, d, J = 5.4 Hz), 7.1
1-7.14 (2H, m), 7.27-7.32 (1
H, m), 7.40-7.45 (2H, m), 7.97.
(1H, s), 8.30 (1H, s)

(2) 1- [2-deoxy-3,5-O-
(1,1,3,3-tetraisopropyldisilox-
Synthesis of 1,3-diyl) -β-D-ribofuranosyl] adenine (formula (II), B = adenine, R ₁ = TIPDS) Example 1 was performed using 116 mg of the compound obtained in (1).
Perform the same operation as in method 1 of (1), and perform silica gel column chromatography (3 g, hexane: ethyl acetate =
Purification by elution (3: 1) gave 56 mg (yield 63%) of the title compound as a white powder.

¹ H-NMR (CDCl ₃ ) δ: 0.94-
1.26 (28H, m), 2.60-2.75 (2H,
m), 3.88-3.92 (1H, m), 4.05-
4.06 (2H, m), 4.93-4.99 (1H,
m), 5.61 (2H, s), 6.28-6.30 (1
H, m), 8.03 (1H, s), 8.32 (1H,
s) Further, a compound in which R ₁ is a hydrogen atom can be synthesized by a method commonly used as a method for removing a silyl group such as an acid or fluorine ion treatment.

Example 4: 1- [2,3-dideoxy-5
-O- (tert-butyldimethylsilyl) -β-D-
Ribofuranosyl] adenine (Formula (IV), B = _{adenine, R 1 = t-Bu (} Me) 2 Si) preparation of) (1) 1- [2-deoxy-3-phenoxypropyl thiocarbonyloxy -5-O-( tert-butyldimethylsilyl) -β-D-ribofuranosyl] adenine (formula (II
I), B = adenine, R ₁ = t-Bu (Me) ₂ Si, R
₃ = PhO (S) C)) 1- [2-deoxy-5-O- (tert-butyldimethylsilyl) -β-D-ribofuranosyl] -adenine 3
The same operation as (1) of Example 1 was performed using 00 mg,
Purification by silica gel column chromatography (9 g, eluted with chloroform: methanol = 99: 1) gave the title compound as a white foam, 226 mg (yield 55%).

¹ H-NMR (CDCl ₃ ) δ: 0.13
(3H, s), 0.19 (3H, s), 0.93 (9
H, s), 2.84-2.88 (2H, m), 3.97.
-4.05 (2H, m), 5.64 (2H, brs),
5.89-5.90 (1H, m), 6.60-6.64
(1H, m), 7.12-7.14 (2H, m), 7.
30-7.35 (1H, m), 7.43-7.47 (2
H, m), 8.22 (1H, s), 8.37 (1H,
s)

(2) 1- [2,3-dideoxy-5-O
-(Tert-Butyldimethylsilyl) -β-D-ribofuranosyl] adenine (formula (IV), B = adenine, R
₁ = t-Bu (Me) ₂ Si)) Method 1: Using 100 mg of the compound obtained in (1), the same operation as in Method 1 of Example 1 (2) was carried out, and silica gel column chromatography ( 3 g, eluted with hexane: ethyl acetate = 1: 2) to give 38 mg (yield 54%) of the title compound as a white powder. Method 2: Using 100 mg of the compound obtained in (1), the same operation as in Method 2 of Example 1 (2) was carried out, and silica gel column chromatography (3 g, eluting with hexane: ethyl acetate = 1: 2) was used. Purification yielded 30 mg (42% yield) of the title compound as a white powder.

¹ H-NMR (CDCl ₃ ) δ: 0.10.
(3H, s), 0.11 (3H, s), 0.93 (9
H, s), 2.01-2.19 (2H, m), 2.41.
-2.54 (2H, m), 3.76-3.80 (1H,
m), 3.98-4.01 (1H, m), 4.22-
4.28 (1H, m), 5.68 (2H, brs),
6.32-6.35 (1H, m), 8.29 (1H,
s), 8.34 (1H, s) Further, a compound in which R ₁ is a hydrogen atom can be synthesized by a method commonly used as a method for removing a silyl group such as an acid or fluorine ion treatment.

Example 5: 1- [2-cyano-2-deoxy-3,5-O- (1,1,3,3, -tetraisopropyldisilox-1,3-diyl) -β-D- arabinofuranosyl] -N ⁴ - acetyl cytosine (formula (VI),
B = N ⁴ -acetylcytosine, R ₁ = TIPDS, R ₃ =
CN) (1) 1- [2-cyano-2-phenoxythiocarbonyloxy-3,5-O- (1,1,3,3, -tetraisopropyldisilox-1,3-diyl) -β -D- arabinofuranosyl] -N ⁴ - acetyl cytosine (formula ^{(V), B = N 4} - acetyl cytosine, R ₁ = TIPD
S, R ₂ = PhO (S) C, R ₃ = CN))

1- [2-cyano-3,5-O- (1,
1,3,3-tetraisopropyldisilox-1,3
-Diyl) -β-D-arabinofuranosyl] -N ⁴ -acetylcytosine (1.08 g) and 4-dimethylaminopyridine (27 mg) were dissolved in anhydrous acetonitrile (30 ml), and phenoxythiocarbonyl chloride 0 was added at 0 ° C. under an argon stream. 0.54 ml and triethylamine 0.54 ml
Was added, and the mixture was stirred at room temperature for 3 hours. After completion of the reaction, diethyl ether was added and washed twice with ion-exchanged water. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was purified by silica gel column chromatography (30 g, eluted with hexane: ethyl acetate = 3: 2) to give the title compound as a yellowish white foam, 1.1.
6 g (86% yield) was obtained.

¹ H-NMR (CDCl ₃ ) δ: 0.94-
1.28 (28H, m), 2.27 (3H, s), 4.
05-4.25 (3H, m), 5.03-5.07 (1
H, m), 6.99-7.49 (6H, m), 7.71
(1H, d, J = 7.8Hz), 9.63 (1H, br
s) In addition, a compound in which R ₁ is a hydrogen atom can be synthesized by a method commonly used as a method for removing a silyl group such as an acid or fluoride ion treatment.

(2) 1- [2-cyano-2-deoxy-
3,5-O- (1,1,3,3, -tetraisopropyldisilox-1,3-diyl) -β-D-arabinofuranosyl] -N ⁴ -acetylcytosine (formula (VI), B =
N ⁴ - acetyl _{cytosine, R 1 = TIPDS, R 3} = C
Synthesis of N) Method 1: Using 800 mg of the compound obtained in (1), the same operation as in Method 1 of Example 1 (2) was carried out, and silica gel column chromatography (24 g, hexane: ethyl acetate = 2: 3). And eluted with hexane and ethyl acetate to crystallize the title compound as white crystals (221 mg).
(Yield 35%) was obtained. Method 2: Using 800 mg of the compound obtained in (1), the same operation as in Method 2 of Example 1 (2) was carried out, and the product was subjected to silica gel column chromatography (24 g, eluted with hexane: ethyl acetate = 2: 3). Purified and crystallized from hexane and ethyl acetate to give the title compound as white crystals, 231 mg.
(Yield 37%) was obtained.

¹ H-NMR (CDCl ₃ ) δ: 0.96-
1.27 (28H, m), 2.28 (3H, s), 3.
72 (1H, dd, J = 6.8, 8.8Hz), 3.8
7-3.90 (1H, m), 4.06-4.19 (2
H, m), 4.61-4.66 (1H, m), 6.33.
(1H, d, J = 6.8), 7.53 (1H, d, J =
7.8), 8.06 (1H, d, J = 7.8), 9.4.
3 (1H, brs)

Claims (4)

[Claims] 1. A radical reduction using an organic silane having a boiling point of 90 ° C. or higher in the presence of a radical initiator, using a nucleoside derivative obtained by converting a hydroxyl group at a site to be deoxylated to a thiocarbonyl group or a phosphonyl group as a raw material compound. A method for producing a deoxynucleoside, which comprises deoxygenating with. 2. A raw material compound of the formula (I): (In the formula, B is a nucleobase or a nucleobase derivative, R ₁ is a hydrogen atom or a hydroxyl-protecting group, and R ₂ is a thiocarbonyl group or a phosphonyl group.) Using a nucleoside derivative represented by the formula (II) [Chemical 2] (In the formula, B represents a nucleobase or a nucleobase derivative, and R ₁ represents a hydrogen atom or a hydroxyl-protecting group.) 2 ′
-The process according to claim 1, wherein deoxynucleosides are obtained. 3. A compound represented by the formula (III): (Wherein B represents a nucleobase or a nucleobase derivative, R ₁ represents a hydrogen atom or a hydroxyl-protecting group, and R ₂ represents a thiocarbonyl group or a phosphonyl group.), A nucleoside derivative represented by the formula (IV) [Chemical 4] The method according to claim 1, wherein 2 ′, 3′-dideoxynucleoside represented by the formula (B represents a nucleobase or a nucleobase derivative, and R ₁ represents a hydrogen atom or a hydroxyl-protecting group) is obtained. . 4. A compound of formula (V): (In the formula, B represents a nucleobase or a nucleobase derivative, R ₁ represents a hydrogen atom or a hydroxyl-protecting group, R ₂ represents a thiocarbonyl group or a phosphonyl group, and R ₃ represents a cyano group, a lower alkyl group or a substituted lower alkyl group. .) Using a nucleoside derivative represented by the formula (VI): (Wherein B represents a nucleobase or a nucleobase derivative, R ₁ represents a hydrogen atom or a hydroxyl-protecting group, and R ₃ represents a cyano group, a lower alkyl group or a substituted lower alkyl group). The production method according to claim 1, wherein a -deoxy-2'-substituted nucleoside is obtained.