JPS62267294A - Novel method for synthesizing nucloside - Google Patents

Abstract

PURPOSE:To obtain the titled compound in high yield and simply, by reacting a specific fluorinated saccharide with a silylated base in the presence of Lewis acid catalyst. CONSTITUTION:A fluorinated saccharide (e.g. O<2>', O<3>', O<5>'-tribenzyl-1-fluorinated-alpha- D-ribofuranose, etc.) shown by formula I [R<1> and R<2> are OH-protective group; l, m and n are 0-3 and l+m+n=2-3) is reacted with a compound [e.g. bis(trimethylsilyl)uracil, etc.] shown by formula B-[Si(CH3)3]p [B is pyrimidine or purine residue which may be replaced; p is 1-3) in the presence of Lewis acid catalyst (preferably silicon tetrafluoride, trimethylsilyl triflate or boron trifluoride) usually in an inert solvent such as diethyl ether, dichloromethane, etc., preferably at -78-100 deg.C for 30min-72hr to give the aimed compound shown by formula II (R<3> and R<4> are H or OH-protecting group).

Description

DETAILED DESCRIPTION OF THE INVENTION [Object] The present invention relates to a method for producing nucleosides easily and with high yield.

The development of efficient methods for synthesizing nucleosides is an important issue from the viewpoint of the synthesis of natural nucleosides that are medically and pharmaceutically interesting, or the effective supply of derivatives that exhibit superior effects.

Conventionally, the following methods are known as chemical synthesis methods for nucleosides.

1) A heavy metal salt method in which sugar bromide or chloride is condensed with a heavy metal base such as a silver salt or mercury salt of various purine bases 2) An improved method of 1) above in which 2-deoxyribose chloride is condensed with a sodium salt of purine 3) Bath melting method in which the acylated sugar and base are heated and melted, then an acid catalyst such as a Lewis acid is added, and further melted under reduced pressure.4) Holble-Yutsken method in which the acylated sugar and silylated base are reacted in the presence of a Lewis acid catalyst.However, The above methods have unstable starting sugars, low yields, complicated operations, are not economical, and are not suitable for large-scale synthesis, or the product is contaminated with α and especially β isomers. There were problems such as.

As a result of many years of intensive research into a high-yield and simple synthesis method for nucleosides, the present inventors have discovered (1)
Contrary to expectations, nucleosides can be produced in high yields by reacting fluorinated sugar, which is stable under extreme pressure and is easy to handle, with a silylated base in the presence of a Lewis acid catalyst. (2) It is easy to operate and economical. Kurami has completed the present invention by being suitable for large-scale synthesis.

〔composition〕

The production method of the present invention uses K as shown in the following formula:
11-, and the sum of t, m, and n is 2 to 3t-.

)tP and a compound t having the general formula %) () (wherein B represents an optionally protected pyrimidine or zoline residue, and p represents 1 to 3r); The reaction is carried out in the presence of a Lewis acid catalyst, and the protecting group is removed if desired.t General formula (wherein B3 and B4 are the same or different and represent a hydrogen atom or a protecting group for a hydroxyl group, t, m , n and B have the same meanings as above.) 1- Manufacturability of the compound having.

Examples of the "hydroxyl protecting group" in the definitions of Bl, B2, R5 and B4 include formyl, acetyl,
Aliphatic acyl groups such as chloroacetyl, dichloroacetyl, trichloroacetyl, trifluoroacetyl, methoxyacetyl, propionyl, n-butyryl, (2-methyl-2-butenoyl, isobutyryl, pentanoyl, pivaloyl; benzoyl, 0- (dibromomethyl) to 7 Soi k, 0-(methoxycarbonyl)benzoyl, p-phenylbenzoyl, 2,4.6-)limethylpenzoyl, p-1 luoyl, p-anisoyl, p
- aromatic acyl groups such as chlorobenzoyl, p-nitrobenzoyl, 0-nitrobenzoyl, α-su7toyl; methoxymethyl, ethoxymethyl, n-propoxymethyl, isopropoxymethyl, n-butoxymethyl, t-
butoxymethyl, 2-methoxyethoxymethyl, 2,2
．． Lower alkyloxymethyl groups such as 2-trichloroethoxymethyl, bis(2-chloroethoxy)methyl; 1-ethoxyethyl, l-methyl-1-methoxyethyl, 1-(isopropoxy)ethyl, 2.2.2 − )
+770 Substituted ethyl groups such as loethyl, 2-(phenylzelenyl)ethyl; benzyl, phenethyl, 3-phenylzolobyl, p-methoxybenzyl, 0-nitrobenzyl/I/, T)-nitropenzole, p-halohensyl, p- Aralkyl groups such as cyanopenol, nophenylmethyl, triphenylmethyl, α-especially β-naphthylmethyl, α-naphthyldiphenylmethyl, p-me)xyphenyldiphenylmethyl; tetrahydrobilan-2-yl, 4-methoxytetrahydrobilane Tetrahydropyranyl group nitrimethylsilyl such as -4-yl, tri-lower alkylsilyl such as triethylsilyl, isopropylzmethylsilyl, t-butyldimethylsilyl, methylsilylable pyrsilyl, methyldi-t-butylsilyl, triisopropylsilyl groups; acetal or ketal type protecting groups such as ethylidene, isopropylidene, methoxymethylidene, ethoxyethylidene, benzylidene, cyclohexylidine; methoxycarbonyl, ethoxycarbonyl, t-butoxycarbonyl, 2,2.2-) Alkyloxycarbonyl groups such as chloroethoxycarbonyl, isobutoxycarbonyl, 2-methylsilylethyloxycarbonyl; alkenyloxycarbonyl groups such as vinyloxycarbonyl, allyloxycargenyl or penzyloxycarbonyl, p - All aralkyloxycarbonyl groups such as methoxypenzyloxycarbinyl, 3,4-nomethoxyhensyloxycarzenyl, 0-nitrobenzyloxycarbinyl, p-nitrobenzyloxycarbinyl, are preferred. Examples include aliphatic acyl groups, aromatic acyl groups, and aralkyl groups.

[Pyridine or purine residue] in the definition of B is, for example, the general formula, or the general formula % formula % In the above formula, B5 and B6 are the same or different, and are a hydrogen atom, a hydroxyl group, a substituted hydroxyl group, Mercapto group, substituted mercapto group, amine group, substituted amino group, halogen atom The parent represents a log atom or an imino group, and B represents a halogen atom or a lower alkyl group that may be halogenated. shows.

The substituents for the [substituted hydroxyl group] in the definitions of B and B6 are preferably methyl, ethyl, propyl,
Isopropyl, butyl, isobutyl, s-7'thyl,
Mention may be made of lower alkyl groups such as t-butyl, pentyl, hexyl.

The substituent for the "substituted mercapto group" in the definitions of B5 and B6 is preferably the lower alkyl group.

The "substituted amino group" in the definitions of B5 and B6 refers to a group substituted with one or two of the following substituents, and the substituents include the above-mentioned lower alkyl group; lower alkyloxy group ; Said aralkyl group; Aralkyloxy group; Hydroxyl group; 2-hydroxyethyl, 3-hydroxy! Hydroxy-substituted lower alkyl group such as 2-
Aminoethyl, 3-aminopropyl or more amino-substituted lower alkyl group or phenyl, p-) IJl, p-
Methoxyphenyl, p-chlorophenyl, αtL (β
-Aryl group like naphthyl? Preferably, they are an aralkyl group, a hydroxyl group, a lower alkyloxy group, or an aralkyloxy group.

The "optionally halogenated lower alkyl group" in the definitions of B51R6 and B9 includes the lower alkyl group, fluoromethyl, difluoromethyl, trifluoromethyl, trifluoroethyl, bromomethyl, chloroethyl, tribromomethyl, trichloromethyl. can be mentioned.

The "halogen atom" in the definitions of R5, R6 and B represents fluorine, chlorine, bromine and iodine.

In the definition of B, the "protecting group" that "may be protected" refers to the same group as the above-mentioned "hydroxyl protecting group" in the case of a hydroxyl group protecting group, and preferably an aliphatic acyl group. or an aromatic acyl group.

In the case of a protecting group for an amino group or a substituted amino group, there are one or two of the following protecting groups. The nuclear protecting group is not limited as long as it is normally used as a protecting group for amino groups, but preferably the above aliphatic acyl group; the above aromatic acyl group or N,N-tumethylaminomethylene , benzylidene, p-methoxybenzylidene, p-nitrobenzylidene, salicylidene, 5-chlorosalicylidene/, sophenylmethylene, (5-chloro-
2-Hydroxyphenyl) is a substituted methylene group that forms a Schiff base such as phenylmethylene.

In the case of a protecting group for a mercapto group, there are no limitations to what is normally used to protect a mercapto group, but preferably,
The aliphatic acyl group or the aromatic acyl group.

The compounds il+ and (1111) of the present invention have several asymmetric carbon ligations in their molecules, and there are stereoisomers in which each of them is S-coordinated or S-coordinated. Any mixture of these is included in the present invention.

The synthesis method of the present invention uses 1-position fluorinated sugar (1) and trimethylene.

A glycosidation reaction is carried out by reacting in a solvent in the presence of a Lewis acid catalyst. It is a method of building.

Trimethylsilylation reactions of various nucleobases are described, for example, by Sears et al., Sirelation of Organic Knowledge, 434j [, 1961E.

(A, E, Pierce, et al, 5i
Lylation of Organic Compou
nds, 434+ (196B)) in a conventional manner. The catalyst is not limited as long as it is a Lewis acid, but Lewis acids such as silicon tetrafluoride, trimethylsilyl triflate, and boron trifluoride are preferably used.

The solvent is not particularly limited as long as it does not inhibit the reaction, but suitable examples include ethers such as diethyl ether and nooxane, halogenated hydrocarbons such as dichloromethane and dichloroethane, and nitriles such as acetonitrile. It is a polar solvent.

Although the reaction temperature is not particularly limited, it is preferably about -78°C to 100°C, and the reaction is preferably carried out for 30 minutes to 72 hours. The substituent of the nucleobase having formula (IV &) or formula (F/b) k is a hydrogen atom, a hydroxyl group, a substituted hydroxyl group, a substituted amino group, a substituted mercapto group, a mercapto group, a halogen atom, - - If the substituent of the optionally logogenated lower alkyl group or the nucleobase having the formula (IVc)k is an oxygen atom, a sulfur atom, or an imino group, the silylation reaction can be carried out as is, In the case of an amino group, it is preferable to protect the amino group with a protecting group such as a lower aliphatic acyl group such as an acetyl group and then silylate it. Further, when the nucleobase (BH) used is a purine compound, the production ratio of isomers at the 7th and 9th positions, which are the reaction product proboscis, may vary from the reaction temperature 9.

After completion of the reaction, the target compound can be isolated from the reaction mixture according to conventional methods. For example, a pure product can be obtained by purification by recrystallization, preparative thin layer chromatography, column chromatography, etc.

Removal of the protecting group varies depending on the type of protecting group, but is generally carried out as follows by methods well known in the art.

First, regarding the removal of the protecting group for the hydroxyl group, when the protecting group for the hydroxyl group is an alkyloxycarbonyl group or an aralkyl group, it can be removed by contacting with a reducing agent. For example, catalytic reduction is carried out using a catalyst such as radium on carbon or platinum at room temperature, or using an alkali metal sulfide such as sodium sulfide or potassium sulfide. The reaction is carried out in the presence of a solvent, and the solvent used is not particularly limited as long as it is not involved in this reaction, but alcohols such as methanol and ethanol, ethers such as tetrahydrofuran and dioxane, or Preferred are fatty acids such as acetic acid and mixed solvents of these organic solvents and water.

The reaction temperature is usually around 0° C. to room temperature, and the reaction time varies depending on the raw material compound and the type of reducing agent, but is usually 5 minutes to 12 hours.

When the hydroxyl group is an aliphatic acyl group, aromatic acyl group or alkyloxycarbonyl group, it can be removed by treatment with a base in the presence of an aqueous solvent. The solvent used is not particularly limited as long as it is used in ordinary hydrolysis reactions, and water or water and alcohols such as methanol, ethanol, n-gulononol, or tetrahydrofuran or dioxane are used. Mixed solvents with organic solvents such as ethers are suitable. The base is not particularly limited as long as it does not affect other parts of the compound, but suitable bases include alkali metal carbonates such as sodium carbonate and potassium carbonate, sodium hydroxide, and potassium hydroxide. It is carried out using alkali metal hydroxides or concentrated ammonia-methanol. For deprotection of the nucleic acid base moiety, concentrated ammonia methanol is used; in other cases, 1N hydroxide is used).It is preferable to use 1Wk of IJum water.The degree of reaction source is not particularly limited, but side reactions can be suppressed. Therefore, a temperature around 0°C to 150°C is suitable. The reaction time varies depending on the type of raw material compound, reaction temperature, etc., but is usually 1 to 10 hours.

When the protecting group for the hydroxyl group is an alkyloxymethyl group, a tetrahydropyranyl group, a tetrahydrofuranyl group, an acetal or ketal type protecting group, or a substituted ethyl group, it can be removed by treatment with an acid in a solvent. can. Preferred acids used include hydrochloric acid, acetic acid-sulfuric acid, and tosylic acid. The solvent is not particularly limited as long as it does not participate in this reaction, but alcohols such as methanol and ethanol, tetrahydrofuran,
Ethers such as dioxane or a mixed solvent of these organic solvents and water are suitable. The reaction temperature is usually 0°C to 50°C, and the reaction time is usually 10 minutes to 18 hours, although it varies depending on the raw material compound and the type of acid.

When the protecting group for the hydroxyl group is an alkenyloxycargenyl group, the protecting group for the hydroxyl group is usually an aliphatic acyl group,
It can be removed by treatment with a base under the same conditions as the removal reaction for aromatic acyl groups or alkyloxycarbonyl groups. In the case of allyloxycarbonyl, removal using radium and triphenylphosphine or nickel tetracarbonyl is particularly convenient and can be carried out with fewer side reactions.

When the protecting group for the hydroxyl group is a tri-lower alkylsilyl group, the protecting group can be removed using a fluoride anionic compound such as tetrabutylammonium fluoride. This can be carried out by treatment with a compound that produces f-. The solvent used is not particularly limited, but ethers such as tetrahydrofuran and dioxane are suitable. The reaction preferably comprises
This is carried out by processing for 10 to 18 hours at around room temperature.

In addition, by the above-described operation for removing the hydroxyl group-protecting group, the mercapto group-protecting group and/or the amino group-protecting group may be removed at the same time.

After completion of the reaction, the target compound can be isolated from the reaction mixture according to conventional methods. For example, a pure product can be obtained by purification by recrystallization, preparative thin layer chromatography, or column chromatography.

Next, regarding the removal of the protecting group for the mercapto group, when the protecting group for the mercapto group is an aliphatic acyl group or an aromatic acyl group, it can be removed by treatment with a base. The reaction conditions are the same as those for the removal reaction described in the case where the hydroxyl protecting group is an aliphatic acyl group, an aromatic acyl group or an alkyloxycarbonyl group.

Note that this reaction may also simultaneously remove a hydroxyl group-protecting group and/or an amino group-protecting group.

After the completion of the reaction, the desired compounds are collected from the reaction mixture according to conventional methods, and if necessary, they can be further purified, for example, by recrystallization, preparative thin layer chromatography, column chromatography, etc.

Regarding the removal of the protecting group of the amino group, if the protecting group of the amino group is an aliphatic acyl group, an aromatic acyl group, or a substituted methylene group that forms a Schiff base, it can be removed by treatment with a base. The reaction conditions are the same as those for the removal reaction described in the case where the hydroxyl protecting group is an aliphatic acyl group, an aromatic acyl group or an alkyloxycarbonyl group.

In addition, by the above-mentioned operation for removing the amino group-protecting group, the hydroxyl group-protecting group and/or the mercapto group-protecting group may be removed at the same time.

After completion of the reaction, the target compound can be isolated from the reaction mixture according to conventional methods. For example, a pure product can be obtained by purification by recrystallization, preparative thin layer chromatography, column chromatography, etc.

Note that the above-mentioned hydroxyl-protecting group removal reaction, amino group removal reaction, and mercapto-protecting group removal reaction may be carried out in any order, depending on the desired removal reaction. It can be carried out sequentially.

The starting material, fluorinated sugar (1), is a known compound,
It can be synthesized more efficiently by using the corresponding 1-0-acetylated sugar or a sugar in which the 1-position is unprotected, using an inexpensive and easily available fluorinated water-pyridine mixture, and reacting with the conventional method.

EXAMPLES The present invention will be specifically described with reference to Examples below. All of the products are known compounds, and the instrumental data for each product corresponds to that of known compounds, and based on this, α
The production ratio r of isomers and β-bodies was determined.

Instrumental data of the obtained compounds are described below. still,
All IH-NMR data were measured at 90 MHz;
cnct was used as a solvent.

3.6-3.8 (m, 2) 1) 4.0-4.2 (m, IB) 4.3-4.8
(m, 9 I()6, 28 (d lJ
=5 Hz, IE)7.0-7.4 (m,
15 H) 7.7 (d, J = 88z
, IB) 8.6 (BS, IH) 3.6-4.1 (m, 4 H) 4.3-4.6 (un, 5 H) 4.8
(a, IH) 5.1 (s, 1B) 5.3 (d, J=8Hz, 1) 1) 6.1
(d*J”2Hz, IH)7.0~
7.4 (m, 15 B) 7.9 (d
, J-8Hz, 1B) 8.7 (bs, IB) 4.6-4.9 (m, 3H) 5, 6-5.9 (m*3B) 6.32
(d, J=5.3Hz, IH) 7.2-7.7, 7.
8-8.2 (m, 16 B) 9.0
(bs, IH) 4.4-4.8 (m, 3E) 6.0-6.5
(m, 3H) 7.2-7.6, 7.8-8.2 (m, 20H)8.
3 (β, IB) 8.6 (a, IH) 2.18 (s, 3H) 2.20 (s, 3H) 4.8-5.2 (m, 2H) 3.6-4.0 (m, 3H) 6.8 (t, J=3)1z, IH)7,7
(d e J ~8 Ez, I H) 2.4
(s, 3H) 2・2 (s, 3B) 4.8~5.2 (m, 2H) 3.6~4.0 (m, 3B) 6.6
(t, J=3Hz, IH) 7.9 (d, J
=8Hz, IH) 2.05, 2.10 (8 each, 3 each
B) 2.5-2.7 (m, 2B) 4.2-4
．． 4 (m, 3)] )5.4 (bd
, 1) 1) 6.6 (bs, IH) 7, 4~7゜6, 8.0~8.4 (m, 5H) 8
．． 5 (s, IE) 8.6 (s, IH) 2.07.2.15 (each 8. each 3H) 2, 7-3.2 (m a 2 H) 4.39 (a, 3B) 5 .50 (bd, 1) 1) 6.52 (t, J=6Hz, IH37,2~'1
．． 'l, 7.8~8.2 (rrr, 5)1
) 8.4 (a, IB) 8.7 (s, IB) 9.9 (a, IB) 3.6-3.7 (m, 2 H) 3.9-4.2 (m, 3 H ) 4, : 3-4.7 (m, 5 B) 5.4-5-
7 (m a 2 H) 5.9 (d, J=6Hz, IH) 7.8
(d a J ~8 Hz - I B )8.5
(bs, IH) After heating and drying under reduced pressure, o2 was added to the reaction vessel replaced with arganese.
', o5', o5' -) Ripenno-1-fluoride-α-D-lyfurano-X (5001m9.1.1
8mmot) k, add acetonitrile (5r
Bis(trimethylsilyl)uracil (36o1 ng + 1.40 mmoL) dissolved in K syringe was added. Next, at 0°C, silicon tetrafluoride was added to an acetonitrile solution (0.08M, 1.5mA+, 0.08M, 1.5mA+,
12 mmot) was added, and the mixture was stirred at this temperature for 2 hours.

After the reaction was completed, the reaction mixture was poured into a saturated hydrogen carbonate solution (201d) and extracted with ethyl acetate (50 mJ x 2). The organic layer was washed with a saturated aqueous solution of hydrogen carbonate (20 mJ x 2) and saturated brine (10 mJ x 1), and the solvent was distilled off.

The obtained crude product was subjected to silica gel column chromatography (silica 20v, hexane:ethyl acetate 1:1) to yield the title compound (514η).

85 chi) was obtained. Ratio of α-anomer and β-anomer (
1:5.2) was determined by the integral ratio of the base part (6th position) of the uridine derivative in I HNME.

The following Examples 2 to 3 were carried out using the same method as in Example 1, with the column Ftl changed as described below.

TABLE 1 Condition Product 2 Sochloromethane * 84 1
．． 5:13 Diethyl ether *
82 1.1:1*) 4 people were exposed to 81F4 gas reaction solvent for 2 minutes.

According to the same method as in Example 1, 0"J
O" + 0" -FRepensol-l-Fluoride-β-D
−Using ribofuranose τ and changing the conditions as below,
Examples 4-6 below were conducted.

TABLE 2 Example Completed Medium SiFν佽oA% Yiel
d(11α:β4 sochloromethy *
82 2.1:15 Acetonitrile
10 88 1:5.26 Diethyl ether * 82 1.4:1 Examples 7 and 8 were carried out in the same manner as in Example 1 except that the catalyst was changed.

TABLE 3 Example Catalyst rnoL% yield
(%)α:β7 Trimethylsilyl triflate 5
0 82 1:48 Boron trifluoride
50 84 1:3 By the same operation as in Example 1, 021, Osr,
Os/-tribenzoyl-1-fluoride-〇-trifuranose (48ON, 1.03 mmot) and bis(trimethylsilyl)uracil (356,6 wI, 1.30
Into the acetonitrile solution of silicon tetrafluoride W (0.08M + 2.5m
+ 0.2 mmot) k and stirred at this temperature for 4 hours. After the reaction was completed, the reaction mixture was treated in the same manner as in Example 1, and the β-form of the title compound (470 cm, 82%) was not produced, nor was the corresponding α-form.

15ONMR (CDCA 5) δ 2 63.7,
71.4, 73.8, 80.8°88.48.103.
4, 128-130l28-130 (aro.

133.4, 133.6, 139.4, 161.8, 1
65.2 Following a method similar to Example 9, changing the catalyst,
In Examples 10 to 11, only the β-form was produced in this case as well.

10) Limethylsilyl triflate 50
8711 Boron trifluoride 50
85 Example 12 0", O", O", N'-tetrapeyzoyladenokune Following the same method as in Example 9, fluorinated sugar (300 ■ r 0
．． 65 mmot) and N6-penzoyl-N6.65 instead of bis(trimethylsilyl)uracil. N9-bis(
trimethylsilyl) adenine (30711v.

When the protecting group was removed using sodium methylate, adenosine' could be obtained in 82 mm. α-form was not obtained.

Rasil 05, o5-diacetyl-2-deoxy-1-fluorinated-lyzefuranose (101,0 + 0.46 mmo
t) and bis(trimethylsilyl)-5-fluoroura'
/)' (189N+0.69mmot) in acetonitrile (2d) solution at -20°C, 0.08M 81F
4-acetonitrile@liquid (0.5d, Q, 05mm
ot) k was added and stirred for 2 hours. After treatment according to the method of Example 1, the obtained crude product was subjected to silica gel column chromatography (ethyl acetate-hexane = 2:1) to obtain the title compound (115, 76). The ratio of α and β forms was 2:3.

Adenine According to the method of Example 13, N6-penzoyl-N6. When conducted using N9-bis(trimethylsilyl)adenine, the indicated target compound = 1681,
It was possible to obtain the α-form and β-form at a ratio of 1:1.

By the operation of Example 1, 02/, Os1. ,0s
l-tribenzyl-1-fluorinated-D-arabinofuranose (200η+ 0.47 mr++oA) and bis(
trimethylsilyl) uracil (154~+0.6 m
Add silicon tetrafluoride acetonitrile solution (0.08M, 1.2mL 0
．． 9 mmot) k was added at 0°C, stirred at this temperature for 3 hours, and then post-treated to obtain the α-form of the title compound (201 mg, 8
4%). β-body was not obtained.

L5CN■(CDC6,)δ: 65.7, 70.1
, 72.1.73.4° 82.4 , 84.0 , 8
8.7, 92.3, 102.5, 128-138
(benzyl), 141.9, 149.6,
When using 163.2 arabinose derivative as a substrate,
Either benzoyl or benzyl can be used as a protecting group for the hydroxyl group.
Only the α-anomer was obtained in any of the solvents used: acetonitrile, dichloromethane, and diethyl ether.

Claims (1)

[Claims] General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (I) (In the formula, R^1 and R^2 are the same or different and represent a protecting group for a hydroxyl group, l, m, and n are the same or different and represent 0 to 3, and the sum of l, m, and n represents 2 to 3.)
and a fluorinated sugar having the general formula B-[Si(CH_3)_3]_p (II) (wherein, B
represents an optionally protected pyrimidine or purine residue, and p represents 1 to 3. ),
General formulas ▲Mathematical formulas, chemical formulas, tables, etc.▼(III) (In the formula, R^3 and R^4 are the same or differently, a hydrogen atom or a hydroxyl group-protecting group, and l, m, n and B have the same meanings as above.