JPH051093A - Method for succinylating nucleoside - Google Patents
Method for succinylating nucleosideInfo
- Publication number
- JPH051093A JPH051093A JP14887591A JP14887591A JPH051093A JP H051093 A JPH051093 A JP H051093A JP 14887591 A JP14887591 A JP 14887591A JP 14887591 A JP14887591 A JP 14887591A JP H051093 A JPH051093 A JP H051093A
- Authority
- JP
- Japan
- Prior art keywords
- nucleoside
- group
- amino group
- pyridine
- succinyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
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- Saccharide Compounds (AREA)
Abstract
Description
【0001】[0001]
【産業上の利用分野】本発明は、ヌクレオシドの塩基部
のアミノ基をスクシニル基で効率よく保護する方法に関
するものである。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for efficiently protecting an amino group at the base of a nucleoside with a succinyl group.
【0002】[0002]
【従来の技術】スクシニル基は、DNA型オリゴヌクレ
オチドの化学合成において問題となるデプリネーション
を抑制でき(Nucleic Acids Res., 12, 8525(1984)) 、
さらにホスホロアミダート法におけるアニリノ基の除去
の際に伴う塩基部のアミノ基の欠落を防止できる(Hete
roatom Chem., 2 ,187(1991))という優れた特性を有す
ることから、ヌクレオシドの塩基部のアミノ基の保護基
として大変好ましいものである。2. Description of the Related Art A succinyl group can suppress depletion, which is a problem in the chemical synthesis of DNA type oligonucleotides (Nucleic Acids Res., 12 , 8525 (1984)),
Furthermore, it is possible to prevent the lack of the amino group at the base part that accompanies the removal of the anilino group in the phosphoramidate method (Hete
roatom Chem., 2 , 187 (1991)), which is very preferable as a protecting group for the amino group in the base part of a nucleoside.
【0003】[0003]
【発明が解決しようとする課題】従来、ヌクレオシドの
塩基部のアミノ基をスクシニル基で保護する方法として
は、ピリジン中、大過剰の塩化トリメチルシリルおよび
トリエチルアミンの存在下、ヌクレオシドと10倍モル
の無水コハク酸とを約100℃の温度条件下で反応させ
るという畑らの方法(Nucleic Acids Res., 12, 8525(1
984)) 、および畑らの方法をさらに改良した西野らの方
法(Heteroatom Chem., 2 ,187(1991)が報告されてい
る。しかし、上記従来法の反応収率は高々30〜40%
程度であり、このような低収率が、スクシニル基が上述
したように優れた保護基であるにもかかわらずオリゴヌ
クレオチドの合成において実際あまり使用されていない
ことの主な原因となっていた。よって、本発明はヌクレ
オシドの塩基部のアミノ基をスクシニル基により効率よ
く保護する新規な方法を提供することを目的とする。Conventionally, as a method of protecting the amino group of the base portion of a nucleoside with a succinyl group, the nucleoside and 10-fold molar amount of anhydrous succinic acid in pyridine were used in the presence of a large excess of trimethylsilyl chloride and triethylamine. The method of Hata et al. (Nucleic Acids Res., 12 , 8525 (1
984)), and Nishino et al.'S method (Heteroatom Chem., 2 , 187 (1991)), which is a modification of Hata's method, but the reaction yield of the above-mentioned conventional method is at most 30-40%.
Such a low yield was a major cause of the fact that the succinyl group, despite being an excellent protecting group as described above, is rarely used in the synthesis of oligonucleotides. Therefore, an object of the present invention is to provide a novel method for efficiently protecting the amino group of the base part of a nucleoside with a succinyl group.
【0004】[0004]
【課題を解決するための手段】本発明者らは、上記の目
的に即して種々研究を重ねた結果、原料化合物としてヌ
クレオシドの水酸基をアシル基で保護したもの(以下、
ヌクレオシドのアシル体とも称する)を使用し、この原
料化合物とハロゲン化アルキルスクシニルとを塩基性溶
媒中で反応させることによりヌクレオシドの塩基部のア
ミノ基へスクシニル基を効率よく導入できることを見出
し、本発明を完成させるに至った。すなわち、本発明
は、ヌクレオシドの塩基部のアミノ基をスクシニル基で
保護する方法であって、原料化合物としてヌクレオシド
のアシル体を使用し、この原料化合物とハロゲン化アル
キルスクシニルとを塩基性溶媒中で反応させ、次いで閉
環反応に付すことを特徴とするヌクレオシドの塩基部の
アミノ基をスクシニル基で保護する方法を提供するもの
である。また、本発明は、ヌクレオシドの塩基部のアミ
ノ基をスクシニル基で保護する方法であって、原料化合
物としてヌクレオシドのアシル体を使用し、この原料化
合物とハロゲン化アルキルスクシニルとを塩基性溶媒中
で反応させ、次いで水酸基のアシル基を除去後閉環反応
に付すことを特徴とするヌクレオシドの塩基部のアミノ
基をスクシニル基で保護する方法を提供するものであ
る。Means for Solving the Problems The present inventors have conducted various studies in accordance with the above-mentioned objects, and as a result, as a raw material compound, a hydroxyl group of a nucleoside protected with an acyl group (hereinafter,
It was found that a succinyl group can be efficiently introduced into the amino group of the base portion of a nucleoside by reacting this starting compound with an alkylsuccinyl halide in a basic solvent using an nucleoside acyl derivative). Has been completed. That is, the present invention is a method of protecting an amino group of a base portion of a nucleoside with a succinyl group, wherein an acyl body of a nucleoside is used as a raw material compound, and the raw material compound and an alkylsuccinyl halide are mixed in a basic solvent. The present invention provides a method for protecting an amino group at the base portion of a nucleoside with a succinyl group, which comprises reacting and then subjecting to a ring closure reaction. Further, the present invention is a method of protecting an amino group of a base portion of a nucleoside with a succinyl group, wherein an acyl derivative of a nucleoside is used as a raw material compound, and the raw material compound and an alkylsuccinyl halide are mixed in a basic solvent. The present invention provides a method for protecting an amino group at the base portion of a nucleoside with a succinyl group, which comprises reacting, then removing the acyl group of the hydroxyl group, and then subjecting the ring to a ring-closing reaction.
【0005】以下、本発明を詳しく説明する。本発明方
法において原料化合物として使用するヌクレオシドのア
シル体は塩基部にアミノ基を有するヌクレオシドのアシ
ル体であれば特に限定されない。たとえば、3′,5′
‐ジ‐O‐アシル‐2′‐デオキシアデノシン、3′,
5′‐ジ‐O‐アシル‐2′‐デオキシグアノシン、
3′,5′‐ジ‐O‐アシル‐2′‐デオキシシチジン
などの2′‐デオキシヌクレオシドのアシル体、または
2′,3′,5′‐トリ‐O‐アシルアデノシン、
2′,3′,5′‐トリ‐O‐アシルグアノシン、
2′,3′,5′‐トリ‐O‐アシルシチジンなどのリ
ボヌクレオシドのアシル体を例示することができる。原
料化合物中のアシル基は特定されず、通常は炭素数1〜
5程度のアシル基でよい。具体的にはアセチル、プロピ
オニル、ブチリルなどが例示される。The present invention will be described in detail below. The acyl body of the nucleoside used as the starting compound in the method of the present invention is not particularly limited as long as it is an acyl body of a nucleoside having an amino group at the base portion. For example, 3 ', 5'
-Di-O-acyl-2'-deoxyadenosine, 3 ',
5'-di-O-acyl-2'-deoxyguanosine,
An acyl derivative of 2'-deoxynucleoside such as 3 ', 5'-di-O-acyl-2'-deoxycytidine, or 2', 3 ', 5'-tri-O-acyl adenosine,
2 ', 3', 5'-tri-O-acylguanosine,
Illustrative examples are acyl ribonucleosides such as 2 ', 3', 5'-tri-O-acyl cytidine. The acyl group in the raw material compound is not specified and usually has 1 to 10 carbon atoms.
An acyl group of about 5 is sufficient. Specific examples include acetyl, propionyl, butyryl and the like.
【0006】本発明方法に使用するハロゲン化アルキル
スクシニルとしては、炭素数1〜3程度のアルキル基を
含むものでよく、たとえば、塩化メチルスクシニル、塩
化エチルスクシニル、臭化メチルスクシニル、臭化プロ
ピルスクシニル、塩化プロピルスクシニルなどが挙げら
れる。The alkylsuccinyl halide used in the method of the present invention may contain an alkyl group having about 1 to 3 carbon atoms, and examples thereof include methylsuccinyl chloride, ethylsuccinyl chloride, methylsuccinyl bromide and propylsuccinyl bromide. , Propylsuccinyl chloride and the like.
【0007】反応溶媒としてはピリジン、ピコリン、ジ
エチルアニリン、トリメチルアミン、トリエチルアミン
などの塩基性溶媒単独もしくは、上記塩基性溶媒とエー
テル系溶媒(エチルエーテル、テトラヒドロフラン、
1,4‐ジオキサンなど)、ハロゲン化炭化水素類(塩
化メチレン、クロロホルム、四塩化炭素など)、芳香族
炭化水素類(ベンゼン、トルエンなど)、アミド類
(N,N‐ジメチルホルムアミド、N,N‐ジメチルア
セトアミドなど)、ニトリル類(アセトニトリルなど)
などとの混合溶媒を使用することができる。特に上記溶
媒中でもピリジンまたはピリジンと他の溶媒との混合溶
媒が好ましい。As the reaction solvent, a basic solvent such as pyridine, picoline, diethylaniline, trimethylamine and triethylamine may be used alone, or the above basic solvent and an ether solvent (ethyl ether, tetrahydrofuran,
1,4-dioxane, etc., halogenated hydrocarbons (methylene chloride, chloroform, carbon tetrachloride, etc.), aromatic hydrocarbons (benzene, toluene, etc.), amides (N, N-dimethylformamide, N, N) -Dimethylacetamide, etc.), Nitriles (acetonitrile, etc.)
It is possible to use a mixed solvent with such as. Among the above solvents, pyridine or a mixed solvent of pyridine and another solvent is particularly preferable.
【0008】原料化合物とハロゲン化アルキルスクシニ
ルとの反応は、上記溶媒中、原料化合物1モルに対して
ハロゲン化アルキルスクシニルを2〜3倍モル使用し、
10〜40℃で1〜5時間程度反応させることにより実
施することができる。上記反応によりアミノ基に2つの
3‐カルボキシアルキルプロピオニル基が導入された場
合、上記反応液にアンモニア水を加えて室温で反応させ
ることにより、アミノ基に3‐カルボキシアルキルプロ
ピオニル基が1つ導入された目的物を得ることができ
る。また、アシル基の除去が必要な場合には、通常の除
去法を適用すればよく、たとえば、水酸化ナトリウム、
水酸化カリウム、濃アンモニア水などのアルカリ触媒を
用いるアルカリ性加水分解法などを採用することができ
る。The reaction between the starting material compound and the alkylsuccinyl halide is carried out in the above solvent using 1 to 3 moles of the starting compound and 2 to 3 times the molar amount of the alkylsuccinyl halide.
It can be carried out by reacting at 10 to 40 ° C. for about 1 to 5 hours. When two 3-carboxyalkylpropionyl groups are introduced into the amino group by the above reaction, one 3-carboxyalkylpropionyl group is introduced into the amino group by adding aqueous ammonia to the reaction solution and reacting at room temperature. The desired product can be obtained. When it is necessary to remove the acyl group, a usual removal method may be applied. For example, sodium hydroxide,
An alkaline hydrolysis method using an alkali catalyst such as potassium hydroxide or concentrated aqueous ammonia can be employed.
【0009】次に、アミノ基に導入した3‐カルボキシ
アルキルプロピオニル基の閉環反応は既知の方法をその
まま適用すればよい。たとえば、ハロゲン化トリアルキ
ルシリル(たとえば、塩化トリメチルシリルなど)と無
水カルボン酸(たとえば、無水酢酸など)を使用する方
法(Nucleic Acids Res., 12, 8525(1984)) 、または縮
合剤〔N,N'- ジシクロヘキシルカルボジイミド(DCC) 、
N,N′ジイソプロビルカルボジイミド(DIC) 、2,
4,6‐トリイソプロビルベンゼンスルホニルクロライ
ド(TPS) など〕とリン酸化剤(2‐クロロフェニル‐N
‐(4‐メトキシフェニル)クロロホスホロアミダート
など)を使用する方法(HeteroatomChem.,2 ,187(199
1))などにより実施することができる。このようにして
得られたアミノ基をスクシニル基で保護されたヌクレオ
シドは、通常のヌクレオシドの単離精製法により単離精
製すればよい。Next, for the ring-closing reaction of the 3-carboxyalkylpropionyl group introduced into the amino group, a known method may be applied as it is. For example, a method using a trialkylsilyl halide (eg, trimethylsilyl chloride) and a carboxylic acid anhydride (eg, acetic anhydride) (Nucleic Acids Res., 12 , 8525 (1984)), or a condensing agent [N, N '-Dicyclohexylcarbodiimide (DCC),
N, N 'diisoprobecarbodiimide (DIC), 2,
4,6-triisoprobylbenzenesulfonyl chloride (TPS) etc.] and phosphorylating agent (2-chlorophenyl-N
-(4-methoxyphenyl) chlorophosphoramidate etc.) (Heteroatom Chem., 2 , 187 (199)
1)) and the like. The thus obtained amino group-protected succinyl group-protected nucleoside may be isolated and purified by a conventional nucleoside isolation and purification method.
【0010】[0010]
【実施例】以下、実施例を示し、本発明をより具体的に
説明する。本実施例においては、DNA型オリゴヌクレ
オチドの合成原料として有用な5′‐O‐ジメトキシト
リチル‐N6‐スクシニル‐2′‐デオキシアデノシン
を例に挙げて説明するが、これをフロチャートで示せば
以下のとおりである。EXAMPLES Hereinafter, the present invention will be described more specifically by showing examples. In this example, 5'-O-dimethoxytrityl-N 6 -succinyl-2'-deoxyadenosine, which is useful as a raw material for synthesizing a DNA-type oligonucleotide, will be described as an example. It is as follows.
【化1】 [Chemical 1]
【0011】実施例1
2′‐デオキシアデノシン(1.256g、5mmol)を
ピリジン(5ml×3)で共沸脱水した後、ピリジン(2
5ml)に溶かし、無水酢酸(2.35ml、25mmol)を
加えて室温で3.5時間攪拌した。次いで、冷却しなが
らメタノール(10ml)を加え、しばらく攪拌してから
飽和炭酸水素ナトリウム水溶液を加えて反応を停止さ
せ、クロロホルム(25ml×3)で抽出し、水(20m
l)で洗浄後有機相を減圧下濃縮し、さらにシリカゲル
カラムクロマトグラフィーにより精製して3′,5′‐
ジ‐O‐アセチル‐2′‐デオキシアデノシンを1.5
87g(94%)得た。1
H‐NMR(DMSO−d6、TMS):δ2.02
(3H,s,CH3CO−)、2.10(3H,s,C
H3CO−)、2.51−2.56(1H,m,H−
2′)、3.14−3.21(1H,m,H−2″)、
4.20−4.36(3H,m,H−4′,H−5′,
5″)、5.41−5.43(1H,m,H−3′)、
6.39(1H,dd,J1',2' =6.56Hz,
J1',2″=7.60Hz,H−1′)、7.30(2H,
s,N6H2)、8.17(1H,s,H−2)、8.
34(1H,s,H−8) Example 1 2'-Deoxyadenosine (1.256 g, 5 mmol) was azeotropically dehydrated with pyridine (5 ml x 3), and then pyridine (2
5 ml), acetic anhydride (2.35 ml, 25 mmol) was added, and the mixture was stirred at room temperature for 3.5 hours. Then, while cooling, add methanol (10 ml), stir for a while, add saturated aqueous sodium hydrogencarbonate solution to stop the reaction, and extract with chloroform (25 ml × 3), water (20 ml).
After washing with l), the organic phase was concentrated under reduced pressure and further purified by silica gel column chromatography to obtain 3 ', 5'-
Di-O-acetyl-2'-deoxyadenosine 1.5
87 g (94%) were obtained. 1 H-NMR (DMSO-d 6 , TMS): δ2.02
(3H, s, CH 3 CO -), 2.10 (3H, s, C
H 3 CO -), 2.51-2.56 ( 1H, m, H-
2 '), 3.14-3.21 (1H, m, H-2 "),
4.20-4.36 (3H, m, H-4 ', H-5',
5 ″), 5.41−5.43 (1H, m, H-3 ′),
6.39 (1H, dd, J 1 ', 2' = 6.56Hz,
J 1 ', 2 "= 7.60 Hz, H-1'), 7.30 (2H,
s, N 6 H 2), 8.17 (1H, s, H-2), 8.
34 (1H, s, H-8)
【0012】3′,5′‐ジ‐O‐アセチル‐2′‐デ
オキシアデノシン(3.353g、10mmol)をピリジ
ン(7ml×3)で共沸脱水した後、塩化メチレン(65
ml)に溶かし、ピリジン(1.62ml、20mmol)を加
え、次いでさらに塩化エチルスクシニル(2.82ml、
20mmol)を加えて攪拌した。2時間後TLC上で原料
のスポットが認められたのでさらにピリジン(0.81
ml、10mmol)と塩化エチルスクシニル(0.7ml、5
mmol)を加えて35分間攪拌した後、飽和炭酸水素ナト
リウム水溶液(50ml)を加えて反応を停止させた。2
8%(v/v)アンモニア水(20ml)を加えて10分間攪
拌し、減圧下濃縮してアンモニアを除いた後、クロロホ
ルム(50ml×3)で抽出し、水(30ml)で洗浄後有
機相を減圧下濃縮し、3′,5′‐ジ‐O‐アセチル‐
N6‐エチルスクシニル‐2′‐デオキシアデノシンを
得た。得られた3′,5′‐ジ‐O‐アセチル‐N6‐
エチルスクシニル‐2′‐デオキシアデノシンをピリジ
ン(40ml)に溶解させ、氷冷下2N水酸化ナトリウム
水溶液(35ml、70mmol)を加えて18分間反応さ
せ、次いで水(20ml)を加えた。続けてDowex-50W(H-
form)で中和後、樹脂を除き、これを減圧下濃縮した。
得られた残渣を、ピリジン(7ml×3)で共沸脱水した
後、ピリジン(40ml)に溶かし、トリメチルシリルク
ロライド(6.35ml、50mmol)を加えて3時間攪拌
した後、無水酢酸(2.83ml、30mmol)を加え、さ
らに2時間攪拌した。このものを吸引濾過し(無水ピリ
ジンで洗浄)、得られた濾液に水(40ml)を加えて2
0分間攪拌し、次いで減圧下で濃縮して粗N6‐スクシ
ニル‐2′‐デオキシアデノシンを得た。1
H−NMR(CDCl3−TMS):δ2.63(4
H,s,−COCH2CH2CO−)、3.83(2
H,m,H−5′,5″)、4.10(1H,m,H−
4′)、4.62(1H,m,H−3′)、6.48
(1H,m,H−1′)、8.19(1H,s,H−
2)、8.32(1H,s,H−8)After azeotropic dehydration of 3 ', 5'-di-O-acetyl-2'-deoxyadenosine (3.353 g, 10 mmol) with pyridine (7 ml x 3), methylene chloride (65
pyridine (1.62 ml, 20 mmol) and then more ethylsuccinyl chloride (2.82 ml,
20 mmol) was added and stirred. After 2 hours, a spot of the raw material was observed on TLC.
ml, 10 mmol) and ethylsuccinyl chloride (0.7 ml, 5
mmol) and stirred for 35 minutes, a saturated aqueous sodium hydrogen carbonate solution (50 ml) was added to stop the reaction. Two
8% (v / v) aqueous ammonia (20 ml) was added, stirred for 10 minutes, concentrated under reduced pressure to remove ammonia, extracted with chloroform (50 ml × 3), washed with water (30 ml), and then organic phase. Was concentrated under reduced pressure to give 3 ', 5'-di-O-acetyl-
N 6 -ethylsuccinyl-2′-deoxyadenosine was obtained. The resulting 3 ', 5'-di -O- acetyl -N 6 -
Ethylsuccinyl-2'-deoxyadenosine was dissolved in pyridine (40 ml), 2N aqueous sodium hydroxide solution (35 ml, 70 mmol) was added under ice-cooling and the mixture was reacted for 18 minutes, and then water (20 ml) was added. Continuously Dowex-50W (H-
After neutralization with form), the resin was removed and this was concentrated under reduced pressure.
The obtained residue was azeotropically dehydrated with pyridine (7 ml × 3), dissolved in pyridine (40 ml), trimethylsilyl chloride (6.35 ml, 50 mmol) was added, and the mixture was stirred for 3 hours, and then acetic anhydride (2.83 ml). , 30 mmol) was added, and the mixture was further stirred for 2 hours. This product was suction filtered (washed with anhydrous pyridine), and water (40 ml) was added to the obtained filtrate to obtain 2
Stir for 0 min, then concentrate under reduced pressure to give crude N 6 -succinyl-2′-deoxyadenosine. 1 H-NMR (CDCl 3 -TMS): δ 2.63 (4
H, s, -COCH 2 CH 2 CO -), 3.83 (2
H, m, H-5 ', 5 "), 4.10 (1H, m, H-
4 '), 4.62 (1H, m, H-3'), 6.48
(1H, m, H-1 '), 8.19 (1H, s, H-
2), 8.32 (1H, s, H-8)
【0013】得られた粗N6‐スクシニル‐2′‐デオ
キシアデノシンをピリジン(7ml×3)で共沸脱水した
後、ピリジン(45ml)に溶かし、ジメトキシトリチル
クロライド(3.727g、11mmol)を加えて室温で
1.5時間反応させた。飽和炭酸水素ナトリウム水溶液
(50ml)を加えて反応を停止させ、次いで塩化メチレ
ン(50ml×3)で抽出し、有機相を減圧下濃縮し、さ
らにシリカゲルカラムクロマトグラフィー(塩化メチレ
ン‐メタノール)で精製して5′‐O‐ジメトキシトリ
チル‐N6‐スクシニル‐2′‐デオキシアデノシンを
4.595g(73%:3′,5′‐ジ‐O‐アセチレ
ン‐2′‐デオキシアデノシンからの収率)得た。1
H−NMR(CDCl3−TMS):δ2.47−
2.59(1H,m,H−2″)、2.74−2.87
(1H,m,H−2′)、3.00(4H,s,−CO
CH2CH2CO−)、3.35−3.47(2H,
m,H−5′,5″)、3.76(6H,s,−OCH
3)、4.10−4.21(1H,m,H−4′)、
4.62−4.73(1H,m,H−3′)、6.49
(1H,t,J6.5Hz、H−1′)、6.76−6.
82,7.14−7.40(13H,m,Ph−H)、
8.33(1H,s,H−8)、8.91(1H,s,
H−2)
元素分析 C35H33N5O7として
The crude N 6 -succinyl-2'-deoxyadenosine obtained was azeotropically dehydrated with pyridine (7 ml × 3), dissolved in pyridine (45 ml), and dimethoxytrityl chloride (3.727 g, 11 mmol) was added. And reacted at room temperature for 1.5 hours. The reaction was stopped by adding saturated aqueous sodium hydrogen carbonate solution (50 ml), then extracted with methylene chloride (50 ml x 3), the organic phase was concentrated under reduced pressure, and further purified by silica gel column chromatography (methylene chloride-methanol). To give 4.5'g of 5'-O-dimethoxytrityl-N 6 -succinyl-2'-deoxyadenosine (73%: yield from 3 ', 5'-di-O-acetylene-2'-deoxyadenosine) It was 1 H-NMR (CDCl 3 -TMS): δ2.47-
2.59 (1H, m, H-2 ″), 2.74-2.87
(1H, m, H-2 '), 3.00 (4H, s, -CO
CH 2 CH 2 CO -), 3.35-3.47 (2H,
m, H-5 ', 5 "), 3.76 (6H, s, -OCH
3 ), 4.10-4.21 (1H, m, H-4 '),
4.62-4.73 (1H, m, H-3 '), 6.49
(1H, t, J6.5Hz, H-1 '), 6.76-6.
82, 7.14-7.40 (13H, m, Ph-H),
8.33 (1H, s, H-8), 8.91 (1H, s,
H-2) Elemental analysis As C 35 H 33 N 5 O 7
【0014】[0014]
【発明の効果】本発明方法と従来法とを比較してみる
と、本発明方法は使用する試薬が少量で済み、反応条件
も温和で、しかも簡単な操作で目的物を収率よく調製で
きるという従来法にはない優れた効果を有する。When the method of the present invention is compared with the conventional method, a small amount of reagents are used in the method of the present invention, the reaction conditions are mild, and the desired product can be prepared in a high yield by a simple operation. It has an excellent effect not found in the conventional method.
Claims (2)
ニル基で保護する方法であって、原料化合物としてヌク
レオシドの水酸基をアシル基で保護したものを使用し、
該原料化合物とハロゲン化アルキルスクシニルとを塩基
性溶媒中で反応させ、次いで閉環反応に付すことを特徴
とするヌクレオシドの塩基部のアミノ基をスクシニル基
で保護する方法。1. A method for protecting an amino group of a base portion of a nucleoside with a succinyl group, which comprises using as a raw material a compound in which a hydroxyl group of a nucleoside is protected with an acyl group,
A method for protecting an amino group at the base portion of a nucleoside with a succinyl group, which comprises reacting the starting compound with an alkylsuccinyl halide in a basic solvent and then subjecting the ring to a ring closure reaction.
ニル基で保護する方法であって、原料化合物としてヌク
レオシドの水酸基をアシル基で保護したものを使用し、
該原料化合物とハロゲン化アルキルスクシニルとを塩基
性溶媒中で反応させ、次いで水酸基のアシル基を除去後
閉環反応に付すことを特徴とするヌクレオシドの塩基部
のアミノ基をスクシニル基で保護する方法。2. A method for protecting an amino group of a base portion of a nucleoside with a succinyl group, wherein a raw material compound in which a hydroxyl group of the nucleoside is protected with an acyl group is used,
A method for protecting an amino group at the base part of a nucleoside with a succinyl group, which comprises reacting the starting compound with an alkylsuccinyl halide in a basic solvent, and then removing the acyl group of the hydroxyl group and then subjecting the ring to a ring closure reaction.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP14887591A JPH051093A (en) | 1991-06-20 | 1991-06-20 | Method for succinylating nucleoside |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP14887591A JPH051093A (en) | 1991-06-20 | 1991-06-20 | Method for succinylating nucleoside |
Publications (1)
Publication Number | Publication Date |
---|---|
JPH051093A true JPH051093A (en) | 1993-01-08 |
Family
ID=15462678
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP14887591A Pending JPH051093A (en) | 1991-06-20 | 1991-06-20 | Method for succinylating nucleoside |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPH051093A (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002284761A (en) * | 2001-01-17 | 2002-10-03 | Toray Ind Inc | Optically active 3-aminopyrrolidine-2,5-dione derivative and method of producing optically active 3- aminopyrrolidine derivative |
-
1991
- 1991-06-20 JP JP14887591A patent/JPH051093A/en active Pending
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002284761A (en) * | 2001-01-17 | 2002-10-03 | Toray Ind Inc | Optically active 3-aminopyrrolidine-2,5-dione derivative and method of producing optically active 3- aminopyrrolidine derivative |
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