JPH055838B2 - - Google Patents
Info
- Publication number
- JPH055838B2 JPH055838B2 JP4964587A JP4964587A JPH055838B2 JP H055838 B2 JPH055838 B2 JP H055838B2 JP 4964587 A JP4964587 A JP 4964587A JP 4964587 A JP4964587 A JP 4964587A JP H055838 B2 JPH055838 B2 JP H055838B2
- Authority
- JP
- Japan
- Prior art keywords
- silicon
- sugar hydroxyl
- group
- nucleoside
- hydroxyl group
- 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.)
- Expired - Lifetime
Links
- 239000002777 nucleoside Substances 0.000 claims description 14
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 238000006460 hydrolysis reaction Methods 0.000 claims description 5
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 5
- 230000007062 hydrolysis Effects 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 1
- 150000007522 mineralic acids Chemical class 0.000 claims 1
- 150000007524 organic acids Chemical class 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 20
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 14
- 150000001875 compounds Chemical class 0.000 description 11
- -1 nucleoside silicon derivative Chemical class 0.000 description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 7
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 229940104230 thymidine Drugs 0.000 description 7
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical group [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 5
- 230000006399 behavior Effects 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- PDYPRPVKBUOHDH-UHFFFAOYSA-N ditert-butyl(dichloro)silane Chemical compound CC(C)(C)[Si](Cl)(Cl)C(C)(C)C PDYPRPVKBUOHDH-UHFFFAOYSA-N 0.000 description 4
- 150000003377 silicon compounds Chemical class 0.000 description 4
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000005549 deoxyribonucleoside Substances 0.000 description 3
- 150000007523 nucleic acids Chemical class 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 125000003835 nucleoside group Chemical group 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 229910020175 SiOH Inorganic materials 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 229910001961 silver nitrate Inorganic materials 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- LOSXTWDYAWERDB-UHFFFAOYSA-N 1-[chloro(diphenyl)methyl]-2,3-dimethoxybenzene Chemical compound COC1=CC=CC(C(Cl)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1OC LOSXTWDYAWERDB-UHFFFAOYSA-N 0.000 description 1
- YKBGVTZYEHREMT-KVQBGUIXSA-N 2'-deoxyguanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 YKBGVTZYEHREMT-KVQBGUIXSA-N 0.000 description 1
- CKTSBUTUHBMZGZ-ULQXZJNLSA-N 4-amino-1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-tritiopyrimidin-2-one Chemical compound O=C1N=C(N)C([3H])=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 CKTSBUTUHBMZGZ-ULQXZJNLSA-N 0.000 description 1
- RBWNDBNSJFCLBZ-UHFFFAOYSA-N 7-methyl-5,6,7,8-tetrahydro-3h-[1]benzothiolo[2,3-d]pyrimidine-4-thione Chemical compound N1=CNC(=S)C2=C1SC1=C2CCC(C)C1 RBWNDBNSJFCLBZ-UHFFFAOYSA-N 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- 238000006642 detritylation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- KBHVEPCBCHPCDC-UHFFFAOYSA-N dichloro-propan-2-yl-tri(propan-2-yl)silyloxysilane Chemical compound CC(C)[Si](Cl)(Cl)O[Si](C(C)C)(C(C)C)C(C)C KBHVEPCBCHPCDC-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 238000005475 siliconizing Methods 0.000 description 1
- 150000003378 silver Chemical class 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- KZJPVUDYAMEDRM-UHFFFAOYSA-M silver;2,2,2-trifluoroacetate Chemical compound [Ag+].[O-]C(=O)C(F)(F)F KZJPVUDYAMEDRM-UHFFFAOYSA-M 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
Description
【発明の詳細な説明】
産業上の利用分野
本発明は新規なヌクレオシドケイ素誘導体の製
造法に関し、さらに詳しくいえば、デオキシリボ
ヌクレオシドの3′糖水酸基をケイ素化合物により
保護した誘導体の製造法に関するものである。ヌ
クレオシドは核酸類の基本骨格を構成する重要な
生体物質であつて、近年遺伝子工学の発展に伴
い、核酸類の化学合成における出発物質として盛
んに研究されており、またそれ自身も興味ある化
合物として医薬品分野において研究されている。
本発明により製造されるヌクレオシドケイ素誘導
体は3′糖水酸基がケイ素基により保護されており
核酸類の化学合成において重要な中間体として知
られる3′アセチル化ヌクレオシドに対応するもの
であるが、フツ化物イオンにより脱保護できるこ
とにより合成中間体として極めて有用である。こ
の発明の製造方法の産業上の利用分野としては、
有機化学工業及び生物化学工業に好適である。DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to a method for producing a novel nucleoside silicon derivative, and more specifically, to a method for producing a derivative in which the 3' sugar hydroxyl group of a deoxyribonucleoside is protected with a silicon compound. be. Nucleosides are important biological substances that constitute the basic skeleton of nucleic acids, and with the development of genetic engineering in recent years, they have been actively studied as starting materials in the chemical synthesis of nucleic acids, and they are also interesting compounds in their own right. It is being researched in the pharmaceutical field.
The nucleoside silicon derivatives produced by the present invention correspond to 3' acetylated nucleosides in which the 3' sugar hydroxyl group is protected by a silicon group and are known as important intermediates in the chemical synthesis of nucleic acids. It is extremely useful as a synthetic intermediate because it can be deprotected with ions. The industrial application field of the manufacturing method of this invention is as follows:
Suitable for organic chemical industry and biochemical industry.
従来の技術
従来、3′糖水酸基を保護したヌクレオシドケイ
素誘導体としては、tert−ブチルジメチルシリル
化ヌクレオシドが知られているが、このような
3′糖水酸基を保護した誘導体は、(1)5′糖水酸基を
あらかじめトリチル基のような保護基で保護した
後に、(2)3′糖水酸基にケイ素化合物を反応させて
ケイ素基を導入し、(3)この後5′糖水酸基の保護基
を脱離させることにより製造されており、多数の
煩雑な操作を必要とするという欠点を有してい
る。Conventional technology Tert-butyldimethylsilylated nucleosides have been known as nucleoside silicon derivatives with protected 3' sugar hydroxyl groups;
Derivatives with a protected 3′ sugar hydroxyl group are obtained by (1) protecting the 5′ sugar hydroxyl group with a protecting group such as a trityl group in advance, and then (2) introducing a silicon group by reacting the 3′ sugar hydroxyl group with a silicon compound. , (3) are produced by subsequently removing the protecting group from the 5' sugar hydroxyl group, which has the disadvantage of requiring a large number of complicated operations.
発明が解決しようとする問題点
先の項で述べたように、従来の製造法では3′糖
水酸基を保護した化合物をヌクレオシドから合成
しようとすると反応性のたかい5′糖水酸基が共存
するために、あらかじめ5′糖水酸基に別の保護基
を導入しておくこと、また最後にこれを脱離させ
る必要があるなどの煩雑さがある。本発明はこの
ような煩雑な工程を経ることなく、デオキシリボ
ヌクレオシドより直ちに3′糖水酸基をケイ素基に
より保護した化合物を合成することを目的とした
ものである。Problems to be Solved by the Invention As stated in the previous section, when attempting to synthesize a compound with a protected 3' sugar hydroxyl group from a nucleoside using conventional production methods, it is difficult to synthesize a compound with a protected 3' sugar hydroxyl group due to the coexistence of a highly reactive 5' sugar hydroxyl group. However, there are complications such as the need to introduce another protecting group to the 5' sugar hydroxyl group in advance and the need to remove it at the end. The object of the present invention is to immediately synthesize a compound in which the 3' sugar hydroxyl group is protected with a silicon group from a deoxyribonucleoside without going through such complicated steps.
問題を解決するための手段
本発明者はあらかじめ保護基を導入することな
く、デオキシリボヌクレオシドより直ちに3′糖水
酸基を保護した化合物を合成することを目的とし
て、鋭意研究を重ね、3′及び5′糖水酸基の間に環
状ケイ素化合物を合成することが可能であること
に着目し、その選択的な加水分解反応を見出し、
これに基づいて本発明を完成させるに至つた。Means for Solving the Problem The present inventor has conducted extensive research with the aim of synthesizing a compound in which the 3' sugar hydroxyl group is immediately protected from the deoxyribonucleoside without introducing a protecting group in advance. Focusing on the fact that it is possible to synthesize cyclic silicon compounds between sugar hydroxyl groups, we discovered a selective hydrolysis reaction,
Based on this, the present invention has been completed.
本発明方法において用いるヌクレオシドは、未
保護の、又は保護された核酸塩基を含む前記一般
式で表わされる化合物であり、このようなものと
しては、例えばチミジン、デオキシシチジン、デ
オキシグアノシン、デオキシアデノシンなど及び
これらのＮ−ベンゾイルやＮ−イソブチリル置換
体などが好ましくあげられる。 The nucleoside used in the method of the present invention is a compound represented by the above general formula containing an unprotected or protected nucleobase, such as thymidine, deoxycytidine, deoxyguanosine, deoxyadenosine, etc. Preferred examples include N-benzoyl and N-isobutyryl substituted products.
本発明方法において用いるケイ素化合物は、前
記一般式でしめされる二官能性ケイ素ハロゲン化
物であつて、式中のＲ及びR′はそれぞれtert−ブ
チル基、イソプロピル基であり、Ｘとしては塩素
原子が好適である。このようなものとしては、ジ
−tert−ブチルジクロロシラン、テトライソプロ
ピルジクロロシランなどが好ましく用いられる。 The silicon compound used in the method of the present invention is a bifunctional silicon halide represented by the above general formula, in which R and R' are a tert-butyl group and an isopropyl group, respectively, and X is a chlorine atom. is suitable. As such, di-tert-butyldichlorosilane, tetraisopropyldichlorosilane, etc. are preferably used.
前記一般式で示される本発明のヌクレオシドケ
イ素誘導体は、酸類の銀塩の存在下、有機溶媒中
において、前記一般式で示されるケイ素ハロゲン
化物を反応させ、続いて酸性又はアルカリ性にお
いて加水分解させることによつて得られる。 The nucleoside silicon derivative of the present invention represented by the above general formula can be obtained by reacting a silicon halide represented by the above general formula in an organic solvent in the presence of a silver salt of an acid, and then hydrolyzing it in acidic or alkaline conditions. obtained by.
銀塩としては硝酸銀、過塩素酸銀、トリフルオ
ロスルホン酸銀及びトリフルオロ酢酸銀などが好
ましく用いられ、溶媒としてはピリジン、Ｎ，Ｎ
−ジメチルホルムアミドなどが好ましくもちいら
れる。 As silver salts, silver nitrate, silver perchlorate, silver trifluorosulfonate, silver trifluoroacetate, etc. are preferably used, and as solvents, pyridine, N,N
-Dimethylformamide and the like are preferably used.
反応終了後、目的とするヌクレオシドケイ素誘
導体は、カラムクロマトグラフイーにより単離さ
れる。 After the reaction is completed, the desired nucleoside silicon derivative is isolated by column chromatography.
発明の効果
本発明により従来少なくとも３工程以上を要し
ていた製造工程はほぼ１工程で済むようになり大
幅に短縮された。また本発明により製造されたヌ
クレオシド3′ケイ素化合物を用いて5′アセチル化
チミジンの合成を検討した結果、ケイ素基が保護
基として十分な性能を有することが確かめられ、
3′糖水酸基の保護基として他のケイ素基より簡便
に用いられることが明らかとなつた。Effects of the Invention According to the present invention, the manufacturing process, which conventionally required at least three steps, can now be reduced to just one step, thereby significantly shortening the manufacturing process. Furthermore, as a result of examining the synthesis of 5' acetylated thymidine using the nucleoside 3' silicon compound produced according to the present invention, it was confirmed that the silicon group has sufficient performance as a protecting group.
It has become clear that it can be used more easily as a protecting group for 3' sugar hydroxyl groups than other silicon groups.
実施例
次に実施例によつて本発明をさらに詳細に説明
する。EXAMPLES Next, the present invention will be explained in more detail with reference to Examples.
参考例
従来の製造法によつて3′ケイ素化ヌクレオシド
を合成する工程を3′ケイ素化チミジンを例として
示す。Reference Example A process for synthesizing a 3'-silicinated nucleoside by a conventional production method will be shown using 3'-silicinated thymidine as an example.
(1) 無水条件下、チミジンをピリジンに溶解し、
1.1当量のジメトキシトリチルクロリドを加え
２時間反応させたのち溶媒を留去しベンゼン−
ｎ−ヘキサンよりトリチル体を分離する。(1) Dissolve thymidine in pyridine under anhydrous conditions,
After adding 1.1 equivalent of dimethoxytrityl chloride and reacting for 2 hours, the solvent was distilled off and benzene-trityl chloride was added.
Separate the trityl compound from n-hexane.
(2) トリチル体をジメチルホルムアミドに溶解し
触媒の共存下ジ−tert−ブチルジクロロシラン
などのケイ素化試薬と反応させる。必要に応じ
単離する。(2) The trityl compound is dissolved in dimethylformamide and reacted with a siliconizing reagent such as di-tert-butyldichlorosilane in the presence of a catalyst. Isolate if necessary.
(3) 脱トリチル化反応のためにケイ素化体を80％
酢酸に溶解し脱離を薄層クロマトグラフイーに
より確認したのちカラムクロマトグラフイーに
かけて目的物を分離する。(3) 80% siliconized product for detritylation reaction
Dissolve in acetic acid, confirm desorption using thin layer chromatography, and then apply column chromatography to separate the target product.
実施例 １
無水条件下、チミジン0.4ｍmolと硝酸銀0.88ｍ
molをＮ，Ｎ−ジメチルホルムアミド２mlに溶解
し、反応器の空間は乾燥窒素で置換した。次いで
1.1倍モルのジ−tert−ブチルジクロロシランを加
え、室温で30分間反応させた後、200マイクロリ
ツトルの水を加えて一晩放置してシリカゲルを用
いたカラムクロマトグラフイーにより目的物120
mgを収率75％で単離した。Example 1 Thymidine 0.4 mmol and silver nitrate 0.88 m under anhydrous conditions
mol was dissolved in 2 ml of N,N-dimethylformamide and the space of the reactor was purged with dry nitrogen. then
After adding 1.1 times the mole of di-tert-butyldichlorosilane and reacting at room temperature for 30 minutes, 200 microliters of water was added and left overnight.
mg was isolated in 75% yield.
このものの赤外吸収スペクトルには3500cm-1付
近に糖水酸基とSiOHに基づく特性吸収があらわ
れ、さらに900cm-1付近にSiOH、2900cm-1付近に
tert−ブチル基に基づく吸収の出現が認められ、
参考例に従つて合成された化合物と各種のクロマ
トグラフイー上に挙動が一致し、その構造が確認
された。 In the infrared absorption spectrum of this product, characteristic absorption based on sugar hydroxyl groups and SiOH appears around 3500 cm -1 , SiOH around 900 cm -1 , and characteristic absorption around 2900 cm -1 .
The appearance of absorption based on tert-butyl group was observed,
The behavior matched that of the compound synthesized according to the reference example in various chromatography tests, and its structure was confirmed.
本例に見るように合成の工程はほぼ１段とな
り、従来法と比べて大幅に短縮化された。 As seen in this example, the synthesis process is approximately one step, which is significantly shorter than the conventional method.
実施例 ２
実施例１におけるチミジンの代わりにデオキシ
アデノシンを用い加水分解を３時間とする以外
は、実施例１と全く同様にして処理したところ、
42％の収率で3′糖水酸基がケイ素化された目的物
が得られた。構造は参考例と同様にして合成され
た化合物と各種のクロマトグラフイー上の挙動が
一致することにより確認された。Example 2 When treated in exactly the same manner as in Example 1 except that deoxyadenosine was used instead of thymidine in Example 1 and the hydrolysis was carried out for 3 hours,
The desired product in which the 3' sugar hydroxyl group was siliconized was obtained in a yield of 42%. The structure was confirmed by the consistency of various chromatographic behaviors with a compound synthesized in the same manner as the reference example.
実施例 ３
実施例１におけるジ−tert−ブチルジクロロシ
ランの代わりにテトライソプロピルジクロロジシ
ロキサンを用い加水分解を５分とする以外は、実
施例１と全く同様にして処理したところ、73％の
収率で3′糖水酸基がケイ素化された目的物が得ら
れた。構造は参考例と同様にして合成された化合
物と各種のクロマトグラフイー上の挙動が一致す
ることにより確認された。Example 3 The process was carried out in exactly the same manner as in Example 1, except that tetraisopropyldichlorodisiloxane was used instead of di-tert-butyldichlorosilane and the hydrolysis was carried out for 5 minutes, resulting in a yield of 73%. The target product was obtained in which the 3' sugar hydroxyl group was silicified at a high rate. The structure was confirmed by the consistency of various chromatographic behaviors with a compound synthesized in the same manner as the reference example.
実施例 ４
実施例１における加水分解において水をメタノ
ール性１規定水酸化ナトリウムとする以外は、実
施例１と全く同様にして処理したところ、83％の
収率で3′糖水酸基がケイ素化された目的物が得ら
れた。各種のクロマトグラフイー上の挙動は実施
例１で得られた化合物と一致した。Example 4 The same procedure as in Example 1 was carried out except that the water in the hydrolysis in Example 1 was replaced with methanolic 1N sodium hydroxide. As a result, the 3' sugar hydroxyl group was silicified with a yield of 83%. The desired object was obtained. Various chromatographic behaviors were consistent with the compound obtained in Example 1.
実施例 ５
実施例４におけるチミジンの代わりにデオキシ
アデノシンを用い加水分解を行う以外は、実施例
４と全く同様にして処理したところ、82％の収率
で3′糖水酸基がケイ素化された目的物が得られ
た。各種のクロマトグラフイー上の挙動は実施例
２で得られた化合物と一致した。Example 5 The process was carried out in exactly the same manner as in Example 4, except that deoxyadenosine was used instead of thymidine in Example 4, and the 3' sugar hydroxyl group was siliconized with a yield of 82%. I got something. Various chromatographic behaviors were consistent with the compound obtained in Example 2.
Claims (1)
である） で表わされるヌクレオシドに、一般式 R2SiX2 或いは XSiR′2OSiR′2X （式中のＸはハロゲン原子、Ｒ及びR′はそれぞ
れtert−ブチル基及びイソプロピル基である） で表わされるケイ素ハロゲン化物を反応させ、
続いて加水分解することを特徴とする、 一般式 【式】或いは 【式】 （式中のＢは未保護の、又は保護された核酸塩
基、Ｒ及びR′はそれぞれtert−ブチル基及びイソ
プロピル基である） で表わされるヌクレオシドケイ素誘導体の製造
法。[Claims] 1. In the presence of an inorganic or organic acid silver salt, the general formula (wherein B is an unprotected or protected nucleobase) The nucleoside represented by the general formula R 2 SiX 2 or XSiR' 2 OSiR' 2 X (wherein X is a halogen atom, R and R′ is a tert-butyl group and an isopropyl group, respectively).
The general formula [Formula] or [Formula] (where B is an unprotected or protected nucleobase, R and R' are a tert-butyl group and an isopropyl group, respectively), which is characterized by subsequent hydrolysis. A method for producing a nucleoside silicon derivative represented by
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4964587A JPS63215693A (en) | 1987-03-04 | 1987-03-04 | Production of nucleoside silicon derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4964587A JPS63215693A (en) | 1987-03-04 | 1987-03-04 | Production of nucleoside silicon derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS63215693A JPS63215693A (en) | 1988-09-08 |
| JPH055838B2 true JPH055838B2 (en) | 1993-01-25 |
Family
ID=12836943
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4964587A Granted JPS63215693A (en) | 1987-03-04 | 1987-03-04 | Production of nucleoside silicon derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS63215693A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5214134A (en) * | 1990-09-12 | 1993-05-25 | Sterling Winthrop Inc. | Process of linking nucleosides with a siloxane bridge |
-
1987
- 1987-03-04 JP JP4964587A patent/JPS63215693A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS63215693A (en) | 1988-09-08 |
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| EXPY | Cancellation because of completion of term |