JPS63215693A - Production of nucleoside silicon derivative - Google Patents
Production of nucleoside silicon derivativeInfo
- Publication number
- JPS63215693A JPS63215693A JP4964587A JP4964587A JPS63215693A JP S63215693 A JPS63215693 A JP S63215693A JP 4964587 A JP4964587 A JP 4964587A JP 4964587 A JP4964587 A JP 4964587A JP S63215693 A JPS63215693 A JP S63215693A
- Authority
- JP
- Japan
- Prior art keywords
- nucleoside
- formula
- tert
- group
- silicon
- 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.)
- Granted
Links
- 239000002777 nucleoside Substances 0.000 title claims abstract description 16
- 238000004519 manufacturing process Methods 0.000 title description 8
- -1 silicon halide Chemical class 0.000 claims abstract description 13
- 150000003833 nucleoside derivatives Chemical class 0.000 claims abstract description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 6
- 229910052710 silicon Inorganic materials 0.000 claims abstract description 5
- 239000010703 silicon Substances 0.000 claims abstract description 5
- 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 abstract description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims abstract 3
- 125000005843 halogen group Chemical group 0.000 claims abstract 2
- 150000007522 mineralic acids Chemical class 0.000 claims abstract 2
- 150000007524 organic acids Chemical class 0.000 claims abstract 2
- 239000000126 substance Substances 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 abstract description 12
- 238000000034 method Methods 0.000 abstract description 9
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 abstract description 6
- 150000007523 nucleic acids Chemical class 0.000 abstract description 5
- 102000039446 nucleic acids Human genes 0.000 abstract description 5
- 108020004707 nucleic acids Proteins 0.000 abstract description 5
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- PDYPRPVKBUOHDH-UHFFFAOYSA-N ditert-butyl(dichloro)silane Chemical compound CC(C)(C)[Si](Cl)(Cl)C(C)(C)C PDYPRPVKBUOHDH-UHFFFAOYSA-N 0.000 abstract description 4
- 229910001961 silver nitrate Inorganic materials 0.000 abstract description 3
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 abstract description 2
- 239000002253 acid Substances 0.000 abstract description 2
- 230000003301 hydrolyzing effect Effects 0.000 abstract description 2
- 239000004332 silver Substances 0.000 abstract description 2
- 229910052709 silver Inorganic materials 0.000 abstract description 2
- 239000007795 chemical reaction product Substances 0.000 abstract 2
- 229910052736 halogen Inorganic materials 0.000 abstract 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 18
- 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
- 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
- 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
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 125000003835 nucleoside group Chemical group 0.000 description 4
- 150000003377 silicon compounds Chemical class 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 239000005549 deoxyribonucleoside Substances 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent 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
- 229910020175 SiOH Inorganic materials 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- SLUNEGLMXGHOLY-UHFFFAOYSA-N benzene;hexane Chemical compound CCCCCC.C1=CC=CC=C1 SLUNEGLMXGHOLY-UHFFFAOYSA-N 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000006642 detritylation reaction 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
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000005475 siliconizing Methods 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
- 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
Abstract
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って、近年遺伝子工
学の発展に伴い。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 make up the basic skeleton of nucleic acids, and with the recent development of genetic engineering.
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
間体として知らレル３′アセチル化ヌクレオシドに対応
するものであるが、フッ化物イオン（こより脱保護でき
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。It is being actively studied as a starting material in the chemical synthesis of nucleic acids, and is itself being studied as an interesting compound in the pharmaceutical field. The nucleoside silicon derivatives produced by the present invention have a 3' sugar hydroxyl group protected by a silicon group and correspond to 3' acetylated nucleosides, which 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 from ions.The production method of the present invention is suitable for the organic chemical industry and the 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。Conventional technology Conventionally, tert-butyldimethylsilylated nucleosides have been known as nucleoside silicon derivatives with protected 3' sugar hydroxyl groups. After protecting the hydroxyl group in advance with a protective group such as a trityl group, 2) reacting the 3' sugar hydroxyl group with a silicon compound to introduce the silicon group, and 3)
It is then produced by removing the protective group from the 5' sugar hydroxyl group.
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
。This method 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
と反応性のだかい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（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 mentioned in the previous section, when trying to synthesize a compound with a protected 3' sugar hydroxyl group from a nucleoside using conventional production methods, a large reactive 5' sugar hydroxyl group coexists. In this case, another protecting group is introduced into the 5' sugar hydroxyl group in advance.
Furthermore, there is a complication in that it is necessary to remove it at the end. The present invention does not require such complicated steps,
The purpose of this method is to immediately synthesize a compound in which the 3' sugar hydroxyl group is protected with a silicon group from a deoxyribonucleoside.
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
に至った。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. We focused on the fact that it is possible to synthesize a cyclic silicon compound between sugar hydroxyl groups, discovered a selective hydrolysis reaction thereof, and based on this we completed the present invention.
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２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−イン
ブチリル置換体などが好ましくあげられる。The nucleosides used in the method of the present invention are unprotected,
or a compound represented by the above general formula containing a protected nucleobase, such as thymidine, deoxycytidine, deoxyguanosine, deoxyadenosine, and N-benzoyl or N-imbutyryl substituted products thereof. are preferred.
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って２式
中のＲ及びＲ′はそれぞれｔｅｒｔ−ブチル基、−（ソ
プロピル基であり、Ｘとしては塩素原子が好適である。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 a -(sopropyl group, respectively), and X is a tert-butyl group and a -(sopropyl group). Chlorine atoms are preferred.
このようなものとしては。As something like this.
ジー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。Di-tert-butyldichlorosilane, tetraisopropyldichlorosilane, and the like 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
って得られる。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 the silver salt, silver nitrate, silver perchlorate, silver trifluorosulfonate, silver trifluoroacetate, etc. are preferably used, and as the solvent, pyridine, N,N-dimethylformamide, etc. 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ィ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。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. Further, as a result of studying 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.
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った。It has become clear that it can be used more easily as a protecting group for the 3' sugar hydroxyl group than other silicon groups.
実施例 次に実施例によって本発明をさらに詳細に説明する。Example Next, the present invention will be explained in more detail with reference to Examples.
参考例
従来の製造法によって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'-silicified nucleoside by a conventional production method will be described using 3'-silicified thymidine as an example.
■）無水条件下、チミジンをピリジンに溶解し。■) Dissolve thymidine in pyridine under anhydrous conditions.
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。After adding 1.1 equivalents of dimethoxytrityl chloride and reacting for 2 hours, the solvent was distilled off and the trityl compound was separated from benzene-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
共存下ジー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ィーにより確認した
のちカラムクロマトグラフィーにかけて目的物を分離す
る。3) For the detritylation reaction, the siliconized product is dissolved in 80% acetic acid, the elimination is confirmed by thin layer chromatography, and the target product is separated by column chromatography.
実施例１
無水条件下、チミジン０．４ ｍｍｏ Ｉと硝酸銀０．
８８ｍｍｏｌ をＮ、Ｎ−ジメチルホルムアミド２ｄ
に溶解し１反応器の空間は乾燥窒素で置換した。次いで
１．１倍モルのジー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シリカゲルを用いたカラ
ムクロマトグラフィーにより目的物１２０■を収率７５
％で単離した。。Example 1 Thymidine 0.4 mmol I and silver nitrate 0.4 mmol under anhydrous conditions.
88 mmol of N,N-dimethylformamide 2d
The reactor space was replaced with dry nitrogen. Next, 1.1 times the mole of di-tert-butyldichlorosilane was added, and the reaction was allowed to proceed for 30 minutes at room temperature. After that, 200 microliters of water was added and the mixture was allowed to stand overnight, followed by column chromatography using silica gel to obtain 120 μl of the desired product. Yield 75
isolated in %. .
このものの赤外吸収スペクトルには３５００ ｃｍ’付
近に糖水酸基と５ｉＯＨに基づく特性吸収があられれ、
さらに９００ｃｍ−’付近にＳ ｉＯＨ，２９００ｃｍ
−’付近にｔｅｒｔ−ブチル基に基づく吸収の出現が認
められ、参考例に従って合成された化合物と各種のクロ
マトグラフィー上の挙動が一致し、その構造が確認され
た。The infrared absorption spectrum of this product shows a characteristic absorption based on sugar hydroxyl groups and 5iOH near 3500 cm'.
Furthermore, SiOH near 900cm-', 2900cm
Absorption based on a tert-butyl group was observed near -', and the various chromatographic behaviors matched those of the compound synthesized according to the reference example, confirming its structure.
本例に見るように合成の工程はほぼ１段となり。As seen in this example, the synthesis process is approximately one step.
従来法と比べて大幅に短縮化された。This 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。Example 2 Example 1 except that deoxyadenosine was used instead of thymidine and the hydrolysis was carried out for 3 hours.
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。When treated in exactly the same manner as in Example 1, the target product in which the 3' sugar hydroxyl group was siliconized was obtained in a yield of 42%.
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
ロマトグラフィー上の挙動が一致することにより確認さ
れた。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におけるジーｔｅｒ Ｌ−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ィー
上の挙動か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 G-ter L-butyldichlorosilane in Example 1, and the hydrolysis was carried out for 5 minutes, resulting in a yield of 73%. A target product was obtained in which the 3' sugar hydroxyl group was silicified at a high rate. The structure was confirmed by matching 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
ラフィ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 In the hydrolysis in Example 1, water was converted into methanol 1
When treated in exactly the same manner as in Example 1 except that normal sodium hydroxide was used, the target product in which the 3' sugar hydroxyl group was siliconized was obtained with a yield of 83%. 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、８２９６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
フィ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 target product in which the 3' sugar hydroxyl group was siliconized was obtained in a yield of 8296. was gotten. Various chromatographic behaviors were consistent with the compound obtained in Example 2.
Claims (1)
） 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 ▲数式、化学式、表等があります▼或いは▲数式、化学
式、表等があります▼ （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 a silver salt of an inorganic or organic acid, a general formula ▲ includes a mathematical formula, a chemical formula, a table, etc. ▼ (B in the formula is an unprotected or protected nucleobase) A nucleoside represented by is reacted with a silicon halide represented by the general formula R_2SiX_2 or XSiR'_2OSiR'_2X (in the formula, X is a halogen atom, R and R' are a tert-butyl group and an isopropyl group, respectively), General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ Or ▲ There are mathematical formulas, chemical formulas, tables, etc. , R and R' are a tert-butyl group and an isopropyl group, respectively).
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 true JPS63215693A (en) | 1988-09-08 |
| JPH055838B2 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) |
Cited By (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
Cited By (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 |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH055838B2 (en) | 1993-01-25 |
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