JPS607620B2 - Method for producing carbon nucleoside derivatives - Google Patents
Method for producing carbon nucleoside derivativesInfo
- Publication number
- JPS607620B2 JPS607620B2 JP59040551A JP4055184A JPS607620B2 JP S607620 B2 JPS607620 B2 JP S607620B2 JP 59040551 A JP59040551 A JP 59040551A JP 4055184 A JP4055184 A JP 4055184A JP S607620 B2 JPS607620 B2 JP S607620B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- represented
- tables
- formulas
- general formula
- 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
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 4
- -1 carbon nucleoside derivatives Chemical class 0.000 title description 8
- 229910052799 carbon Inorganic materials 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 14
- 239000000126 substance Substances 0.000 claims description 7
- 235000000346 sugar Nutrition 0.000 claims description 7
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 claims description 5
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- ZBKFYXZXZJPWNQ-UHFFFAOYSA-N isothiocyanate group Chemical group [N-]=C=S ZBKFYXZXZJPWNQ-UHFFFAOYSA-N 0.000 claims description 3
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 description 7
- 239000002777 nucleoside Substances 0.000 description 5
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- WQZGKKKJIJFFOK-SVZMEOIVSA-N (+)-Galactose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-SVZMEOIVSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- PYMYPHUHKUWMLA-LMVFSUKVSA-N aldehydo-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 2
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 2
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 150000002540 isothiocyanates Chemical class 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- FZHXIRIBWMQPQF-UHFFFAOYSA-N Glc-NH2 Natural products O=CC(N)C(O)C(O)C(O)CO FZHXIRIBWMQPQF-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- SRBFZHDQGSBBOR-OWMBCFKOSA-N L-ribopyranose Chemical compound O[C@H]1COC(O)[C@@H](O)[C@H]1O SRBFZHDQGSBBOR-OWMBCFKOSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000003843 furanosyl group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 230000000506 psychotropic effect Effects 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- RHUVFRWZKMEWNS-UHFFFAOYSA-M silver thiocyanate Chemical compound [Ag+].[S-]C#N RHUVFRWZKMEWNS-UHFFFAOYSA-M 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【発明の詳細な説明】 本発明は新規なヌクレオシド誘導体の製法に関する。[Detailed description of the invention] The present invention relates to a novel method for producing nucleoside derivatives.
さらに詳細に述べれば、本発明は次の一般式（こ）にＲ
，は次式の基を表わし、Ａは水酸基の保護基としてのア
セチル基を表わす）で示されるイソチオシアナート基を
もつ糖酸化合物に、次式で示されるオルトフェニレンジ
アミンを反応させることを特徴とする次の一般式（ここ
にＲ，は前記と同じ意義を有する）で表わされるヌクレ
オシド誘導体の製法に関する。More specifically, the present invention relates to the following general formula (R)
, represents a group of the following formula, and A represents an acetyl group as a protecting group for a hydroxyl group) A sugar acid compound having an isothiocyanate group represented by the following formula is reacted with orthophenylenediamine represented by the following formula. The present invention relates to a method for producing a nucleoside derivative represented by the following general formula (where R has the same meaning as above).
本発明者等は、従来から種々のヌクレオシドの合成の研
究を行って来たが、（１）式で示されるィソチオシアナ
ート基をもつ糖酸化合物に（ロ）式で示されるオルトフ
ェニレンジアミンを反応させることにより、一段階で（
ｍ）式で示されるヌクレオシド化合物が得られることを
発見し、本発明を完成した。The present inventors have conventionally conducted research on the synthesis of various nucleosides. In one step, by reacting (
m) It was discovered that a nucleoside compound represented by the formula can be obtained, and the present invention was completed.
本発明の方法は（１）式の化合物と（ロ）式の化合物を
無水の条件、例えばベンゼン、トルェン、キシレンある
いはそれらの混合溶媒等の炭化水素類、テトラヒドロフ
ランなどのエーテル類、ジメチルアセトァミドなどの酸
アミド類の溶媒に溶解し反応させることにより実施する
のが好ましい。The method of the present invention is to prepare the compound of formula (1) and the compound of formula (b) under anhydrous conditions, such as hydrocarbons such as benzene, toluene, xylene or a mixed solvent thereof, ethers such as tetrahydrofuran, dimethylacetamide, etc. It is preferable to carry out the reaction by dissolving an acid amide in a solvent such as the following.
これら化合物が上記溶媒に溶解し難い時はジメチルホル
ムアミド、ジエチルアミン、トルエチルアミン、ピベリ
ジン、モルホリン、ピリジン、キノリン等の第２級アミ
ン、第３級アミンを加えてこられの存在下に反応を行わ
せることも出来る。使用する原料化合物（１）と反応剤
オルトフェニレンジアミン（ロ）は、当モル量で脱水縮
合反応させれば十分であり、反応温度は５０〜１５０ｑ
ｏが適当である。When these compounds are difficult to dissolve in the above solvents, a secondary or tertiary amine such as dimethylformamide, diethylamine, toluethylamine, piverizine, morpholine, pyridine, or quinoline may be added to carry out the reaction in the presence of these. You can also do it. It is sufficient to carry out a dehydration condensation reaction in equimolar amounts of the raw material compound (1) and the reactant orthophenylenediamine (b) used, and the reaction temperature is 50 to 150q.
o is appropriate.
通常は、水浴上で、加熱又は油裕上で還流を行う。反応
時間は反応させる物質によって異なるが、１０分かち２
日間も要する場合がある。Refluxing is usually carried out on a water bath, heated or on an oil bath. The reaction time varies depending on the substance to be reacted, but it takes about 10 minutes or 2 minutes.
It may take even days.
反応の終末点を決定するためには薄層クロマトグラフィ
ーを利用するのが適当である。こ）で一般式（１）で表
わされる糖酸ィソチオシアナート化合物は、例えばＤー
グルコース、Ｄーアラビノース、Ｄ−リボース、Ｄーキ
シローズ、Ｄ川ガラクトース、２ーアミノー２ーデオキ
シグルコースなどの糖に対応する糖酸のピラノシル型又
はフラノシル型又は鎖状型化合物のィソチオシアナート
誘導体を初めとしてィソチオシアナート基を持った糖化
合物であることができ、本法では、この糠酸化合物はそ
の水酸基をアセチル基で保護された保護体の形で使用さ
れる。Thin layer chromatography is suitably used to determine the end point of the reaction. In this), the sugar acid isothiocyanate compound represented by the general formula (1) corresponds to sugars such as D-glucose, D-arabinose, D-ribose, D-xyrose, D-galactose, and 2-amino-2-deoxyglucose. It can be a sugar compound having an isothiocyanate group, including isothiocyanate derivatives of pyranosyl or furanosyl type or chain type compounds of sugar acids, and in this method, the bran acid compound has its hydroxyl group It is used in the form of a protected form protected with an acetyl group.
一般式（１）で表わされるィソチオシアネート化合物を
本発明者等は炭素ヌクレオシド合成試薬と命名した。本
合成試薬は袷膳所に保存するのが望ましい。この炭素ヌ
クレオシド反応試薬、すなわち一般式（１）の化合物は
、いずれも新規化合物であって、例えば使用する糖の水
酸基をアセチル基で保護した保護体をチオニルクロラィ
ド、三塩化燐、又は五塩化燐等で塩素化し、次いでチオ
シアン酸銀を作用させることにより調製できる。The present inventors named the isothiocyanate compound represented by the general formula (1) a carbon nucleoside synthesis reagent. It is desirable to store this synthetic reagent in a storage container. This carbon nucleoside reaction reagent, that is, the compound of general formula (1), is a new compound. It can be prepared by chlorinating with phosphorous chloride or the like and then reacting with silver thiocyanate.
本発明の方法における反応終了後、メタノ−ル、エタノ
ール等の有機溶媒を使用して再結晶を行い精製品を得る
。After completion of the reaction in the method of the present invention, recrystallization is performed using an organic solvent such as methanol or ethanol to obtain a purified product.
一般式（ｍ）で表わされる化合物の糖の水酸基部分を保
護しているアセチル基は必要に応じて常法で脱離できる
。The acetyl group protecting the hydroxyl group of the sugar of the compound represented by general formula (m) can be removed by a conventional method if necessary.
こうして得られた一般式（ｍ）で表わされたヌクレオシ
ド化合物は、すべて文献未収載の新規物質であって、抗
菌性、抗ウイルス性、向精神作用などの薬理活性を示し
、医薬品として有用である。The nucleoside compounds represented by the general formula (m) obtained in this way are all new substances that have not been described in any literature, and exhibit pharmacological activities such as antibacterial, antiviral, and psychotropic effects, and are useful as pharmaceuticals. be.
次に本発明によって得られる目的生成物（ｍ）を出発原
料化合物（１）及び反応剤化合物（０）と共に化学構造
式で表わすと次の表１に示した如くである。Next, the chemical structural formula of the target product (m) obtained by the present invention together with the starting material compound (1) and the reactant compound (0) is as shown in Table 1 below.
表 １
但し上記の表中でＲ℃○−基は次式
（式中Ａｃはアセチル基）で示される２・３・４１５・
６ーベンタ−○ーアセチルーＤーグルコニル基を表わす
。Table 1 However, in the above table, R℃○- group is 2, 3, 415, represented by the following formula (where Ac is an acetyl group).
Represents a 6-venter-○-acetyl-D-gluconyl group.
次に本発明を実施例により示すが本発明はこれに限定さ
れるものではない。Next, the present invention will be illustrated by examples, but the present invention is not limited thereto.
実施例 １
オルトフエニレンジアミンと２・３・４・５・６−ペン
夕−○−アセチルーＤ−グルコニルイソチオシアナート
との反応無水ベンゼン１０必中に２・３・４１５・６−
ペンター○−アセチルーＤーグルコニルイソチオシアナ
ート４５０肌９（０．００１モル）とオルトフエニレン
ジアミン１０８の９（０．００１モル）とを入れて水浴
上（５０〜６０ｏ ）３０分間加熱した後に溶媒を減圧
下留去した。Example 1 Reaction of orthophenylenediamine and 2,3,4,5,6-penta-○-acetyl-D-gluconyl isothiocyanate 2,3,415,6-
After adding penta-acetyl-D-gluconyl isothiocyanate 450 skin 9 (0.001 mol) and orthophenylenediamine 108-9 (0.001 mol) and heating on a water bath (50 to 60o) for 30 minutes, The solvent was distilled off under reduced pressure.
Claims (1)
を表わす）で示されるイソチオシアナート基をもつ糖酸
化合物に、次式▲数式、化学式、表等があります▼ で示されるオルトフエニレンジアミンを反応させること
を特徴とする次の一般式▲数式、化学式、表等がありま
す▼ （ここにＲ＿１は前記と同じ意義を有する）で表わされ
るヌクレオシド誘導体の製法。[Scope of Claims] 1. Represents the group of the following general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (Here, R_1 represents the group of the following formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼, and A is a hydroxyl group-protecting group. The following method is characterized in that a sugar acid compound having an isothiocyanate group represented by (representing an acetyl group) is reacted with orthophenylenediamine represented by the following formula ▲There are mathematical formulas, chemical formulas, tables, etc.▼ A method for producing a nucleoside derivative represented by the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (where R_1 has the same meaning as above).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59040551A JPS607620B2 (en) | 1984-03-05 | 1984-03-05 | Method for producing carbon nucleoside derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59040551A JPS607620B2 (en) | 1984-03-05 | 1984-03-05 | Method for producing carbon nucleoside derivatives |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP11163274A Division JPS5928558B2 (en) | 1974-09-30 | 1974-09-30 | Method for producing carbon nucleoside derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS59216880A JPS59216880A (en) | 1984-12-06 |
| JPS607620B2 true JPS607620B2 (en) | 1985-02-26 |
Family
ID=12583583
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP59040551A Expired JPS607620B2 (en) | 1984-03-05 | 1984-03-05 | Method for producing carbon nucleoside derivatives |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS607620B2 (en) |
-
1984
- 1984-03-05 JP JP59040551A patent/JPS607620B2/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| JPS59216880A (en) | 1984-12-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Kissman et al. | Puromycin. Synthetic studies. XI. D-ribofuranosyl derivatives of 6-dimethylaminopurine | |
| Nair et al. | Novel, stable congeners of the antiretroviral compound 2', 3'-dideoxyadenosine | |
| CN112679420A (en) | Preparation method of 2,5-dibromopyridine | |
| Henry et al. | 1, 3-and 1, 4-Dialkyl-5-iminotetrazoles | |
| CN111704582A (en) | Preparation method of Favipiravir and derivatives thereof | |
| CH500203A (en) | Preparation of nucleosides | |
| JPS6026373B2 (en) | anti-intestinal ulcer agent | |
| Wiley et al. | Erythromycin. XII. 1 The Isolation, properties and partial structure of erythromycin C | |
| Carson | The reaction of fructose with aliphatic amines | |
| JPS607620B2 (en) | Method for producing carbon nucleoside derivatives | |
| SU747425A3 (en) | Method of producing derivatives of aminoalkoxybenzofuranes | |
| JPS5928558B2 (en) | Method for producing carbon nucleoside derivatives | |
| US4160828A (en) | Analgesic phosphinyl compounds and compositions | |
| FI82239B (en) | FRAMSTAELLNING AV AMINDERIVAT. | |
| JPS60190776A (en) | Thiophenes and their production | |
| CN106008631B (en) | 1,2,4- triazole -3- 40 thione derivatives containing glucosamine molecules and preparation method thereof and purposes | |
| JPS5946511B2 (en) | 1-(N-hydroxyalkylcarbamoyl)-5-fluorouracils and their production method | |
| JPH05509328A (en) | Method for producing 2-methyl-3,5-dialkylpyridines by dealkylation using sulfur | |
| KR850001040B1 (en) | Process for preparing allophanoylpiperazine compounds | |
| Catesby et al. | Some glycosyl derivatives of piperazine | |
| KR860000295A (en) | Method for preparing oxycam derivative | |
| Bera et al. | Synthesis and reactions of allenic sulfone-modified thymidine: The first allenic sulfone to alkylate deoxyadenosine | |
| JPS6130660B2 (en) | ||
| Hall et al. | Reactions of 1-Nitro-2-nitramino-2-propylaminoimidazolidine with Acetyl Chloride | |
| JPS5946509B2 (en) | 1-Substituted cyclohexylcarbamoyl-5-fluorouracils and their production method |