JPS589115B2 - Shinkina Nucleoside Yudotaino Seizouhouhou - Google Patents
Shinkina Nucleoside Yudotaino SeizouhouhouInfo
- Publication number
- JPS589115B2 JPS589115B2 JP7783874A JP7783874A JPS589115B2 JP S589115 B2 JPS589115 B2 JP S589115B2 JP 7783874 A JP7783874 A JP 7783874A JP 7783874 A JP7783874 A JP 7783874A JP S589115 B2 JPS589115 B2 JP S589115B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- isothiocyanate
- general formula
- nucleoside
- reaction
- 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
- 150000003833 nucleoside derivatives Chemical class 0.000 title claims description 4
- 239000002777 nucleoside Substances 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 11
- 235000000346 sugar Nutrition 0.000 claims description 6
- 125000003277 amino group Chemical group 0.000 claims description 4
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000003172 aldehyde group Chemical group 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 125000004185 ester group Chemical group 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- -1 nucleoside compound Chemical class 0.000 description 9
- JZPHAJFIZZEAEK-UHFFFAOYSA-N 3-chloro-6-methoxy-2h-indazole Chemical compound COC1=CC=C2C(Cl)=NNC2=C1 JZPHAJFIZZEAEK-UHFFFAOYSA-N 0.000 description 7
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 7
- TXHIDIHEXDFONW-UHFFFAOYSA-N benzene;propan-2-one Chemical compound CC(C)=O.C1=CC=CC=C1 TXHIDIHEXDFONW-UHFFFAOYSA-N 0.000 description 7
- 239000008096 xylene Substances 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 239000000126 substance Substances 0.000 description 5
- BXFUZKVJSUIZLS-WLDMJGECSA-N (2r,3s,4s,5r)-2-(hydroxymethyl)-6-isothiocyanatooxane-3,4,5-triol Chemical compound OC[C@H]1OC(N=C=S)[C@H](O)[C@@H](O)[C@@H]1O BXFUZKVJSUIZLS-WLDMJGECSA-N 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- VAMXMNNIEUEQDV-UHFFFAOYSA-N methyl anthranilate Chemical compound COC(=O)C1=CC=CC=C1N VAMXMNNIEUEQDV-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-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
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000000921 elemental analysis Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-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
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 150000001299 aldehydes Chemical class 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
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 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
- PBQWMVZQUIWTIL-UHFFFAOYSA-N chloroform;hexane;propan-2-one Chemical compound CC(C)=O.ClC(Cl)Cl.CCCCCC PBQWMVZQUIWTIL-UHFFFAOYSA-N 0.000 description 2
- OAIVIYSBZFEOIU-UHFFFAOYSA-N chloroform;propan-2-one Chemical compound CC(C)=O.ClC(Cl)Cl OAIVIYSBZFEOIU-UHFFFAOYSA-N 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 210000003918 fraction a Anatomy 0.000 description 2
- 150000002540 isothiocyanates Chemical class 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- BXFUZKVJSUIZLS-TVPFVARWSA-N (2R,3R,4S,5R)-2-(hydroxymethyl)-6-isothiocyanatooxane-3,4,5-triol Chemical compound C1([C@H](O)[C@@H](O)[C@@H](O)[C@H](O1)CO)N=C=S BXFUZKVJSUIZLS-TVPFVARWSA-N 0.000 description 1
- WZGNUGQMDKVJOC-JDJSBBGDSA-N (2R,3S,4R)-2-(hydroxymethyl)-5-isothiocyanatooxolane-3,4-diol Chemical compound OC[C@H]1OC(N=C=S)[C@H](O)[C@@H]1O WZGNUGQMDKVJOC-JDJSBBGDSA-N 0.000 description 1
- 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
- BOOMHTFCWOJWFO-UHFFFAOYSA-N 3-aminopyridine-2-carboxylic acid Chemical compound NC1=CC=CN=C1C(O)=O BOOMHTFCWOJWFO-UHFFFAOYSA-N 0.000 description 1
- RWHNHACQOJVHCE-IANNHFEVSA-N C1([C@H](O)[C@@H](O)[C@H](O)CO1)N=C=S Chemical compound C1([C@H](O)[C@@H](O)[C@H](O)CO1)N=C=S RWHNHACQOJVHCE-IANNHFEVSA-N 0.000 description 1
- RWHNHACQOJVHCE-JDJSBBGDSA-N C1([C@H](O)[C@H](O)[C@H](O)CO1)N=C=S Chemical compound C1([C@H](O)[C@H](O)[C@H](O)CO1)N=C=S RWHNHACQOJVHCE-JDJSBBGDSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-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
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 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
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000001816 cooling 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
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- ZBKFYXZXZJPWNQ-UHFFFAOYSA-N isothiocyanate group Chemical group [N-]=C=S ZBKFYXZXZJPWNQ-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000000746 purification Methods 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
- 150000003335 secondary amines Chemical class 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
Landscapes
- Saccharide Compounds (AREA)
- 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造法な関する。[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弐Ｒ１ＮＣ＝Ｓ
（Ｉ）
〔こゝにＲ１はアルデヒド糖の残基、例えばグルコース
、アラビノース、リボース、キシロース、ガラクトース
、グルコサミンから選ばれる糖の残基を表わす〕で示さ
れる化合物に次の一般式（こゝにＲ２はこれに隣接する
−Ｃ−Ｃ−結合と一緒になって１つのアリール基又は複
素環基を表わし、Ａはアミノ基又はイミノ基を表わし、
Ｂはカルボキシル基又はこれのエステル基あるいはアル
デヒド基を表わす）で示される化合物を反応させること
を特徴とする、次の一般式
（こゝにＲ１、Ｒ２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造法に関する。More specifically, the present invention relates to the following general 2R1NC=S
(I) [Here, R1 represents a residue of an aldehyde sugar, such as a residue of a sugar selected from glucose, arabinose, ribose, xylose, galactose, and glucosamine.] The following general formula (herein, R2 together with the adjacent -C-C- bond represents one aryl group or heterocyclic group, A represents an amino group or imino group,
B represents a carboxyl group, an ester group thereof, or an aldehyde group), which is represented by the following general formula (where R1 and R2 have the same meanings as above) This invention relates to a method for producing nucleoside derivatives.
本発明者等は、従来から種々のヌクレオシドの合成研究
を行って来たが、（Ｉ）式で示されるインチオシアナー
ト基を持つ糖類に、（■）式で示されるオルト位にアミ
ノ基又はイミノ基を有するカルボン酸またはそのエステ
ルまたはアルデヒド化合物を反応させることにより、一
段階で（■）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, and found that a saccharide having an inthiocyanate group represented by formula (I) has an amino group or The present invention was completed by discovering that a nucleoside compound represented by the formula (■) can be obtained in one step by reacting a carboxylic acid having an imino group, its ester, or an aldehyde compound.
本発明の方法は（Ｉ）式と（■）式の化合物を無水の条
件、例えばベンゼン、トルエン、キシレンあるいはそれ
らの混合溶媒、炭化水素系、エーテル系の無極性溶媒に
溶解し反応させることにより実施されるのが好ましい。The method of the present invention is carried out by dissolving the compounds of formulas (I) and (■) in anhydrous conditions, such as benzene, toluene, xylene or a mixed solvent thereof, or a nonpolar solvent such as a hydrocarbon or ether. Preferably, it is carried out.
（Ｉ）式、（■）式の化合物が複素環化合物、アミノ酸
等で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、トリエチルアミン、ピペリジン、モル
ホリン、ピリジン、キノリン等の２級アミン、３級アミ
ンを加えて反応を行わせることも出来る。When the compound of formula (I) or formula (■) is a heterocyclic compound, amino acid, etc. and is difficult to dissolve in the above solvent, dimethylformamide,
The reaction can also be carried out by adding secondary or tertiary amines such as diethylamine, triethylamine, piperidine, morpholine, pyridine, and quinoline.
使用する反応試薬は、当モル量で反応させれば十分であ
り、反応温度は６０°〜２００℃が適当である。It is sufficient that the reaction reagent used is reacted in an equimolar amount, and the reaction temperature is suitably 60° to 200°C.
通常は、水浴上で、加熱又は油浴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、２０分から３
日間も要する場合がある。Usually, the reaction time for refluxing on a water bath, heating, or oil bath varies depending on the substance to be reacted, but it ranges from 20 minutes to 30 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イ
ーを利用するのが適当である。Thin layer chromatography is suitably used to determine the end point of the reaction.
ここで一般式（Ｉ）で表わされる化合物はアルテヒド糖
のイソチオシアナート誘導体であるが、これの例として
例えば、Ｄ−グルコピラノシルイソチオシアナート、Ｄ
−アラビノピラノシルインチオシアナート、Ｄ−リボピ
ラノシルイソチオシアナート、Ｄ−キシロピラノシルイ
ソチオシアナート、Ｄ−ガラクトピラノシルイソチオシ
アナート、２−アミノ−２−テオキシグルコピラノシル
イソチオシアナート等を初めとしてイソチオシアナート
基を持った糖のすべてが使用可能でありまた通常はアセ
チル基、ベンゾイル基等の公知の水酸基保護基で水酸基
を保護した化合物を出発原料として使用する。Here, the compound represented by the general formula (I) is an isothiocyanate derivative of altehyde sugar, and examples thereof include D-glucopyranosyl isothiocyanate, D-glucopyranosyl isothiocyanate,
-arabinopyranosyl inthiocyanate, D-ribopyranosyl isothiocyanate, D-xylopyranosyl isothiocyanate, D-galactopyranosyl isothiocyanate, 2-amino-2-theoxyglucopyra All sugars with an isothiocyanate group, including nosyl isothiocyanate, etc. can be used, and compounds whose hydroxyl groups are protected with known hydroxyl protecting groups such as acetyl and benzoyl groups are usually used as starting materials. do.
また一般式（■）で表わされる化合物としては、隣接す
る位置にアミノ基またはイミノ基とカルボキシル基また
はそのエステルまたはアルテヒド基を有する化合物はす
べて使用できるが例えば３−アミノピラゾール−４−カ
ルボン酸、アントラニル酸、アントラニル酸アルキルエ
ステル特にメチルエステル、３−アミノピコリン酸又は
３−アミノイソピコリン酸等があげられる。As the compound represented by the general formula (■), any compound having an amino group or imino group and a carboxyl group or an ester or altehyde group thereof at adjacent positions can be used, such as 3-aminopyrazole-4-carboxylic acid, Examples include anthranilic acid, anthranilic acid alkyl esters, especially methyl esters, 3-aminopicolinic acid, and 3-aminoisopicolinic acid.
反応終了後、メタノール、エタノール等の有機溶媒を使
用して再結晶を行い標品を得る。After the reaction is completed, recrystallization is performed using an organic solvent such as methanol or ethanol to obtain a standard sample.
一般式（■）で表わされる化合物のアルデヒド糖の水酸
基部分がアセチル基、ベンゾイル基等の水酸基保護基に
より保護されていた場合は、必要に応じて加水分解反応
により保護基を脱離させることも可能である。If the hydroxyl group of the aldehyde sugar of the compound represented by the general formula (■) is protected by a hydroxyl protecting group such as an acetyl group or benzoyl group, the protecting group may be removed by a hydrolysis reaction if necessary. It is possible.
こうして得られた一般式（■）で表わされた化合物は、
すべて文献未収載の新規物質であって、抗菌性、抗ウイ
ルス性などの薬埋活性を示し、医薬品として有用である
。The compound represented by the general formula (■) obtained in this way is
All of these substances are new substances that have not yet been described in the literature, and they exhibit antibacterial and antiviral properties, making them useful as pharmaceuticals.
次に本発明によって得られる目的化合物を出発原料と共
に化学構造式で示すと次の如くである。Next, the chemical structural formula of the target compound obtained by the present invention together with the starting materials is as follows.
次に本発明を実施例によって説明する。Next, the present invention will be explained by examples.
実施例１
Ｄ−グルコピラノシルイソチオシアナートと３＝アミノ
ピラゾール−４−カルボン酸との反応無水キシレン１５
ｍｌ中に２・３・４・５−テトラ−Ｏ−アセチルーＤ−
グルコピラノシルインチオシアナート３９０ｍｇ（０．
０１モル）と３−アミノピラゾール−４−カルボン酸１
３０ｍｇ（０．０１モル分子量１２７）とを加えて、５
時間還流し放冷後、未反応の不溶な原料３−アミノピラ
ゾール−４−カルボン酸５２ｍｇを回収する。Example 1 Reaction of D-glucopyranosyl isothiocyanate with 3=aminopyrazole-4-carboxylic acid Anhydrous xylene 15
2,3,4,5-tetra-O-acetyl D- in ml
Glucopyranosyl thiocyanate 390 mg (0.
01 mol) and 3-aminopyrazole-4-carboxylic acid 1
30 mg (0.01 molar molecular weight 127) and 5
After refluxing for a period of time and allowing the mixture to cool, 52 mg of unreacted and insoluble raw material 3-aminopyrazole-4-carboxylic acid is recovered.
その後キシレンを減圧下留去した。Thereafter, xylene was distilled off under reduced pressure.
カラムクロマトグラフイー（シリカゲル、ヘキサンーク
ロロホルム−アセトン）で精製し、クロロホルムーアセ
トン（２５：１）のフラクションから目的物を得た。The product was purified by column chromatography (silica gel, hexane-chloroform-acetone), and the target product was obtained from a fraction of chloroform acetone (25:1).
収量１５５ｍｇ（３０％）、ｍｐ１３６−１３７°（未
補正）、赤外部吸収ス１７４０ｃｍ−１（ＣＯＯＣＨ３
）元素分析：理論値、Ｃ４５．７８ Ｈ４．４５ Ｎ１
１．２４％；測定値、Ｃ４５．４４ Ｈ４．９７ Ｎ８
．０４％。Yield 155 mg (30%), mp 136-137° (uncorrected), infrared absorption 1740 cm-1 (COOCH3
) Elemental analysis: theoretical value, C45.78 H4.45 N1
1.24%; Measured value, C45.44 H4.97 N8
．． 04%.
実施例２
Ｄ−グルコピラノシルイソチオシアナートとアントラニ
ル酸との反応
無水キシレン１５１ｎ９中に２・３・４・５−テトラ−
Ｏ−アセチルＤ−グルコピラノシルイソチオシアナート
３９０ｍｇ（０．０１モル）とアントラニル酸１４０ｍ
ｇ（０．０１モル、分子量１３７）と加えて油浴上４時
間還流後放冷し減圧下キシレンを留去し残分をカラムク
ロマトグラフイー（シリカゲル、ヘキサン−クロロホル
ム−アセトン）で精製した。Example 2 Reaction of D-glucopyranosyl isothiocyanate with anthranilic acid 2,3,4,5-tetra- in anhydrous xylene 151n9
390 mg (0.01 mol) of O-acetyl D-glucopyranosyl isothiocyanate and 140 m of anthranilic acid
g (0.01 mol, molecular weight 137), and after refluxing on an oil bath for 4 hours, the mixture was allowed to cool, xylene was distilled off under reduced pressure, and the residue was purified by column chromatography (silica gel, hexane-chloroform-acetone).
クロロホルム−アセトン（１９：１）のフラクションか
ら結晶を得た。Crystals were obtained from the chloroform-acetone (19:1) fraction.
エーテル−ヘキサンから再結晶し無色針状晶を得た。Recrystallization from ether-hexane gave colorless needles.
収量１００ｍｇ（２０％）、ｍｐ１７５−１７６°（未
補正）赤１７４０（ＣＯＯＣＨ３）１６９０（＝Ｎ−Ｃ
＝Ｓ）１６１０、７５０ｃｍ−１（フエニル）
実施例３
Ｄ−アラビノピラノシルイソチオシアナートとアントラ
ニル酸メチルエステルとの反応
無水ベンゼン１５ｍｌ中に２・３・４−トリ−Ｏ−アセ
チルーＤ−アシビノピラノシルイソチオシアナート３１
９ｍｇ（１ミリモル）とアントラニル酸メチルエステル
１７０ｍｇ（１ミリモル、分子量１６７）とを加え水浴
上で２０時間還流後溶媒を減圧下留去させてコロイド状
の残渣を得た。Yield 100 mg (20%), mp 175-176° (uncorrected) Red 1740 (COOCH3) 1690 (=N-C
=S) 1610, 750 cm-1 (phenyl) Example 3 Reaction of D-arabinopyranosyl isothiocyanate with anthranilic acid methyl ester 2,3,4-tri-O-acetyl-D- in 15 ml of anhydrous benzene Acibinopyranosyl isothiocyanate 31
9 mg (1 mmol) and 170 mg (1 mmol, molecular weight 167) of anthranilic acid methyl ester were added, and after refluxing on a water bath for 20 hours, the solvent was distilled off under reduced pressure to obtain a colloidal residue.
カラムクロマトグラフイ−（シリカゲル、ベンゼン−ア
セトン）で精製した。It was purified by column chromatography (silica gel, benzene-acetone).
ベンゼン−アセトン９５：５のフラクションから融点１
２３−１２４°（未補正）の閉環体を得た。Melting point 1 from benzene-acetone 95:5 fraction
A closed ring of 23-124° (uncorrected) was obtained.
収量２３０ｍｇ（８２％）１７４０、１７００、１６０
０ｃｍ−１元素分析、理論値、Ｃ５２．３０，Ｈ４．６
２、Ｎ６．４２％；測定値；Ｃ５２．４０、Ｈ４．６５
、Ｎ６．５４％。Yield 230mg (82%) 1740, 1700, 160
0cm-1 elemental analysis, theoretical value, C52.30, H4.6
2, N6.42%; Measured value; C52.40, H4.65
, N6.54%.
実施例４
Ｄ−リボフラノシルイソチオシアナートとアントラニル
酸との反応
無水ベンゼンｌＯｒｒＬｌ中に２・３・５−トリ−Ｏ−
ベンゾイル−Ｄ−リボフラノシルイソチオシアナート４
９０ｍｇ（１ミリモル、分子量４８９）とアントラニル
酸１４０ｍｇ（１ミリモル、分子量１３７）とを加え、
水浴上で１７時間加熱還流した。Example 4 Reaction of D-ribofuranosyl isothiocyanate with anthranilic acid 2,3,5-tri-O- in anhydrous benzene lOrrLl
Benzoyl-D-ribofuranosylisothiocyanate 4
90 mg (1 mmol, molecular weight 489) and 140 mg (1 mmol, molecular weight 137) of anthranilic acid were added,
The mixture was heated under reflux on a water bath for 17 hours.
放冷後減圧下濃縮し実施例３と同様に処理しベンゼン−
アセトン９５：５のフラクションから融点１７４−１７
５°（未補正）の結晶を得た。After cooling, it was concentrated under reduced pressure and treated in the same manner as in Example 3 to give benzene.
Melting point 174-17 from acetone 95:5 fraction
A 5° (uncorrected) crystal was obtained.
エタノールで再結晶して無色針状晶を得た。Recrystallization from ethanol gave colorless needles.
収量４９８ｍｇ（８０％）赤外部吸収スペクトル：１５
９０、７００ｃｍ−１、元素分析；理論値、Ｃ６５．５
９、Ｈ４．２１、Ｎ４．５０％；測定値、Ｃ６５．６２
、Ｈ４２４、Ｎ４４８％。Yield 498mg (80%) Infrared absorption spectrum: 15
90, 700 cm-1, elemental analysis; theoretical value, C65.5
9, H4.21, N4.50%; Measured value, C65.62
, H424, N448%.
実施例５
Ｄ−アラビノピラノシルイソチオシアナートと３−アミ
ノピラゾール−４−カルボン酸との反応
無水キシレン１５ｍｌ中に２・３・４−トリ−Ｏ−アセ
チル−Ｄ−アラビラノシルイソチオシアナート３１９ｍ
ｇ、（１ミリモル）と３−アミノピラゾール−４−カル
ボン酸１３０ｍｇ（１ミリモル、分子量１３７）とを加
えて油浴上（１００℃）で２０時間加熱還流後放冷し、
未反応の３−アミノピラゾール−４−カルボン酸３０ｍ
ｇを口取後口液を減圧下濃縮してシロップを得た。Example 5 Reaction of D-arabinopyranosylisothiocyanate with 3-aminopyrazole-4-carboxylic acid 2,3,4-tri-O-acetyl-D-arabinosylisothiocyanate in 15 ml of anhydrous xylene Nath 319m
g, (1 mmol) and 130 mg (1 mmol, molecular weight 137) of 3-aminopyrazole-4-carboxylic acid were added, heated under reflux on an oil bath (100°C) for 20 hours, and then allowed to cool.
30m of unreacted 3-aminopyrazole-4-carboxylic acid
After taking a mouthful of g, the oral liquid was concentrated under reduced pressure to obtain a syrup.
カラムクロマトグラフイー（シリカゲル、ベンゼン−ア
セトン）で精製し、ベンゼン−アセトン９５：５のフラ
クションから油状物質を得た。Purification by column chromatography (silica gel, benzene-acetone) gave an oily substance from a 95:5 benzene-acetone fraction.
収量２９８ｍｇ７０％）Ｒｆ値０．５５（シリカゲル、
ベンゼン−アセトン４：１）
１７２０、１６００ｃｍ−１
実施例６
Ｄ−リボフラノミルイソチオシアナートと３−アミノピ
ラゾール−４−カルボン酸との反応
無水キシレン２０ｍｌ中に２・３・５−トリ−Ｏ−ベン
ゾイル−Ｄ−リボフラノシルイソチオシアナート５００
ｍｇ（１ミリモル）と３−アミノピラゾール−４−カル
ボン酸１４０ｍｇを入れ実施例５と同様に処理した。Yield 298 mg 70%) Rf value 0.55 (silica gel,
Benzene-acetone 4:1) 1720, 1600 cm Example 6 Reaction of D-ribofuranomylisothiocyanate with 3-aminopyrazole-4-carboxylic acid 2,3,5-tri-O in 20 ml of anhydrous xylene -Benzoyl-D-ribofuranosyl isothiocyanate 500
mg (1 mmol) and 140 mg of 3-aminopyrazole-4-carboxylic acid were added, and the same treatment as in Example 5 was carried out.
ベンゼン−アセトン９５：５のフラクションから生成物
を得た。The product was obtained from a benzene-acetone 95:5 fraction.
収量４６０ｍｇ（７５％）Ｒｆ値０．７５（シリカゲル
、ベンゼン−アセトン４：１）Yield 460 mg (75%) Rf value 0.75 (silica gel, benzene-acetone 4:1)
Claims (1)
る化合物に次の一般式 （こゝにＲ２はこれに隣接する−Ｃ−Ｃ−結合と一緒に
なって１つのアリール基又は複素環基を表わし、Ａはア
ミノ基又はイミノ基を表わし、Ｂはカルボキシル基又は
これのエステル基あるいはアルデヒド基を表わす）で示
される化合物を反応させることを特徴とする、次の一般
式 （こゝにＲ１、Ｒ２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造法。[Scope of Claims] 1. A compound represented by the following general formula R1NC=S(I) (herein, R1 represents a residue of an aldehyde sugar) is combined with the following general formula (herein, R2 is adjacent to this) -C-C- together represent one aryl group or heterocyclic group, A represents an amino group or imino group, and B represents a carboxyl group or its ester group or aldehyde group) A method for producing a nucleoside derivative represented by the following general formula (wherein R1 and R2 have the same meanings as above), which comprises reacting a compound.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7783874A JPS589115B2 (en) | 1974-07-09 | 1974-07-09 | Shinkina Nucleoside Yudotaino Seizouhouhou |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7783874A JPS589115B2 (en) | 1974-07-09 | 1974-07-09 | Shinkina Nucleoside Yudotaino Seizouhouhou |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS516978A JPS516978A (en) | 1976-01-20 |
| JPS589115B2 true JPS589115B2 (en) | 1983-02-18 |
Family
ID=13645174
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP7783874A Expired JPS589115B2 (en) | 1974-07-09 | 1974-07-09 | Shinkina Nucleoside Yudotaino Seizouhouhou |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS589115B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6294665A (en) * | 1985-10-18 | 1987-05-01 | 石川島播磨重工業株式会社 | Air raising - air down method |
-
1974
- 1974-07-09 JP JP7783874A patent/JPS589115B2/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| JPS516978A (en) | 1976-01-20 |
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