JPH0427994B2 - - Google Patents
Info
- Publication number
- JPH0427994B2 JPH0427994B2 JP14498783A JP14498783A JPH0427994B2 JP H0427994 B2 JPH0427994 B2 JP H0427994B2 JP 14498783 A JP14498783 A JP 14498783A JP 14498783 A JP14498783 A JP 14498783A JP H0427994 B2 JPH0427994 B2 JP H0427994B2
- Authority
- JP
- Japan
- Prior art keywords
- coumarinyl
- general formula
- crown
- compound
- 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
- -1 (7-methoxy-4-coumarinyl)methyl group Chemical group 0.000 claims description 9
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 description 9
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 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
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 125000000332 coumarinyl group Chemical group O1C(=O)C(=CC2=CC=CC=C12)* 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 235000011181 potassium carbonates Nutrition 0.000 description 3
- CTENSLORRMFPDH-UHFFFAOYSA-N 4-(bromomethyl)-7-methoxychromen-2-one Chemical compound BrCC1=CC(=O)OC2=CC(OC)=CC=C21 CTENSLORRMFPDH-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical group O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical group C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 2
- 150000003983 crown ethers Chemical class 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 239000012156 elution solvent Substances 0.000 description 2
- ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical class C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- VFTFKUDGYRBSAL-UHFFFAOYSA-N 15-crown-5 Chemical compound C1COCCOCCOCCOCCO1 VFTFKUDGYRBSAL-UHFFFAOYSA-N 0.000 description 1
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 1
- SIXUKEZSCHIZGC-USXIJHARSA-N 5-fluoro-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3-[(7-methoxy-2-oxochromen-4-yl)methyl]pyrimidine-2,4-dione Chemical compound C=1C(=O)OC2=CC(OC)=CC=C2C=1CN(C1=O)C(=O)C(F)=CN1[C@H]1C[C@H](O)[C@@H](CO)O1 SIXUKEZSCHIZGC-USXIJHARSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical group CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- CODNYICXDISAEA-UHFFFAOYSA-N bromine monochloride Chemical compound BrCl CODNYICXDISAEA-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229960000956 coumarin Drugs 0.000 description 1
- 235000001671 coumarin Nutrition 0.000 description 1
- YSSSPARMOAYJTE-UHFFFAOYSA-N dibenzo-18-crown-6 Chemical compound O1CCOCCOC2=CC=CC=C2OCCOCCOC2=CC=CC=C21 YSSSPARMOAYJTE-UHFFFAOYSA-N 0.000 description 1
- UNTITLLXXOKDTB-UHFFFAOYSA-N dibenzo-24-crown-8 Chemical compound O1CCOCCOCCOC2=CC=CC=C2OCCOCCOCCOC2=CC=CC=C21 UNTITLLXXOKDTB-UHFFFAOYSA-N 0.000 description 1
- BBGKDYHZQOSNMU-UHFFFAOYSA-N dicyclohexano-18-crown-6 Chemical compound O1CCOCCOC2CCCCC2OCCOCCOC2CCCCC21 BBGKDYHZQOSNMU-UHFFFAOYSA-N 0.000 description 1
- QMLGNDFKJAFKGZ-UHFFFAOYSA-N dicyclohexano-24-crown-8 Chemical compound O1CCOCCOCCOC2CCCCC2OCCOCCOCCOC2CCCCC21 QMLGNDFKJAFKGZ-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- 235000011118 potassium hydroxide Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000009385 viral infection Effects 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、一般式（）
〔式中、Ｘは（７−メトキシ−４−クマリニ
ル）メチル基を示し、Ｙは水素原子又はアセチル
基を示す。〕で表わされる新規なクマリニルフル
オロデオキシウリジン誘導体に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to the general formula () [In the formula, X represents a (7-methoxy-4-coumarinyl)methyl group, and Y represents a hydrogen atom or an acetyl group. This invention relates to a novel coumarinylfluorodeoxyuridine derivative represented by
本発明に係るクマリニルフルオロデオキシウリ
ジン誘導体は、優れた螢光特性をする新規化合物
であり、従つて例えば、ピリミジン環を有する化
合物の螢光高速液体クロマトグラフイーによる微
量定量方法における標準品として使用し得る有用
な化合物である。また、本発明の化合物は、代謝
拮抗性の医薬品として、例えば抗癌剤、カビ・ビ
ールス感染症治療薬等としての用途を有するもの
である。 The coumarinyl fluorodeoxyuridine derivative according to the present invention is a new compound with excellent fluorescent properties, and is therefore used, for example, as a standard product in a microquantitative method using fluorescent high performance liquid chromatography for compounds having a pyrimidine ring. It is a useful compound that can be used as a compound. Furthermore, the compound of the present invention has uses as an antimetabolite drug, such as an anticancer agent, a drug for treating fungal and viral infections, and the like.
一般式（）で表わされる本発明の化合物は、
一般式（）
（式中、Ｙは水素原子又はアセチル基を示す）
で表わされるフルオロデオキシウリジン誘導体
と、一般式（）
（式中、Ｚはクロル、ブロム、ヨード、フルオ
ロ等のハロゲン原子、特にブロム原子を示す）で
表わされるクマリニルハロゲナイドを反応させる
ことによつて製造することができる。 The compound of the present invention represented by the general formula () is
General formula () (In the formula, Y represents a hydrogen atom or an acetyl group)
A fluorodeoxyuridine derivative represented by the general formula () It can be produced by reacting coumarinyl halogenide represented by (wherein Z represents a halogen atom such as chloro, bromine, iodo, or fluoro, particularly a bromine atom).
この反応は、通常、有機溶液中で、好ましくは
無水の状態で行うことができる。 This reaction can usually be carried out in an organic solution, preferably in an anhydrous state.
上記反応に用いることができる有機溶媒として
は、アセトン、メチルエチルケトン、ジエチルケ
トン等のケトン類、エーテル、イソプロピルエー
テル、ジオキサン、テトラヒドロフラン等のエー
テル類、ベンゼン、トルエ等の芳香族炭化水素
類、アセトニトリル、ジメチルホルムアミド等、
好ましくは、アセトン、メチルエチルケトン、ト
ルエン等を挙げることができる。 Organic solvents that can be used in the above reaction include ketones such as acetone, methyl ethyl ketone, and diethyl ketone, ethers such as ether, isopropyl ether, dioxane, and tetrahydrofuran, aromatic hydrocarbons such as benzene and toluene, acetonitrile, dimethyl Formamide etc.
Preferred examples include acetone, methyl ethyl ketone, and toluene.
反応は、室温ないし溶媒の還流温度、特に好ま
しくは45℃ないし95℃で、15分ないし３時間行う
のが好都合である。 The reaction is conveniently carried out at room temperature to the reflux temperature of the solvent, particularly preferably from 45°C to 95°C, for 15 minutes to 3 hours.
反応系中に、塩類、例えば炭酸カリウム、炭酸
ナトリウム、炭酸水素カリウム、炭酸水素ナトリ
ウム、水酸化カリウム、水酸化ナトリウム等の無
機塩基性塩、酢酸カリウム、酢酸ナトリウム等の
有機酸塩が存在していることが好ましく、また、
所望により、触媒としてクラウンエーテル類、例
えば、18−クラウン−６、15−クラウン−５、ジ
シクロヘキシル−18−クラウン−６、ジシクロヘ
キシル−24−クラウン−８、ジベンゾ−24−クラ
ウン−８、ジベンゾ−18−クラウン−６等を用い
て反応の円滑な進行をはかることができる。 Salts such as inorganic basic salts such as potassium carbonate, sodium carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate, potassium hydroxide, and sodium hydroxide, and organic acid salts such as potassium acetate and sodium acetate are present in the reaction system. It is preferable that
If desired, crown ethers such as 18-crown-6, 15-crown-5, dicyclohexyl-18-crown-6, dicyclohexyl-24-crown-8, dibenzo-24-crown-8, dibenzo-18 - Crown-6 or the like can be used to ensure smooth progress of the reaction.
上記の反応における、一般式（）で表わされ
るフルオロデオキシウリジン誘導体と一般式
（）で表されるクマリニルハロゲナイドとの使
用割合は、特定されないが、前者の１モルに対し
て後者１ないし15モル程度を用いればよく、ま
た、クラウンエーテル類を用いる場合は、一般式
（）の化合物１モルに対して１モル以下、特に
0.2モル付近の使用割合が好ましい。 In the above reaction, the ratio of the fluorodeoxyuridine derivative represented by the general formula () and the coumarinyl halide represented by the general formula () is not specified, but the ratio of the latter to 1 mole of the former is not specified. It is sufficient to use about 15 moles, and when crown ethers are used, it is not more than 1 mole per mole of the compound of general formula (), especially
A usage ratio of around 0.2 mol is preferred.
当該反応によつて生成する前記一般式（）で
表わされる化合物の単離、取得は、通常の処理操
作により行うことができる。例えば、反応混合物
を過し、不溶物を去し、凌を減圧下で濃縮
し、残留分を再結晶させることによつて、又はク
ロマトグラフイー等によつて単離精製することに
よつて、一般式（）で表わされる化合物を取得
することができる。 The compound represented by the general formula () produced by the reaction can be isolated and obtained by conventional processing operations. For example, by filtering the reaction mixture to remove insoluble materials, concentrating the residue under reduced pressure, and recrystallizing the residue, or by isolating and purifying it by chromatography or the like. A compound represented by the general formula () can be obtained.
以下に、本発明の実施例を掲げる。 Examples of the present invention are listed below.
実施例 １
乾燥アセトン100ml中に1.0ｇの５−フルオロ−
2′−デオキシウリジン、1.42ｇの（７−メトキシ
−４−クマリニル）メチルブロマイド及び2.0ｇ
の微粉末状の無水炭酸カリウムを懸濁させ、水浴
（浴温：75℃）上で、1.5時間還流させた。不溶物
を去し、液を減圧下に濃縮した。残留物をシ
リカゲルカラムクロマトグラフイー（溶出溶媒：
20％アセトン含有クロロホルム、続いて50％アセ
トン含有クロロホルム）によつて分離し、目的画
分を集め、減圧下に濃縮した。得られた固状残留
物を水−エタノール（１：２）から再結晶する
と、1.18ｇ（67.0％）の３−（７−メトキシ−４
−クマリニル）メチル−５−フルオロ−2′−デオ
キシウリジンが無色の針状晶として得られた。融
点：160〜163℃。Example 1 1.0 g of 5-fluoro- in 100 ml of dry acetone
2'-deoxyuridine, 1.42 g (7-methoxy-4-coumarinyl)methyl bromide and 2.0 g
Finely powdered anhydrous potassium carbonate was suspended and refluxed for 1.5 hours on a water bath (bath temperature: 75°C). Insoluble matter was removed, and the liquid was concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (elution solvent:
The desired fractions were collected and concentrated under reduced pressure. The resulting solid residue was recrystallized from water-ethanol (1:2) to yield 1.18 g (67.0%) of 3-(7-methoxy-4
-coumarinyl)methyl-5-fluoro-2'-deoxyuridine was obtained as colorless needles. Melting point: 160-163℃.
UV λEtOH naxnm：217（sh）、276、322
NMRδ（ppm，DMSO−d6）：ウリジン部分、2.21
（2H，broad ｔ，Ｊ＝６Hz，C2′−Ｈ）、3.5〜
3.7（2H，ｍ，C5′−Ｈ）、3.7〜3.9（1H，ｍ，
C4′−Ｈ）、4.2〜4.4（1H，ｍ，C3′−Ｈ）、5.1〜
5.3（2H，ｍ，OH×２，D2O添加で消失）、6.16
（1H，broad ｔ，Ｊ＝６Hz，C1′−Ｈ）、8.42
（1H，ｄ，Ｊ＝７Hz，C6−Ｈ）；クマリン部分、
3.88（3H，ｓ，OCH3）、5.17（2H，ｓ，CH2）、
6.05（1H，ｓ，C3−Ｈ）、6.9〜7.1（1H，ｍ，C6
−Ｈ）、70.5（1H，ｓ，C8−Ｈ）、7.85（1H，ｄ，
Ｊ＝10Hz，C5−Ｈ）
元素分析値：C20H19FH2O8として
計算値（％）：Ｃ、55.30；Ｈ、4.41；Ｎ、6.45
実測値（％）：Ｃ、55.45；Ｈ、4.46；Ｎ、6.53
実施例 ２
乾燥アセトン100ml中に1.0ｇの3′，5′−ジ−Ｏ
−アセチル−５−フルオロ−2′−デオキシウリジ
ン、1.06ｇの（７−メトキシ−４−クマリニル）
メチルブロマイド及び1.50ｇの微粉末状の無水炭
酸カリウムを懸濁させ、水浴（浴温：75℃）上
で、１時間還流させた。不溶物を去し、液を
減圧下に濃縮した。その残留物をシリカゲルカラ
ムクロマトグラフイー（溶出溶媒：クロロホル
ム、続いて２％メタノール含有クロロホルム）に
よつて分離し、目的画分を集め、減圧下に濃縮し
た。得られた油状残留物を少量のエーテルと撹拌
することにより固化させると、1.14ｇ（72.7％）
の３−（７−メトキシ−４−クマリニル）メチル
−3′，5′−ジ−Ｏ−アセチル−５−フルオロ−
2′−デオキシウリジンが無色の粉末として得られ
た。融点：88〜92℃。UV λ EtOH nax nm: 217 (sh), 276, 322 NMR δ (ppm, DMSO−d 6 ): Uridine moiety, 2.21
(2H, broad t, J=6Hz, C 2 '-H), 3.5~
3.7 (2H, m, C 5 '-H), 3.7~3.9 (1H, m,
C 4 ′-H), 4.2-4.4 (1H, m, C 3 ′-H), 5.1-
5.3 (2H, m, OH x 2, disappeared by addition of D 2 O), 6.16
(1H, broad t, J = 6Hz, C 1 '-H), 8.42
(1H, d, J = 7Hz, C 6 −H); coumarin part,
3.88 (3H, s, OCH 3 ), 5.17 (2H, s, CH 2 ),
6.05 (1H, s, C3 -H), 6.9-7.1 (1H, m, C6
-H), 70.5 (1H, s, C 8 -H), 7.85 (1H, d,
J=10Hz, C5 -H) Elemental analysis value: C20H19FH2O8 Calculated value (%): C, 55.30; H, 4.41; N , 6.45 Actual value (%): C , 55.45 ; H , 4.46; N, 6.53 Example 2 1.0 g of 3',5'-di-O in 100 ml of dry acetone
-acetyl-5-fluoro-2'-deoxyuridine, 1.06 g (7-methoxy-4-coumarinyl)
Methyl bromide and 1.50 g of finely powdered anhydrous potassium carbonate were suspended and refluxed for 1 hour on a water bath (bath temperature: 75°C). Insoluble matter was removed, and the liquid was concentrated under reduced pressure. The residue was separated by silica gel column chromatography (elution solvent: chloroform, followed by chloroform containing 2% methanol), and the desired fractions were collected and concentrated under reduced pressure. The resulting oily residue was solidified by stirring with a small amount of ether to give 1.14 g (72.7%)
3-(7-methoxy-4-coumarinyl)methyl-3',5'-di-O-acetyl-5-fluoro-
2'-deoxyuridine was obtained as a colorless powder. Melting point: 88-92℃.
UV λEtOH naxnm：220、275、322
NMRδ（ppm，CDCl3）：ウリジン部分、2.10
（3H，ｓ，COCH3）、2.16（3H，ｓ，COCH3）、
2.0〜2.8（2H，ｍ，C2′−Ｈ）、4.2〜4.5（3H，
ｍ，C4′−ＨとC5′−Ｈ）、5.1〜5.4（3H，ｍ，
C3′−Ｈとクマリン部分のCH2）、6.30（1H，
broad ｔ，Ｊ＝６Hz，C1′−Ｈ）、7.78（1H，
ｄ，Ｊ＝６Hz，C6−Ｈ）；クマリン部分、3.88
（3H，ｓ，OCH3）、5.86（1H，ｓ，C3−Ｈ）、
6.85（1H，ｓ，C8−Ｈ）、6.8〜7.0（1H，ｍ，C6
−Ｈ）、7.61（1H，ｄ，Ｊ＝９Hz、C5−Ｈ）
元素分析値：C24H23FN2O10として
計算値（％）：Ｃ、55.60；Ｈ、4.47；Ｎ、5.40
実測値（％）：Ｃ、55.57；Ｈ、4.57；Ｎ、5.59UV λ EtOH nax nm: 220, 275, 322 NMRδ (ppm, CDCl 3 ): Uridine moiety, 2.10
(3H, s, COCH 3 ), 2.16 (3H, s, COCH 3 ),
2.0 to 2.8 (2H, m, C 2 ′-H), 4.2 to 4.5 (3H,
m, C 4 ′-H and C 5 ′-H), 5.1 to 5.4 (3H, m,
C 3 ′-H and CH 2 of the coumarin moiety), 6.30 (1H,
broad t, J = 6 Hz, C 1 ′-H), 7.78 (1H,
d, J = 6 Hz, C 6 −H); coumarin part, 3.88
(3H, s, OCH 3 ), 5.86 (1H, s, C 3 −H),
6.85 (1H, s, C 8 -H), 6.8~7.0 (1H, m, C 6
-H), 7.61 (1H, d, J = 9Hz, C 5 -H) Elemental analysis value: C 24 H 23 FN 2 O 10 Calculated value (%): C, 55.60; H, 4.47; N, 5.40 Actual measurement Value (%): C, 55.57; H, 4.57; N, 5.59
Claims (1)
ル）メチル基を示し、Ｙは水素原子又はアセチル
基を示す。〕で表わされるクマリニルフルオロデ
オキシウリジン誘導体。[Claims] 1. General formula [In the formula, X represents a (7-methoxy-4-coumarinyl)methyl group, and Y represents a hydrogen atom or an acetyl group. ] A coumarinyl fluorodeoxyuridine derivative.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14498783A JPS6036495A (en) | 1983-08-10 | 1983-08-10 | Coumarinyl fluorodeoxyuridien derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14498783A JPS6036495A (en) | 1983-08-10 | 1983-08-10 | Coumarinyl fluorodeoxyuridien derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6036495A JPS6036495A (en) | 1985-02-25 |
| JPH0427994B2 true JPH0427994B2 (en) | 1992-05-13 |
Family
ID=15374838
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP14498783A Granted JPS6036495A (en) | 1983-08-10 | 1983-08-10 | Coumarinyl fluorodeoxyuridien derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6036495A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0354149Y2 (en) * | 1986-08-14 | 1991-11-28 |
-
1983
- 1983-08-10 JP JP14498783A patent/JPS6036495A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6036495A (en) | 1985-02-25 |
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