JPS63188696A - Production of 5-(perfluoroalkyl)uridine derivative - Google Patents
Production of 5-(perfluoroalkyl)uridine derivativeInfo
- Publication number
- JPS63188696A JPS63188696A JP1912887A JP1912887A JPS63188696A JP S63188696 A JPS63188696 A JP S63188696A JP 1912887 A JP1912887 A JP 1912887A JP 1912887 A JP1912887 A JP 1912887A JP S63188696 A JPS63188696 A JP S63188696A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- uridine derivative
- general formula
- uridine
- carboxylic acid
- 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.)
- Pending
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 5
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical class O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 claims abstract description 15
- BLIQUJLAJXRXSG-UHFFFAOYSA-N 1-benzyl-3-(trifluoromethyl)pyrrolidin-1-ium-3-carboxylate Chemical compound C1C(C(=O)O)(C(F)(F)F)CCN1CC1=CC=CC=C1 BLIQUJLAJXRXSG-UHFFFAOYSA-N 0.000 claims abstract description 6
- -1 perfluoro Chemical group 0.000 claims abstract description 4
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 3
- 150000001735 carboxylic acids Chemical class 0.000 claims abstract 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 abstract description 4
- 150000001875 compounds Chemical class 0.000 abstract 2
- 239000003443 antiviral agent Substances 0.000 abstract 1
- AUFUWRKPQLGTGF-FMKGYKFTSA-N uridine triacetate Chemical compound CC(=O)O[C@@H]1[C@H](OC(C)=O)[C@@H](COC(=O)C)O[C@H]1N1C(=O)NC(=O)C=C1 AUFUWRKPQLGTGF-FMKGYKFTSA-N 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 229910052724 xenon Inorganic materials 0.000 description 3
- FHNFHKCVQCLJFQ-UHFFFAOYSA-N xenon atom Chemical compound [Xe] FHNFHKCVQCLJFQ-UHFFFAOYSA-N 0.000 description 3
- LRMSQVBRUNSOJL-UHFFFAOYSA-N 2,2,3,3,3-pentafluoropropanoic acid Chemical compound OC(=O)C(F)(F)C(F)(F)F LRMSQVBRUNSOJL-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- GLXNCCKMEDEHOO-UHFFFAOYSA-N 1,1,1-trifluoro-n-nitroso-n-(trifluoromethyl)methanesulfonamide Chemical compound FC(F)(F)N(N=O)S(=O)(=O)C(F)(F)F GLXNCCKMEDEHOO-UHFFFAOYSA-N 0.000 description 1
- OIQOUHIUUREZOM-UHFFFAOYSA-N 1,1-dichloro-1,2-difluoroethane Chemical compound FCC(F)(Cl)Cl OIQOUHIUUREZOM-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- UEJHQHNFRZXWRD-UAKXSSHOSA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-(trifluoromethyl)pyrimidine-2,4-dione Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(C(F)(F)F)=C1 UEJHQHNFRZXWRD-UAKXSSHOSA-N 0.000 description 1
- HJHNQOOYBACTPQ-RRKCRQDMSA-N 1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-(1,1,2,2,2-pentafluoroethyl)pyrimidine-2,4-dione Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(C(F)(F)C(F)(F)F)=C1 HJHNQOOYBACTPQ-RRKCRQDMSA-N 0.000 description 1
- YLZOPXRUQYQQID-UHFFFAOYSA-N 3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]propan-1-one Chemical compound N1N=NC=2CN(CCC=21)CCC(=O)N1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F YLZOPXRUQYQQID-UHFFFAOYSA-N 0.000 description 1
- 102100040996 Cochlin Human genes 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 101000748988 Homo sapiens Cochlin Proteins 0.000 description 1
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 1
- MCQDRSXCGLYGLH-PEBGCTIMSA-N [(2r,3r,4r,5r)-2-(2,4-dioxopyrimidin-1-yl)-4-hydroxy-5-(hydroxymethyl)oxolan-3-yl] acetate Chemical compound CC(=O)O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 MCQDRSXCGLYGLH-PEBGCTIMSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000000850 deacetylating effect Effects 0.000 description 1
- 238000003381 deacetylation reaction Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- VSQQQLOSPVPRAZ-RRKCRQDMSA-N trifluridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(C(F)(F)F)=C1 VSQQQLOSPVPRAZ-RRKCRQDMSA-N 0.000 description 1
Landscapes
- Saccharide Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
〈産業上の利用分野〉
本発明は、医薬品として重要な抗ウィルス剤の合成中間
体として有用な一般式〔！〕〔式中ｓ Ｒ１は水素原子
またはアセトキシ基を表わし％Ｒ１はペルフルオロ低級
アルキル基を表わす。〕
で示されるウリジン誘導体の製造方法に関するものであ
る。[Detailed Description of the Invention] <Industrial Application Field> The present invention provides a general formula [! ] [In the formula, s R1 represents a hydrogen atom or an acetoxy group, and %R1 represents a perfluoro lower alkyl group. ] The present invention relates to a method for producing a uridine derivative shown in the following.
〈従来の技術〉
５−トリフルオロメチル−２′−デオキシウリジン（以
下ＴＰＴと記す。）は抗つイノース剤として用いられて
いる。<Prior Art>5-Trifluoromethyl-2'-deoxyuridine (hereinafter referred to as TPT) is used as an anti-tinose agent.
従来、ＴＰＴの製造方法としては（１）σ−トリフルオ
ロメチルアクリロニトリルを出発物質として６エ程を経
て合成する方法（Ｊ、 Ａｍ、 Ｃｈｅｍ。Conventionally, methods for producing TPT include (1) a synthesis method using σ-trifluoromethylacrylonitrile as a starting material through 6 steps (J, Am, Chem.
Ｓｏｃ、 、 ８４巻、８５９７頁、１９６２年）、（
１）Ｉ’ｆｆ記一般式（１）においてＲ１がトリフルオ
ロメチル基で表わされるウリジン誘導体を脱アセチル化
する方法が知られている。Soc, vol. 84, p. 8597, 1962), (
1) A method of deacetylating a uridine derivative in the general formula (1) in which R1 is represented by a trifluoromethyl group is known.
上記（１）の方法において該ウリジン誘導体の製法とし
ては、８１．５１−ジー０−アセチル−５−ヨードウリ
ジンを銅の存在下にトリフルオロメチルヨーシトと反応
させる方法（Ｊ、 Ｃｈｅｍ、 Ｓｏｃ。In the method (1) above, the uridine derivative is produced by a method in which 81.51-di-0-acetyl-5-iodouridine is reacted with trifluoromethyl iosito in the presence of copper (J, Chem, Soc.
Ｐｅｒｋｉｎｌ、２７５５頁（１９８０）’）および２
′。Perkinl, p. 2755 (1980)') and 2
'.
８’、５’−）リーＯ−アセチルウリジンをＮ−トリフ
ルオロメチル−Ｎ−ニトロソトリフルオロメタンスルホ
ンアミドと反応させる方法（Ｂｕｌｌ。8',5'-) Reaction of O-acetyluridine with N-trifluoromethyl-N-nitrosotrifluoromethanesulfonamide (Bull.
Ｃｈｅｍ、 Ｓｏｃ、 Ｊｐｎ、 、 ５９巻、４４７
頁（１９８６））等が知られている。Chem, Soc, Jpn, 59, 447
Page (1986)) etc. are known.
〈発明が解決しようとする問題点〉
しかしながら、上記の方法は工程数の長さや、一般式〔
！〕で示されるウリジン誘導体を製造する際に用いられ
る試薬の調整、反応の操作性等の点で必ずしも満足すべ
きものではない。<Problems to be solved by the invention> However, the above method has a long number of steps and a general formula [
! ] are not necessarily satisfactory in terms of the preparation of reagents used in the production of the uridine derivatives, the operability of the reaction, etc.
く問題点を解決するための手段〉
本発明者らは一般式ＣＩ）で示されるウリジン誘導体の
簡便な製造法について鋭意検討した結果、一般式（Ｉｆ
）
〔式中ｓＲ１は前記と同じ意味を表わす。〕で示される
ウリジン誘導体と一般式〔■〕Ｒ，Ｃ０ＯＨ（１）
〔式中、Ｒ１は前記と同じ意味を表わす。〕で示される
カルボン酸とをニフッ化キセノンの存在下に反応させる
ことにより、容易な操作で一般式゛〔！〕で示されるウ
リジン誘導体が得られることを見い出し本発明に至った
。Means for Solving the Problems〉 As a result of intensive studies by the present inventors on a simple method for producing the uridine derivative represented by the general formula CI), the present inventors found that the general formula (If
) [In the formula, sR1 represents the same meaning as above. ] Uridine derivatives represented by the general formula [■] R, COOH (1) [wherein R1 represents the same meaning as above. ] By reacting the carboxylic acid represented by the formula in the presence of xenon difluoride, the general formula ゛〔! ] It was discovered that a uridine derivative represented by the formula can be obtained, leading to the present invention.
以下１本発明についてさらに詳しく説明す５゜本発明に
おいて用いられるニフ、化キセノンは。The present invention will be explained in more detail below.
例えばキセノンと７．素からＩｎｏｒｇａｎｉｃ ５ｙ
ｎｔｈｅ−ｓｉｓ ｌ１巻、１４７頁、 ＭｃＧｒａｗ
ｈｉ １１ （１９６８）に記載の方法に準じて合成で
き、また市販されてもいる。反応に用いられる試薬の量
は一般式（ＩＩ）で示されるウリジン誘導体１モルに対
して、ニフッ化キセノンおよび一般式（１）で示される
カルボン酸を夫々１〜１０モル、好ましくは１〜５モル
の割合である。反応温度および反応時間は通常−１θ〜
８０℃、１〜２０時間である。For example, xenon and 7. Inorganic 5y
nthe-sis Volume 1, Page 147, McGraw
It can be synthesized according to the method described in hi 11 (1968), and is also commercially available. The amount of reagents used in the reaction is 1 to 10 mol, preferably 1 to 5 mol, of xenon difluoride and the carboxylic acid represented by general formula (1), respectively, per 1 mol of the uridine derivative represented by general formula (II). It is a molar ratio. The reaction temperature and reaction time are usually -1θ~
80°C for 1 to 20 hours.
本反応は通常、不活性溶媒中で行なわれ、使用し得る溶
媒としては例えば、ジクロロメタン、クロロホルム、四
塩化炭素、１・２−ジクロロエタン、トリフレンまたは
ジフルオロジクロロエタン等のハロゲン化炭化水素等が
あげられる。This reaction is usually carried out in an inert solvent, and examples of solvents that can be used include halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, trifrene, and difluorodichloroethane.
尚、上記反応で得られた一般式（Ｉ）で示されるウリジ
ン誘導体は塩基性条件下で脱アセチル化することにより
ＴＰＴなどの一般式（ＩＶ）〔式中、Ｒ１およびＲ１は
前記と同じ意味を表わす。〕
で示されるウリジン誘導体に導（ことができる。Incidentally, the uridine derivative represented by the general formula (I) obtained in the above reaction is deacetylated under basic conditions to form a general formula (IV) such as TPT [wherein R1 and R1 have the same meanings as above]. represents. ] It is possible to lead to the uridine derivative shown in the following.
脱アセチル化反応は例えば一般式ＣＩ）で示されるウリ
ジン誘導体をアンモニアのアルコール溶液に加え、−１
，０〜８０℃に１〜２０時間保つことにより容易に行な
い得る。In the deacetylation reaction, for example, a uridine derivative represented by the general formula CI) is added to an alcoholic solution of ammonia, and -1
, by keeping the temperature at 0 to 80°C for 1 to 20 hours.
〈実施例〉 以下に、実施例および参考例を示す。<Example> Examples and reference examples are shown below.
実施例１
２’、 ８’、 ５’−）リアセチルウリジン８７０’
９ （１，０ｍｍｏｌ ）およびトリフルオロ酢酸４
００’Ｐ（８，５ｍｍｏｌ ）ｃＦ）ジクロロメタン溶
液２−に室温下でニフフ化キセノン８８８１ｑ（２，０
ｍｍｏｌ ）を少量づつ攪拌しながら加えた後、５時
間攪拌した。Example 1 2', 8', 5'-)lyacetyluridine 870'
9 (1,0 mmol) and trifluoroacetic acid 4
00'P (8,5 mmol) cF) In a dichloromethane solution 2-, niphelated xenon 8881q (2,0
mmol) was added little by little with stirring, and the mixture was stirred for 5 hours.
反応液を水ｌＯ−に注ぎ、ジクロロメタン５−で抽出し
、□ジクロロメタン層を水洗し。The reaction solution was poured into water lO-, extracted with dichloromethane 5-, and the dichloromethane layer was washed with water.
硫酸ナトリウムで乾燥後ジクロロメタンを減圧留去した
。残渣をシリカゲルクロマトグラフィー〔展開溶媒；ク
ロロホルム：酢酸エチル−５：ｌ）で処理し５−トリフ
ルオロメチル−２′・８′・６′−トリアセチルウリジ
ン１４５キ得た。 ゛
収率８８％
’Ｈ−ＮＭＲスペクトル（ＣＤＣ１，％ＴＭＳ内部標準
）ａ値（ｐｐｍ）
９．５０（ｂｒｓ、ＩＨ） ８．１０（ｓ、ＩＨ
）６．１０（ｄｄ、ｌＨ） ５．４０（ｍ、２Ｈ
）４．４１（ｍ、８Ｈ） ２．１２（Ｓ、９Ｈ
）”Ｆ−ＮＭＲスペクトル（ｃＤｃＩｔ、、ＣＦ、Ｃ０
ＯＨ外部標準）６値（ｐｐｍ）
“ −１５，０（８，８Ｆ）
ＥＩ−Ｍａｓｓスペクトル
ｍ／ｅ ８７ｇ （Ｍ −０ＣＯＣＨａ ）２５９
（糖）
実施例２
２／ 、 ｓ／ 、 ５／−トリアセチルウリジン８７
０”？ （１，０ｍｍｏｌ ） およびペンタフルオ
ロプロピオン酸５７４ｊＩＰ（８，５ｍｍｏｌ） の
ジクロロタン溶液２−に室温下でニフッ化キセノン８８
８ Ｑ （２，０ｍｍｏｌ）を少量づつ攪拌しながら加
えた。その後さらに室温で８時間攪拌した。After drying with sodium sulfate, dichloromethane was distilled off under reduced pressure. The residue was treated with silica gel chromatography (developing solvent: chloroform:ethyl acetate-5:l) to obtain 145 pieces of 5-trifluoromethyl-2', 8', 6'-triacetyluridine.゛Yield 88%'H-NMR spectrum (CDC1, %TMS internal standard) a value (ppm) 9.50 (brs, IH) 8.10 (s, IH
) 6.10 (dd, lH) 5.40 (m, 2H
) 4.41 (m, 8H) 2.12 (S, 9H
)"F-NMR spectrum (cDcIt,, CF, C0
OH external standard) 6 values (ppm) "-15,0 (8,8F) EI-Mass spectrum m/e 87g (M-0COCHa)259
(Sugar) Example 2 2/, s/, 5/-triacetyluridine 87
(1,0 mmol) and pentafluoropropionic acid 574jIP (8,5 mmol) in dichlorothane solution 2- at room temperature.
8Q (2.0 mmol) was added little by little with stirring. Thereafter, the mixture was further stirred at room temperature for 8 hours.
反応液を水１０−に注ぎジクロロメタン６−で抽出し、
ジクロロメタン層を水洗し、硫酸ナトリウムで乾燥後ジ
クロロメタンを減圧留去した。残渣をシリカゲルクロマ
トグラフィー〔展開溶媒；クロロホルム：酢酸エチル５
：１）で処理し６−ペンタフルオロエチル−２’、 ８
’、 ５’−）リアセチルウリジン１８７岬を得た。The reaction solution was poured into water (10) and extracted with dichloromethane (6).
The dichloromethane layer was washed with water, dried over sodium sulfate, and dichloromethane was distilled off under reduced pressure. The residue was subjected to silica gel chromatography [developing solvent: chloroform: ethyl acetate 5
:1) and treated with 6-pentafluoroethyl-2', 8
', 5'-)lyacetyluridine 187 was obtained.
収率２８％
’Ｈ−ＮＭＲスペクトル（ＣＤＣｌ、 、ＴＭ Ｓ内部
標準）δ値（ｐＩ）ｍ）
９．４０（ｂｒｓ、ｌＨ） ８．１０（ｓ、１Ｈ
）６．１０（ｄｄ、ＩＨ） ５．４０（ｍ、２Ｈ
）４．４１（ｍ 、８Ｈ） ２．１１（８，９Ｈ
）”Ｆ−ＮＭＲスペクトル（ＣＤＣ１，、ＣＦ、Ｃ０Ｏ
Ｈ外部標準）δ値（ｐｌ）ｍ）
−５，４（ｂｒｓ 、 ８ Ｆ ）
−８４，２（ｂｒｓ 、 ２Ｆ ）
Ｅ Ｉ−Ｍａｓｓスペクトル
ｍ／ｅ ４２８ ＣＭ” −０ＣＯＣＨｓ ）２５９
（糖）
実施例８
実施例１と同様の方法で８’、５’−ジアセチル−２′
−デオキシウリジン１．５１ｉ（４，８１皿ｏ１ ）ペ
ンタフルオロプロピオン酸２．７６Ｐ（１６，８４ｍｍ
ｏｌ ）およびニフ、化キセノン１．６８９ （９，
６２ｍｍｏｌ ） を用ｔ＋’ｒ５−ヘ：ｚタフルオ
ロエチル−８’、５’−ジアセチル−２′−デオキシウ
リジン６４１”９を得た。Yield 28% 'H-NMR spectrum (CDCl, , TMS internal standard) δ value (pI) m) 9.40 (brs, lH) 8.10 (s, 1H
) 6.10 (dd, IH) 5.40 (m, 2H
) 4.41 (m , 8H) 2.11 (8,9H
)"F-NMR spectrum (CDC1,, CF, C0O
H external standard) δ value (pl) m) -5,4 (brs, 8 F) -84,2 (brs, 2F) E I-Mass spectrum m/e 428 CM" -0 COCHs) 259
(Sugar) Example 8 8',5'-Diacetyl-2' was prepared in the same manner as in Example 1.
-Deoxyuridine 1.51i (4,81 dishes o1) Pentafluoropropionic acid 2.76P (16,84mm
ol) and nif, xenon 1.689 (9,
62 mmol) was used to obtain 641"9 of t+'r5-he:ztafluoroethyl-8',5'-diacetyl-2'-deoxyuridine.
収率８１％
融点１１７〜１１９℃
’Ｈ−ＮＭＲスペクトル（ＣＤＣ１，、ＴＭＳ内部標準
）ａ値（１）ｐｍ）
９．４０（ｂｒｓ、ＩＨ） ８．１０（ｓ、ＬＨ）
６．８０（ｄｄ 、ＩＨ） ５．８０（ｍ、ＬＨ）
４．８５（ｍ 、８Ｈ） ２．５０（ｍ、２Ｈ）２
．１０（ｓ 、８Ｈ） ２．０５（ｓ、８Ｈ）１
・Ｆ −ＮＭ Ｒｘ ヘク） Ｊｌｚ （ＣＩ）Ｃｌｓ
、 ＣＦｓ Ｃ０ＯＨ外部標準）δ値（ｐｐｍ）
−５，４（ｂｒｓ、８Ｆ ）
−８４，２（ｂｒｓ 、 ２ Ｆ ）
ＦＤ −Ｍａｓｓ ｘベクトル
ｍ／ｅ ４８０ （Ｍ ）
２０１（糖）
実施例４
実施例１と同様の方法で、８′、５′−ジアセチル−２
′−デオキシウリジン０．５（１（１，６０ｍｍｏｌ）
、ヘプタフルオロ醋酸１．１０Ｆ（４，８０ｍｍｏｌ
）およびニフッ化キセノン０．５４ Ｐ（ＪＩ２０ｍｍ
ｏｌ）を用いて５−へブタフルオロプロピル−、，７，
５’−ジアセチル−２′−デオキシウリジンＯ，１６Ｆ
を得た。Yield 81% Melting point 117-119°C 'H-NMR spectrum (CDC1, TMS internal standard) a value (1) pm) 9.40 (brs, IH) 8.10 (s, LH)
6.80 (dd, IH) 5.80 (m, LH)
4.85 (m, 8H) 2.50 (m, 2H)2
．． 10 (s, 8H) 2.05 (s, 8H) 1
・F -NM Rx Heku) Jlz (CI)Cls
, CFs C0OH external standard) δ value (ppm) -5,4 (brs, 8F) -84,2 (brs, 2F) FD -Mass x vector m/e 480 (M) 201 (sugar) Example 4 Implementation In a similar manner to Example 1, 8',5'-diacetyl-2
'-Deoxyuridine 0.5 (1 (1,60 mmol)
, heptafluoroacetic acid 1.10F (4.80 mmol
) and xenon difluoride 0.54 P (JI20mm
5-hebutafluoropropyl-, 7,
5'-Diacetyl-2'-deoxyuridine O,16F
I got it.
収率２１％
融点９１〜９２℃
”Ｆ−ＮＭＲスペクトル（ＣＤＣ＃３、ＣＦｓＣＯＯＨ
外部標準）δ値（１）１）ｍ）
−２，５（ｔ、８Ｆ、Ｊ−ｘｏＨｚ）
−８０，５（ｍ、２Ｆ）
−４６，０（ｄ、２Ｆ、Ｊ−２０Ｈｚ）ＦＤ−Ｍａｓｓ
ｘベクトル
ｍ／ｅ ４８０（Ｍ ）
２０１（糖）
参考例１
実施例１で得た６−トリフルオロメチル−２’、 ８’
、 ５’−）リアセチルウリジン１００■を、アンモニ
アで飽和したメタノール５−に溶解し一夜放置した。反
応液を減圧下に濃縮し、ヘキサン−エーテル（１：ｌ）
混合液をｌ−加え、冷蔵庫に放置した。析出した結晶を
Ｐ取し、乾燥して５−（トリフルオロメチル）ウリジン
５１”Ｐを得た。Yield 21% Melting point 91-92℃ "F-NMR spectrum (CDC#3, CFsCOOH
External standard) δ value (1) 1) m) -2,5 (t, 8F, J-xoHz) -80,5 (m, 2F) -46,0 (d, 2F, J-20Hz) FD-Mass
x vector m/e 480 (M) 201 (sugar) Reference example 1 6-trifluoromethyl-2', 8' obtained in Example 1
, 5'-)lyacetyluridine was dissolved in methanol 5-saturated with ammonia and left overnight. The reaction solution was concentrated under reduced pressure and diluted with hexane-ether (1:l).
1 of the mixture was added and left in the refrigerator. The precipitated crystals were collected and dried to obtain 5-(trifluoromethyl)uridine 51''P.
収率７１％
融点１８１−１８４℃（文献値＊１８４〜１８５℃）
＊ Ｊ、 Ｃｈｅｍ、 Ｓｏｃ、 ＰｅｒｋｉｎＩ 、
２’１６５頁（１９８０’）参考例２
実施例８で得た５−ペンタフルオロエチル−８’、５’
−ジアセチル−２′−デオキシウリジン８００”Ｐをア
ンモニアで飽和したメタノールｌＯ−を用いて↓Ｗと同
様の方法で５−ペンタフルオロエチル−２′−デオキシ
ウリジン１９８”Ｐを得た。Yield 71% Melting point 181-184°C (literature value *184-185°C) * J, Chem, Soc, PerkinI,
2' p. 165 (1980') Reference Example 2 5-pentafluoroethyl-8', 5' obtained in Example 8
5-pentafluoroethyl-2'-deoxyuridine 198''P was obtained in the same manner as ↓W using -diacetyl-2'-deoxyuridine 800''P and methanol 1O- saturated with ammonia.
収率８５％ 融点１７２−．１７５℃Yield 85% Melting point 172-. 175℃
Claims (1)
。〕 で示されるウリジン誘導体と一般式 Ｒ＿２ＣＯＯＨ 〔式中、Ｒ＿２はペルフルオロ低級アルキル基を表わす
。〕 で示されるカルボン酸とを二フッ化キセノンの存在下に
反応させることを特徴とする一般式▲数式、化学式、表
等があります▼ 〔式中、Ｒ＿１およびＲ＿２は上記と同じ意味を表わす
。〕 で示されるウリジン誘導体の製造方法。[Claims] General formula ▲ Numerical formula, chemical formula, table, etc. ▼ [In the formula, R_1 represents a hydrogen atom or an acetoxy group. ] A uridine derivative represented by the general formula R_2COOH [wherein R_2 represents a perfluoro lower alkyl group]. ] A general formula characterized by reacting a carboxylic acid represented by the following in the presence of xenon difluoride ▲ There are numerical formulas, chemical formulas, tables, etc. ▼ [In the formula, R_1 and R_2 represent the same meanings as above. ] A method for producing a uridine derivative.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1912887A JPS63188696A (en) | 1987-01-29 | 1987-01-29 | Production of 5-(perfluoroalkyl)uridine derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1912887A JPS63188696A (en) | 1987-01-29 | 1987-01-29 | Production of 5-(perfluoroalkyl)uridine derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS63188696A true JPS63188696A (en) | 1988-08-04 |
Family
ID=11990821
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1912887A Pending JPS63188696A (en) | 1987-01-29 | 1987-01-29 | Production of 5-(perfluoroalkyl)uridine derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS63188696A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014510743A (en) * | 2011-03-31 | 2014-05-01 | シェファー、コンスタンツェ | Perfluorinated compounds for non-viral introduction of nucleic acids |
-
1987
- 1987-01-29 JP JP1912887A patent/JPS63188696A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014510743A (en) * | 2011-03-31 | 2014-05-01 | シェファー、コンスタンツェ | Perfluorinated compounds for non-viral introduction of nucleic acids |
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