JPH0134236B2 - - Google Patents

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Publication number
JPH0134236B2
JPH0134236B2 JP56157691A JP15769181A JPH0134236B2 JP H0134236 B2 JPH0134236 B2 JP H0134236B2 JP 56157691 A JP56157691 A JP 56157691A JP 15769181 A JP15769181 A JP 15769181A JP H0134236 B2 JPH0134236 B2 JP H0134236B2
Authority
JP
Japan
Prior art keywords
group
general formula
methylpurine
formula
groups
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
Application number
JP56157691A
Other languages
Japanese (ja)
Other versions
JPS5859999A (en
Inventor
Shinji Sakata
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Yamasa Shoyu KK
Original Assignee
Yamasa Shoyu KK
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Yamasa Shoyu KK filed Critical Yamasa Shoyu KK
Priority to JP15769181A priority Critical patent/JPS5859999A/en
Publication of JPS5859999A publication Critical patent/JPS5859999A/en
Publication of JPH0134236B2 publication Critical patent/JPH0134236B2/ja
Granted legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60—Sugars; Derivatives thereof
    • A61K8/606—Nucleosides; Nucleotides; Nucleic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/74—Biological properties of particular ingredients
    • A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
    • A61K2800/782—Enzyme inhibitors; Enzyme antagonists

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Epidemiology (AREA)
  • Birds (AREA)
  • Molecular Biology (AREA)
  • Chemical & Material Sciences (AREA)
  • Dermatology (AREA)
  • Cosmetics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)

Description

【発明の詳細な説明】 本発明は、新規な２―置換―６―メチルプリン
ヌクレオシド、およびその製造法に関するもので
ある。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel 2-substituted-6-methylpurine nucleoside and a method for producing the same.

本発明化合物は、文献未記載の新規化合物であ
り、次の一般式〔〕で表わされる。 The compound of the present invention is a novel compound that has not been described in any literature, and is represented by the following general formula [].

該式中、R1は保護基を有することあるボース
残基、アラビノース残基、キシロース残基、２―
デオキシリボース残基または３―デオキシリボー
ス残基を示し、Ｘは―SR2基、―OR2基または―
NR3R4基を示す。R2は低級アルキル基、R3は低
級アルキル基、ヒドロキシル基またはアミノ基、
R4は水素または低級アルキル基を示す。R2，R3
およびR4における低級アルキル基とは、さらに
好ましくは炭素１〜４の低級アルキル基を意味
し、具体的には、メチル、エチル、プロピル、ブ
チルなどが例示できる。また、糖残基R1の保護
基としては特に限定はないが、具体的にはヌクレ
オシド化学分野で使用されるものが例示でき、た
とえばアシル基（アセチル、ブチリル、ベンゾイ
ルなど）、アルキリデン基（イソプロピリデン、
エチリデンなど）、アルアルキリデン基（ベンジ
リデンなど）、アルアルキル基（トリチル、ベン
ジルなど）、アルコキシアルキリデン基（メトキ
シメチレン、エトキシメチレン、エトキシエチレ
ンなど）、テトラヒドロピラニル基などが挙げら
れる。これら本発明化合物は、６―メチルプリン
ヌクレオシドと同様にアデニルデアミナーゼ阻害
活性、抗腫瘍活性を有し、生化学研究用試薬とし
て有用である。また、特に波長295〜315mnに紫
外線吸収極大を有するものは日焼止め用の紫外線
吸収剤としての用途も有する。 In this formula, R 1 is a bose residue, an arabinose residue, a xylose residue, a 2-
Deoxyribose residue or 3-deoxyribose residue, X is -SR 2 group, -OR 2 group or -
Indicates NR 3 R 4 group. R 2 is a lower alkyl group, R 3 is a lower alkyl group, a hydroxyl group or an amino group,
R 4 represents hydrogen or a lower alkyl group. R2 , R3
The lower alkyl group in R 4 more preferably means a lower alkyl group having 1 to 4 carbon atoms, and specific examples thereof include methyl, ethyl, propyl, and butyl. There are no particular limitations on the protecting group for the sugar residue R1 , but specific examples include those used in the field of nucleoside chemistry, such as acyl groups (acetyl, butyryl, benzoyl, etc.), alkylidene groups (isopropyl, etc.), Liden,
ethylidene, etc.), aralkylidene groups (benzylidene, etc.), aralkyl groups (trityl, benzyl, etc.), alkoxyalkylidene groups (methoxymethylene, ethoxymethylene, ethoxyethylene, etc.), and tetrahydropyranyl groups. These compounds of the present invention have adenyl deaminase inhibitory activity and antitumor activity similar to 6-methylpurine nucleoside, and are useful as reagents for biochemical research. In addition, those having maximum ultraviolet absorption in the wavelength range of 295 to 315 mn are also used as ultraviolet absorbers for sunscreens.

本発明化合物は、一般式〔〕 〔式中、R1は前記一般式〔〕のものと同意
義である。〕で表わされる２―フルオロ―６―メ
チルプリンヌクレオシドに、目的化合物の種類に
応じて、一般式R2S-，R2O-またはHNR3R4〔式
中、R2，R3およびR4は前記一般式〔〕のもの
と同意義である。〕で表わされる求核試薬から選
ばれるものを反応させる方法により得ることがで
きる。 The compound of the present invention has the general formula [] [In the formula, R 1 has the same meaning as in the above general formula []. ] to the 2-fluoro-6-methylpurine nucleoside represented by the general formula R 2 S - , R 2 O - or HNR 3 R 4 [where R 2 , R 3 and R 4 has the same meaning as in the general formula [] above. It can be obtained by a method of reacting with a nucleophile selected from the following.

原料化合物の２―フルオロ―６―メチルプリン
ヌクレオシドのリボシド体およびキシロシド体は
既知であり、その他の糖残基のものも２―フルオ
ロ―６―メチルプリンと対応する糖誘導体とを溶
融させる方法や、本発明者らが開発した次のよう
な反応工程により合成することができる。 The riboside and xyloside forms of the raw material compound 2-fluoro-6-methylpurine nucleoside are known, and other sugar residues can also be obtained by melting 2-fluoro-6-methylpurine and the corresponding sugar derivative. , can be synthesized by the following reaction process developed by the present inventors.

〔式中、R5はアルキル基（たとえばメチル、
エチルなど）またはアリール基（たとえば４―メ
チルフエニル、４―ブロモフエニル、２，４，６
―トリメチルフエニルなど）、R6は低級アルキル
基（たとえばメチル、エチル、プロピル、ブチル
など）を示す。〕 求核試薬との反応は溶媒中で行われ、求核試薬
としてR2O-を用いる場合は、アルコール類をは
じめ、Ｎ，Ｎ―ジメチルホルムアミド、ジメチル
スルホキシド、Ｎ，Ｎ―ジメチルアセトアミド、
アセトニトリル、ジオキサンなどの極性溶媒が適
用でき、また求核試薬としてR2S-または
HNR3R4を用いる場合にはアルコールを除く極
性溶媒が使用できる。 [In the formula, R 5 is an alkyl group (e.g. methyl,
ethyl) or aryl groups (e.g. 4-methylphenyl, 4-bromophenyl, 2,4,6
-trimethylphenyl, etc.), R 6 represents a lower alkyl group (such as methyl, ethyl, propyl, butyl, etc.). ] The reaction with the nucleophile is carried out in a solvent, and when R 2 O - is used as the nucleophile, alcohols, N,N-dimethylformamide, dimethyl sulfoxide, N,N-dimethylacetamide,
Polar solvents such as acetonitrile and dioxane can be applied, and as nucleophiles R 2 S - or
When using HNR 3 R 4 , polar solvents other than alcohol can be used.

反応条件には特に制約がなく、０〜100℃程度
の範囲内であればよく、室温で十分である。 There are no particular restrictions on the reaction conditions, as long as they are within the range of about 0 to 100°C, and room temperature is sufficient.

反応液からの目的化合物の単離精製は常法によ
ればよく、たとえば吸着クロマトグラフイー、再
結晶などの精製手段を適宜に応用すればよい。 Isolation and purification of the target compound from the reaction solution may be carried out by conventional methods, for example, purification means such as adsorption chromatography and recrystallization may be appropriately applied.

以下、実施例を挙げて本発明をより具体的に説
明する。 Hereinafter, the present invention will be explained in more detail with reference to Examples.

実施例 １ ２―フルオロ―６―メチルプリンリボシド200
mgを無水ジメチルホルムアミド35mlに溶解させた
後、11％無水ジメチルアミン―Ｎ，Ｎ―ジメチル
ホルムアミド溶液１mlを加え、室温4.5時間攪拌
した。反応終了後、減圧濃縮乾固し、残渣を水か
ら再結晶して２―ジメチルアミノ―６―メチル―
９―β―Ｄ―リボフラノシルプリンの白色針状結
晶184mgを得た（収率83.6％）。Example 1 2-fluoro-6-methylpurine riboside 200
mg was dissolved in 35 ml of anhydrous dimethylformamide, 1 ml of 11% anhydrous dimethylamine-N,N-dimethylformamide solution was added, and the mixture was stirred at room temperature for 4.5 hours. After the reaction was completed, it was concentrated to dryness under reduced pressure, and the residue was recrystallized from water to give 2-dimethylamino-6-methyl-
184 mg of white needle-like crystals of 9-β-D-ribofuranosylpurine was obtained (yield 83.6%).

融点 223℃ 元素分析 C13H19N5O4として 計算値（％）：Ｃ，50.48；Ｈ，6.19； Ｎ，22.64 実測値（％）：Ｃ，50.45；Ｈ，6.08； Ｎ，22.64 質量分析スペクトル ｍ／e309（M+） 紫外線吸収スペクトル nm λH2O nax 324，256，225 λ0.1N-HCl nax 335，255（sh），231 λ0.1N-NaOH nax 324，256，228 核磁気共鳴スペクトル（DMSO―d6）δppm 8.16（1H，ｓ，８―Ｈ） 5.82（1H，ｄ，1′―Ｈ） 3.13（6H，ｓ，Ｎ（CH3）2） 2.52（3H，ｓ，６―CH3） 実施例 ２ ２―フルオロ―６―メチルプリンリボシド200
mgをＮ，Ｎ―ジメチルホルムアミド35mlに溶解さ
せた後、15％メチルメルカプタンナトリウム水溶
液0.7mlを加え、室温下で２時間攪拌した。反応
液を酢酸で中和後、減圧下濃縮乾固し、得られた
残渣を水から再結晶して２―メチルチオ―６―メ
チル―９―β―Ｄ―リボフラノシルプリンの白色
針状晶163mgを得た（収率73.4％）。Melting point 223℃ Elemental analysis Calculated value (%) as C 13 H 19 N 5 O 4 : C, 50.48; H, 6.19; N, 22.64 Actual value (%): C, 50.45; H, 6.08; N, 22.64 Mass spectrometry Spectrum m/e309 (M + ) Ultraviolet absorption spectrum nm λ H2O nax 324, 256, 225 λ 0.1N-HCl nax 335, 255 (sh), 231 λ 0.1N-NaOH nax 324, 256, 228 Nuclear magnetic resonance spectrum ( DMSO-d 6 ) δppm 8.16 (1H, s, 8-H) 5.82 (1H, d, 1'-H) 3.13 (6H, s, N(CH 3 ) 2 ) 2.52 (3H, s, 6-CH 3 ) Example 2 2-fluoro-6-methylpurine riboside 200
mg was dissolved in 35 ml of N,N-dimethylformamide, 0.7 ml of 15% sodium methyl mercaptan aqueous solution was added, and the mixture was stirred at room temperature for 2 hours. After neutralizing the reaction solution with acetic acid, it was concentrated to dryness under reduced pressure, and the resulting residue was recrystallized from water to obtain white needle-like crystals of 2-methylthio-6-methyl-9-β-D-ribofuranosylpurine. 163 mg was obtained (yield 73.4%).

融点 147℃ 元素分析 C12H16N4O4Sとして 計算値（％）：Ｃ，46.15；Ｈ，5.16； Ｎ，17.94 実験値（％）：Ｃ，45.87；Ｈ，5.23； Ｎ，18.06 質量分析スペクトルｍ／e312（M+） 紫外線吸収スペクトル nm λH2O nax 297，260，230 λ0.1N-HCl nax 301（sh），268，242 λ0.1N-NaOH nax 297，258，230 核磁気共鳴スペクトル（DMSO―d6）δppm 8.52（1H，ｓ，８―Ｈ） 5.93（1H，ｄ，1′―Ｈ） 2.67，2.57（各3H，ｓ，２―SCH3，６―CH3） 実施例 ３ ２―フルオロ―６―メチルプリンリボシド200
mgを無水メタノール35mlに溶解させた後、28％ナ
トリウムメトキサイド0.36mlを加え、室温下で
5.5時間攪拌した。反応液を酢酸で中和した後、
減圧下濃縮乾固した。得られた残渣を水から再結
晶し、２―メトキシ―６―メチル―９―β―Ｄ―
リボフラノシルプリンの白色針状晶196mgを得た
（収率89.6％）。Melting point 147℃ Elemental analysis Calculated value (%) as C 12 H 16 N 4 O 4 S: C, 46.15; H, 5.16; N, 17.94 Experimental value (%): C, 45.87; H, 5.23; N, 18.06 Mass Analysis spectrum m/e312 (M + ) Ultraviolet absorption spectrum nm λ H2O nax 297, 260, 230 λ 0.1N-HCl nax 301 (sh), 268, 242 λ 0.1N-NaOH nax 297, 258, 230 Nuclear magnetic resonance spectrum (DMSO-d 6 ) δppm 8.52 (1H, s, 8-H) 5.93 (1H, d, 1'-H) 2.67, 2.57 (3H, s, 2-SCH 3 , 6-CH 3 each) Example 3 2-Fluoro-6-methylpurine riboside 200
After dissolving mg in 35 ml of anhydrous methanol, add 0.36 ml of 28% sodium methoxide and leave at room temperature.
Stirred for 5.5 hours. After neutralizing the reaction solution with acetic acid,
It was concentrated to dryness under reduced pressure. The obtained residue was recrystallized from water to give 2-methoxy-6-methyl-9-β-D-
196 mg of white needle-like crystals of ribofuranosylpurine were obtained (yield 89.6%).

融点 153〜154℃ 元素分析 C12H16N4O5として 計算値（％）：Ｃ，48.65；Ｈ，5.44； Ｎ，18.91 実験値（％）：Ｃ，48.07；Ｈ，5.46； Ｎ，18.49 質量分析スペクトル ｍ／e296（M+） 紫外線吸収スペクトル nm λH2O nax 277，235 λ0.1N-HCl nax 284 λ0.1N-NaOH nax 275，222 核磁気共鳴スペクトル（DMSO―d6）δppm 8.46（1H，ｓ，８―Ｈ） 5.89（1H，ｄ，1′―Ｈ） 3.94（3H，ｓ，２―OCH3） 2.64（3H，ｓ，６―CH3）Melting point 153-154℃ Elemental analysis Calculated value (%) as C 12 H 16 N 4 O 5 : C, 48.65; H, 5.44; N, 18.91 Experimental value (%): C, 48.07; H, 5.46; N, 18.49 Mass spectrometry spectrum m/e296 (M + ) Ultraviolet absorption spectrum nm λ H2O nax 277, 235 λ 0.1N-HCl nax 284 λ 0.1N-NaOH nax 275, 222 Nuclear magnetic resonance spectrum (DMSO-d 6 ) δppm 8.46 (1H , s, 8-H) 5.89 (1H, d, 1'-H) 3.94 (3H, s, 2-OCH 3 ) 2.64 (3H, s, 6-CH 3 )

Claims (1)

【特許請求の範囲】 １ 一般式〔〕 〔式中、R1は保護基を有することあるリボー
ス残基を示し、Ｘは―SCH3基、―OCH3基また
は―Ｎ（CH3）2基を示す。〕で表される２―置換―
６―メチルプリンヌクレオシド。 ２ 一般式〔〕 〔式中、R1は保護基を有することあるリボー
ス残基を示す。〕で表される２―フルオロ―６―
メチルプリンヌクレオシドに一般式CH3S-，
CH3O-またはHN（CH3）2で表わされる求核試薬
を反応させて一般式〔〕 〔式中、R1は前記と同意義、Ｘは―SCH3基、
―OCH3基または―Ｎ（CH3）2基を示す。〕で表さ
れる２―置換―６―メチルプリンヌクレオシドを
合成することを特徴とする２―置換―６―メチル
プリンヌクレオシドの製造法。[Claims] 1. General formula [] [In the formula, R 1 represents a ribose residue which may have a protecting group, and X represents a -SCH 3 group, -OCH 3 group or -N(CH 3 ) 2 group. 2-replacement- represented by ]
6-Methylpurine nucleoside. 2 General formula [] [In the formula, R 1 represents a ribose residue that may have a protecting group. ] 2-fluoro-6-
Methylpurine nucleoside has the general formula CH 3 S - ,
By reacting a nucleophile represented by CH 3 O - or HN(CH 3 ) 2, the general formula [] [In the formula, R 1 has the same meaning as above, X is -SCH 3 group,
Indicates -OCH 3 groups or -N(CH 3 ) 2 groups. A method for producing a 2-substituted-6-methylpurine nucleoside, which comprises synthesizing a 2-substituted-6-methylpurine nucleoside represented by the following.
JP15769181A 1981-10-02 1981-10-02 2-substituted-6-methylpurine nucleoside Granted JPS5859999A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP15769181A JPS5859999A (en) 1981-10-02 1981-10-02 2-substituted-6-methylpurine nucleoside

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP15769181A JPS5859999A (en) 1981-10-02 1981-10-02 2-substituted-6-methylpurine nucleoside

Publications (2)

Publication Number Publication Date
JPS5859999A JPS5859999A (en) 1983-04-09
JPH0134236B2 true JPH0134236B2 (en) 1989-07-18

Family

ID=15655272

Family Applications (1)

Application Number Title Priority Date Filing Date
JP15769181A Granted JPS5859999A (en) 1981-10-02 1981-10-02 2-substituted-6-methylpurine nucleoside

Country Status (1)

Country Link
JP (1) JPS5859999A (en)

Also Published As

Publication number Publication date
JPS5859999A (en) 1983-04-09

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