JPS5959698A - Inosinohalogen derivative and its preparation - Google Patents
Inosinohalogen derivative and its preparationInfo
- Publication number
- JPS5959698A JPS5959698A JP16961282A JP16961282A JPS5959698A JP S5959698 A JPS5959698 A JP S5959698A JP 16961282 A JP16961282 A JP 16961282A JP 16961282 A JP16961282 A JP 16961282A JP S5959698 A JPS5959698 A JP S5959698A
- Authority
- JP
- Japan
- Prior art keywords
- derivative
- inodinohalogen
- reaction
- reaction mixture
- inosine
- 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.)
- Granted
Links
- 125000005843 halogen group Chemical group 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 239000004020 conductor Substances 0.000 claims 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 claims 1
- 229930010555 Inosine Natural products 0.000 abstract description 8
- -1 S-inosylcysteine Chemical class 0.000 abstract description 8
- 239000013078 crystal Substances 0.000 abstract description 8
- 229960003786 inosine Drugs 0.000 abstract description 8
- 239000011541 reaction mixture Substances 0.000 abstract description 8
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 abstract description 4
- 239000005457 ice water Substances 0.000 abstract description 4
- 239000000126 substance Substances 0.000 abstract description 4
- 150000001875 compounds Chemical class 0.000 abstract description 3
- 150000007523 nucleic acids Chemical class 0.000 abstract description 3
- 102000039446 nucleic acids Human genes 0.000 abstract description 3
- 108020004707 nucleic acids Proteins 0.000 abstract description 3
- 229910052736 halogen Inorganic materials 0.000 abstract description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 abstract 1
- 230000000259 anti-tumor effect Effects 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- 238000003756 stirring Methods 0.000 description 9
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000000843 powder Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 230000000767 anti-ulcer Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- SAEXFNRQXFBCIC-NVKWYWNSSA-L disodium;(2r)-2-amino-3-sulfanylpropanoate Chemical compound [Na+].[Na+].SC[C@H](N)C([O-])=O.SC[C@H](N)C([O-])=O SAEXFNRQXFBCIC-NVKWYWNSSA-L 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Saccharide Compounds (AREA)
Abstract
Description
【発明の詳細な説明】 本発明は、一般式。[Detailed description of the invention] The present invention is based on a general formula.
１
０
（式中、Ｘはハロゲン原子を示す）
で表わされる新規なイノジノハロゲン誘導体およびその
製造方法に関する。The present invention relates to a novel inodinohalogen derivative represented by 10 (wherein, X represents a halogen atom) and a method for producing the same.
一般式（１）で表わされるイノジノハロゲン誘導体は例
えば抗潰瘍作用を有するＳ−イノシルシスティン等の核
酸類の合成中間体として有用な化合物である。The inodinohalogen derivative represented by the general formula (1) is a compound useful as a synthetic intermediate for nucleic acids such as S-inosylcysteine, which has an antiulcer effect.
本発明に係る一般式（１）で表わされるイノジノハロゲ
ン誘導体は９本発明方法によシイノシンとハロゲン化チ
オニルとを反応させることによシ製造することができる
。The inodinohalogen derivative represented by the general formula (1) according to the present invention can be produced by reacting cyinosine and thionyl halide according to the method of the present invention.
この場合のハロゲンとしては、塩素まだは臭素を挙げる
ことができ、ハロゲン化チオニルとして塩化チオニルを
用いるときは、一般式（１）におけるＸが塩素であるイ
ノジノクロル誘導体が得られ、臭化チオニルを用いると
きは、イノシップロム誘導体が得られる。In this case, the halogen can be chlorine or bromine, and when thionyl chloride is used as the thionyl halide, an inodinochlor derivative in which X in general formula (1) is chlorine is obtained, and when thionyl bromide is used, Inosyprom derivatives are obtained.
上記の反応は、通常、溶媒とし、てピリジン捷たはヘキ
サメテルホ′スホリツクアミド等の極性有機溶媒を用い
て行なわれ、原料イノシン１モルに対し、５〜７倍モル
程度のノ・ロゲン化チオニルを用いて、１０＝４０℃、
好ましくは、１０〜２０℃の温度で６０分〜２時間反応
を行なわせるのが好都合である。The above reaction is usually carried out using a polar organic solvent such as pyridine or hexamethane phosphoric amide as a solvent. So, 10=40℃,
Preferably, it is convenient to carry out the reaction at a temperature of 10 to 20°C for 60 minutes to 2 hours.
反応終了後に、反応混合物から通常行なわれている処理
手段によシ一般式（１）で表わされる目的物を単離する
ことができる。この場合、例えば、未反応のハロゲン化
チオニルを分解させるために、攪拌下に、反応混合物を
氷水中に注ぎ、必要に応じて、重炭酸ナトリウム、重炭
酸カリウム等の弱塩基物質を加えて分解反応を行なわせ
、次に、反応混合物を冷却することによって、一般式（
１）で表わされるイノジノハロゲン誘導体を結晶として
析出させ、分離することができる。After completion of the reaction, the target product represented by general formula (1) can be isolated from the reaction mixture by conventional treatment means. In this case, for example, in order to decompose unreacted thionyl halide, the reaction mixture is poured into ice water while stirring, and if necessary, a weak base substance such as sodium bicarbonate or potassium bicarbonate is added to decompose the unreacted thionyl halide. By allowing the reaction to take place and then cooling the reaction mixture, the general formula (
The inodinohalogen derivative represented by 1) can be precipitated as crystals and separated.
次に実施例を挙げ本発明を説明する。Next, the present invention will be explained with reference to Examples.
実施例 １
冷却攪拌下に、塩化チオニル１５．５．９ ＣＩ］、１
６モル）をピリジン６０−に加え、この溶液にイノシン
５ｇ（０，０１９モル）を加え１０〜２０℃で２時間反
応させる。Example 1 Thionyl chloride 15.5.9 CI], 1 under cooling stirring
6 mol) is added to pyridine 60-, and 5 g (0,019 mol) of inosine is added to this solution and reacted at 10 to 20°C for 2 hours.
反応終了後、反応混合物を氷水中に注ぎ込み、攪拌下に
放置する。これを冷却し、生成した析出結晶を炉取し、
少量の冷水で洗浄した後、乾燥すると５６ｇの５７−ク
ロル−５′−デオキシ−１，ｓ’−ｏ−スルフィニルイ
ノシン（収率８４％）が粉末結晶として得られた。After the reaction is complete, the reaction mixture is poured into ice water and left under stirring. This is cooled, and the precipitated crystals formed are taken out in a furnace.
After washing with a small amount of cold water and drying, 56 g of 57-chloro-5'-deoxy-1,s'-o-sulfinyl inosine (yield 84%) was obtained as a powder crystal.
このものは融点２０２．５〜２０５°Ｃ（分解）を示す
。This has a melting point of 202.5-205°C (decomposed).
Ｒｆ値 ０６５（展開溶媒 クロロホルム：メタノール
＝３５：１０）
元素分析値 Ｃ４ｏＨ９Ｎ４０５ＳＣ１計算値（％）：
Ｃ１ろ６．１０； Ｈ，２，７３； Ｎ、１６．８４；
Ｓ、９．６４； Ｃ２，１０，、！５５実測値（％）
：Ｃ１ろ６．１６； Ｈ，２，６９； Ｎ、１６．７３
；Ｓ、９．６５； Ｃ７，１０ろ９
実施例 ２
イ／ シフ ２５ 、！ｉ’ （０，０９！１モル）を
ヘキサメチルホスホリックトリアミｌ−’２５０Ｔｎｌ
に懸濁し、これに臭化チオニル４０ｄ（０，５２モル）
を冷却攪拌下に滴下する。次いで１５時間攪拌を続けた
後、反応液を氷水中に注ぎ込み、以下、実施例１と同様
に処理すると、融点２０５〜２４０’Ｃ（分解）の５′
−ブロム−５７−ジオキシ−２’、３’−０−スルフィ
ニルイノシン１７、５．９ （４９，７％）が得られた
。Rf value 065 (Developing solvent chloroform:methanol = 35:10) Elemental analysis value C4oH9N405SC1 calculated value (%):
C1ro 6.10; H, 2,73; N, 16.84;
S, 9.64; C2, 10,,! 55 Actual value (%)
:C1ro 6.16; H, 2,69; N, 16.73
;S, 9.65; C7,10ro9 Example 2 I/Schiff 25,! i' (0,09!1 mol) as hexamethylphosphoric triamyl-'250Tnl
thionyl bromide 40d (0.52 mol)
is added dropwise while stirring while cooling. After stirring for 15 hours, the reaction solution was poured into ice water and treated in the same manner as in Example 1 to obtain 5' with a melting point of 205-240'C (decomposition).
-Bromo-57-dioxy-2',3'-0-sulfinyl inosine 17.5.9 (49.7%) was obtained.
Ｒｆ値 ０６７（展開溶媒 クロロホルム：メタノール
＝ろ５：１０）
元素分析値 Ｃ＋ ｏＨ９１”Ｊ４０５ｓＢｒ計算値（
％） ： Ｃ，３１，８４； Ｈ，２，４０； Ｎ、１
４．８５；Ｓ 、 ８．５０ ：Ｂｒ、２１．１９実測
値（＠ ： Ｃ，３１，７６； Ｈ，２，３９； Ｎ、
１４．７９；Ｓ、８．６３； Ｂｒ、２１．３４
実施例 ６
冷却攪拌下に、塩化チオニル１９．ｙ（０：１６モル）
をピリジン４０ｒｎｌに加え、この溶液にイノシン（Ｓ
、５．９（０，０２４モル）を加えて、３５〜４０℃で
０．５時間反応させる。Rf value 067 (developing solvent chloroform:methanol = filter 5:10) Elemental analysis value C+ oH91"J405sBr calculated value (
%): C, 31,84; H, 2,40; N, 1
4.85; S, 8.50: Br, 21.19 actual value (@: C, 31,76; H, 2,39; N,
14.79; S, 8.63; Br, 21.34 Example 6 Thionyl chloride 19. y (0:16 mol)
was added to 40rnl of pyridine, and inosine (S
, 5.9 (0,024 mol) and reacted at 35 to 40°C for 0.5 hour.
反応終了後、実施例１と同様に処理して、６、５ Ｆの
５７−クロル−５′−デオキシ−２： ３’ −０−ス
ルフィニルイノシン（１８１％）が粉末結晶として得ら
れた。このものの物性値は実施例１で得たものの物性値
と一致した。After the reaction was completed, the same treatment as in Example 1 was carried out to obtain 6,5F 57-chloro-5'-deoxy-2:3'-0-sulfinyl inosine (181%) as a powder crystal. The physical properties of this product were consistent with those obtained in Example 1.
実施例 ４
冷却攪拌下に、塩化チオニル２３．７．！？（０，２モ
ル）をヘキサメチルホスホリックｌｌアミド９５７に加
え、この溶液に、イノシン９．６．９（００６６モル）
を攪拌下に加えて、１５時間攪拌を続ける。次いで、実
施例１と同様にして、反応混合物を処理すると１０１ｇ
の５′−クロル−５７−ジオキシ−２’、３’−０−ス
ルフイニルイノシン（収率８５係）が粉末結晶として得
られた。このものの物性値は実施例１で得たものの物性
値と一致した。Example 4 While cooling and stirring, thionyl chloride 23.7. ! ? (0,2 mol) was added to hexamethylphosphoric llamide 957 and to this solution was added 9.6.9 (0,066 mol) of inosine.
is added under stirring and stirring is continued for 15 hours. The reaction mixture was then treated in the same manner as in Example 1 to yield 101 g
5'-chloro-57-dioxy-2',3'-0-sulfininylinosine (yield: 85%) was obtained as a powder crystal. The physical properties of this product were consistent with those obtained in Example 1.
本発明に係る新規物質、イノジノハロゲン誘導体からＳ
−イノシルシスティンを製造する例を参考例として、以
下に示す。この参考例に示されるように、本発明に係る
イノシノノ・ロゲン誘導体は、有用な核酸類物質の合成
中間体として重要なものである。New substance according to the present invention, S from inodinohalogen derivative
- An example of producing inosylcysteine is shown below as a reference example. As shown in this reference example, the inosinologen derivative according to the present invention is important as a synthetic intermediate for useful nucleic acid substances.
参考例：
５′−クロル−グーデオキシ−２′、６′−〇−スルフ
ィニルイノシン２ＩとＬ−システィンジナトリウム塩６
Ｉとをジメチルホルムアミド３０ｆｎｌ中で、攪拌下に
２４時間反応させる。Reference example: 5'-chloro-gudeoxy-2',6'-〇-sulfinyl inosine 2I and L-cysteine disodium salt 6
I in 30 fnl of dimethylformamide for 24 hours with stirring.
反応終了後、反応混合物を冷却下に放置し、析出する結
晶を沢取し、少量のジメチルホルムアミドで洗浄し、次
いでエタノールで洗浄した後、水１６−に溶解し、濃塩
酸で中和する。次いで、この溶液を冷却下に放置し、析
出する結晶をＰ取する。これを水から再結晶すると、０
．４８，１２１％）の無色結晶のＳ−イノシルシスティ
ンが得られる。After the reaction is complete, the reaction mixture is left to cool, and the precipitated crystals are collected, washed with a small amount of dimethylformamide, then washed with ethanol, dissolved in water, and neutralized with concentrated hydrochloric acid. Next, this solution is left to cool and precipitated crystals are collected. When this is recrystallized from water, 0
．． 48,121%) of colorless crystalline S-inosylcysteine is obtained.
Claims (1)
塩素原子であることを特徴とするイノジノハロゲン誘導
体。 （３） イノシンとノ・ロゲン化チオニルとを反応さ
せることを特徴とする一般式 （式中、Ｘは）・ロゲン原子を示す） で表わされるイノジノハロゲン誘導体の製造方法。 （４）特許請求の範囲第６項において、溶媒としてピリ
ジンまたはへキサメチルホスホリックトリアミドを用い
て反応を行なうことを特徴とするイノジノハロゲン誘導
体の製造方法。 （５）特許請求の範囲第６項において反応を１０〜４０
℃の温匣で行なうことを特徴とするイノジノハロゲン誘
導体の製造方法。[Scope of Claims] (1) An inosinono-rogen-visiting conductor represented by the general formula (wherein, X represents a rogen atom). (2. Claim 1) An inodinohalogen derivative characterized in that the halogen atom is a chlorine atom. (3) A method for producing an inodinohalogen derivative represented by the general formula (wherein, (4) The method for producing an inodinohalogen derivative according to claim 6, characterized in that the reaction is carried out using pyridine or hexamethylphosphoric triamide as a solvent. (5) In claim 6, the reaction is 10 to 40
A method for producing an inodinohalogen derivative, characterized in that the process is carried out in a warm box at ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP16961282A JPS5959698A (en) | 1982-09-30 | 1982-09-30 | Inosinohalogen derivative and its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP16961282A JPS5959698A (en) | 1982-09-30 | 1982-09-30 | Inosinohalogen derivative and its preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5959698A true JPS5959698A (en) | 1984-04-05 |
| JPH027317B2 JPH027317B2 (en) | 1990-02-16 |
Family
ID=15889719
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP16961282A Granted JPS5959698A (en) | 1982-09-30 | 1982-09-30 | Inosinohalogen derivative and its preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5959698A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108558960A (en) * | 2018-05-16 | 2018-09-21 | 新乡拓新药业股份有限公司 | A kind of preparation method of tri--O- acetyl group -5- deoxidations-β of 1,2,3--D-ribose |
-
1982
- 1982-09-30 JP JP16961282A patent/JPS5959698A/en active Granted
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108558960A (en) * | 2018-05-16 | 2018-09-21 | 新乡拓新药业股份有限公司 | A kind of preparation method of tri--O- acetyl group -5- deoxidations-β of 1,2,3--D-ribose |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH027317B2 (en) | 1990-02-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPH0371431B2 (en) | ||
| JPS5959698A (en) | Inosinohalogen derivative and its preparation | |
| JPS5949221B2 (en) | Method for producing 3-acylamino-4-homoisotwistane | |
| JP4159022B2 (en) | Preparation of diazonaphthoquinonesulfonyl chloride using diphosgene and triphosgene. | |
| JPH03153680A (en) | Biphenyl compound and its preparation | |
| JPS6025957A (en) | Method for producing 2-nitrobenzaldehyde | |
| JPH08208591A (en) | 2-aminobenzenesulfonic acid derivative and 2-aminobenzenesulfonyl chloride,derivative their production,and their use as synthetic intermediates | |
| JPS5959699A (en) | Novel preparation of inosine derivative | |
| JPS59155400A (en) | Improved preparation of c-amp acyl derivative | |
| JPS61218555A (en) | Manufacture of acids substituted with trifluorodichloroethylgroup and zinc compounds | |
| JPS6261966A (en) | Propionamidine derivatives and manufacture | |
| JP2632732B2 (en) | Method for producing N- (3 ', 4'-dimethoxycinnamoyl) anthranilic acid | |
| US2436360A (en) | Preparation of z-amino-s-chloro | |
| US1906200A (en) | 4-brom-diethylacetylamino-1-phenyl-2, 3-dimethyl-5-pyrazolone and the process of preparing the same | |
| JPH0340040B2 (en) | ||
| JPS6351146B2 (en) | ||
| KR820000786B1 (en) | Process for preparing uracil derivatives | |
| JPH0324046A (en) | Production of n-(3',4'-dimethoxycinnamoyl)-anthranilic acid | |
| JPH02282345A (en) | Production of 2,4,5-trifluorobenzoic acid | |
| JPS6144882A (en) | Preparation of alpha-(2-aminothiazol-4-yl)-beta-sulfonylacrylic acid derivative | |
| JPS61205237A (en) | Halogenonitroaniline derivative and production thereof | |
| JPH02256680A (en) | Production of 5-(3754/24)2-chloro-benzyl)-4,5,6,7-tetrahydrothieno(3,2-c)pyridine or salt thereof | |
| JPS6021148B2 (en) | New optically active pyridinium salt and method for producing the same | |
| JPH01313471A (en) | Production of n-sulfamoylamidine compound | |
| JPH026442A (en) | Method for manufacturing a tetrapropyl ammonium bromide |