JPS5953260B2 - 3. Method for producing 6-substituted-2(IH)-pyridone - Google Patents
3. Method for producing 6-substituted-2(IH)-pyridoneInfo
- Publication number
- JPS5953260B2 JPS5953260B2 JP7838773A JP7838773A JPS5953260B2 JP S5953260 B2 JPS5953260 B2 JP S5953260B2 JP 7838773 A JP7838773 A JP 7838773A JP 7838773 A JP7838773 A JP 7838773A JP S5953260 B2 JPS5953260 B2 JP S5953260B2
- Authority
- JP
- Japan
- Prior art keywords
- pyridone
- substituted
- producing
- reaction
- gluco
- 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 6-substituted-2(IH)-pyridone Chemical class 0.000 title claims description 4
- 238000004519 manufacturing process Methods 0.000 title claims description 3
- 150000008065 acid anhydrides Chemical class 0.000 claims description 4
- 125000002252 acyl group Chemical group 0.000 claims description 3
- 125000001931 aliphatic group Chemical group 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 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
- 150000001875 compounds Chemical class 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-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
- 239000000203 mixture Substances 0.000 description 3
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 239000003814 drug 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
- BGMYHTUCJVZIRP-GASJEMHNSA-N nojirimycin Chemical compound OC[C@H]1NC(O)[C@H](O)[C@@H](O)[C@@H]1O BGMYHTUCJVZIRP-GASJEMHNSA-N 0.000 description 2
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- IZSRJDGCGRAUAR-MROZADKFSA-N 5-dehydro-D-gluconic acid Chemical compound OCC(=O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O IZSRJDGCGRAUAR-MROZADKFSA-N 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- BGMYHTUCJVZIRP-UHFFFAOYSA-N Nojirimycin Natural products OCC1NC(O)C(O)C(O)C1O BGMYHTUCJVZIRP-UHFFFAOYSA-N 0.000 description 1
- 108010093894 Xanthine oxidase Proteins 0.000 description 1
- 102100033220 Xanthine oxidase Human genes 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- UXTMROKLAAOEQO-UHFFFAOYSA-N chloroform;ethanol Chemical compound CCO.ClC(Cl)Cl UXTMROKLAAOEQO-UHFFFAOYSA-N 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- UJQMLHKSZKBMMO-UHFFFAOYSA-N n,n-diethylethanamine;pyridine Chemical compound C1=CC=NC=C1.CCN(CC)CC UJQMLHKSZKBMMO-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 229940081066 picolinic acid Drugs 0.000 description 1
- 235000021395 porridge Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Pyridine 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１
ＲＯＣＨ、／αＯＲ（１）
（式中Ｒは低級脂肪族アシル基を示す）で表わされる３
．６−置換−２（ＩＨ）−ビリドンの製法に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention provides 3 compounds represented by the general formula 1 ROCH, /αOR (1) (wherein R represents a lower aliphatic acyl group).
．． The present invention relates to a method for producing 6-substituted-2(IH)-pyridone.
本発明の出発物質であるＤ−グルコ−δ−ラクタムは本
発明者等の発見した方法に従つて、抗生物質ノジリマイ
シン（５−アミノー５−デオキシーＤ−グルコピラノー
ス）の酸化（テトラヘドロン、２３巻、２１２５頁、１
９６８年）又は５一ケトグルコン酸のオキシムの還元（
日本特許６３４５４６）によつて容易に得られる。The starting material of the present invention, D-gluco-δ-lactam, was prepared by oxidation of the antibiotic nojirimycin (5-amino-5-deoxy-D-glucopyranose) (tetrahedron, 23 Volume, 2125 pages, 1
968) or the reduction of the oxime of 5-ketogluconic acid (
Japanese Patent No. 634546).
このＤ−グルコ−δ−ラクタムをピリジン中酸無水物で
冷時〜室温下（Ｏ℃〜２５℃）で処理すると通常のアシ
ル誘導体すなわちテトラー０−アシル体を与える。When this D-gluco-delta-lactam is treated with an acid anhydride in pyridine at cold to room temperature (0 DEG C. to 25 DEG C.), the usual acyl derivative, ie, the tetra0-acyl compound, is obtained.
しかし本反応を加熱下に行つた所、テトラーＯ−アシル
体の生成は殆んど認めらへれずその代りに脱水・閉壌物
である３．６−置換一２（ＩＨ）−ビリドンを得、本発
明を完成させるに致つた。本発明によれば（１）式の化
合物はＤ−グルコ−δ−ラクタムを反応に不活性な溶媒
、例えばジメチルホルムアミド、ジオキサン等に懸濁し
、ピリジントリエチルアミン、ピペリジン等の塩基の存
在下に酸無水物を作用させアシル化と同時に脱水反応を
起させることで得られるが、最も収率のよい組合せは、
ピリジンを溶媒として用いて酸無水物を作用させる方法
である。However, when this reaction was carried out under heating, almost no tetra-O-acyl formation was observed, and instead, a dehydrated and locked product, 3,6-substituted 1-2(IH)-pyridone, was obtained. , we have completed the present invention. According to the present invention, the compound of formula (1) is obtained by suspending D-gluco-δ-lactam in a solvent inert to the reaction, such as dimethylformamide, dioxane, etc., and adding acid anhydride in the presence of a base such as pyridine triethylamine or piperidine. It can be obtained by causing a dehydration reaction at the same time as acylation, but the combination with the highest yield is
This is a method in which pyridine is used as a solvent and an acid anhydride is used.
反応温度は通常のアシル化反応より高温を必要とし、７
０〜１１０℃が適当である。The reaction temperature requires a higher temperature than normal acylation reaction, and 7
A temperature of 0 to 110°C is suitable.
反応時間は反応温度にもよるが、１００℃の場合約２０
時間で反応が完結する。本発明で得られる化合物はいず
れもキサンチンオキシダーゼの酵素活性を強力に阻害し
、痛風薬等の医薬品として有用である。The reaction time depends on the reaction temperature, but at 100°C it is about 20
The reaction completes in time. All of the compounds obtained in the present invention strongly inhibit the enzymatic activity of xanthine oxidase and are useful as pharmaceuticals such as gout medicines.
更に、本発明化合物はピコリン酸系降圧剤の製造原料と
しても有用である。Furthermore, the compound of the present invention is useful as a raw material for producing picolinic acid-based antihypertensive agents.
次に実施例により本発明を説明する。Next, the present invention will be explained with reference to Examples.
実施例 １
Ｄ−グルコ−δ−ラクタム６０ｇを冷却管付きの２１容
フラスコに取りピリジン５００“、無水酢酸２２０“を
加え室温にて２時間放置後１０５℃にて１５時間加熱還
流する。Example 1 60 g of D-gluco-δ-lactam was placed in a 21-volume flask equipped with a condenser, and 500 g of pyridine and 220 g of acetic anhydride were added thereto, allowed to stand at room temperature for 2 hours, and then heated under reflux at 105° C. for 15 hours.
反応液はそのまま濃縮乾固する。The reaction solution is directly concentrated to dryness.
残渣をクロロホルム２００ｄに溶解し、炭末にて脱色後
、略１００ｄまで濃縮しエタノール３００ｄを添加し低
温にて放置すると結晶が析出する。クロロホルム−メタ
ノールより再結し、６−アセチルオキシメチル−３−ア
セチルオキシ−２（ＩＨ）−ピリドンの白色針状結晶６
５ｆ！を得た。融点：１３５−１３６℃
元素分析値（９１４：Ｃ５３．２５％，Ｈ５．ｌ２％，
Ｎ６．２３％分子式：Ｃ，ＯＨｌｌＯ５Ｎ実施例 ２
Ｄ−グルコ−δ−ラクタム６ｆ１を冷却管付き２００Ｒ
ｔ容フラスコに取り、ピリジン６０ｍ１１無水プロピオ
ン酸３０ｄを加え１１０℃にて１７時間かくはん下に加
熱還流する。The residue is dissolved in 200 d of chloroform, decolorized with charcoal powder, concentrated to about 100 d, added with 300 d of ethanol, and left at a low temperature to precipitate crystals. Recrystallization from chloroform-methanol yields white needle-shaped crystals of 6-acetyloxymethyl-3-acetyloxy-2(IH)-pyridone 6
5f! I got it. Melting point: 135-136℃ Elemental analysis value (914: C53.25%, H5.12%,
N6.23% Molecular formula: C, OHllO5N Example 2 D-gluco-δ-lactam 6f1 in 200R with cooling tube
The mixture was placed in a T-volume flask, and 60ml of pyridine and 30d of propionic anhydride were added thereto, and the mixture was heated under reflux at 110°C for 17 hours with stirring.
反応液はそのまま濃縮乾固する。残渣をクロロホルム８
０１！１１に溶解し、水洗後、略２０７ｎ１，まで濃縮
し、エタノール７０ｄを加え低温にて放置すると結晶が
析出する。クロロホルム−エタノールより再結し６−プ
ロピオニルオキシメチル−３−プロピオニルオキシ−２
（ＩＨ）−ビリドンの白色針状結晶５．２９を得た。融
点：１３８−１３９℃元素分析値（粥：Ｃ５７．Ｏ８％
，Ｈ５．８２％，Ｎ５．４８％分子式：Ｃｌ２Ｈ，５Ｏ
５Ｎ実施例 ３
Ｄ−グルコ−δ−ラクタム３９を２００ｄ容フラスコに
取り、ピリジン３５ｄ１無水酪酸２０１ｎ１を加えかく
はん下１１０℃にて２０時間反応させる。The reaction solution is directly concentrated to dryness. Distill the residue in chloroform 8
01!11, washed with water, concentrated to approximately 207 n1, added with 70 d of ethanol, and left at a low temperature to precipitate crystals. Reconsolidated from chloroform-ethanol to give 6-propionyloxymethyl-3-propionyloxy-2
5.29 g of white needle crystals of (IH)-pyridone were obtained. Melting point: 138-139℃ Elemental analysis value (porridge: C57.O8%
, H5.82%, N5.48% Molecular formula: Cl2H,5O
5N Example 3 D-gluco-δ-lactam 39 was placed in a 200 d flask, 35 d of pyridine, 201 n1 of butyric anhydride were added, and the mixture was reacted at 110° C. for 20 hours with stirring.
Claims (1)
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は低級脂肪族アシル基）で表わされる３．６−
置換−２（ＩＨ）−ピリドンの製造法。[Claims] 1 A general formula characterized by the action of an acid anhydride on D-gluco-δ-lactam ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R is a lower aliphatic acyl group) 3.6- represented
Method for producing substituted-2(IH)-pyridone.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7838773A JPS5953260B2 (en) | 1973-07-13 | 1973-07-13 | 3. Method for producing 6-substituted-2(IH)-pyridone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7838773A JPS5953260B2 (en) | 1973-07-13 | 1973-07-13 | 3. Method for producing 6-substituted-2(IH)-pyridone |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5029568A JPS5029568A (en) | 1975-03-25 |
| JPS5953260B2 true JPS5953260B2 (en) | 1984-12-24 |
Family
ID=13660591
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP7838773A Expired JPS5953260B2 (en) | 1973-07-13 | 1973-07-13 | 3. Method for producing 6-substituted-2(IH)-pyridone |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5953260B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS599704B2 (en) * | 1978-01-11 | 1984-03-05 | 住友金属工業株式会社 | architectural structure |
-
1973
- 1973-07-13 JP JP7838773A patent/JPS5953260B2/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5029568A (en) | 1975-03-25 |
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