JPH0513144B2 - - Google Patents
Info
- Publication number
- JPH0513144B2 JPH0513144B2 JP16401884A JP16401884A JPH0513144B2 JP H0513144 B2 JPH0513144 B2 JP H0513144B2 JP 16401884 A JP16401884 A JP 16401884A JP 16401884 A JP16401884 A JP 16401884A JP H0513144 B2 JPH0513144 B2 JP H0513144B2
- Authority
- JP
- Japan
- Prior art keywords
- cyclopentenone
- hydroxy
- nitric acid
- nitrate ester
- 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 - Lifetime
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
【発明の詳細な説明】
本発明は、式〔〕
で示されるシクロペンテノンの硝酸エステルおよ
びその製造法に関する。[Detailed Description of the Invention] The present invention relates to the formula [] This invention relates to a cyclopentenone nitrate ester represented by the following formula and a method for producing the same.
上記式〔〕で示されるシクロペンテノンの硝
酸エステルは本発明者らによつて初めて合成され
た新規化合物であつて、医薬あるいは農薬等の中
間体として有用である。とくに光学活性なシクロ
ペンテノンの硝酸エステルは、プロスタグランデ
インの重要原料である光学活性４−ヒドロキシ−
２−シクロペンテノンの４−位の水酸基の反転を
行うための中間体として重要であり、本化合物を
経由すれば高純度、高光学純度で立体反転を行う
ことができる。 The cyclopentenone nitric acid ester represented by the above formula [] is a novel compound synthesized for the first time by the present inventors, and is useful as an intermediate for pharmaceuticals or agricultural chemicals. In particular, optically active cyclopentenone nitrate ester is an important raw material for prostaglandin, optically active 4-hydroxy-
It is important as an intermediate for inverting the hydroxyl group at the 4-position of 2-cyclopentenone, and stereoinversion can be carried out with high purity and high optical purity via this compound.
すなわち、上記ルートで示すように、シクロペ
ンテノンの硝酸エステルがたとえばＳ配位であれ
ば、これを加水分解、反転して得られる４−ヒド
ロキシ−２−シクロペンテノンはＲ配位となる。 That is, as shown in the above route, if the nitrate ester of cyclopentenone has, for example, S coordination, 4-hydroxy-2-cyclopentenone obtained by hydrolyzing and inverting this has R coordination.
光学活性な４−ヒドロキシ−２−シクロペンテ
ノンについては特開昭57−159777号公報に記載さ
れており、4R−ヒドロキシ−２−シクロペンテ
ノンが天然物と同じ配位のプロスタグランデイン
として用いられる旨記載されている。従つて、そ
の逆の配位の4S−ヒドロキシ−２−シクロペン
テノンがＲ−配位に変換できればその経済的価値
は非常に高くなる。 Optically active 4-hydroxy-2-cyclopentenone is described in JP-A-57-159777, and 4R-hydroxy-2-cyclopentenone is used as a prostaglandin with the same coordination as the natural product. It is stated that Therefore, if 4S-hydroxy-2-cyclopentenone, which has the opposite configuration, can be converted to the R-configuration, its economic value would be extremely high.
また、4S−ヒドロキシ−２−シクロペンテノ
ンは新しいタイプのプロスタグランデイン誘導体
として有用であり、従つて、4R−ヒドロキシ−
２−シクロペンテノンがＳ−配位に変換できて
も、プロスタグランデイン誘導体の合成上極めて
意義深いものがある。 Additionally, 4S-hydroxy-2-cyclopentenone is useful as a new type of prostaglandin derivative, and therefore 4R-hydroxy-2-cyclopentenone is useful as a new type of prostaglandin derivative.
Even if 2-cyclopentenone can be converted to S-coordination, it is extremely significant in the synthesis of prostaglandin derivatives.
このように、シクロペンテノンの硝酸エステル
は光学活性な４−ヒドロキシ−２−シクロペンテ
ノンの４−位の水酸基の光学配位をそれぞれの目
的に応じて反転し得るための中間体として極めて
重要である。 In this way, cyclopentenone nitric ester is extremely important as an intermediate for inverting the optical coordination of the hydroxyl group at the 4-position of optically active 4-hydroxy-2-cyclopentenone according to each purpose. It is.
本発明は、このように特に光学活性な４−ヒド
ロキシ−２−シクロペンテノンの４−位の水酸基
の光学配位を反転するための中間体として重要な
前記式〔〕で示されるシクロペンテノンの硝酸
エステルおよびその製造法を提供するものであ
る。 The present invention is directed to a cyclopentenone represented by the above formula [], which is an important intermediate for inverting the optical coordination of the hydroxyl group at the 4-position of the optically active 4-hydroxy-2-cyclopentenone. The present invention provides a nitrate ester and a method for producing the same.
かかる式〔〕で示されるシクロペンテノンの
硝酸エステルは式〔〕
で示される４−ヒドロキシ−２−シクロペンテノ
ンと硝酸を反応させることにより製造することが
できる。 The nitrate ester of cyclopentenone represented by the formula [] is represented by the formula [] It can be produced by reacting 4-hydroxy-2-cyclopentenone represented by nitric acid with nitric acid.
ここで、原料として用いられる４−ヒドロキシ
−２−シクロペンテノンはｄ−体であつてもよ
く、4R体あるいは4S体の光学活性体であつても
よい。 Here, 4-hydroxy-2-cyclopentenone used as a raw material may be in the d-form, or may be in the optically active form of the 4R form or the 4S form.
４−ヒドロキシ−２−シクロペンテノンと硝酸
との反応は、通常、溶媒の存在下に脱水縮合する
ことにより行われる。 The reaction between 4-hydroxy-2-cyclopentenone and nitric acid is usually carried out by dehydration condensation in the presence of a solvent.
この反応において溶媒を使用する場合、その溶
媒としては、たとえばテトラヒドロフラン、ジオ
キサン、アセトン、エチルエーテル、トルエン、
クロロホルム、ジメチルホルムアミド等の脂肪族
もしくは芳香族炭化水素、エーテル、ハロゲン化
炭化水素等の反応に不活性な溶媒の単独または混
合物があげられ、その使用量については特に制限
されない。 When a solvent is used in this reaction, examples of the solvent include tetrahydrofuran, dioxane, acetone, ethyl ether, toluene,
Examples include solvents that are inert to the reaction, such as aliphatic or aromatic hydrocarbons such as chloroform and dimethylformamide, ethers, and halogenated hydrocarbons, either alone or as a mixture, and the amount used is not particularly limited.
反応に用いる硝酸は４−ヒドロキシ−２−シク
ロペンテノン１当量に対して１当量以上必要であ
り、好ましくは1.2〜３当量の範囲である。もち
ろんこれ以上の使用も可能である。硝酸は通常の
濃硝酸はもちろんのこと発煙硝酸も使用される。
この反応は脱水縮合であるため、使用する硝酸は
高濃度の方が好ましく、通常は濃度60重量％以上
のものが使用される。 The amount of nitric acid used in the reaction is required to be at least 1 equivalent per equivalent of 4-hydroxy-2-cyclopentenone, preferably in the range of 1.2 to 3 equivalents. Of course, more uses are possible. As nitric acid, not only normal concentrated nitric acid but also fuming nitric acid is used.
Since this reaction is a dehydration condensation, it is preferable to use a high concentration of nitric acid, and usually a concentration of 60% by weight or more is used.
この反応で脱水剤を使用することは有効であ
り、たとえば無水酢酸、無水プロピオン酸等を溶
媒を兼ねて、もしくは溶媒とともに用いることが
できる。 It is effective to use a dehydrating agent in this reaction; for example, acetic anhydride, propionic anhydride, etc. can be used also as a solvent or together with a solvent.
かかる脱水剤を用いる場合、その使用量は４−
ヒドロキシ−２−シクロペンテノンに対して１当
量以上あるいは使用する硝酸中の水分含量に対し
て等モル以上が好ましい。高濃度硝酸を用いて脱
水剤を使用しないこともできる。 When such a dehydrating agent is used, the amount used is 4-
It is preferably at least 1 equivalent relative to hydroxy-2-cyclopentenone or at least equimolar relative to the water content of the nitric acid used. It is also possible to use high concentration nitric acid without using a dehydrating agent.
反応温度は通常−30〜80℃であり、好ましくは
−20〜50℃の範囲である。 The reaction temperature is usually -30 to 80°C, preferably -20 to 50°C.
反応時間については特に制限されない。 There is no particular restriction on the reaction time.
反応終了後、反応混合物から抽出、濃縮、クロ
マトグラフイー等の通常の操作により、目的とす
るシクロペンテノンの硝酸エステルを単離する
ことができる。 After the reaction is completed, the desired cyclopentenone nitrate ester can be isolated from the reaction mixture by conventional operations such as extraction, concentration, and chromatography.
以下、実施例により本発明を説明する。 The present invention will be explained below with reference to Examples.
実施例 １
反応フラスコに4S−ヒドロキシ−２−シクロ
ペンテノン（光学純度90％）9.8ｇおよび無水酢
酸30ｇを仕込み、−15℃〜−５℃にて発煙硝酸9.4
ｇを１時間を要して滴下する。同温度にて１時間
保温ののち、反応混合物を氷中にあけ、酢酸エチ
ル80mlにて抽出する。有機層はさらに水、２％重
ソウ水、水にて順次洗浄する。有機層は硫酸マグ
ネシウムにて乾燥後、濃縮する。Example 1 A reaction flask was charged with 9.8 g of 4S-hydroxy-2-cyclopentenone (optical purity 90%) and 30 g of acetic anhydride, and 9.4 g of fuming nitric acid was heated at -15°C to -5°C.
g was added dropwise over a period of 1 hour. After incubating at the same temperature for 1 hour, the reaction mixture was poured into ice and extracted with 80 ml of ethyl acetate. The organic layer is further washed successively with water, 2% sodium hydroxide solution, and water. The organic layer is dried over magnesium sulfate and then concentrated.
濃縮残渣をトルエン−酢酸エチル混合液（混合
重量比５：２）を用いてシリカゲルカラムクロマ
トグラフイーにて精製し、4S−ヒドロキシ−２
−シクロペンテノンの硝酸エステル12.8ｇを得
た。 The concentrated residue was purified by silica gel column chromatography using a toluene-ethyl acetate mixture (mixing weight ratio 5:2) to obtain 4S-hydroxy-2
- 12.8 g of cyclopentenone nitrate were obtained.
α〕D 25 −71.7° （Ｃ＝１，CHC3）
ｎ〕D 25 1.4976
光学純度97％の4S−ヒドロキシ−２−シクロ
ペンテノンを用いる以外は上記と同様に硝酸と反
応させ、同様に処理して4S−ヒドロキシ−２−
シクロペンテノンの硝酸エステル12.6ｇを得た。 α〕 D 25 -71.7° (C = 1, CHC 3 ) n〕 D 25 1.4976 React with nitric acid and treat in the same manner as above, except that 4S-hydroxy-2-cyclopentenone with optical purity of 97% is used. and 4S-hydroxy-2-
12.6 g of cyclopentenone nitrate was obtained.
α〕D 25 −77.3° （Ｃ＝１，CHC3）
ｎ〕D 25 1.4962
実施例 ２
ｄ−４−ヒドロキシ−２−シクロペンテノン
4.9ｇおよび無水酢酸15ｇをテトラヒドロフラン
15mlに溶解し、−10℃にて発煙硝酸4.4ｇを１時間
を要して滴下する。 α] D 25 −77.3° (C=1, CHC 3 ) n] D 25 1.4962 Example 2 d-4-hydroxy-2-cyclopentenone
4.9 g and 15 g of acetic anhydride in tetrahydrofuran.
Dissolve the solution in 15 ml, and add 4.4 g of fuming nitric acid dropwise at -10°C over 1 hour.
同温度にて１時間保温ののち、反応混合物を氷
中にあけ、酢酸エチル50mlにて抽出する。後、実
施例１と同様に後処理精製し、４−ヒドロキシ−
２−シクロペンテノンの硝酸エステル6.1ｇを得
た。 After incubating at the same temperature for 1 hour, the reaction mixture was poured into ice and extracted with 50 ml of ethyl acetate. After that, it was purified by post-treatment in the same manner as in Example 1, and 4-hydroxy-
6.1 g of 2-cyclopentenone nitric ester was obtained.
nD 25 1.4968
実施例 ３
反応フラスコに4R−ヒドロキシ−２−シクロ
ペンテノン4.9ｇ（光学純度95％）および無水酢
酸20ｇを仕込み、−15〜−10℃に冷却する。同温
度にて発煙硝酸５ｇを30分にて滴下する。後１時
間保温する。後、実施例１と同様に後処理、精製
して4R−ヒドロキシ−２−シクロペンテノンの
硝酸エステル6.36ｇを得る。 n D 25 1.4968 Example 3 A reaction flask is charged with 4.9 g of 4R-hydroxy-2-cyclopentenone (95% optical purity) and 20 g of acetic anhydride and cooled to -15 to -10°C. At the same temperature, 5 g of fuming nitric acid was added dropwise over 30 minutes. Keep warm for another 1 hour. Thereafter, the product was post-treated and purified in the same manner as in Example 1 to obtain 6.36 g of 4R-hydroxy-2-cyclopentenone nitric acid ester.
α〕D 25 ＋76.0° （Ｃ＝１，CHC3） nD 25 1.4988 α〕 D 25 +76.0° (C=1, CHC 3 ) n D 25 1.4988
Claims (1)
載のシクロペンテノンの硝酸エステル。 ３ ４−ヒドロキシ−２−シクロペンテノンと硝
酸を反応させることを特徴とする式 で示されるシクロペンテノンの硝酸エステルの製
造法。 ４ ４−ヒドロキシ−２−シクロペンテノンが光
学活性体であり、得られるシクロペンテノンの硝
酸エステルがそれと同じ配位を有する光学活性体
である特許請求の範囲第３項に記載のシクロペン
テノンの硝酸エステルの製造法。[Claims] 1 formula Nitrate ester of cyclopentenone. 2. The nitrate ester of cyclopentenone according to claim 1, which is an optically active substance. 3 Formula characterized by reacting 4-hydroxy-2-cyclopentenone and nitric acid A method for producing cyclopentenone nitrate ester. 4. Cyclopentenone according to claim 3, wherein 4-hydroxy-2-cyclopentenone is an optically active form, and the obtained nitrate ester of cyclopentenone is an optically active form having the same coordination as that of the 4-hydroxy-2-cyclopentenone. A method for producing nitrate ester.
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP16401884A JPS6143145A (en) | 1984-08-03 | 1984-08-03 | Nitric ester or cyclopentenone and its preparation |
| US06/758,801 US4683323A (en) | 1984-07-31 | 1985-07-25 | Method for inversion of optically active 4-hydroxy-2-cyclopentenones |
| EP85305343A EP0170506B1 (en) | 1984-07-31 | 1985-07-26 | Method for inversion of optically active 4-hydroxy-2-cyclopentenones |
| DE8585305343T DE3582201D1 (en) | 1984-07-31 | 1985-07-26 | METHOD FOR INVERSING OPTICALLY ACTIVE 4-HYDROXY-2-CYCLOPENTENONES. |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP16401884A JPS6143145A (en) | 1984-08-03 | 1984-08-03 | Nitric ester or cyclopentenone and its preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6143145A JPS6143145A (en) | 1986-03-01 |
| JPH0513144B2 true JPH0513144B2 (en) | 1993-02-19 |
Family
ID=15785219
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP16401884A Granted JPS6143145A (en) | 1984-07-31 | 1984-08-03 | Nitric ester or cyclopentenone and its preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6143145A (en) |
-
1984
- 1984-08-03 JP JP16401884A patent/JPS6143145A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6143145A (en) | 1986-03-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5247083A (en) | Direct esterification of mycophenolic acid | |
| FR1449628A (en) | Process for the preparation of deacylated polynuclear indoles, in particular esters of the deacetyl-vincaleucoblastine and deacetylvincristine series | |
| SU656526A3 (en) | Method of obtaining derivatives of cephalosporanic acid isomers | |
| JPH0768163B2 (en) | Process for producing cyclopentenone derivative | |
| US3910958A (en) | Process for preparing arylacetic acids and esters thereof | |
| JPS62146B2 (en) | ||
| JPH01233255A (en) | Cyclopentenone derivative and production thereof | |
| JPS6341896B2 (en) | ||
| JPS6143145A (en) | Nitric ester or cyclopentenone and its preparation | |
| JPS58194853A (en) | Cyclohexane-acetyloxime derivative | |
| JP2668435B2 (en) | Cyclopentenone derivatives and their production | |
| JPS5823374B2 (en) | Method for producing 3-hydroxy-5-oxo-2-substituted-cyclopentane alkenoic acid | |
| CN1034808Y (en) | The synthetic method of 4,5-dihydro-3-butylphthalide | |
| JPH0528693B2 (en) | ||
| JPS6140669B2 (en) | ||
| JPS5852995B2 (en) | Method for producing furfural derivatives | |
| JPH03261744A (en) | 1,3-pentadiene derivative and production thereof | |
| JP2880203B2 (en) | Preparation of furanone derivatives | |
| JPS61197573A (en) | 5,6-epoxidized trans-vitamin d3 | |
| JPH0523756B2 (en) | ||
| JPH0527617B2 (en) | ||
| JPS6317841A (en) | Synthesis of 7-membered ring ketone compound from 6-membered ring ketone compound | |
| JPH0149277B2 (en) | ||
| JPH0477752B2 (en) | ||
| JPS5845415B2 (en) | Trimethylcyclohexene derivative |