JPH0662617B2 - Method for preparing (+/-) 14,15-dihydro- (3β, 14α, 16α) -20,21-dinorebulenamenin-14-ol - Google Patents
Method for preparing (+/-) 14,15-dihydro- (3β, 14α, 16α) -20,21-dinorebulenamenin-14-olInfo
- Publication number
- JPH0662617B2 JPH0662617B2 JP61283026A JP28302686A JPH0662617B2 JP H0662617 B2 JPH0662617 B2 JP H0662617B2 JP 61283026 A JP61283026 A JP 61283026A JP 28302686 A JP28302686 A JP 28302686A JP H0662617 B2 JPH0662617 B2 JP H0662617B2
- Authority
- JP
- Japan
- Prior art keywords
- dihydro
- dinorebulenamenin
- dichloromethane
- hydrogen peroxide
- dinorebulenamenine
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D461/00—Heterocyclic compounds containing indolo [3,2,1-d,e] pyrido [3,2,1,j] [1,5]-naphthyridine ring systems, e.g. vincamine
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【発明の詳細な説明】 この発明の方法は、下記の一般式（Ｉ）および（II）で
それぞれ示される、（＋／−）１４，１５−ジヒドロ−
（３β，１４α，１６α）−２０，２１−ジノルエブル
ナメニン−１４−オールを（＋／−）−（３β，１６
α）−２０，２１−ジノルエブルナメニンから高収率で
製造するために創案されたものである。DETAILED DESCRIPTION OF THE INVENTION The method of the present invention is represented by the following general formulas (I) and (II): (+/−) 14,15-dihydro-
(3β, 14α, 16α) -20,21-dinorebulenamenin-14-ol is (+/−)-(3β, 16
It was invented for producing a high yield from α) -20,21-dinorebulenamenine.
この化合物（Ｉ）は製薬学的に非常に重要であり、脳不
全の治療において用いられ、また極めて毒性が低い。 This compound (I) is of great pharmaceutical importance, used in the treatment of brain failure, and has extremely low toxicity.
この方法は、過酸化水素によるエポキシド化反応によ
り、ならびに次に、溶媒として塩基性媒体中に水および
ジクロルメタン混合物を含むものを用い、臭化エチルの
存在のもとに不均一相において水素化硼素テトラブチル
アンモニウムのような四級アンモニウム還元剤塩を用い
て相間移動触媒反応によって還元することにより式（I
I）の化合物を（＋／−）１４，１５−ジヒドロ−（３
β，１４α，１６α）−２０，２１−ジノルエブルナメ
ニン−１４−オールに変形することからなる。This method is carried out by the epoxidation reaction with hydrogen peroxide and then using as solvent the mixture of water and dichloromethane in a basic medium, in the presence of ethyl bromide in a heterogeneous phase in the presence of boron hydride. By reducing by a phase transfer catalytic reaction with a quaternary ammonium reducing agent salt such as tetrabutylammonium, the formula (I
The compound of (I) was added to (+/−) 14,15-dihydro- (3
.beta., 14.alpha., 16.alpha.)-20,21-dinorebulenamenin-14-ol.
これらの双方のプロセスは、単一の工程で行なわれ、か
つ反応は以下のようにして行なわれる： この方法の効果は、アルケン（II）からエポキシドへの
酸化およびその開環を単一工程で行なうことによりアル
コール（Ｉ）を高収率で得られることにある。Both of these processes are carried out in a single step, and the reaction is carried out as follows: The effect of this method is that the alcohol (I) can be obtained in a high yield by carrying out the oxidation of the alkene (II) to the epoxide and the ring opening thereof in a single step.
この発明による方法は、単なる例示として以下に示す実
施例によりより一層理解されるであろう。The method according to the invention will be better understood by the examples given below by way of example only.
実施例１ １０ｇの（＋／−）−（３β，１６α）−２０，２１−
ジノルエブルナメニン（II）を２０mlのジクロルメタン
と２５mlの２０％水酸化ナトリウム水溶液との混合物中
に分散させる。この反応を、攪拌しつつ１５分間維持す
る。次に１２ｇの過酸化水素を添加し（１００体積
部）、さらに９．２ｇの水素化硼素テトラブチルアンモ
ニウムおよび４ｇの臭化エチルを添加する。強く攪拌し
つつ、この反応を２０℃の温度で２４時間維持する。反
応が終了したら、２５℃より低い温度にして加水分解さ
せ、かつ反応物をジクロルメタンにより抽出する。この
抽出物は一連の異性体からなり、調製クロマトグラフに
より精製され、その主生成物として（＋／−）１４，１
５−ジヒドロ−（３β，１４α，１６α）−２０，２１
−ジノルエブルナメニン−１４−オールが分離される。
収率は５０％であり、融点は２３０〜２３２℃である。Example 1 10 g of (+/-)-(3β, 16α) -20,21-
The dinorebrunamenine (II) is dispersed in a mixture of 20 ml of dichloromethane and 25 ml of 20% aqueous sodium hydroxide solution. The reaction is maintained for 15 minutes with stirring. Then 12 g of hydrogen peroxide are added (100 parts by volume), followed by 9.2 g of tetrabutylammonium borohydride and 4 g of ethyl bromide. The reaction is maintained at a temperature of 20 ° C. for 24 hours with vigorous stirring. When the reaction is complete, the temperature is brought below 25 ° C. for hydrolysis and the reaction product is extracted with dichloromethane. This extract consists of a series of isomers and is purified by preparative chromatography and has (+/-) 14,1 as its main product.
5-dihydro- (3β, 14α, 16α) -20,21
-Dinolubrenamenin-14-ol is isolated.
The yield is 50% and the melting point is 230-232 ° C.
前述した方法に導入することができ、かつこの方法の必
須の特徴を変更しない変形例は、添付の特許請求の範囲
に含まれるものと理解するであろう。It will be understood that variations which can be introduced into the above method and which do not alter the essential features of this method are included in the appended claims.
Claims (2)
トリウムの２０％水溶液との混合物を用い、臭化エチル
の存在の下に、四級アンモニウム塩還元剤により触媒さ
れた不均一相中において、酸化−還元反応により、２０
℃の温度で強く攪拌しつつ２４時間の間（＋／−）−
（３β，１６α）−２０，２１−ジノルエブルナメニン
を過酸化水素と反応させ、 反応物の温和な加水分解を行なうことを特徴とする、下
記の一般式（Ｉ）で表される（＋／−）１４，１５−ジ
ヒドロ−（３β，１４α，１６α）−２０，２１−ジノ
ルエブルナメニン−１４−オールの調製方法。 1. Oxidation in a heterogeneous phase catalyzed by a quaternary ammonium salt reducing agent in the presence of ethyl bromide using a mixture of dichloromethane as a solvent and a 20% aqueous solution of sodium hydroxide. -By reduction reaction, 20
(+/-)-for 24 hours with strong stirring at a temperature of ℃
(3β, 16α) -20,21-dinorebulenamenine is reacted with hydrogen peroxide to perform mild hydrolysis of the reaction product, which is represented by the following general formula (I) ( +/−) 14,15-Dihydro- (3β, 14α, 16α) -20,21-dinorebulenamenin-14-ol.
リウム水溶液の等量混合物からなる溶媒中において相間
移動により触媒された還元反応において、１モルの（＋
／−）−（３β，１６α）−２０，２１−ジノルエブル
ナメニンを、２モルを超える過酸化水素、１モルを超え
る水素化硼素テトラブチルアンモニウムおよび１モルを
超える臭化エチルと反応させることを特徴とする、特許
請求の範囲第１項記載の（＋／−）１４，１５−ジヒド
ロ−（３β，１４α，１６α）−２０，２１−ジノルエ
ブルナメニン−１４−オールの調製方法。2. In a reduction reaction catalyzed by phase transfer in a solvent consisting of an equal mixture of dichloromethane and 20% aqueous sodium hydroxide solution, 1 mol of (+
/-)-(3β, 16α) -20,21-dinorebulenamenine is reacted with more than 2 moles of hydrogen peroxide, more than 1 mole of tetrabutylammonium borohydride and more than 1 mole of ethyl bromide. A method for preparing (+/−) 14,15-dihydro- (3β, 14α, 16α) -20,21-dinorebulenamenin-14-ol according to claim 1. .
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES549399A ES8604957A1 (en) | 1985-11-28 | 1985-11-28 | Preparation of (+/-)14, 15-dihydro-(3 beta, 14 alpha, 16 alpha)-20, 21-dinoreburunamenine-14-ol |
| ES549399 | 1985-11-28 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS62145082A JPS62145082A (en) | 1987-06-29 |
| JPH0662617B2 true JPH0662617B2 (en) | 1994-08-17 |
Family
ID=8490315
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61283026A Expired - Lifetime JPH0662617B2 (en) | 1985-11-28 | 1986-11-26 | Method for preparing (+/-) 14,15-dihydro- (3β, 14α, 16α) -20,21-dinorebulenamenin-14-ol |
Country Status (3)
| Country | Link |
|---|---|
| JP (1) | JPH0662617B2 (en) |
| ES (1) | ES8604957A1 (en) |
| FR (1) | FR2590572B1 (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2623501B1 (en) * | 1987-11-19 | 1990-03-16 | Roussel Uclaf | NOVEL SUBSTITUTED DERIVATIVES OF 20.21-DINOREBURNAMENINE, THEIR PREPARATION PROCESS AND THE NOVEL INTERMEDIATES THUS OBTAINED, THEIR APPLICATION AS DRUGS AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM |
| FR2623503B1 (en) * | 1987-11-19 | 1991-04-05 | Roussel Uclaf | |
| FR2865649A1 (en) * | 2004-01-30 | 2005-08-05 | Biocortech | Use of 14,15-dihydro-20,21-dinor-14-eburnameninol to prepare a pharmaceutical composition for treating or preventing major depression |
| FR2865650B1 (en) * | 2004-01-30 | 2008-06-13 | Biocortech | USE OF 14,15 DIHYDRO 20,21-DINOREBURNAMENIN14-OL FOR THE TREATMENT AND / OR PREVENTION OF MAJOR LOWERS AND SLEEP-RELIEF CYCLE DISORDERS |
-
1985
- 1985-11-28 ES ES549399A patent/ES8604957A1/en not_active Expired
-
1986
- 1986-11-26 JP JP61283026A patent/JPH0662617B2/en not_active Expired - Lifetime
- 1986-11-28 FR FR868616623A patent/FR2590572B1/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| ES549399A0 (en) | 1986-03-16 |
| FR2590572A1 (en) | 1987-05-29 |
| ES8604957A1 (en) | 1986-03-16 |
| JPS62145082A (en) | 1987-06-29 |
| FR2590572B1 (en) | 1990-05-25 |
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