JPS6032789A - Preparation of yohimbones - Google Patents

Preparation of yohimbones

Info

Publication number
JPS6032789A
JPS6032789A JP58141884A JP14188483A JPS6032789A JP S6032789 A JPS6032789 A JP S6032789A JP 58141884 A JP58141884 A JP 58141884A JP 14188483 A JP14188483 A JP 14188483A JP S6032789 A JPS6032789 A JP S6032789A
Authority
JP
Japan
Prior art keywords
dehydroyohimbanone
yohimbone
formula
positions
dehydroyohimbone
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
Application number
JP58141884A
Other languages
Japanese (ja)
Other versions
JPH0452274B2 (en
Inventor
Kazuya Ninomiya
二宮 一弥
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.)
Ueno Seiyaku Oyo Kenkyujo KK
Original Assignee
Ueno Seiyaku Oyo Kenkyujo 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 Ueno Seiyaku Oyo Kenkyujo KK filed Critical Ueno Seiyaku Oyo Kenkyujo KK
Priority to JP58141884A priority Critical patent/JPS6032789A/en
Publication of JPS6032789A publication Critical patent/JPS6032789A/en
Publication of JPH0452274B2 publication Critical patent/JPH0452274B2/ja
Granted legal-status Critical Current

Links

Classifications

    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02PCLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00Technologies relating to chemical industry
    • Y02P20/50Improvements relating to the production of bulk chemicals
    • Y02P20/52Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts

Landscapes

  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

PURPOSE:To obtain the titled compound useful as a steroselective ysnthetic intermediate for yohimbane alkaloid simply ih high yield, by reacting 19,20-dehydroyohimbanone with an organic acid under heating, and, reducing the reaction product, if necessary. CONSTITUTION:19,20-Dehydroyohimbanone is reacted with an organic acid (e.g., tartaric acid, etc.) having one or more acid groups with about 3PKa in a solvent under heating at 30-120 deg.C. The prepared dehydroyohimbone shown by the formula (double bond at 19 and 19 positions) is optionally catalytically reduced in the presence of a catalyst of Pd-C to give yohimbone shown by the formula (single bond at 18 and 19 positions).

Description

【発明の詳細な説明】 本発明はヨヒンボン類の新規な製法に関する。[Detailed description of the invention] The present invention relates to a novel method for producing yohimbones.

デヒドロヨヒンボンはヨヒンビノン合成の中間体として
、ヨヒンビンの全合成に有用な化合物である。本発明者
は先に次式 で表わされるインドロピリジン類のハルマランから、ヨ
ヒンバン骨格を有する19.20−デヒドロヨヒンバノ
ンの立体選択的合成に成効した。そしてさらに研究を進
めた結果、本発明を完成した。
Dehydroyohimbone is a compound useful in the total synthesis of yohimbine as an intermediate in the synthesis of yohimbinone. The present inventor has previously succeeded in the stereoselective synthesis of 19,20-dehydroyohimbanone having a yohimbane skeleton from harmalan, an indropyridine represented by the following formula. As a result of further research, the present invention was completed.

本発明は、19 、20−デヒドロヨヒンバノンヲ有機
酸と加熱し、所望により還元することを特徴とする、次
式 (式中18−19位の点線は二重結合の存在しうろこと
を示す)で表わされるヨヒンボン類の製法である。
The present invention is characterized in that 19,20-dehydroyohimbanone is heated with an organic acid and optionally reduced. This is a method for producing yohimbone compounds represented by

出発物質である19.20−デヒドロヨヒンバノンは、
「ヘテロサイクルズ」18巻1982年216頁に記載
の方法により製造できる。
The starting material, 19.20-dehydroyohimbanone, is
It can be produced by the method described in "Heterocycles", Vol. 18, 1982, p. 216.

有機酸としては、pKaが3程度の酸基を1個以上有す
るもの、例えば酒石酸、くえん酸、オキザロ酢酸などが
好ましい。
Preferred organic acids include those having one or more acid groups with a pKa of about 3, such as tartaric acid, citric acid, and oxaloacetic acid.

本発明を実施するに際しては、19.20−デヒドロヨ
ヒンバノンを有機酸と反応させる。本反応は溶媒の存在
下に行うことが好ましい。溶媒としては例えばエーテル
、炭化水素、ケトン、好ましくはジオキサン、ハロゲン
化炭化水素などが用いられる。反応温度は60〜120
℃、好ましくは40〜100℃であり、反応は数分ない
し十数時間で終了する。生成物は常法により単離される
In practicing the invention, 19.20-dehydroyohimbanone is reacted with an organic acid. This reaction is preferably carried out in the presence of a solvent. As the solvent, for example, ether, hydrocarbon, ketone, preferably dioxane, halogenated hydrocarbon, etc. are used. Reaction temperature is 60-120
The temperature is preferably 40 to 100°C, and the reaction is completed in several minutes to more than ten hours. The product is isolated using conventional methods.

反応が還元条件下で行われるときはヨヒンボンが生成す
るが、そうでない場合はデヒドロヨヒンボンが生成する
。このデヒドロヨヒンボンを還元してヨヒンポンを製造
するには、パラジウム−炭素、酸化白金などの触媒の存
在下に接触還元することが好ましい。還元反応は、通常
は常温、常圧下に行われ、1時間ないし数時間で終了す
る。生成物は常法により単離される。
When the reaction is carried out under reducing conditions, yohimbone is produced; otherwise, dehydroyohimbone is produced. In order to reduce this dehydroyohimbone to produce yohimbone, it is preferable to carry out catalytic reduction in the presence of a catalyst such as palladium-carbon or platinum oxide. The reduction reaction is usually carried out at room temperature and under normal pressure, and is completed in one to several hours. The product is isolated using conventional methods.

こ5して得られたヨヒンボンは、ヨヒンバン骨格を有す
るので、ヨヒンビンアルカロイド類、レセルピンアルカ
ロイド類、デセルピンアルカロイド類などのアドレナリ
ン遮断剤、血圧降下剤、トランキライザーなどに有用な
アルカロイド類の合成に用いることができる。
Since the yohimbone obtained in this manner has a yohimbane skeleton, it can be used for the synthesis of alkaloids useful as adrenergic blockers, antihypertensive agents, tranquilizers, etc., such as yohimbine alkaloids, reserpine alkaloids, and deserpine alkaloids. I can do it.

本発明方法によれば、ヨヒンビノン、ヨヒンビンなとの
ヨヒンバンアルカロイドの立体選択的合成の中間体とし
て有用なデヒドロヨヒンボン及びヨヒ/ボンが、簡易か
つ高収率で得られる。
According to the method of the present invention, dehydroyohimbone and yohi/bone, which are useful as intermediates for the stereoselective synthesis of yohimbane alkaloids such as yohimbinone and yohimbine, can be obtained easily and in high yields.

 3 一 実施例1 デヒドロヨヒンボンの製造 19.20−fヒドロヨヒン デヒドロヨヒンボンバノ
ン 19 、20−デヒドロヨヒンバノン2001ngをジ
オキサン15m/4に溶解し、溶液に酒石酸2001n
9を加えて、80℃で8時間加熱する。次いで反応液を
水で希釈し、炭酸水素す) IJウムでアルカリ性にし
、塩化メチレンで抽出する。抽出液を水洗し、乾燥した
のち、溶媒を留去し、残留物に少量のエチルエーテルを
加えて結晶化させると、融点218〜220°Cのデヒ
ドロヨヒンボンの黄色結晶が1501n9得られる。収
率75 %。
3 Example 1 Production of dehydroyohimbone 19.20-fhydroyohine Dehydroyohimbanone 19 2001 ng of 20-dehydroyohimbanone was dissolved in 15 m/4 of dioxane, and 2001 ng of tartaric acid was added to the solution.
Add 9 and heat at 80°C for 8 hours. The reaction solution is then diluted with water, made alkaline with hydrogen carbonate and extracted with methylene chloride. After washing the extract with water and drying, the solvent is distilled off and the residue is crystallized by adding a small amount of ethyl ether to obtain 1501n9 yellow crystals of dehydroyohimbone with a melting point of 218-220°C. Yield 75%.

4− NMR(δ): 7.80(IH,s、NH)6.80
 (I H,dd、J=10.1,5.19−H) 6.08 (I H,ad、 J=10.3.18−H
)IRu 0H”3ffi−” : 3480.168
0ax 実施例2 ヨヒンボンの製法 デヒドロヨヒンボン ヨヒンボン 10m1に溶解し、溶液にパラジウム−炭素50■を加
え、常温常圧下に水素ガスを通じて2時間接触還元する
。次いで触媒を1別し、r液を濃縮し、残留物に少量の
エチルエーテルを加えて結晶化させると、ヨヒンボンの
白色結晶が45m9得られる。収率95%。得られたヨ
ヒンボンは、公知方法により得られたヨヒンポンと各種
スペクトルが一致することにより同定された。
4-NMR (δ): 7.80 (IH, s, NH) 6.80
(I H, dd, J=10.1,5.19-H) 6.08 (I H, ad, J=10.3.18-H
) IRu 0H"3ffi-": 3480.168
0ax Example 2 Production method of yohimbone Dehydroyohimbone Dissolved in 10 ml of yohimbone, added 50 ml of palladium-carbon to the solution, and catalytically reduced it by passing hydrogen gas at room temperature and pressure for 2 hours. Next, the catalyst was separated, the r liquid was concentrated, and a small amount of ethyl ether was added to the residue to crystallize it, yielding 45 m9 of white crystals of yohimbone. Yield 95%. The obtained yohimbone was identified because its various spectra matched with yohimbone obtained by a known method.

出願人 株式会社上野製薬応用研究所 代理人 弁理士 小 林 正 雄  7−Applicant: Ueno Pharmaceutical Application Research Institute Co., Ltd. Agent: Patent Attorney Masao Kobayashi 7-

Claims (1)

【特許請求の範囲】 19.20−デヒドロヨヒンバノンを有機酸と加熱し、
所望により還元することを特徴とする、次式 (式中18−19位の点線は二重結合の存在しうろこと
を示す)で表わされるヨヒンボン類の製法。
[Claims] 19. Heating 20-dehydroyohimbanone with an organic acid,
A method for producing a yohimbone compound represented by the following formula (in the formula, the dotted line at positions 18-19 indicates the presence of a double bond), which is reduced if desired.
JP58141884A 1983-08-04 1983-08-04 Preparation of yohimbones Granted JPS6032789A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP58141884A JPS6032789A (en) 1983-08-04 1983-08-04 Preparation of yohimbones

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP58141884A JPS6032789A (en) 1983-08-04 1983-08-04 Preparation of yohimbones

Publications (2)

Publication Number Publication Date
JPS6032789A true JPS6032789A (en) 1985-02-19
JPH0452274B2 JPH0452274B2 (en) 1992-08-21

Family

ID=15302399

Family Applications (1)

Application Number Title Priority Date Filing Date
JP58141884A Granted JPS6032789A (en) 1983-08-04 1983-08-04 Preparation of yohimbones

Country Status (1)

Country Link
JP (1) JPS6032789A (en)

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
HETEROCYCLES=1892 *

Also Published As

Publication number Publication date
JPH0452274B2 (en) 1992-08-21

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