JPS60190760A - Pyrrolidine derivative and its production - Google Patents
Pyrrolidine derivative and its productionInfo
- Publication number
- JPS60190760A JPS60190760A JP4527284A JP4527284A JPS60190760A JP S60190760 A JPS60190760 A JP S60190760A JP 4527284 A JP4527284 A JP 4527284A JP 4527284 A JP4527284 A JP 4527284A JP S60190760 A JPS60190760 A JP S60190760A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- pyrrolidine derivative
- general formula
- alkyl group
- pyrrolidine
- 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.)
- Pending
Links
Landscapes
- Pyrrole Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
本発明は新規などロリジン誘導体及びその製造法に関す
る。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to novel loridine derivatives and methods for producing the same.
格を有するアルカロイドが、一般に、抗菌性、抗カビ性
等の生理活性を有することは知られているが、これらア
ルカロイドを化学合成によシ得ようとする検討も種々性
なわれている。Although it is generally known that alkaloids having various properties have physiological activities such as antibacterial and antifungal properties, various studies have been made to obtain these alkaloids by chemical synthesis.
本発明者は、かかるアルカロイドの全合成のキーステッ
プとなるアミド化合物の立体選択的環化反応につき鋭意
検討した。The present inventors have made extensive studies on the stereoselective cyclization reaction of amide compounds, which is a key step in the total synthesis of such alkaloids.
一般にアミド化合物を環化してピロリジン誘導体を合成
する際には、アミンの塩基性を下げる必要があシ、例え
ば、電子求引性基を導入する方法などが考えられるが、
本発明者が検討したアミド化合物の場合、電子求引性基
として特定のスルホニル基を導入し、ハロアミド化を行
なわせると、特に高立体選択的に新規でアルカミイド系
の医薬あるいは農薬の中間体として有用なピロリジン誘
導体が得られることを知得し、本発明を完成するに到っ
た。Generally, when cyclizing an amide compound to synthesize a pyrrolidine derivative, it is necessary to lower the basicity of the amine. For example, a method of introducing an electron-withdrawing group may be considered.
In the case of the amide compound studied by the present inventors, when a specific sulfonyl group is introduced as an electron-withdrawing group and haloamidation is performed, it can be used as a novel intermediate for alkamide-based drugs or agricultural chemicals with particularly high stereoselectivity. The inventors have learned that useful pyrrolidine derivatives can be obtained, and have completed the present invention.
即ち、本発明は、一般式（１）
（式中、Ｘはハロゲン原子を表わし、Ｒ１及びＲ２は水
素原子又はアルキル基を表わし、Ｈａはアルキル基で置
換されていてもよいフェニル基を表わす。）
で示されるピロリジン誘導体及び
一般式（ＩＩ）
１
（式中、Ｒ１、Ｂ２及びＲ８は一般式（１）で定義した
通シである。）
で示されるアミド化合物とハロゲン類とを反応させるこ
とを特徴とする一般式（１）で示されるピロリジン誘導
体の製造法に存する。That is, the present invention is based on the general formula (1) (wherein, X represents a halogen atom, R1 and R2 represent a hydrogen atom or an alkyl group, and Ha represents a phenyl group which may be substituted with an alkyl group). ) and an amide compound represented by the general formula (II) 1 (wherein R1, B2 and R8 are the same as defined in the general formula (1)) and a halogen. The present invention relates to a method for producing a pyrrolidine derivative represented by the general formula (1), characterized by:
以下本発明を説明するに、本発明のピロリジン誘導体は
前記一般式（１）で示される化合物である。To explain the present invention below, the pyrrolidine derivative of the present invention is a compound represented by the general formula (1).
式中、又は臭素原子、ヨウ素原子等のノ・ロゲン原子を
表わし２、Ｒ１及びＲ２は水素原子又はメチル基、エチ
ル基等のアルキル基を表わし Ｒ８はフェニル基、トリ
ル基等のアルキル基で置換されていてもよいフェニル基
を表わす。In the formula, 2, R1 and R2 represent a hydrogen atom or an alkyl group such as a methyl group or an ethyl group, and R8 is substituted with an alkyl group such as a phenyl group or a tolyl group. represents an optionally substituted phenyl group.
具体的には、例えば、下記の様な化合物が挙げられる。Specifically, for example, the following compounds may be mentioned.
本発明のピロリジン誘導体は、例えば、一般式（ＩＩ）
１
（式中、Ｒ１、Ｒ２及びＲ３け一般式（１１で定義した
通シである。）
で示されるアミド化合物を、ジメトキシエタン、エーテ
ル、アセトニトリル、塩化メチレン等の溶媒中、室温乃
至−１０℃で、臭素、ヨウ素、Ｎ−７’ｏ ｈコバｌｔ
Ｒイミ）’、Ｎ−ヨード−コハク酸イミド等のハロゲン
類と５分乃至５時間反応させることによって得ることが
できる。The pyrrolidine derivative of the present invention is, for example, an amide compound represented by the general formula (II) 1 (wherein R1, R2 and R3 are the general formula defined in 11), dimethoxyethane, ether, Bromine, iodine, N-7'oh cobalt in a solvent such as acetonitrile or methylene chloride at room temperature to -10°C.
It can be obtained by reacting with a halogen such as R imi)' or N-iodo-succinimide for 5 minutes to 5 hours.
又、式（Ｉｌｌで示されるアミド化合物は一般式（ｍン
１
（式中、Ｒ１及びＲ２は、一般式（Ｉ）で定義した通シ
である。）
で示されるアミン類を、ピリジン、α−ピコリン等の塩
基の存在下、一般式（ＩＶ）
Ｒ”−８０２−０１・・・・・・曲・・ （ＥＶ）（式
中Ｒ３は一般式（１）で定義した通シである。）で示さ
れる塩化スルホニル化合物と常法に従って反応すること
によって容易に得られる。In addition, the amide compound represented by the formula (Ill) is an amine represented by the general formula (m1 (wherein, R1 and R2 are the same as defined in the general formula (I)), pyridine, α - In the presence of a base such as picoline, the general formula (IV) R''-802-01... Song... (EV) (wherein R3 is the same as defined in the general formula (1)). ) can be easily obtained by reacting with a sulfonyl chloride compound shown in ) according to a conventional method.
かくして得られる本発明のピロリジン誘導体は、アルカ
ロイド系の医薬、農薬の中間体として利用されることが
、期待される。The pyrrolidine derivative of the present invention thus obtained is expected to be used as an intermediate for alkaloid drugs and agricultural chemicals.
以下に実施例を挙げて、本発明を具体的に説明するが、
本発明はその要旨を越えない限り実施例に限定されるも
のではない。The present invention will be specifically explained with reference to Examples below.
The present invention is not limited to the examples unless it goes beyond the gist thereof.
実施例−ｌ
ジメトキシエタン（ｌ虎ｅ）、水（０，ｊｍｌ）に下記
式（ｎａ ）で示されるアばド化合物（／ｍｍｏｌ ）
を溶解し、θ〜−ｊ℃に冷却下、攪拌しながら、同温度
でＮ−ブロモコハク酸イミド（／、／ｍｍｏｌ）の固体
を投入した。約１時間攪拌後、反応混合物をエーテルλ
Ｏ−で希釈し、稀Ｎａ２ＢＯＢで洗滌し、エーテル抽出
液をＭｇ８０４で乾燥後、濃縮することにより、はぼ単
一物として下記式（Ｉａ）のピロリジン誘導体を得た。Example-l Abad compound (/mmol) represented by the following formula (na) in dimethoxyethane (l-e), water (0, jml)
was dissolved, and solid N-bromosuccinimide (/,/mmol) was added at the same temperature while stirring while cooling to θ to −j°C. After stirring for about 1 hour, the reaction mixture was diluted with ether λ
The pyrrolidine derivative of the following formula (Ia) was obtained as a single substance by diluting with O-, washing with dilute Na2BOB, drying the ether extract with Mg804, and concentrating the extract.
次いで、カラムクロマトグラフィー（シリカゲル、ベン
ゼン−酢酸エチル勾配法）によシ、（ｌａ）をタタチの
収率で得た。生成物（ｌａ）は立体異性体の混合物（ｃ
ｉａ／１ｒａｎ８＝７！’、ｊ ）である。Then, by column chromatography (silica gel, benzene-ethyl acetate gradient method), (la) was obtained in a perfect yield. The product (la) is a mixture of stereoisomers (c
ia/1ran8=7! ', j).
（Ｉ［ａ） 生成物（Ｉａ）の物性は下記の通シであった。(I[a) The physical properties of the product (Ia) were as shown below.
実施例−２
ジエチルエーテル（、ｚｍ／）、水（θ、ｊｍ／）Ｋ前
記式（Ｉｌａ ）で示されるアミド化合物（ｔ ｍｍｏ
ｌ）を溶解し、００〜−５℃に冷却し、攪拌しながら同
温度でヨウ素（八ｊ ｍｍｏｌ）及びＮａＨＣＯ２（／
、ｊｍｍｏｌ）を添加し反応した。Example-2 Diethyl ether (, zm/), water (θ, jm/) K, amide compound represented by the above formula (Ila) (t mmo
l), cooled to 00~-5°C, and added iodine (8j mmol) and NaHCO2 (/
, jmmol) and reacted.
実施例−／と同様の処理をして、下記式（Ｉ ｂ）のピ
ロリジン誘導体を２ｊ％の収率で得た。生成物（Ｉｂ）
は立体異性体の混合物（ｃｉｓ／１ｒａｎ日＝り６／グ
）である。The same treatment as in Example-// was carried out to obtain a pyrrolidine derivative of the following formula (Ib) at a yield of 2j%. Product (Ib)
is a mixture of stereoisomers (cis/ran day = 6/g).
生成物（Ｉｂ）の物性は下記の通シであった。The physical properties of the product (Ib) were as follows.
実施例−３
実施例−７において、アミド化合物として下記式（Ｉｌ
ｂ ）の化合物を使用するほかは同様にして、下記式（
１０）で示されるピロリジン誘導体を得た。Example-3 In Example-7, the following formula (Il
b) The following formula (
A pyrrolidine derivative represented by 10) was obtained.
生成物（ｌｃ）の物性は下記の通シであった。The physical properties of the product (lc) were as follows.
Claims (2)
ｉ水素原子又はアルキル基を表わし、Ｒ８はアルキル基
で置換されていてもよいフェニル、基を表わす。） で示されるピロリジン誘導体。(1) General formula (1) (in the formula, or represents a halogen atom, R1 and R2I'
i represents a hydrogen atom or an alkyl group, and R8 represents a phenyl group which may be substituted with an alkyl group. ) A pyrrolidine derivative represented by
し Ｒ３はアルキル基で置換されていてもよいフェニル
基を表わす。） で示されるアミド化合物とハロゲン類とを反応させるこ
とを特徴とする一般式ＣＩ）（式中、又はハロゲン原子
を表わし、Ｒ１、Ｒ２およびＲ３は前記と同義針表わす
。） で示されるピロリジン誘導体の製造法。(2) An amide compound represented by the general formula (n) (wherein R1 and R2 represent a hydrogen atom or an alkyl group, and R3 represents a phenyl group which may be substituted with an alkyl group) and a halogen. A method for producing a pyrrolidine derivative represented by the general formula CI) (in which a halogen atom is represented, and R1, R2, and R3 represent the same meanings as above), characterized by reacting the pyrrolidine derivative.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4527284A JPS60190760A (en) | 1984-03-09 | 1984-03-09 | Pyrrolidine derivative and its production |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4527284A JPS60190760A (en) | 1984-03-09 | 1984-03-09 | Pyrrolidine derivative and its production |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS60190760A true JPS60190760A (en) | 1985-09-28 |
Family
ID=12714674
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4527284A Pending JPS60190760A (en) | 1984-03-09 | 1984-03-09 | Pyrrolidine derivative and its production |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS60190760A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5036153A (en) * | 1989-05-11 | 1991-07-30 | Braish Tamim F | Preparation of 2,5-diazabicyclo[2.2.1]heptanes and intermediates |
| US5417331A (en) * | 1990-09-08 | 1995-05-23 | Kabushiki Kaisha Ace Denken | Conveyance equipment for paper or the like, and paper money collection system in game island employing the same |
| CN103214407A (en) * | 2013-05-07 | 2013-07-24 | 北京大学 | Method for preparing pyrrolidine derivative |
-
1984
- 1984-03-09 JP JP4527284A patent/JPS60190760A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5036153A (en) * | 1989-05-11 | 1991-07-30 | Braish Tamim F | Preparation of 2,5-diazabicyclo[2.2.1]heptanes and intermediates |
| US5417331A (en) * | 1990-09-08 | 1995-05-23 | Kabushiki Kaisha Ace Denken | Conveyance equipment for paper or the like, and paper money collection system in game island employing the same |
| CN103214407A (en) * | 2013-05-07 | 2013-07-24 | 北京大学 | Method for preparing pyrrolidine derivative |
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