JPS61204153A - Production of synthetic intermediate for shikonin - Google Patents
Production of synthetic intermediate for shikoninInfo
- Publication number
- JPS61204153A JPS61204153A JP4369885A JP4369885A JPS61204153A JP S61204153 A JPS61204153 A JP S61204153A JP 4369885 A JP4369885 A JP 4369885A JP 4369885 A JP4369885 A JP 4369885A JP S61204153 A JPS61204153 A JP S61204153A
- Authority
- JP
- Japan
- Prior art keywords
- shikonin
- compound
- formula
- diacetoxy
- ring
- 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
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】
（産業上の利用分野）
不発明は、シコニン合成中間体の製造法、特に５．８−
ジヒドロキシ−２−（５’、’５’−ジメチルー２−テ
トラハイドロフラニル）−１，４−ナフトキノンなどか
ら開環反応多こよりシコニン合成中間体を製造する方法
に関する。Detailed Description of the Invention (Industrial Field of Application) The invention relates to a method for producing a shikonin synthetic intermediate, particularly 5.8-
The present invention relates to a method for producing a shikonine synthetic intermediate from dihydroxy-2-(5','5'-dimethyl-2-tetrahydrofuranyl)-1,4-naphthoquinone and the like through a ring-opening reaction.
（従来の技術）
日本、中国、朝鮮に産するムラサキの根は紫根と呼ばれ
、その皮部に赤紫色の色素を含んでいる。(Prior art) The roots of the purple root grown in Japan, China, and Korea are called purple roots, and their skin contains a reddish-purple pigment.
この色素の主成分がシコニン（１）である。この色素は
、抗炎症性、抗菌性、抗腫瘍性作用があり、更に染料及
び化粧品の原料として現在広範囲に使用されている。′
また、紫雲膏として日本薬局法の第■部にも記載されて
いる。シコニン（１）は、下記の反応式（１）のように
プロトン酸、ルイス酸のような酸触媒の存在下、簡単に
閉環して５．８−ジヒドロキシ−２−（５’、５’−ジ
メチル−２−テトラハイドロフラニル）−１，４−ナフ
トキノン（ＩＩ）、丁なわち、テトラヒドロフラン環ヲ
生成する性質があり、この閉環の容易さが過去において
シコニン合成を阻んだ大きな一原因になっていたと考え
られる。すなわち、シコニンの化学合成の過程において
も簡単に閉環化合物（Ｉｆ）を生じてしまうのである。The main component of this pigment is shikonin (1). This pigment has anti-inflammatory, anti-bacterial and anti-tumor properties and is currently widely used as a raw material for dyes and cosmetics. ′
It is also listed in Part 2 of the Japanese Pharmacopoeia Act as Shiun-gyo. Shikonin (1) is easily ring-closed in the presence of an acid catalyst such as a protonic acid or a Lewis acid, as shown in reaction formula (1) below. Dimethyl-2-tetrahydrofuranyl)-1,4-naphthoquinone (II) has the property of forming a tetrahydrofuran ring, and the ease of ring closure was one of the major reasons for hindering the synthesis of shikonin in the past. It is thought that That is, even in the process of chemically synthesizing shikonin, a closed ring compound (If) is easily generated.
以上の記述から容易に結論できるが、この閉環化合物（
］ＩＩは、熱、元、溶剤に対して開放鎖式化金物である
シコニンなどよりも安定な化合物であるＯ
■ 亘
（発明が解決しようとする問題点）
前記のようｆこシコニン合成の過程で簡単に生成してし
まう閉環化合物（１）は、シコニン合成上極めてやっか
いな問題である。本発明は、この閉環化合物（１）又は
その５．８位をジアセトキシ化した化合物をシコニン合
成中間体に転化して有用な再利用を図るものである。It can be easily concluded from the above description that this ring-closed compound (
]II is a compound that is more stable against heat, elements, and solvents than shikonin, which is an open-chain metal compound. The ring-closed compound (1), which is easily produced in , is an extremely troublesome problem in the synthesis of shikonin. The present invention aims at useful reuse by converting this ring-closed compound (1) or a compound obtained by diacetoxylating its 5.8-position into an intermediate for shikonin synthesis.
（問題点を解決するための手段）
本発明者らは、上記問題を解決すべく鋭意努力した結果
、次の方法によりこの問題を解決することができた。す
ムわち、この発明は、５．８−ジヒドロキシ−２−（５
’、５’−ジメチル−２−テトラハイドロフラニル）−
１，４−ナフトキノン（ＩＩ）又は５．８−ジアセトキ
シ−２−（５’、 ｆｉ’−ジメチル−２−テトラハイ
ドロフラニル）−１，４−ナフトキノン（Ｉ）５−酸性
触媒の存在下に無水酢酸中で開環して５，８−ジアセト
キシ−２−（１’、４’−ジアセトキシ−４′−メチル
ペンチル）−１，４−ナフトキノンを得るシコニン合成
中間体の製造性である。(Means for solving the problem) As a result of the inventors' earnest efforts to solve the above problem, they were able to solve this problem by the following method. In summary, this invention provides 5,8-dihydroxy-2-(5
',5'-dimethyl-2-tetrahydrofuranyl)-
1,4-naphthoquinone (II) or 5,8-diacetoxy-2-(5', fi'-dimethyl-2-tetrahydrofuranyl)-1,4-naphthoquinone (I) in the presence of a 5-acidic catalyst This is the manufacturability of a shikonine synthetic intermediate which is ring-opened in acetic anhydride to obtain 5,8-diacetoxy-2-(1',4'-diacetoxy-4'-methylpentyl)-1,4-naphthoquinone.
本発明を次の反応式（２）
％式％
（反応式（２）において、ＡＣはアセチル基を、ＴｓＯ
Ｈはｐ−トルエンスルホン酸を示す）によって一層詳細
に説明する。The present invention is carried out using the following reaction formula (2) % formula % (In reaction formula (2), AC represents an acetyl group, TsO
(H represents p-toluenesulfonic acid).
閉環化合物（ｎ）を一般に酢化反応に便利に用いられる
溶剤、例えばピリジンに溶し、無水酢酸を刀口えると５
．８−ジアセトキシ−２−（５’、 ５’−ジメチル−
２−テトラハイドロフラニル）−１，４−ナフトキノン
（１）を得る。（１）を無水酢酸中で（１）と等モル量
の例えば、有機溶媒に溶けやすいｐ−トルエンスルホン
酸などを触媒として作用させると平滑に反応が進み、開
環した中間体５．８−ジアセトキシ−２−（１’、４’
−ジアセトキシ−４′−メチルペンチル） −１，４−
ナフトキノン（ＩＴ）を生じる。（ＩＹ）はアルカリで
加水分解すれば（Ｖ）とすることは容易である。また途
中で（１）を分離することなく（■）を酸性触媒の存在
下無水酢酸中で開環して（■）から一段階で（ＩＶ）を
得ることができることも本発明者らによって明らかにさ
れている。ここに得られたすべての化合物は、元素分析
、赤外分光分析（ＩＲ）、プロトン核磁気共鳴法（ＮＭ
Ｒ）によって、それぞれの化学構造を確実に有すること
が証明された。When the ring-closing compound (n) is dissolved in a solvent commonly used for acetylation reactions, such as pyridine, and acetic anhydride is added, 5
．． 8-diacetoxy-2-(5', 5'-dimethyl-
2-tetrahydrofuranyl)-1,4-naphthoquinone (1) is obtained. When (1) is treated in acetic anhydride with an equimolar amount of p-toluenesulfonic acid, which is easily soluble in organic solvents, as a catalyst, the reaction proceeds smoothly, resulting in a ring-opened intermediate 5.8- diacetoxy-2-(1', 4'
-diacetoxy-4'-methylpentyl) -1,4-
yields naphthoquinone (IT). (IY) can easily be converted into (V) by hydrolysis with an alkali. The present inventors also revealed that (IV) can be obtained in one step from (■) by ring-opening (■) in acetic anhydride in the presence of an acidic catalyst without separating (1) during the process. It is being done. All the compounds obtained here were analyzed by elemental analysis, infrared spectroscopy (IR), and proton nuclear magnetic resonance (NM).
R), it was proven that they definitely have the respective chemical structures.
（ＩＶ）の加水分解で得られる５、８−ジヒドロキシ−
２−（１’、４’−ジヒドロキシ−４′−メチルペンチ
ル）−１，４−ナフトキノン（Ｖ）からシコニンを製造
する方法については、例えば、特開昭５９−１７５４４
９号公報に記載される。5,8-dihydroxy- obtained by hydrolysis of (IV)
A method for producing shikonin from 2-(1',4'-dihydroxy-4'-methylpentyl)-1,4-naphthoquinone (V) is described, for example, in JP-A-59-17544.
It is described in Publication No. 9.
（実施例〕
次に実施例によって本発明の内容を更に詳細に説明する
。(Example) Next, the content of the present invention will be explained in more detail with reference to Examples.
実施例１
化合物（１）（２０１部）（重量部、以下同じ）をピリ
ジン（ａｏｏｏ部）に溶し、０〜５℃でこれに無水酢酸
（２０００部）を加えたのち２時間３０分攪拌した。反
応終了後、氷水を加え、クロロホルｔ・で抽出し、抽出
液を食塩水で洗浄、無水硫酸ナトリウムで乾燥後、濃縮
した。シリカゲルのカラムクロマト法でｍ製して５，８
−ジアセトキシ−２−（５′、５′−ジメチル−２−テ
トラハイドロフラニル） −１，４−ナフトキノン（１
）２４９部（収量９６％）を得た。（１）の分析値は次
の通りである。Example 1 Compound (1) (201 parts) (parts by weight, same hereinafter) was dissolved in pyridine (aooo parts), and acetic anhydride (2000 parts) was added thereto at 0 to 5°C, followed by stirring for 2 hours and 30 minutes. did. After the reaction was completed, ice water was added and extracted with chloroform t. The extract was washed with brine, dried over anhydrous sodium sulfate, and concentrated. 5,8 made by silica gel column chromatography
-diacetoxy-2-(5',5'-dimethyl-2-tetrahydrofuranyl) -1,4-naphthoquinone (1
) 249 parts (yield 96%) were obtained. The analytical values for (1) are as follows.
ｍｐ１２６〜１２９℃、ＩＲ（ＫＢｒ）： １７７０，
１７５５（エステルＧ＝Ｏ）、１８５０ （キノン０＝
Ｏ）ｃｒｒＬ＋Ｎ Ｍ Ｒ（０ＤＯ１８）δ： １．．
３１ （Ｓ、 ２０Ｈ３，６Ｈ） 、 ２゜４２゜２．
４３ （ぞれぞれ、ｏＡｃ 、 ８１ ） 、 ５．０
０ （ｔ、 ＯＨ。mp126-129℃, IR (KBr): 1770,
1755 (ester G=O), 1850 (quinone 0=
O) crrL+NMR(0DO18)δ: 1. ．．
31 (S, 20H3,6H), 2゜42゜2.
43 (respectively oAc, 81), 5.0
0 (t, OH.
ＬＨ）。元素分析値： ０．６３．８３ ： Ｈ，５，
４９。LH). Elemental analysis value: 0.63.83: H, 5,
49.
Ｃ２０Ｈ２００７としての計算値： ０ 、６４．５１
； Ｉ（、５，４１゜化合物（１）（１２７部）を無
水酢＃Ｉ（３０００部）に溶し、ｐ−トルエンスルホン
酸（６４部）を加え室温で一夜反応させる。反応終了後
、氷水を加え、酢酸エチルで抽出し、食塩水で洗浄、無
水硫酸ナトリウムで乾燥後、濃縮した。シリカゲルのカ
ラムクロマトで精製して５，８−ジアセトキシ−２−（
１’、４’−ジアセトキシ−４′−メチルペンチル）−
１，４−ナフトキノン（１７）を８３部（収量４７％）
得た。（ＩＶ）の分析値は次の通りである。工Ｒ（ＫＢ
ｒ）： １７７０．１７３５ （エステルａ＝Ｏ）。Calculated value as C20H2007: 0, 64.51
I (, 5,41° Compound (1) (127 parts) is dissolved in anhydrous vinegar #I (3000 parts), p-toluenesulfonic acid (64 parts) is added and reacted overnight at room temperature. After completion of the reaction, Ice water was added, extracted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, and concentrated. Purified with silica gel column chromatography to obtain 5,8-diacetoxy-2-(
1',4'-diacetoxy-4'-methylpentyl)-
83 parts of 1,4-naphthoquinone (17) (yield 47%)
Obtained. The analytical values for (IV) are as follows. Engineering R (KB
r): 1770.1735 (ester a=O).
１６６５ （キノン（３＝Ｏ） 、 １１８０ ｃｍ
ｏＮＭＲ（０ＤＣ１３）δ： １．４２ （Ｓ、 ２
０Ｈ３，６Ｈ） 、 １．９５ （Ｓ。1665 (quinone (3=O), 1180 cm
oNMR(0DC13)δ: 1.42 (S, 2
0H3,6H), 1.95 (S.
−（ＯＨ８）、０４ｃ 、 ３Ｉｌ） 、 ２．１３
（Ｓ、 −ＣＨ（ｏＡｃ）−，３Ｈ）。-(OH8), 04c, 3Il), 2.13
(S, -CH(oAc)-, 3H).
２．４３（Ｓ、２ｍ−０Ａｃ、 ６Ｈ） 、 ５．８３
（ｔ、ＣＨ，ＩＥＩ ）。2.43 (S, 2m-0Ac, 6H), 5.83
(t, CH, IEI).
化合物（ｆｆ） （１６部）を窒素雰囲気下、ＩＮ。Compound (ff) (16 parts) was added IN under a nitrogen atmosphere.
Ｎ ａＯＨ水溶液（１０００部）に溶し、０〜５℃で５
時間反応させる。反応終了後、酢酸で酸性とし、塩化メ
チレンで抽出、食塩水で洗浄、無水硫酸ナトリウムで乾
燥後、濃縮した。シリカゲルのカラムクロマトで精製し
て５，８−ジヒドロキシ−２−（１′、４′−ジヒドロ
キシ−４′−メチルペンチル）−１，４−ナフトキノン
（Ｖ）を８部（収ｉ７８％）得た。化合物（Ｖ）の分析
値は、本発明者らが既に別途合成して所有している標準
試料のそれとすべて一致した成績を示した。Dissolved in NaOH aqueous solution (1000 parts) and heated at 0 to 5°C for 50 minutes.
Allow time to react. After the reaction was completed, the mixture was acidified with acetic acid, extracted with methylene chloride, washed with brine, dried over anhydrous sodium sulfate, and concentrated. Purification by silica gel column chromatography yielded 8 parts (yield: 78%) of 5,8-dihydroxy-2-(1',4'-dihydroxy-4'-methylpentyl)-1,4-naphthoquinone (V). . The analytical values of compound (V) all showed results that were consistent with those of a standard sample that the present inventors had already synthesized separately and owned.
実施例２
化合物（ｎ）（１１３部）を無水酢酸（２０００部）に
溶し、ｐ−トルエンスルホン酸（７８部〕を加え、室温
で一夜反応させる。反応終了後、氷水を加え、酢酸エチ
ルで抽出、食塩水で洗浄、無水硫酸すＩ−ＩＪウムで乾
燥後、濃縮した。シリカゲルのカラムクロマトで精製し
て５，８−ジアセトキシ−２−（１’、４’−ジアセト
キシ−１′−メチルペンチル）−１，４−ナフトキノン
（ＩＶ）を５２部（収１ｉ１３１係〕得た。これの分析
値は実施例１で合成しｆ、ＬＭ）のそれらと良く一致し
た。Example 2 Compound (n) (113 parts) was dissolved in acetic anhydride (2000 parts), p-toluenesulfonic acid (78 parts) was added, and the mixture was allowed to react overnight at room temperature. After the reaction was completed, ice water was added and ethyl acetate was added. , washed with brine, dried over anhydrous sodium sulfate, and concentrated. Purified with silica gel column chromatography to obtain 5,8-diacetoxy-2-(1',4'-diacetoxy-1'- 52 parts of methylpentyl)-1,4-naphthoquinone (IV) (Yield 1i131) were obtained.The analytical values of this were in good agreement with those of f, LM) synthesized in Example 1.
化合物（ＩＴ）を実施例１の場合と同様にアルカリで加
水分解して（Ｖ）を得た。Compound (IT) was hydrolyzed with an alkali in the same manner as in Example 1 to obtain (V).
（発明の効果）
本発明によってシコニンの化学合成の過程（こおいて閉
環化合物を生じても、再び開環する方法を新たに提供す
ることができ、これによって、無駄なくシコニンの中間
原料に戻すことができるようになった。(Effects of the Invention) The present invention makes it possible to provide a new method for re-opening the ring even if a ring-closed compound is produced during the chemical synthesis process of shikonin, thereby returning it to an intermediate raw material for shikonin without waste. Now I can do it.
なお、本発明の方法を応用すれば、既発衣のシコニン合
成の工程数を減少せしめることができると考えられる。It is believed that by applying the method of the present invention, it is possible to reduce the number of steps in the synthesis of pre-dressed shikonin.
Claims (1)
ル−２−テトラハイドロフラニル）−１，４−ナフトキ
ノン又は５，８−ジアセトキシ−２−（５’，５’−ジ
メチル−２−テトラハイドロフラニル）−１，４−ナフ
トキノンを酸性触媒の存在下に無水酢酸中で開環して５
，８−ジアセトキシ−２−（１’，４’−ジアセトキシ
−４’−メチルペンチル）−１，４−ナフトキノンを得
ることを特徴とするシコニン合成中間体の製造法。1,5,8-dihydroxy-2-(5',5'-dimethyl-2-tetrahydrofuranyl)-1,4-naphthoquinone or 5,8-diacetoxy-2-(5',5'-dimethyl- 2-Tetrahydrofuranyl)-1,4-naphthoquinone was ring-opened in acetic anhydride in the presence of an acidic catalyst to obtain 5.
, 8-diacetoxy-2-(1',4'-diacetoxy-4'-methylpentyl)-1,4-naphthoquinone.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4369885A JPS61204153A (en) | 1985-03-07 | 1985-03-07 | Production of synthetic intermediate for shikonin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4369885A JPS61204153A (en) | 1985-03-07 | 1985-03-07 | Production of synthetic intermediate for shikonin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS61204153A true JPS61204153A (en) | 1986-09-10 |
| JPH0159258B2 JPH0159258B2 (en) | 1989-12-15 |
Family
ID=12671043
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4369885A Granted JPS61204153A (en) | 1985-03-07 | 1985-03-07 | Production of synthetic intermediate for shikonin |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS61204153A (en) |
-
1985
- 1985-03-07 JP JP4369885A patent/JPS61204153A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0159258B2 (en) | 1989-12-15 |
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