JPH0579067B2 - - Google Patents
Info
- Publication number
- JPH0579067B2 JPH0579067B2 JP1053658A JP5365889A JPH0579067B2 JP H0579067 B2 JPH0579067 B2 JP H0579067B2 JP 1053658 A JP1053658 A JP 1053658A JP 5365889 A JP5365889 A JP 5365889A JP H0579067 B2 JPH0579067 B2 JP H0579067B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- naphthazarin
- acid catalyst
- following formula
- carbon atoms
- 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
- RQNVIKXOOKXAJQ-UHFFFAOYSA-N naphthazarin Chemical compound O=C1C=CC(=O)C2=C1C(O)=CC=C2O RQNVIKXOOKXAJQ-UHFFFAOYSA-N 0.000 claims description 31
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical group FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- QYKIQEUNHZKYBP-UHFFFAOYSA-N Vinyl ether Chemical compound C=COC=C QYKIQEUNHZKYBP-UHFFFAOYSA-N 0.000 claims description 4
- 239000003377 acid catalyst Substances 0.000 claims description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 4
- 125000004122 cyclic group Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 claims description 2
- 239000011968 lewis acid catalyst Substances 0.000 claims description 2
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 claims 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 238000000034 method Methods 0.000 description 9
- UNNKKUDWEASWDN-UHFFFAOYSA-N alkannin Natural products CC(=CCC(O)c1cc(O)c2C(=O)C=CC(=O)c2c1O)C UNNKKUDWEASWDN-UHFFFAOYSA-N 0.000 description 8
- NEZONWMXZKDMKF-JTQLQIEISA-N Alkannin Chemical group C1=CC(O)=C2C(=O)C([C@@H](O)CC=C(C)C)=CC(=O)C2=C1O NEZONWMXZKDMKF-JTQLQIEISA-N 0.000 description 7
- 241001071917 Lithospermum Species 0.000 description 7
- 239000002994 raw material Substances 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- 238000004566 IR spectroscopy Methods 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 101100109871 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) aro-8 gene Proteins 0.000 description 4
- -1 cyclic acetal compound Chemical class 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000000921 elemental analysis Methods 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- JKTCBAGSMQIFNL-UHFFFAOYSA-N 2,3-dihydrofuran Chemical compound C1CC=CO1 JKTCBAGSMQIFNL-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 150000004292 cyclic ethers Chemical group 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000000049 pigment Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- PHFSBQBIZUORSR-UHFFFAOYSA-N 2,2-dimethyl-3h-furan Chemical compound CC1(C)CC=CO1 PHFSBQBIZUORSR-UHFFFAOYSA-N 0.000 description 1
- ALRXDRQNAJOPCP-GFCCVEGCSA-N 2-[(2r)-5,5-dimethyloxolan-2-yl]-5,8-dihydroxynaphthalene-1,4-dione Chemical compound O1C(C)(C)CC[C@@H]1C1=CC(=O)C2=C(O)C=CC(O)=C2C1=O ALRXDRQNAJOPCP-GFCCVEGCSA-N 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
- NEZONWMXZKDMKF-SNVBAGLBSA-N Shikonin Chemical compound C1=CC(O)=C2C(=O)C([C@H](O)CC=C(C)C)=CC(=O)C2=C1O NEZONWMXZKDMKF-SNVBAGLBSA-N 0.000 description 1
- PHTGVPBJVHRZJY-UHFFFAOYSA-N Shikonine Natural products CC(CC=C(C)C)C1=C(O)C(=O)c2c(O)ccc(O)c2C1=O PHTGVPBJVHRZJY-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000001057 purple pigment Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
Landscapes
- Furan Compounds (AREA)
- Pyrane Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
（産業上の利用分野）
本発明は、医薬品、染料、及び化粧品の原料と
して重要なナフタザリン誘導体の製造法に関す
る。さらに詳しくは、下記の一般式、
(Industrial Application Field) The present invention relates to a method for producing naphthazarin derivatives, which are important as raw materials for pharmaceuticals, dyes, and cosmetics. For more details, see the general formula below,
【式】
〔ただし、R1，R2は水素原子、炭素数２以下
のアルキル基またはアルケニル基もしくは炭素数
６以下の芳香族の炭化水素基を表す〕
で表わされるナフタザリン誘導体の製造法に関す
る。
（従来の技術）
日本、中国、朝鮮に産するムラキサの根は紫根
と呼ばれ、その皮部に赤紫色の色素を含んでい
る。この色素の主成分が次式、[Formula] [wherein R 1 and R 2 represent a hydrogen atom, an alkyl group or alkenyl group having 2 or less carbon atoms, or an aromatic hydrocarbon group having 6 or less carbon atoms]. (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. The main component of this pigment is the following formula:
【式】
で表わされるシコニンである。この色素は抗炎症
性、抗菌性、抗腫瘍性作用があるので医薬品とし
て、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（）の
側鎖の閉環したものが次式、It is shikonin represented by the following formula. This pigment has anti-inflammatory, antibacterial, and antitumor properties and is currently widely used as a pharmaceutical agent and as a raw material for dyes and cosmetics. It is also listed in Part 1 of the Japanese Pharmacopoeia Act as Shiun-gyo. The ring-closed side chain of shikonin () has the following formula:
【式】
で表わされるシクロシコニンで、シクロシコニン
（）からシコニン（）への変換は既知であり
〔寺田 晁、他J.Org.Chem.，52，1437（1987）；
米国特許第4560511号明細書（1985）；特公昭62−
36021号公報；J.Chem.Soc.，Chem.Commu.，
1983，987〕、極めて短い工程で有利にシコニンの
合成を進めることができる。またシクロシコニン
（）もシコニン（）と同様に薬理活性がある
ことが知られている〔U.Sankawa，et al.，
Chem.Pharm.Bull.，25，2392，（1977）〕。
しかしながら、シクロシコニン（）を、次式
、The conversion of cyclocyconine () to shikonine () is known in cyclocyconine represented by [formula] [Akira Terada, et al. J.Org.Chem., 52 , 1437 (1987);
U.S. Patent No. 4560511 (1985);
Publication No. 36021; J.Chem.Soc., Chem.Commu.,
1983, 987], the synthesis of shikonin can be advantageously carried out in an extremely short process. Cycloshikonin () is also known to have pharmacological activity similar to shikonin () [U. Sankawa, et al.,
Chem.Pharm.Bull., 25 , 2392, (1977)]. However, cyclocyconine () can be expressed by the following formula:
【式】
で表わされるナフタザリンから直接得る方法は下
記反応式(1)で示した一例（小堀ら、日本化学会第
53秋季年会予稿集2023，1986）のみしか知られて
いない。An example of a method for directly obtaining naphthazarin expressed by [Formula] is shown in reaction formula (1) below (Kobori et al., Chemical Society of Japan Vol.
53 Autumn Annual Meeting Proceedings 2023, 1986) is only known.
【化】
しかし、このようなナフタザリンに環状アセタ
ール化合物を反応させる従来公知の方法は、収率
が著しく低いか、あるいは反応原料を加熱還流さ
せる等の工程を必要とするという問題点を有して
いた。
（発明が解決しようとする課題）
そこで、シクロシコニンに代表されるような環
状エーテル構造の側鎖を持つナフタザリン誘導体
を簡単に高収率を以て合成する方法の開発が望ま
れていた。
本発明の目的は、ナフタザリンに環状エーテル
構造の側鎖を直接導入することによる頗る簡潔な
シクロシコニン合成法を提供するにある。別の目
的はシコニン合成の工程数を減少せしめることで
ある。
（課題を解決するための手段）
本発明者らは、上記課題を解決すべく努力した
結果、次の方法により解決することができた。す
なわち、この発明は、前記ナフタザリン（）
に、下記式、[Chemical] However, the conventionally known methods of reacting naphthazarine with a cyclic acetal compound have problems such as extremely low yields or the need for steps such as heating and refluxing the reaction raw materials. Ta. (Problems to be Solved by the Invention) Therefore, it has been desired to develop a method for easily synthesizing naphthazarin derivatives having a side chain with a cyclic ether structure, such as cycloshikonine, with high yield. An object of the present invention is to provide a very simple method for synthesizing cycloshikonine by directly introducing a side chain having a cyclic ether structure into naphthazarin. Another objective is to reduce the number of steps in shikonin synthesis. (Means for Solving the Problems) As a result of efforts by the present inventors to solve the above problems, they were able to solve them by the following method. That is, this invention provides the naphthazarin ()
, the following formula,
【式】
〔ただし、R1，R2は水素原子、炭素数２以下
のアルキル基またはアルケニル基もしくは炭素数
６以下の芳香族の炭化水素基を表す〕
で示される環員数５〜６の環状ビニルエーテルを
酸触媒存在下に室温で反応させることよりなる下
記式、[Formula] [However, R 1 and R 2 represent a hydrogen atom, an alkyl group or alkenyl group having 2 or less carbon atoms, or an aromatic hydrocarbon group having 6 or less carbon atoms] A cyclic ring having 5 to 6 ring members represented by The following formula consists of reacting vinyl ether at room temperature in the presence of an acid catalyst,
【式】
〔ただし、R1，R2は上記と同義である〕
で示されるナフタザリン誘導体の製造法である。
（作用）
以下、本発明をその作用とともに詳述する。
本発明方法に適用される環状ビニルエーテル
（）は、５〜６員環のものであり、例えば、２，
３−ジヒドロフラン、３，４−ジヒドロ−2H−
ピランおよびそれらのメチル、エチルビニル、フ
エニル、２−フリル、フルフリル各置換体などが
挙げられる。
また本発明に適用される酸触媒は、例えば三フ
ツ化ホウ素エーテラート（F3Ｂ・OEt2）、塩化第
二スズ、塩化アルミニウムなどのルイス酸触媒が
好ましく、特に三フツ化ホウ素エーテラートは最
適である。
本発明方法においては、ナフタザリン（）を
酢酸に溶解し、環状ビニルエーテルを加えて攪拌
すると室温で容易に反応が進行し、相当するナフ
タザリン誘導体（）が得られる。ここに得られ
たすべての化合物は、後述の実施例で例証するよ
うに、元素分析、赤外分光分析（IR）、プロトン
核磁気共鳴法（1H NMR）によつて、それぞれ
の化学構造を有することが確実に証明された。
（実施例）
次に実施例によつて本発明の内容を更に詳細に
説明する。
実施例 １
ナフタザリン（）（0.485ｇ，2.55mmol）を
酢酸（100ml）に溶かし、２，２−ジメチル−２，
３−ジヒドロフラン（0.300ｇ，3.06mmol）を加
えて30分間室温で攪拌した。続いて三フツ化ホウ
素エーテラート（0.362ｇ 2.55mmol）を加えて
25℃で18時間攪拌した。反応液を氷水中に注ぎ、
クロロホルムで抽出し、抽出液を飽和食塩で洗
浄、無水硫酸ナトリウムで乾燥後、濃縮した。シ
リカゲルの薄層クロマトグラフイーで精製して
（±）シクロシコニン、すなわち、５，８−ジヒ
ドロキシ−２−（５，５−ジメチル−２−フリル）
−１，４−ナフトキノン（ａ）（0.293ｇ、収率
40％）が得られた。尚、この時、原料のナフタザ
リンが0.123ｇ回収された。この原料回収を考慮
すればａの収率は54％である。融点は79.5〜
82.5℃であり、標品〔lit.，79〜81℃；寺田晁、
他、J.Org.Chem.，52，1437（1987）〕と混融して
も融点降下は見られなかつた。また、すべてのス
ペクトルデータは標品のそれらとよく一致した。
実施例 ２
ナフタザリン（）（1.00ｇ，5.26mmol）を酢
酸（200ml）に溶かし、２，３−ジヒドロフラン
（0.442ｇ，6.31mmol）を加えて30分間室温で攪
拌した。続いて三フツ化ホウ素エーテラート
（1.49ｇ，10.5mmol）を加えて25℃で18時間攪拌
した。実施例１と同様に処理して５，８−ジヒド
ロキシ−２−（２−フリル）−１，４−ナフトキノ
ン（ｂ）（0.744ｇ，54％）が得られた。尚、こ
の時、原料のナフタザリンが0.211ｇ回収された。
この回収を考慮すれば、ｂの収率は69％とな
る。ｂの分析値は次の通りである。
mp134.5〜135.5℃（ヘキサン：ベンゼン＝５：２
で再結晶）；
IR（KBr）1608（Ｃ＝０），1570，1450，1210，
1085cm-1；1
H NMR（CDCl3） δ＝1.70〜2.60（ｍ，4H，
CH2），4.03（ｍ，2H，CH2），5.07（ｍ，1H，
CH），7.14（ｓ，1H，ArH），7.19（ｓ，2H，
ArH），12.49（ｓ，1H，ArOH），12.52（ｓ，1H，
ArOH）；
MS，ｍ／z260（M+，100％）、232（21），217
（36），204（33），189（32）．
元素分析値：Ｃ，64.70；Ｈ，4.79％．
C14H12O5としての計算値：Ｃ，64.61；Ｈ，4.65
％．
実施例 ３
ナフタザリン（）（1.00ｇ，5.26mmol）を酢
酸（200ml）に溶かし、３，４−ジヒドロ−2H−
ピラン（1.33ｇ，15.78mmol）を加えて30分間室
温で攪拌した。続いて三フツ化ホウ素エーテラー
ト（0.747ｇ，5.26mmol）を加えて25℃で18時間
攪拌した。実施例１と同様に処理して５，８−ジ
ヒドロキシ−２−（２−テトラヒドロピラニル）−
１，４−ナフトキノン（ｃ）（49.4mg，34％）
が得られた。尚、この時、原料のナフタザリンが
0.347ｇ回収された。この回収を考慮すれば、
ｃの収率は53％となる。ｃの分析値は次の通り
である。
mp167〜168.5℃（ヘキサン：ベンゼン＝20：１
で再結晶）；
IR（KBr）1612（Ｃ＝０），1565，1455，1210，
1095cm-1；1
H NMR（CDCl3） δ＝1.30〜2.20（ｍ，6H，
CH2），3.90（ｍ，2H，CH2），4.58（ｍ，1H，
CH），7.17（ｓ，3H，ArH），12.49（ｓ，1H，
ArOH），12.57（ｓ，1H，ArOH）；
MS，ｍ／z274（M+，100％），228（40），190
（47），85（40）．
元素分析値：Ｃ，66.07；Ｈ，5.30％．
C15H14O5としての計算値：Ｃ，65.69；Ｈ，5.14
％．
（発明の効果）
本発明によつて±シクロシコニンを一段階で合
成できるのみならず、シコニン合成の工程数を著
しく減少できる。すなわち、初期におけるシコニ
ン合成法（寺田 晁、他、J.Chem.Soc.Chem.
Commu.，1983，987）においては12工程を要し
たが本発明方法を応用することにより４工程に短
縮され、工業的に頗る有利である。[Formula] [However, R 1 and R 2 have the same meanings as above.] This is a method for producing a naphthazarine derivative represented by the following formula. (Function) Hereinafter, the present invention will be explained in detail together with its function. The cyclic vinyl ether ( ) applied to the method of the present invention is a 5- to 6-membered ring, for example, 2,
3-dihydrofuran, 3,4-dihydro-2H-
Examples include pyran and methyl, ethylvinyl, phenyl, 2-furyl, and furfuryl substituted products thereof. Further, the acid catalyst applied to the present invention is preferably a Lewis acid catalyst such as boron trifluoride etherate (F 3 B・OEt 2 ), stannic chloride, or aluminum chloride, and boron trifluoride etherate is particularly suitable. be. In the method of the present invention, naphthazarin (2) is dissolved in acetic acid, cyclic vinyl ether is added and stirred, and the reaction proceeds easily at room temperature to yield the corresponding naphthazarin derivative (2). The chemical structures of all the compounds obtained here were determined by elemental analysis, infrared spectroscopy (IR), and proton nuclear magnetic resonance ( 1 H NMR), as illustrated in the examples below. It has been definitely proven that it has. (Example) Next, the content of the present invention will be explained in more detail with reference to Examples. Example 1 Naphthazarin () (0.485 g, 2.55 mmol) was dissolved in acetic acid (100 ml), and 2,2-dimethyl-2,
3-dihydrofuran (0.300 g, 3.06 mmol) was added and stirred at room temperature for 30 minutes. Next, add boron trifluoride etherate (0.362g 2.55mmol)
Stirred at 25°C for 18 hours. Pour the reaction solution into ice water,
The extract was extracted with chloroform, washed with saturated sodium chloride, dried over anhydrous sodium sulfate, and concentrated. Purified by thin layer chromatography on silica gel to produce (±)cyclocykonine, i.e., 5,8-dihydroxy-2-(5,5-dimethyl-2-furyl).
-1,4-naphthoquinone (a) (0.293g, yield
40%) was obtained. At this time, 0.123g of naphthazarin, a raw material, was recovered. Considering this raw material recovery, the yield of a is 54%. Melting point is 79.5 ~
The temperature was 82.5℃, and the standard product [lit., 79-81℃; Akira Terada,
et al., J.Org.Chem., 52 , 1437 (1987)], no drop in the melting point was observed. Moreover, all spectral data were in good agreement with those of the standard specimen. Example 2 Naphthazarine (1.00 g, 5.26 mmol) was dissolved in acetic acid (200 ml), 2,3-dihydrofuran (0.442 g, 6.31 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. Subsequently, boron trifluoride etherate (1.49 g, 10.5 mmol) was added and stirred at 25°C for 18 hours. The same treatment as in Example 1 gave 5,8-dihydroxy-2-(2-furyl)-1,4-naphthoquinone (b) (0.744 g, 54%). At this time, 0.211g of naphthazarin, a raw material, was recovered.
Taking this recovery into account, the yield of b is 69%. The analytical value of b is as follows. mp134.5-135.5℃ (hexane:benzene = 5:2
IR (KBr) 1608 (C=0), 1570, 1450, 1210,
1085cm -1 ; 1 H NMR (CDCl 3 ) δ=1.70~2.60 (m, 4H,
CH 2 ), 4.03 (m, 2H, CH 2 ), 5.07 (m, 1H,
CH), 7.14 (s, 1H, ArH), 7.19 (s, 2H,
ArH), 12.49 (s, 1H, ArOH), 12.52 (s, 1H,
ArOH); MS, m/z260 (M + , 100%), 232 (21), 217
(36), 204 (33), 189 (32). Elemental analysis values: C, 64.70; H, 4.79%. Calculated value as C 14 H 12 O 5 : C, 64.61; H, 4.65
%. Example 3 Naphthazarin () (1.00 g, 5.26 mmol) was dissolved in acetic acid (200 ml) and 3,4-dihydro-2H-
Pyran (1.33 g, 15.78 mmol) was added and stirred at room temperature for 30 minutes. Subsequently, boron trifluoride etherate (0.747 g, 5.26 mmol) was added and stirred at 25°C for 18 hours. Treated in the same manner as in Example 1 to obtain 5,8-dihydroxy-2-(2-tetrahydropyranyl)-
1,4-naphthoquinone (c) (49.4mg, 34%)
was gotten. In addition, at this time, the raw material naphthazarin
0.347g was recovered. Considering this recovery,
The yield of c is 53%. The analytical value of c is as follows. mp167-168.5℃ (hexane:benzene=20:1
IR (KBr) 1612 (C=0), 1565, 1455, 1210,
1095cm -1 ; 1 H NMR (CDCl 3 ) δ=1.30~2.20 (m, 6H,
CH 2 ), 3.90 (m, 2H, CH 2 ), 4.58 (m, 1H,
CH), 7.17 (s, 3H, ArH), 12.49 (s, 1H,
ArOH), 12.57 (s, 1H, ArOH); MS, m/z274 (M + , 100%), 228 (40), 190
(47), 85(40). Elemental analysis value: C, 66.07; H, 5.30%. Calculated value as C 15 H 14 O 5 : C, 65.69; H, 5.14
%. (Effects of the Invention) According to the present invention, ±cycloshikonine can not only be synthesized in one step, but also the number of steps for shikonin synthesis can be significantly reduced. That is, the initial shikonin synthesis method (Akira Terada, et al., J.Chem.Soc.Chem.
Commu., 1983, 987) required 12 steps, but by applying the method of the present invention, this can be shortened to 4 steps, which is extremely advantageous industrially.
Claims (1)
のアルキル基またはアルケニル基もしくは炭素数
６以下の芳香族の炭化水素基を表す〕 で示される環員数５〜６の環状ビニルエーテルを
酸触媒存在下に室温で反応させることよりなる下
記式、 【式】 〔ただし、R1，R2は上記と同義である〕 で示されるナフタザリン誘導体の製造法。 ２ 前記酸触媒が三フツ化ホウ素エーテラート、
塩化第二スズおよび塩化アルミニウムよりなる群
から選ばれたルイス酸触媒である請求項１記載の
ナフタザリン誘導体の製造法。[Scope of Claims] 1 Naphthazarine represented by the following formula, [Formula], [wherein R 1 and R 2 are hydrogen atoms, alkyl groups or alkenyl groups having 2 or less carbon atoms, or 6 carbon atoms] Represents the following aromatic hydrocarbon group] The following formula is obtained by reacting a cyclic vinyl ether having 5 to 6 ring members represented by the following at room temperature in the presence of an acid catalyst, [Formula] [where R 1 and R 2 are Synonymous with the above] A method for producing a naphthazarin derivative. 2 the acid catalyst is boron trifluoride etherate,
2. The method for producing a naphthazarin derivative according to claim 1, wherein the catalyst is a Lewis acid catalyst selected from the group consisting of stannic chloride and aluminum chloride.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5365889A JPH02233673A (en) | 1989-03-08 | 1989-03-08 | Production of naphthazarin derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5365889A JPH02233673A (en) | 1989-03-08 | 1989-03-08 | Production of naphthazarin derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH02233673A JPH02233673A (en) | 1990-09-17 |
| JPH0579067B2 true JPH0579067B2 (en) | 1993-11-01 |
Family
ID=12948959
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5365889A Granted JPH02233673A (en) | 1989-03-08 | 1989-03-08 | Production of naphthazarin derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH02233673A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61251677A (en) * | 1985-05-01 | 1986-11-08 | Nippon Oil Co Ltd | Production of naphthazarin derivative |
| JPS62106090A (en) * | 1985-10-31 | 1987-05-16 | Nippon Oil Co Ltd | Production of naphthazarin derivative |
-
1989
- 1989-03-08 JP JP5365889A patent/JPH02233673A/en active Granted
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61251677A (en) * | 1985-05-01 | 1986-11-08 | Nippon Oil Co Ltd | Production of naphthazarin derivative |
| JPS62106090A (en) * | 1985-10-31 | 1987-05-16 | Nippon Oil Co Ltd | Production of naphthazarin derivative |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH02233673A (en) | 1990-09-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4465862A (en) | Cyclopentendione and cyclopentenone | |
| Chenard et al. | Annelation reactions of quinone monoketals. Studies directed at an efficient synthesis of anthracyclinones | |
| Jacobi et al. | Bis heteroannulation. 4. Facile syntheses of methylene acids, methylbutenolides,. alpha.-methyl-. gamma.-lactones, and related materials. Total syntheses of (.+-.)-ligularone and (.+-.)-petasalbine | |
| Nasini et al. | Stereochemistry of cercosporin | |
| Marchand et al. | Lewis acid-promoted reactions of substituted pentacyclo [5.4. 0.02, 6.03, 1005, 9] undecane-8, 11-diones with ethyl diazoacetate | |
| JP2001233870A (en) | 3-(1-hydroxypentylidene)-5-nitro-3h-benzofuran-2-one, method for producing the same and use thereof | |
| JPH0579067B2 (en) | ||
| Shyamasundar et al. | Conversion of alkoxy-9, 10-anthraquinones to alkoxyanthracenes | |
| KATO et al. | Studies on Ketene and Its Derivatives. LVII. Reaction of Diketene with β-Diketones | |
| Hori et al. | Stable 2-thianaphthalenes: synthesis and reactions with electrophiles | |
| CN115073485B (en) | 3-aryl-7, 8-pyranocoumarin derivative, and preparation method and application thereof | |
| KR100203233B1 (en) | Process of preparation for astaxanthin | |
| JP2868024B2 (en) | Improved process for producing ketone compounds | |
| JPH047346B2 (en) | ||
| Uchiyama et al. | Synthetic Studies on Dehydrorotenone | |
| CA1121823A (en) | 1-pyrrole-and 1-pyrrolidine-carboxylic acid derivatives and process for preparing the same | |
| Friedman et al. | Stereospecific rearrangement during the piperidine-catalyzed condensation of benzaldehyde and bis (ethylsulfonyl) methane. Abnormal Knoevenagel condensation | |
| KR950005737B1 (en) | Separating method of component from gingkolide complex | |
| NL8900329A (en) | CYCLIC TRIKETONE COMPOUNDS AND TRIMETHYLSILYLOXYBUTADIENE COMPOUNDS AND THEIR USE IN THE PREPARATION OF DAUNOMYCIN DERIVATIVES. | |
| KR950009864B1 (en) | Process for preparing benzopyran derivatives | |
| EP4269389A1 (en) | Preparation method for biliverdin or derivative thereof | |
| Yan et al. | A Convenient Two-Step Synthesis of Coenzyme Q1 | |
| CN113929566A (en) | Preparation method of 5H-dibenzo [ a, d ] cycloheptatriene-5-ketone | |
| JPH03215472A (en) | Novel 4-substituted-3,5-dimethylpicolinic acid compound and its production | |
| JPS62207232A (en) | Production of 2-methylazulene compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313111 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| EXPY | Cancellation because of completion of term |