JPS58434B2 - Evodiaminoseihou - Google Patents
EvodiaminoseihouInfo
- Publication number
- JPS58434B2 JPS58434B2 JP15285775A JP15285775A JPS58434B2 JP S58434 B2 JPS58434 B2 JP S58434B2 JP 15285775 A JP15285775 A JP 15285775A JP 15285775 A JP15285775 A JP 15285775A JP S58434 B2 JPS58434 B2 JP S58434B2
- Authority
- JP
- Japan
- Prior art keywords
- evodiamine
- present
- benzene
- solvent
- indole
- 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
Links
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 10
- HMXRXBIGGYUEAX-SFHVURJKSA-N Evodiamine Natural products CN1[C@H]2N(CCc3[nH]c4ccccc4c23)C(=O)c5ccccc15 HMXRXBIGGYUEAX-SFHVURJKSA-N 0.000 claims description 8
- TXDUTHBFYKGSAH-SFHVURJKSA-N Evodiamine Chemical compound C1=CC=C2N(C)[C@@H]3C(NC=4C5=CC=CC=4)=C5CCN3C(=O)C2=C1 TXDUTHBFYKGSAH-SFHVURJKSA-N 0.000 claims description 8
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 5
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 5
- -1 thionyl halide Chemical class 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- WVMBPWMAQDVZCM-UHFFFAOYSA-N N-methylanthranilic acid Chemical compound CNC1=CC=CC=C1C(O)=O WVMBPWMAQDVZCM-UHFFFAOYSA-N 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- VNHBYKHXBCYPBJ-UHFFFAOYSA-N 5-ethynylimidazo[1,2-a]pyridine Chemical compound C#CC1=CC=CC2=NC=CN12 VNHBYKHXBCYPBJ-UHFFFAOYSA-N 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
【発明の詳細な説明】
本発明は、式
で表わされる化合物、すなわち５．７、８．１３．１３
ｂ 。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to compounds of the formula: 5.7, 8.13.13
b.
１４−へキサヒドロ−１４−メチル−５−オキソインド
ロ（２，３−ｃ）−キナゾリン（３，２−ａ）−ピリジ
ン（以下「エボジアミン」という）の製法に関するもの
である。The present invention relates to a method for producing 14-hexahydro-14-methyl-5-oxoindolo(2,3-c)-quinazoline(3,2-a)-pyridine (hereinafter referred to as "evodiamine").
本発明の目的化合物であるエボジアミンは、呉莱黄の果
実に存在するインドールキナゾリン型アルカロイドで、
従来より利尿剤、発汗剤としての作用のあることが知ら
れ、漢方薬として用いられていた。Evodiamine, which is the target compound of the present invention, is an indolequinazoline type alkaloid present in the fruit of Wu Lai Huang.
It has long been known to act as a diuretic and diaphoretic, and has been used as a Chinese herbal medicine.
また、エボジアミシば薬学雑誌Ａ８巻第３１３〜３１７
頁１９２８年に記載のとおり朝比奈、太田等により天然
物から抽出し構造が決定された。Also, Evodia Mishiba Pharmaceutical Journal A8 Volume 313-317
As described in p. 1928, Asahina, Ota et al. extracted it from a natural product and determined its structure.
その後、エボジアミンの合成法については、ジャーナル
・オブ・オルガニック・ケミストリー ２５巻、１６８
０〜１６８２頁１９６０年（Ｊ 、 Ｏｒｇ、 Ｃｈｅ
ｍ、 ）およびジャーナル・オブ・ザ・アメリカン・ケ
ミカル・ソサイテイー８２巻、５１８７〜５１９３頁１
９６０年（Ｊ、 Ａｍｅｒ、 Ｃｈｅｍ、 Ｓｏｃ、）
等をはじめとし数多く報告されている。After that, the synthesis method of evodiamine was described in Journal of Organic Chemistry, Vol. 25, 168.
0-1682 pages 1960 (J, Org, Che
) and Journal of the American Chemical Society, Vol. 82, pp. 5187-51931.
960 (J, Amer, Chem, Soc,)
There have been numerous reports including.
しかし、いずれの方法も、反応処理操作が繁雑で反応時
間も長く、その上収率も非常に低いなど大きな欠点があ
った。However, both methods have major drawbacks such as complicated reaction treatment operations, long reaction times, and very low yields.
本発明者は、これらの欠点に鑑み種々研究した結果、簡
単な処理操作で高収率にエボジアミンを得ることに成功
し本発明をなすに至った。As a result of various studies in view of these shortcomings, the present inventors succeeded in obtaining evodiamine in high yield through simple processing operations, and came up with the present invention.
すなわち本発明は、２−メチルアミノ安息酸にチオニル
ハライドを反応させ、次いで３，４−ジヒドロピリド（
３，４−ｂ、ｌインドールを反応せしめることを特徴と
するエボジアミンの製法である。That is, in the present invention, 2-methylaminobenzoic acid is reacted with thionyl halide, and then 3,4-dihydropyride (
This is a method for producing evodiamine characterized by reacting 3,4-b,l indole.
本発明を実施するに際しては、２−メチルアミノ安息香
酸とチオニルハライドとベンゼンの混合物を窒素気流中
で約２時間加熱還流したのち、ベンゼンおよび残存する
チオニルハライドを減圧上留去する。In carrying out the present invention, a mixture of 2-methylaminobenzoic acid, thionyl halide and benzene is heated under reflux in a nitrogen stream for about 2 hours, and then benzene and remaining thionyl halide are distilled off under reduced pressure.
得られた残渣に３，４−ジヒドロピリド（３，４−ｂ）
インドールをベンゼンに溶解した溶液を加えると瞬間的
に反応し橙黄色沈殿を生成する。3,4-dihydropyride (3,4-b) was added to the obtained residue.
When a solution of indole dissolved in benzene is added, an instantaneous reaction occurs to form an orange-yellow precipitate.
次いで溶媒を留去後生放物をクロロホルムで抽出し、ク
ロロホルム層を１０％水酸化ナトリウム水で洗浄し、水
洗後乾燥し溶媒を留去する。Next, after distilling off the solvent, the raw product is extracted with chloroform, and the chloroform layer is washed with 10% sodium hydroxide, washed with water, dried, and the solvent is distilled off.
残留物をエタノール、メタノール等の有機溶媒より再結
晶すると目的化合物のエボジアミンを淡黄色結晶として
得る。The residue is recrystallized from an organic solvent such as ethanol or methanol to obtain the target compound, evodiamine, as pale yellow crystals.
本発明の反応は次のとおり進行するものと推定される。The reaction of the present invention is presumed to proceed as follows.
次に実施例を挙げて説明する。Next, an example will be given and explained.
実施例
２−メチルアミノ安息香酸５００〜とチオニルクロライ
ド５ｇおよびドライベンゼン２５ｍ１の混合物を窒素気
流中で２時間加熱還流し、減圧下１８〜２０℃でベンゼ
ンおよび残存するチオニルクロライドを留去する。Example 2 - A mixture of 500~ of methylaminobenzoic acid, 5 g of thionyl chloride and 25 ml of dry benzene is heated under reflux in a nitrogen stream for 2 hours, and benzene and remaining thionyl chloride are distilled off at 18-20°C under reduced pressure.
得られた残渣に３，４−ジヒドロピリド（３，４−ｂ）
インドール４０ｍｇをドライベンゼンに溶解した溶液を
加えると橙黄色沈殿を生成する。3,4-dihydropyride (3,4-b) was added to the obtained residue.
Addition of a solution of 40 mg of indole in dry benzene produces an orange-yellow precipitate.
次いで溶媒を留去後生放物をクロロホルムで抽出し、ク
ロロホルム層を１０％水酸化ナトリウム水で洗浄し、水
洗後備酸ナトリウムで乾燥し溶媒を留去する。After evaporating the solvent, the raw product is extracted with chloroform, and the chloroform layer is washed with 10% sodium hydroxide, washed with water, dried over sodium hydroxide, and the solvent is evaporated.
残留物をメタノールより再結晶すると淡黄色結晶のエボ
ジアミンを４６５ｍｇ得る。The residue was recrystallized from methanol to obtain 465 mg of evodiamine as pale yellow crystals.
融 点 ２６８〜２７００Ｇ
元素分析値 Ｃ１，Ｈｌ、Ｎ５Ｏ−Ｈ２ＯとしてＨＮ
計算値ｃ％） ７１．１４５．４２１３．３５実測値
（％） ７１．０３５．３０１３．０８■ＲＣＨＣＩ
Ｉ３．−１ ：
ａＸ
３４７５（インドールつ、１６４０（Ｃ＝０）２９２．
２８３，２７３，２８１
ＮＭＲδ（ＣＤＣ１３）：
２．４〜２．６（３Ｈ，Ｓｉｎｇｌｅｔ、Ｎ−ＣＨ）２
．７〜３．１ （２Ｈ＋ ｔ ｒ ｉ ｐｌ ｅ ｔ
、＝Ｎ ＣＨ２ＣＨ２）３．２〜３．５ （２Ｈ、ｔｒ
ｉｐｌｅｔ 、 ＝Ｎ−ＣＨ２山）５．９ （ＩＨ＋
ｂｒｏａｄ Ｓｉｎｇｌｅｔ 、＝ Ｃ−Ｈ）７．３−
７．８ （８Ｈ２ｍｕｌ ｔ １ｐｌｅｔ 、 ８ ｘ
ＡｒＨ）８．２ （ＩＨ、ｂｒｏａｄ Ｓｉｎｇｌｅｔ
、インドールＮＨ）Ｍａｓｓ ｍ／ｅ ：Melting point 268-2700G Elemental analysis value C1, Hl, HN as N5O-H2O Calculated value c%) 71.145.4213.35 Actual value (%) 71.035.3013.08 ■ RCHCI
I3. -1: aX 3475 (indole, 1640 (C=0) 292.
283,273,281 NMRδ (CDC13): 2.4-2.6 (3H, Singlet, N-CH)2
．． 7 to 3.1 (2H+ t r i p e t
, =N CH2CH2)3.2~3.5 (2H, tr
iplet, =N-CH2 mountain) 5.9 (IH+
broad Singlet, = C-H)7.3-
7.8 (8H2mul t 1plet, 8 x
ArH) 8.2 (IH, broad Singlet
, Indore NH) Mass m/e:
Claims (1)
させ、次いで得られたものと３，４−ジヒドロピリド（
３，４−ｂ）インドールを反応せしめることを特徴とす
るエボジアミンの製法。12-Methylaminobenzoic acid was reacted with thionyl halide, and the resulting product was reacted with 3,4-dihydropyride (
3,4-b) A method for producing evodiamine, which comprises reacting indole.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15285775A JPS58434B2 (en) | 1975-12-23 | 1975-12-23 | Evodiaminoseihou |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15285775A JPS58434B2 (en) | 1975-12-23 | 1975-12-23 | Evodiaminoseihou |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5277098A JPS5277098A (en) | 1977-06-29 |
| JPS58434B2 true JPS58434B2 (en) | 1983-01-06 |
Family
ID=15549630
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP15285775A Expired JPS58434B2 (en) | 1975-12-23 | 1975-12-23 | Evodiaminoseihou |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS58434B2 (en) |
-
1975
- 1975-12-23 JP JP15285775A patent/JPS58434B2/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5277098A (en) | 1977-06-29 |
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