JPH01290694A - Lignane compound - Google Patents

Abstract

NEW MATERIAL: A compd. represented by the formula.

USE: An antiphlogistic.

PROCESS: For instance, the whole of a plant: chaenomeles japonica is extraction- treated with 70% ethanol; the extrat is concentrated, washed with ethyl acetate, and extraction-treated with n-butanol; the resultant extract is concentrated to give a crude extract, which is dissolved in water and extraction-treated with n-butanol. Thus obtd. extract is concentrated and subjected to silica gel column chromatography to be eluated with a chloroform-methanol-water mixture, and the elusion fraction is concentrated. The concentrate is subjected to medium- to low-pressure liq. chromatography and then eluted with acetonitrile-water. The elution fraction is concentrated, dried to a solid, and subjected to high-performance liq. chromatography. The resultant fraction is concentrated and subjected to high-performance chromatography.

COPYRIGHT: (C)1989,JPO

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a novel lignan compound, and more particularly to a novel lignan compound that has an anti-inflammatory effect and is useful as a pharmaceutical.

[Prior art] Conventionally, wild melon [herbal medicine name: 5 taunton]
iBchinensis DC, ) is mainly distributed in China's Tenmian, Xinzhu, Fujian, Hunan, Tozun, and Guangmian regions, and its roots or root bark have been used as an analgesic [Dictionary of Chinese Medicine, Vol. 1]
Vol., p. 331 (1985) Ko.

However, no compounds that exhibit anti-inflammatory effects have been reported.

[Problems to be Solved by the Invention] An object of the present invention is to provide a novel danane compound having anti-inflammatory effects.

[Means for Solving the Problems] The present inventors have discovered that wild melon [Lardizabaceae]
-1aceae) 5tauntonia chin
As a result of intensive research on extracts of the main stem, branches, leaves, and whole plant of the wild melon extract, we found that this wild melon extract contains novel lignans and that these lignans have anti-inflammatory properties. They discovered that there is, and completed the present invention.

The lignan compound provided by the present invention has the following formula I: This is a lignan compound represented by

The compound represented by formula I is isolated by fractionating and purifying an extract obtained by concentrating an extract obtained from wild melon as a raw material.

The extract can be prepared, for example, by immersing water, methanol, ethanol, acetone, ethyl acetate, etc. alone or in a mixture of two or more at room temperature or under heating (not limited to the above solvents, but also other solvents). (6) For extracts containing the compound represented by formula I, for example, n-butanol, ethyl acetate, chloroform, ether, benzene, n-hexane, etc. Fractionation by partitioning between an organic solvent and water, chromatography methods such as silica gel column chromatography, adsorption resin column chromatography, chromatography applying molecular sieves, medium-low pressure liquid chromatography, and high-performance liquid chromatography may be used as appropriate. By combining them, they are fractionated and purified. The elution solvent used here is, for example, ether, petroleum ether, n-hexane, chloroform, benzene, toluene, ethyl acetate,
Acetone, acetonitrile, ethanol, methanol,
The solvent is water, acetic acid, formic acid, phosphoric acid, etc. alone or in combination.

[Effects of the Invention] The compound represented by formula I of the present invention has an anti-inflammatory effect and is useful as a pharmaceutical.

[Example] Next, the present invention will be explained in more detail with reference to Examples and Test Examples.

(Example) (1) 18 kg of dried wild melon whole plant was extracted with 40 volumes of 70% ethanol three times under rapid flow. Combine the extracts to 102
This was washed 5 times with 10 portions of ethyl acetate.

Next, it was extracted five times with n-butanol 102, and the n-butanol layers were combined and concentrated to obtain 266 g of crude extract.

Dissolve this in 2.5 parts of water and add 2.5 parts of ethyl acetate to 2.5 parts of water.
After washing twice, it was extracted four times with n-butanol 21. n
-The butanol layers were combined and concentrated to obtain 70 g of n-butanol extract.

(2) 27.5 g of this n-butanol extract was subjected to silica gel column chromatography (Kieselgel 60, manufactured by Merck & Co., Ltd. 800 mg), and a mixed solvent of chloroform-methanol-water (10:1:0.1) was added to 4.5 g of the n-butanol extract. chloroform-methanol-water (s: 1:0.
Mixed solution of 1) 154,5 It and mixed solvent of chloroform-methanol-water (6:1:0.1)3.
After eluting with 751, both fractions eluted with chloroform-methanol-water (4:1:0.1> mixed solvent 3.751) were collected and concentrated to obtain 3.2 g of concentrate.

(3) 400 mg of the concentrate obtained in (2) was subjected to medium-low pressure liquid chromatography [ODS CPO-223C-
20 (22X 300m5+), manufactured by Kusano Scientific Co., Ltd.] and eluted with 560 d of 15% acetonitrile water.
1~263m4! Both fractions were obtained which eluted in between. Repeat the same operation 4 times, combine the obtained two parts and concentrate to dryness.
20 mg of brown powder was obtained. This was subjected to high-performance liquid chromatography [column: Aquasi manufactured by Senshu Kagaku Co., Ltd.].
155-55-352N (10x250), W3
Medium: Chloroform-methanol-water〈4゜5:1
: 0.1) mixed solvent, flow rate: 5. Om4! /min, temperature: 50'' C2 detection: absorbance K (235 nm)], and fractions with a retention time of 13.5 to 17.5 minutes were collected and concentrated to dryness to give 5.3 mg of pale yellow powder. I got it.

Furthermore, this was subjected to high performance liquid chromatography [column: Asahipak 0DP-90 (21,5
x300mm).

Solvent = 14% acetonitrile water, flow rate: 5. m/min,
Temperature: 50°C2 Detection: Fractionation using absorbance (215 nm), collection of fractions with a retention time of 19.0 to 24.0 minutes, and concentration to dryness to yield 1.1 mg of formula I. The compound was obtained.

(Physical properties) CNMR (CDiOD, 100MHz) See Table 1 below Table 1 Molecular weight: SIMS m/z 529 (M+
N a )”Molecular formula: C□Hs *OII Specific rotation=[α]”--30,75° (C=0.101
, C) 180) 1) (Test example) Anti-inflammatory effect s B age ICR mice (Charles River) were
A group of 10 animals were used. The aqueous solution of the sample was administered through the tail vein, and 1 hour later, 1% λ-Lagenycin (Pycnin, trade name, Cor physiological saline 5-, manufactured by Zushi Kagaku Co., Ltd.) was injected subcutaneously into the left hind leg to reduce edema. caused. Three hours after the injection on the inflamed side, the thickness of foot edema was measured with a caliper, the edema rate was calculated from the value before the injection on the inflamed side, and the suppression rate was determined by comparing with the edema rate of the control group.

The anti-inflammatory action of the compound represented by formula (■) is shown in Table 2 below.

Claims (1)

[Claims] (1) Formula ▲Contains mathematical formulas, chemical formulas, tables, etc.▼ A lignan compound represented by