JPH0216317B2 - - Google Patents

Description

[Detailed description of the invention]

(A) Summary and background of the invention The present invention is based on the general formula [In the formula, R is the formula, It is a residue of 3', 5', 7', 4''-tetrahydroxyflavan represented by the formula, and its 6' or 8' carbon atom is bonded to the 4-position carbon atom of the above formula compound, and its It is assumed that the 7'-position hydroxyl group has an ether bond with the 2-position carbon atom of the compound of the above formula.] Ephedra is a herbal medicine that has been used for the longest time in China. 1887 The discovery and isolation of l-ephedrin and other alkaloids by Dr. Nagai from the stem of this ephedra tree in 2007 is a monumental milestone in the history of Japanese pharmaceutical science, but there are no reports of note regarding the components of the root. However, the present inventor focused on the fact that the root part of Ephedra (Ephedra root) has an action that is contradictory to that of the stem part, and its aqueous exudate has been used as an antiperspirant.As a result of research, the present inventor developed this product. As a result of discovering the fact that the methanol extract of H.
This was named Ephedranin A. Incidentally, flavonoids are almost all components unique to the plant kingdom, and are distributed in all plants except bacteria, fungi, and algae, but what is most interesting are the compounds that gradually become more complex from this class of compounds. The most complex compounds are found in the most advanced Asteraceae and Leguminosae plants, providing strong evidence to support the phylogenetic theory of biological evolution. By the way, more than 600 types of flavonoid compounds have been discovered to date, but in the gymnosperm phylum to which the genus Ephedra belongs, biflavonyl compounds, represented by the cycadoflavones of the following formula, predominate. Therefore, in the compound (), one of the constituent units is 3,6-dihydroxy-4'-hydroxyflavan, and an ether bond is formed between the 2nd carbon of the flavan unit and the 7th hydroxyl group of the flavonol unit. It has a distinctive structure. However, the flavonoids newly discovered by the present inventors in Ephedra root extract ()
is different from the above compound (), and has the following formula ()'
This biflavanil derivative has a structure in which two molecules of 3,5,7,4'-tetrahydroxyflavan are bonded as shown in the following, and has not been described in any literature. This unit compound ()' is a unique compound in which the 4th-position carbon atom on one side is bonded to the 6th-position or 8th-position carbon atom on the other side, and the 2nd-position carbon atom on one side is bonded to the oxygen atom of the 7th-position hydroxyl group on the other side. Forms an endo-type or exo-type cyclic ether bond. The present inventor isolated cyclic etherified biflavonyl compounds belonging to at least three types of compounds () shown in the following formulas (a to c) from a methanol extract of ephedra root, and determined their chemical structures, Mahuannin A (a) and Mahuannin B, respectively.
(b) and Marhuannin C (c). (B) Production of Marhuannins The above-mentioned Marhuannins are present in the roots of plants belonging to the phylum Pinus phylum and the genus Ephedra. Since these marhuannins are easily soluble in lower alcohols, particularly methanol, methanol is preferably used as the extraction solvent. For extraction, any method commonly used for extracting plant medicinal components can be used (for example, Kazutaka Yamaguchi, "Plant component analysis method (volume 1)", Nankodo, Tokyo,
(Refer to the 1950 publication). As an example of an extraction method, for example, the root part of a plant of the genus Mao is cool-soaked in an extraction solvent for a period of about 10 hours or more and up to 3 weeks. The time required for extraction can be shortened by digestion or heat soaking (40-120°C, 1-2 hours), but cold soaking is generally more preferred as it can prevent decomposition of the components. The extract is concentrated to obtain an extract if necessary. Since the marhuannins that are the subject of the present invention are contained in acidic fractions having phenolic hydroxyl groups, the extract or its concentrate is preferably made hydrochloric acidic, and the resulting insoluble matter is treated with a polar solvent immiscible with water. For example, it is dissolved in n-butanol, and this solution is preferably dissolved in an aqueous sodium bicarbonate solution (PH
9.0) to remove neutral components and collect the remaining organic solvent layer. This organic solvent layer is an acidic fraction containing the target compound (). The above acidic fraction is then subjected to conventional means used for the purification and isolation of plant components, such as adsorption chromatography, column chromatography or gel perchromatography, to separate the desired compound. Examples of the adsorbent used here include silica gel, alumina, magnesia, starch, dextrin, and various other adsorbents.
For example, TOYOPEARL is a specific product.
HW-40Fine (trade name of Toyo Soda Kogyo Co., Ltd. product) is preferred. Examples of elution solvents include water, methanol, ethanol, ethyl acetate,
Examples include acetonitrile, chloroform, and benzene, but ethyl acetate is most preferred in order to fractionate compound () in its crude form.
That is, when the silica gel column loaded with the above acidic fraction is eluted with ethyl acetate, the compound ()
is first eluted in an impure state. Therefore, this elution fraction was reloaded onto the column packed with TOYOPEARL HW40Fine and eluted with ethanol.The eluate was further subjected to column chromatography using silica gel, developed with chloroform, and then methanol was added to the elution solvent. increase the polarity of In this way, the fraction eluted with 10-15% methanol and chloroform was added to LS410.
When subjected to high-speed liquid chromatography using an OKDS column and eluted with a mixture of acetonitrile and water = 30:70, the elution pattern shown in attached Figure 1 was obtained, and Fr. Marhuannin C (c) is obtained from Fr.D- in its pure state. Furthermore, when Fr.D- is subjected to high-speed liquid chromatography using the same column and eluted with a mixture of methanol and water = 45:55, Marhuannin (a) is obtained in a pure state. (C) Production example of marhuannins For convenience, this is shown in a flowchart form.

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Claims (1)

[Claims] 1. General formula [In the formula, R is the formula is a residue of 3', 5', 7', 4''-tetrahydroxyflavan represented by the formula, and the carbon atom at the 6' or 8' position is bonded to the carbon atom at the 4 position of the compound of the above formula, and the 7 It is assumed that the hydroxyl group at position ′ has an ether bond with the carbon atom at position 2 of the compound of the above formula.] Novel flavonoids represented by the formula 2. The compound according to claim 1, which is represented by
Ma Huan Ning A. 3 formulas The compound according to claim 1, which is represented by
Ma Huan Ning B. 4 formula The compound according to claim 1, which is represented by
Mahuan Ning C.