JPH01207262A - Novel pentacyclic triterpenic compound - Google Patents

Abstract

NEW MATERIAL:A compound expressed by formula I (R2 is methyl when R1 is H and H when R1 is methyl; R3 is H or group expressed by formula II) or salts thereof. USE:A medicine having anti-acquired immune deficiency syndrome (AIDS) viral action. PREPARATION:A suitable part, e.g., seed, of a plant, belonging to the genus Patrinia and containing the compound expressed by formula I, preferably Patrinia scabiosaefolia Link is extracted with a hydrophilic organic solvent, such as methanol or ethanol, or hydrous solvent while suitably being warmed and the resultant extract solution is then subjected to separating means, such as concentration, fractionation (addition of a nonsolvent) or chromatographic treatment, to afford the aimed compound expressed by formula I.

Description

[Detailed Description of the Invention] [Industrial Application Field] This invention relates to a novel pentafunctional triterpene compound.

[Prior Art] Pentacyclic triterpenes are extremely widely distributed in the plant kingdom and exist in free form or in the form of saponins bound to sugars. Since many saponins exhibit various physiological activities, there is always interest in new saponins extracted from plants as active ingredients in medicines or as model substances for developing compounds with novel pharmacological activities. is leaning.

[Description of the Invention] As a result of repeated research on saponins contained in various plants, the inventor discovered that the genus Ominae of the family Ominaeaceae (P a
The present invention was based on the discovery that plants belonging to the genus Trinia contain novel pentacyclic triterpene saponins, that the saponins exhibit pharmacological activity, and that novel pentacyclic triterpene compounds can be obtained as aglycones from the saponins. It is completed.

[Summary of the Invention] This invention relates to a hydrogen atom having a formula [wherein R1 is hydrogen and R2 is methyl, or
1 is methyl, R7 is hydrogen, and R3 means hydrogen or a group represented by the following formula] or salts thereof.

[Detailed Description] At the position on the structural formula of the compound represented by the above formula (D),
They are numbered as follows.

The above formula (1) includes the following four types of compounds.

(a) Rl = HlRt = CH3, R3 = Sulfapatrinosi
de) ■ (b) RI=CH3, Rt ”I-1, R,=A Sulfapatrinosid
e) (C) R+=H1R1=CHa, R3=H23-hydroxyursolic acid/23-sulfate ester (d) RI=CH3, R2= I-1, R3=H hederagenin/23-sulfate ester As salts of the above compounds salts with alkali metals (e.g. sodium, potassium, etc.), salts with alkaline earth metals (e.g. calcium, magnesium, etc.), salts with inorganic bases such as ammonium salts, and trimedelamine salts, triethylamine. salts with organic bases, such as nclohexylamine salts, ethanolamine salts, jetanolamine salts, tromethamine salts, salts with amino acids (eg, lysine, arginine, etc.). Preferred are non-toxic salts, ie pharmaceutically acceptable salts, as exemplified above.

The above compound is produced as follows.

Compounds (a) and (b) are extracted directly from plants. That is, the above-mentioned compound-containing plants belonging to the genus P. atrinias, preferably P. atrinia scab.
iosaefolia Fischer) is extracted with a solvent capable of dissolving the above-mentioned compound, such as a hydrophilic organic solvent (such as a low-grade alcohol such as methanol or ethanol) or a water-containing solvent, with appropriate heating, By subjecting the extract to separation means such as concentration, fractionation (e.g. addition of a non-solvent), chromatography, etc., a substantially pure product of (a) or (b) or a product of (a) and (b) can be obtained. Obtained as a mixture.

Compounds (c) and (d) are compound (a) or (b)
) with a suitable enzyme, such as a protease, preferably in an acidic medium.

The reaction product is separated and collected according to a conventional method for separating acidic triterpenes.

Above 1g2 & salts of the compound, the compound is treated with a base or with an acidic ion exchange resin in the form of a salt with a base,
Alternatively, it can be obtained by treating the salt of the compound with another base.

The above compound exhibits anti-AIDS virus (I-rtv) activity and is useful as a pharmaceutical raw material.

[Examples] Hereinafter, the present invention will be explained in detail with reference to Examples. Example 1 (Production of compounds (a) and (b)) Patrinia 5cabiosaef
olia Fischer) seeds (+789) were crushed and cold soaked in methanol (600 io, ) for 2 weeks. Repeat the cold steeping two more times to obtain 18 liters of extract.
This was layered to obtain extract (21,79).

The above extract (21,79) was washed with ether (200uQ), and the ether-insoluble portion was further removed with ethyl acetate (300μQ).
12) and the glycoside mixture (11,
259) was obtained.

The glycoside mixture (8 g) was transferred to a silica gel column (Merck,
230-400 Metsunyu, aooy) using Itamae Saji, chloroform; methanol; water (65:35:10)
The lower layer of was sequentially eluted using the elution solvent.

The eluate was fractionated into 12 g fractions, and from fraction 10 a mixture of compounds (a) and (b) (1°57
Li) was obtained. A part of the mixture (0,5y) was subjected to high performance liquid chromatography [column, μm Bondapak CI8,
Waters, semi-preparative, elution solvent = methanol:water (1:l), R1 detection] (see Figure 1)
, compound (a) (144 mg), compound (b) (+55
xg) and a mixture of both (IOIQ) were obtained.

The properties of each compound obtained are as follows.

"C-NMR (100MHz, δc, ds-pyridine)
Position Compound (a) Compound (b)+
38.84 38.862
26.98 26.983 7
+, 62 71.584 42.50
42.895 47.70
48.006 18°38 18.42
7 33.16 32.598
40, +2 39.909 4
7.92 47.90+0 36.8
5 37.271+ 23.63
23.4112 125.89 1
22.7313 138.61 144.
4014 42.87 42.121
5 28.68 28.1816
24.63 23.72+7
48.48 47.06+8 53
．． 29 41.6619 39.32
46.2 +20 39.10
30.742+ 30.82
33.9822 37, +6 32.
7523 70.12 70.262
4 12.95 12.97
25 16.44 16.26
26 17.32 17.5
827 23.68 26.1
228 176.46 176.6
829 17.76 33.0
730 21.21 23.
721°-C95,7295,76 2'-073,7973,85 3'-C78,3678,35 4'-C71,2071,07 5'-077,8977,94 6'-069,7069,53 1" -0105,25105,21 2″-G 75.20 75.16
3”-〇 78.71 78.73
4”-071,6271,71 5”-〇 78.46 78.44
Example 2 (Production of compound (c) by enzymatic decomposition) Compound (aX4
0 mg) in citrate buffer (pH = 4°0),
Protease (type Xll+, obtained from Aspergillus 5aitoi) (500 mg) is added and incubated at 37°C for 48 hours. The reaction solution was poured into water and extracted with n-butanol. The extract was concentrated and purified to obtain 23-hydroxyursolic acid/23-sulfuric acid ester (amorphous powder, zav
g) was obtained.

[ff1D+49.0° (c=0.14, MeOII)
Example 3 (Production of compound (d) by enzymatic decomposition) Compound (bX4
Hederagenin 23-sulfate ester (amorphous powder, I: 31 g) was obtained in the same manner as in Example 2 using 0m9).

[ff1D+49 Reference Example 1 (Acid hydrolysis of compound (a)) Compound (aX301119) was dissolved in 10% sulfuric acid:ethanol (1:2015 mg), and after heating under reflux for 5 hours, the reaction solution was poured into ice water and diluted with ethyl acetate. Extracted. The ethyl acetate layer was concentrated and the residue was recrystallized from methanol to give 23
-Hydroxyursolic acid (8m9) was obtained. In addition, the aqueous layer was neutralized with an ion exchange resin, and the concentrated residue was converted into PPC (developing solvent - ituburobanol: n-butanol: water = 7 liters).
:2, color developed with aniline hydrogen phthalic acid) and GLC (
Identified as TMS sweetened sugar, column: 1.5% 5E-52/
Chromosolve W, 3 xiX 2 m, column temperature 1
Glucose was confirmed at 80°C).

Reference Example 2 (Acid hydrolysis of compound (b)) The same procedure as in Reference Example 1 was carried out using the compound (bX30 mg), and hederagenin (8JII9) and glucose were confirmed.

[Brief explanation of the drawing]

FIG. 1 is a graph showing the high performance liquid chromatography results of fraction 10 obtained in Example 1.

Claims (1)

[Claims] (1) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [In the formula, R_1 is hydrogen and R_2 is methyl, or R_1 is methyl, R_2 is hydrogen, and R_3 is hydrogen or shown in the following formula. A compound or its salts represented by the group ▲Mathematical formula, chemical formula, table, etc.▼(A) means.