JPH07267940A - New 11-membered ring compound - Google Patents

Abstract

PURPOSE:To provide a new 11-membered ring compound expressed by a specific structural formula and useful as a carcinostatic agent, etc. CONSTITUTION:This 11-membered ring compound is expressed by structural formula I. The compound can be produced e.g. by extracting the dried leaf and stalk of Mikania hirsutissima (a plant of the family Compositae) with ethanol, etc., concentrating the extract under reduced pressure and purifying the concentrate by column chromatography, etc.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a novel substance, and more particularly to a novel 11-membered ring compound.

[0002]

2. Description of the Related Art In various industrial fields, in particular, in the field of medicine, the development of new drugs effective against various diseases is expected.

[0003]

Under the background of the prior art described in the preceding paragraph, it is an object of the present invention to provide a novel compound expected to be used as a carcinostatic agent of the present invention.

[0004]

Means for Solving the Problems The present inventor
ompostae) plant Mikania hirsu
It was found that some of the components extracted from dried leaves and stems of tissima have cytotoxicity, and thus, strong growth inhibitory activity, and this component was identified to complete the present invention.

That is, the present invention relates to a novel 11-membered ring compound having the following structural formula (I).

[0006]

[Chemical 2]

The growth inhibitory activity, isolation and identification of the compound of the present invention will be described below.

Mikania hirsutissim
861.9 g of dried leaves and stems of a were powdered with a mixer, extracted with 2 L of ethanol three times while applying ultrasonic waves, and the extracts obtained were combined and concentrated under reduced pressure to give 39.8 g.
The ethanol extract of When this extract was tested for growth inhibitory activity against mouse leukemia cells (L-1210), considerably strong growth inhibition was observed.

That is, the obtained crude extract is "Dia
ion HP-20 "column chromatography, 40% hydrous methanol (2 L), 70% hydrous methanol (2 L), methanol (3 L) and acetone (2 L).
L) was made to flow out sequentially. Then, each 4 fractions were concentrated and subjected to a cell test. As a result, the strongest inhibitory activity was observed in the methanol fraction (referred to as C fraction).

Therefore, this methanol fraction was separated and purified by silica gel column chromatography ("Wacogel C-200" normal phase). As the mobile phase, a hexane-ethyl acetate mixed solvent was used, and hexane: ethyl acetate = 15: 1 (1 L) to hexane: ethyl acetate = 13: 1 (1 L), 10: 1 (1
L), 7: 1 (1 L), 5: 1 (2 L), 3: 1 (2
L), 2: 1 (3L), 1: 1 (2L),
Further, after elution with ethyl acetate (1 L) and methanol (1 L) to divide into about 50 fractions, each fraction was analyzed by thin layer chromatography. Fractions considered to have the same component were collected and a total of 13 fractions were collected. And Each fraction is sequentially MH (C-1), MH (C-2), ...
... and MH (C-13).

Each fraction was tested for cytotoxicity by the method described later. The results are shown in Table 1 below.

[0012]

[Table 1]

Next, MH showing a strong growth inhibitory activity.
The (C-7) fraction was subjected to high performance liquid chromatography (HPL).
C: Silica gel 20φ × 250 mm, flow rate 8.0 ml /
min, hexane: ethyl acetate = 5: 1) for further separation and purification, and using a refractometer (RI detector), 8 fractions corresponding to 8 peaks were obtained. Each fraction is sequentially C7-1,
... and C7-8.

Then, the C7-8 fraction was further subjected to HPLC.
(Silica gel 10φ × 250 mm, flow rate 3.0 ml / m
in, hexane: ethyl acetate = 3: 1), and separated and purified to obtain 5 fractions corresponding to 5 peaks using the same refractometer, and the last fraction was subjected to HPLC under the same conditions. Purification yielded a purified product with a retention time of 17 min. This is MH-6
I will call it.

The details of the cytotoxicity test are as follows.

"RPMI" containing 12% fetal bovine serum and L-glutamine 0.3 g / L manufactured by Nissui Pharmaceutical Co., Ltd.
1640 ”medium (however, kanamycin 100 mg / L
And containing 10% NaHCO ₃ ), mouse leukemia cells (L-1210) were cultured to obtain a cell number of about 10 × 10 ^5.
At the time of reaching cells / ml, the cells were diluted 10-fold with the above medium (10 × 10 ⁴ cells / ml) and dispensed in 2 ml aliquots.

Next, MH- of each concentration shown in Table 2 below.
10 μl of methanol solution of 6 and the same amount of methanol as a control were added, and CO ₂ incubator (CO ₂ 5%, 3
After culturing at 7 ° C) and staining with trypan blue after about 3 days, the number of viable cells was counted.

[0018]

[Table 2]

The inhibition rate is calculated as follows.

[0020]

[Equation 1]

The identification data of MH-6 are as follows.

Mp is 136 to 139 ° C., [α] _D ¹⁴ =-
5.0 ° (MeOH, C = 0.8), HR-MS (high resolution mass spectrum): 222.1661 (M ⁺ ),
The molecular formula was identified as C ₁₄ H ₁₂ O _2, and it can be seen from the NMR chemical shift data shown in Table 3 below that the compound has the above structural formula.

[0023]

[Table 3]

[0024]

INDUSTRIAL APPLICABILITY According to the present invention, a novel substance which can be greatly expected as an anticancer agent has been provided.

Claims (1)

[Claims] 1. A novel 11-membered ring compound having the following structural formula (I): [Chemical 1]