JP4359683B2 - Parviflorene H and Parbiflorene I - Google Patents

Description

  The present invention relates to novel compounds parviflorene H and parbiflorene I.

  Even now, in the 21st century, more than 60% of the world's population uses everyday natural plants and fungi (such as mushrooms) or herbal medicines to treat ordinary diseases and injuries. It is said that On the other hand, some of the medicines currently used in hospitals and homes were originally discovered as chemical components contained in the body of natural animals, plants and microorganisms (hereinafter referred to as “natural products”). ) Is a lot. In addition, many synthetic compounds that are more effective and safer than the original natural products have been developed by improving the chemical structure using natural chemical components as the original form. This search for new and useful natural products can be regarded as a very important starting point for creating drugs.

  However, it is said that less than 10% of all biological species on the earth have been studied as materials for searching for active ingredients so far.

  This invention makes it a subject to provide the novel chemical component contained in natural animals and plants, microorganisms, etc. in view of the situation mentioned above.

  The present inventor, while fully respecting the position of coexistence and conservation between humans and the global environment, focused on the development of unused resources and exploration of active ingredients, and researched the ingredients of the Ginger family plant Curcuma parviflora collected in the field And a new compound was found.

The first aspect of the present invention resides in parbiflorene H characterized by the following (1).

In addition, a second aspect of the present invention is Parbiflorene I, which is represented by the following formula (2).

  The present invention can provide parbiflorene H and parbiflorene I, which are novel compounds derived from the ginger family Curcuma parviflora. This novel compound can be expected to have useful biological activity, and is expected to become a highly useful pharmaceutical product.

  Hereinafter, embodiments of the present invention will be described in detail.

  As for the compound concerning this embodiment, the new compound of the present invention is parbiflorene H (parviflorene H) represented by the above-mentioned formula (1), and parbiflorene I (parviflorene I) represented by the above-mentioned formula (2). This parbiflorene H and parbiflorene I can be produced by isolation from ginger family plants. For example, it can be obtained by extracting components from ginger plant collected in the field using methanol and acetone as solvents and fractionating, and the method is not limited. Moreover, you may synthesize | combine.

  Moreover, parbiflorene H and parbiflorene I according to the present embodiment can be used as cytotoxic substances. Parbiflorene H and Parbiflorene I according to the present embodiment have cytotoxicity against human cervical cancer HeLa cells, and have a novel chemical structure that has never been seen before, so that they are useful as novel cytotoxic substances (therapeutic agents). Sex is expected.

  EXAMPLES Hereinafter, although this invention is demonstrated based on an Example, this invention is not limited to these Examples at all.

(Example)
(1) Isolation of Parbiflorene H and Parbiflorene I An underground part (280 g in total) of Ginger family plant Cucuma parviflora was collected twice with 800 mL of methanol and acetone 500
Extraction was performed once with mL, and the extracts were combined and evaporated to obtain 12.6 g of an extract. This extract was subjected to solvent fractionation using water (200 ml) and ethyl acetate (400 ml twice and 200 ml once) to obtain 8.1 g of an ethyl acetate soluble fraction. The fraction corresponding to this ethyl acetate soluble fraction (2.8
g) was obtained from the same plant whole plant (170 g) collected separately by the same operation.

These fractions were combined and subjected to silica gel column chromatography (column A; φ45 × 570).
mm) and eluted with a mixed solvent of hexane and ethyl acetate. First, a second silica gel column chromatography (φ50 × 400) was performed on a fraction (2.57 g) eluted with a solvent of hexane: ethyl acetate (9: 1).
mm) and eluted with a mixed solvent of hexane and ethyl acetate. A fraction (1.68 g) eluted with a solvent of hexane: ethyl acetate (100: 1) of this column was purified by Sephadex LH20 (φ15 × 550)
mm; eluent, MeOH). As a result, parbiflorene H (5.0 mg) was obtained in a fraction of 105 ml to 120 ml. This scheme is shown in FIG.

Next, a second silica gel column chromatography (φ25 × 200) was performed on the fraction (0.29 g) of the first silica gel column (column A) eluted with a solvent of hexane: ethyl acetate (1: 1 to 0: 1).
mm) and eluted with a mixed solvent of hexane and ethyl acetate. A fraction (71 mg) eluted with a hexane: ethyl acetate (2: 1 to 4: 3) solvent of this column was purified by Sephadex LH20 (φ15 × 500
mm; eluent, MeOH). As a result, parbiflorene I (8.6 mg) was obtained in fractions of 535 ml to 555 ml. (See the scheme in Figure 1)

(2) Structure The physicochemical properties of the obtained parbiflorene H and parbiflorene I were examined. Specifically, measurement was performed for EIMS, HRFABMS, [α], UV, IR, and CD, respectively.

(2-1) Structure of parbiflorene H Since a peak of m / z 426.2523 estimated to be [M ⁺ ] by high performance FABMS was observed, molecular formula C ₃₀ H ₃₄ O ₂
It was estimated that

The UV spectrum and IR spectrum were also measured. The UV spectrum showed values of ε64000 at a wavelength of 242.0 nm and ε10000 at a wavelength of 303.0 nm (see FIG. 2), and 3500, 2960, 2930 in the IR spectrum. , 2870, 1650, 1430
Absorption peaks were observed at cm ⁻¹ , respectively. These values are shown in Table 1.

Measurements were also performed by ¹ H NMR and ¹³ C NMR. The spectrum of ¹ H NMR is shown in FIG. 3, and the data of ¹ H NMR and ¹³ C NMR are shown in Table 2. ^{In 13} C NMR, only 15 signals, which is exactly half the number of carbon atoms (30) included in the estimated molecular formula, were observed, so this compound was estimated to have a symmetric dimeric structure. The ¹ H
In NMR, four signals derived from methyl groups, three signals of hydrogen on the aromatic ring, and one signal derived from OH were observed. In addition, ¹ H- ¹ H
Analysis of COSY, HMQC, and HMBC spectra revealed that this compound is a dimeric compound in which the 2-positions of two aromatic-cyclized cadynenan sesquiterpenes are bonded to each other. In FIG. 4, ¹ H- ¹ H
The correlation data obtained by COSY, HMQC, and HMBC spectra are shown.

Further, when CD and [α] _{D of} this compound were also measured, it was found that the compound was not an optically active substance related to axial asymmetry because it showed zero. Therefore, it was estimated as a racemic mixture.

(2-2) Structure of parbiflorene I Since a peak of m / z 412.1742 estimated to be [M ⁺ ] was observed by high-performance FABMS, it was presumed to have a molecular formula C ₂₇ H ₂₄ O ₄ (Table 1). So far, all the parbiflorenes isolated from this plant have contained 30 carbons, whereas this compound has been found to contain only 3 fewer 27 carbons than them.

The UV spectrum and IR spectrum were also measured. The UV spectrum showed values of ε36000 at a wavelength of 223.0 nm, ε40000 at a wavelength of 313.0 nm (see FIG. 5), and 3390, 2960, 2920 in the IR spectrum. , 2860, 1700, 1610, 1580, and 1300 cm ⁻¹ , respectively, absorption peaks were observed (see Table 1).

¹ H NMR and ¹³ C NMR were also measured (see Table 2). The spectrum of ¹ H NMR is shown in FIG. ¹ H
NMR and ¹³ C NMR suggested that only one isopropyl group was present. Two carbonyl carbon signals were also observed. Analysis of the two-dimensional NMR spectrum revealed that this compound had a structure in which the isopropyl group at the C11, C12, and C13 positions was eliminated from the sesquiterpene dimer skeleton and the ketone was present at the 6th position. It was also revealed that a ketone exists at the 7-position and has an α-diketone type structure. ¹ H- ¹ H
FIG. 7 shows correlation data observed in the COSY, HMQC, and HMBC spectra.

From the above, it was presumed that the structures of parviflorene H and parbiflorene I are shown below.

(3) Cytotoxicity When the cytotoxicity of parbiflorene H and parbiflorene I to HeLa cells was examined, IC ₅₀ values were> 25 and 0.63 μg / mL, respectively.

The figure which shows a series of schemes of Parbiflorene H and Parbiflorene I extraction. UV spectrum of parbiflorene H. ¹ H NMR spectrum of parbiflorene H. The correlation diagram observed in the ¹ H- ¹ H COSY, HMQC, and HMBC spectra of parbiflorene H. UV spectrum of parviflorene I. ¹ H NMR spectrum of parbiflorene I. The correlation diagram observed in the ¹ H- ¹ H COSY, HMQC, and HMBC spectrum of parbiflorene I.

Claims (2)

Parbiflorene H characterized by the following formula (1)
Parbiflorene I, represented by the following formula (2)