JP2007063244A - Triterpene compound, method for producing the same and oncogenesis promotion inhibitor composition containing the same as active ingredient - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new triterpene compound, a method for producing the same and a cancer inhibitor containing the same as an active ingredient. <P>SOLUTION: This cancer inhibitor is obtained by extracting various triterpenes contained in Inonotus obliquus, determining their structures including the new substance of the triterpenes and obtaining the inhibitor capable of inhibiting the promotion process of oncogenesis in each of substances. The method for producing them is also provided. Further, it is elucidated that inotodiol which is a triterpene, has an inhibitory effect against severely malignant p388 mouse lymphocytic leukemia cells. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  An invention relating to a novel triterpene compound, a method for producing the same, and a cancer inhibitor containing the compound as an active ingredient.

More and more people are craving for health who will enter an aging society. Virus variants are also addressed as the latest challenge. Among them, cancer has hit mankind as a serious issue. Cancer is becoming a “cure illness” by the development of medical care and treatment methods, but the number of patients and deaths are still increasing with the progress of an aging society. According to an announcement by the Japanese Cancer Society, one in three deaths are currently reported to have died from cancer. Regarding the suppression of cancer, not only medical treatment after affliction but also the idea of suppressing the occurrence of cancer before it occurs, that is, interest in cancer prevention has been increasing in recent years.
In the suppression of cancer, after treatment for malignant tumors, that is, for cancer, chemotherapy is used in combination with early detection / surgical operation, but many anticancer drugs that are clinically used or tried are For example, there are cases where it must be said that the solid cancer does not necessarily have a sufficiently satisfactory effect.
On the other hand, regarding cancer prevention in the prevention of cancer, regarding the mechanism of cancer onset (chemical carcinogenesis) due to chemical substances, in recent years, a two-stage theory of carcinogenesis that is thought to go through two processes called carcinogenesis initiation and carcinogenesis promotion has been widely accepted. Yes.

Initiation is a process in which substances collectively referred to as carcinogenic initiators irreversibly damage DNA of normal cells to change them into latent cells, and carcinogenesis promotion is collectively referred to as a carcinogenic promoter. This is a process in which a substance acting on a carcinogenic latent cell generated by a carcinogenic initiator leads to a cancer cell. If the processes of both carcinogenesis initiation and carcinogenesis promotion can be suppressed, the occurrence of cancer can be suppressed. In particular, suppression of carcinogenesis promotion is an effective means for suppressing carcinogenesis even for solids that already have latent cells that cannot return to normal cells.

TECHNICAL FIELD OF THE INVENTION

  The present invention relates to a novel triterpene of a wood-rotting fungus mushroom, specifically, a method for producing a triterpene contained in a bamboo shoot (Scientific name: Inonotusobliquus), a composition having a carcinogenic promotion inhibitory activity, and an anticancer agent.

Problems to be solved by the invention

  From the viewpoint of the former treatment, development of a cancer-killing cell active compound has been eagerly desired so that it can be an effective medicament for tumor shrinkage / eradication and growth suppression, while from the viewpoint of the latter carcinogenesis prevention, The development of a compound for inhibiting carcinogenesis promotion containing a component having an activity for suppressing carcinogenesis promotion and effective for the suppression of carcinogenesis is eagerly desired, and an anticancer agent having such an action is provided from a compound of birch moss.

Means for solving the problem

The present inventors have found that triterpene compounds separated and purified from basidiomycete mushrooms, in particular, birch fungus nuclei have an activity of suppressing carcinogenesis promotion (hereinafter sometimes referred to as carcinogenesis promotion inhibitory activity). The headline, the present invention has been reached.
That is, the present invention
1. A triterpene compound represented by the formula (I) or a pharmaceutically acceptable salt thereof.
2. A method for producing a triterpene compound, which comprises a step of extracting the triterpene compound or the pharmaceutically acceptable salt thereof according to item 1 from basidiomycetous mushrooms, particularly, birch fungus nuclei.

The compound of the present invention contains asymmetric carbon, but includes all possible steric compounds as long as they have carcinogenic promotion inhibitory activity.
As for the triterpene component in the birch moss, the extraction method [Non-Patent Document: Eri Yuen et al., European J. et al. For. Res. 1: 43-50 (2000); Japanese Wood Society Hokkaido Branch Lecture No. 30 November 1998, p75-77; Yuso Shin et. al. , International Journal of Medicinal Muscles Vol. 2, pp. 201-207 (2000)], which uses an ethanol extraction method, and therefore it is not appropriate to extract the entire triterpene component contained in the bamboo shoot, because other components are mixed. Moreover, even if the triterpene component was extracted, it was only a part. As a result of various studies, an extraction method using chloroform has been established as shown in Table 1. This had an extraction efficiency about 1000 times that of the ethanol extraction method. After chloroform, extraction with methanol was performed. The triterpene fraction is not eluted in the methanol extract.

  In addition, there has never been proved that the in vitro EBV-EA derivatization inhibitory activity and the in vivo carcinogenesis promotion inhibitory activity of the triterpene of this component, ie, the living body (mouse), have been incorporated into an experimental system. Although this technique is not fully disclosed, a part of this component and in vitro mouse leukemia cell P388 screening results have been clarified at the 125th Annual Meeting of the Japanese Pharmaceutical Society (March 31).

  As a method for measuring the promotion inhibitory activity of the compound of the present invention, for example, an EBV-EA induction test method [reference: Konishi, T .; et al. Biol. Pharm. Bull. , 21, 993 (1998)]. In this test method, an oncogenic promoter such as 12-O-tetradecanoylphorbol-13-acetate (hereinafter referred to as TPA), teleocidin, or the like is an Epstein-Barr virus latently infected human lymphoblastoid cell line derived from Burkitt lymphoma. (Raji cell, available from ATCC) is a method based on a phenomenon of activating Epstein-Barr virus (hereinafter referred to as EBV) latent in the cell, and the measurement step is as described above. An oncogenic promoter and a test substance are brought into contact with Raji cells, and the efficacy of the test substance to suppress EBV activation by the oncogenic promoter is measured. Many compounds have shown a high correlation between the EBV activation inhibitory activity and the in vivo carcinogenesis promotion inhibitory activity measured by this method.

  Furthermore, the promotion inhibitory activity can be examined by an in vivo two-stage carcinogenesis experiment using rodents. For example, the back hair of a mouse is shaved off with a surgical clipper or the like, and an appropriate amount of 7,12-dimethylbenzanthracene (hereinafter referred to as DMBA) dissolved in an organic solvent such as acetone or methanol is applied to the back skin, for example. About 1 μg to 1000 μg. After a certain period (for example, one week) has elapsed since the DMBA application, the test substance is applied to the skin at a certain frequency (for example, about twice a week). Specifically, for example, a test substance dissolved in an organic solvent such as acetone or methanol is first applied to the skin coated with DMBA as described above, and about 1 hour later, TPA dissolved in an organic solvent such as acetone or methanol. Is applied in an appropriate amount (for example, about 0.1 μg to 10 μg). While performing such treatment, observation was performed over time for a certain period (for example, about 10 to 50 weeks), and the number of mice with tumors on the treated back skin and the number of tumors produced Measure the number. The number of mice with tumors and the number of tumors in the group to which the test substance and TPA were applied are the number of mice with tumors and the number of tumors in the group to which the solvent was applied instead of the test substance. By comparing with the above, the carcinogenic promotion inhibitory activity of the test substance can be examined.

  The composition for inhibiting carcinogenesis promotion of the present invention is, for example, a naturally derived extract containing the compound of the present invention or a processed product thereof, the compound of the present invention, or the compound of the present invention and a pharmaceutical carrier or excipient, food ingredient or cosmetic. The composition contains a composition mixed with components and the like, and can be used as a pharmaceutical, food, cosmetic, or the like that suppresses the occurrence of a tumor or cancer and treats the generated tumor or cancer. The used pharmaceutical carrier or excipient, food ingredient, cosmetic ingredient, etc. can be appropriately selected according to the specific use of the cancer suppressor. Moreover, the form of the inhibitor can also be in the form of various solids and liquids, for example, depending on the specific application.

For example, when the compound of the present invention is used as a pharmaceutical product, the dosage form can be appropriately selected as necessary. Specific examples include oral preparations such as tablets, capsules, granules and powders, parenteral preparations such as injections, transdermal absorption agents, lotions, creams, ointments and suppositories. be able to. These preparations may be produced according to conventional methods.

Hereinafter, the present study will be described in more detail with reference to examples, but the present study is not limited thereto.
Reference 1 (Preparation of this compound)
Hokkaido Nayoro-shi Co., Ltd. Salad melon collected in the yard of 10 kg of birch fungus, finely chopped, soaked in 20 L of chloroform at 60 ° C. for 2 weeks, filtered, the filtrate was distilled off under reduced pressure, 200 g of chloroform extract was obtained. As shown in Table 1, the total amount of the extract was dissolved in chloroform and subjected to column chromatography using 3.5 kg of silica gel (silica gel 60, manufactured by Merck) prepared in chloroform, and a mixed solvent of chloroform and ethyl acetate (chloroform: acetic acid). The fraction was fractionated by 1 L by flowing ethyl = 10: 1), and fraction A (18.0 g, 7 × 1 L) collecting fractions 40-46 and fraction B (49.0 g, 6 × 1 L) collecting fractions 47-52 were collected. ) Next, chloroform: ethyl acetate = 5: 1 was flowed to fractionate 1 L at a time, and fraction C (3.0 g, 9 × 1 L) collecting fractions 62-70 and fraction D (6) containing fractions 71-79 were collected. 0.0 g, 9 × 1 L). Further, chloroform: ethyl acetate = 2: 1 was flowed to fractionate 1 L at a time to obtain a fraction E (12.5 g, 26 × 1 L) in which fractions 80-105 were collected. The obtained fractions were further separated and purified by silica gel column chromatography and high performance liquid chromatography using ODS and methanol system to isolate the compounds. Fraction A is subjected to silica gel column chromatography, eluting with compound 3 from the fraction eluting with chloroform, compounds 6 and 7 from the fraction eluting with chloroform: ethyl acetate = 5: 1, and further eluting with chloroform: ethyl acetate = 2: 1. Compounds 8 and 9 were obtained from the fractions, respectively. From fraction B, compounds 1, 4, 5 and 11 were obtained from fractions eluted with chloroform. From fraction D, compound 10 was obtained from a fraction eluted with chloroform, and from fraction E, compound 2 was obtained from a fraction eluted with chloroform: ethyl acetate = 5: 1.

Test Example 1 (Measurement of promotion inhibitory activity)
With respect to the compounds 1, 2, 2-acetate, 3, 4, 5, 6, 7, 7 acetate and 11 obtained in Reference 1, EBV activation inhibition test method (Konishi, T. et. Al., Biol. Pharm) Bull., 21, 993 (1998)), the promotion inhibitory activity was measured. For culture of Parkit lymphoma-derived EBV latently infected human lymphoblast cell line (Raji cells), a medium in which fetal calf serum (GIBCO-BRL) is added to PPMI 1640 medium (Nissui Pharmaceutical) at 10 v / v%. It was used. The activation rate of EBV (the rate of spontaneous induction of Raji cells) when cultured in this medium was 0.1% or less. A culture solution of Raji cells cultured in the above medium was prepared to 1 × 10 ⁶ cells / ml, butyric acid (final concentration 4 mM) dissolved in DMSO and TPA (final concentration 20 ng / ml) were added, and a CO ₂ incubator was added. After culturing at 37 ° C. for 48 hours, a smear of the obtained culture broth was prepared. EBV initial antigen (EBV-EA) was stained by the indirect fluorescent antibody method using serum from patients with nasopharyngeal cancer, and the expression rate of positive cells (cells in which the initial antigen was expressed) was measured to determine the positive control (100 ). On the other hand, Raji cell culture medium prepared as described above was stained with DMSO, and the expression rate of positive cells (cells in which the initial antigen was expressed) was measured, and this was used as a positive control (100). On the other hand, in the culture solution of Raji cells prepared as described above, butyric acid (final concentration 4 mM) and TPA (final concentration 20 ng / ml) dissolved in DMSO
After adding the test compound and culturing in the same manner, the expression rate of positive cells was measured to determine the ratio (%) to the positive control (100). In each test, at least 500 cells were measured and three replicate experiments were performed. In addition, the test about the system (negative control) which added only butyric acid without adding TPA and a test compound each time, and the said positive control was performed in parallel.

The measurement results are shown in Table 2. For any compound, suppression of EBV-EA activation was observed in a dose-related manner. Compounds 1, 2, 2-acetate, 3, 4, 5, 6, 7, 7 acetate and 11 did not show strong toxicity to cells in any test. Mice and pigs are not toxic even by oral administration at 0.1 g (per body weight).

（図２）マウス皮膚二段階発癌実験法により、化合物１のプロモーション抑制活性を測定した結果を示す図である。横軸は、ＴＰＡ及び被検化合物を皮膚に塗布したプロモーションの期間（週）を示す。縦軸は、各処理群におけるパピローマの発生頻度を百分率にて示す。
（図３）マウス皮膚二段階発癌実験法により、化合物１のプロモーション抑制活性を測定した結果を示す図である。横軸は、ＴＰＡ及び被検化合物を皮膚に塗布したプロモーションの期間（週）を示す。縦軸は、各処理群における個体あたりのパピローマの発生数を個数にて示す。Test Example 2 (Measurement of promotion inhibitory activity in mouse skin two-stage carcinogenesis experiment)
About the compound 1 obtained by the reference 1, the promotion inhibitory activity was measured by the two-step carcinogenesis experiment method using the mouse. The back of a 6-week-old ICR female mouse was shaved and compound 1 dissolved in 0.1 ml was applied to the DMBA application site, and the solvent-treated group was replaced with compound 1 with acetone (0.1 ml). Applied. Then, 1 hour later, TPA (1 mg, 1.7 nmol) dissolved in 0.1 ml of acetone was applied to the application site in both the test compound treatment group and the solvent treatment group. Then, TPA was similarly applied over 20 weeks. Three mice were used per group. Promotion inhibitory activity was determined by comparing the number of mice with papilloma and the average number of papillomas per mouse in the test compound-treated group and the solvent-treated group. As a result, as shown in FIGS. 2 and 3, Compound 1 showed inhibitory activity against carcinogenesis promotion by TPA.

(FIG. 2) It is a figure which shows the result of having measured the promotion inhibitory activity of the compound 1 by the mouse skin two-stage carcinogenesis experiment method. The horizontal axis indicates the period of promotion (weeks) in which TPA and the test compound were applied to the skin. The vertical axis shows the occurrence frequency of papilloma in each treatment group as a percentage.
(FIG. 3) It is a figure which shows the result of having measured the promotion inhibitory activity of the compound 1 by the mouse skin two-stage carcinogenesis experiment method. The horizontal axis indicates the period of promotion (weeks) in which TPA and the test compound were applied to the skin. The vertical axis shows the number of occurrences of papilloma per individual in each treatment group.

度ＥＤ_５０（μｇ／ｍｌ）を求めた。The growth inhibition activity test for P388 mouse lymphocytic leukemia cells was performed with 4 types of triterpenes as a representative. (Test samples 1, 2, 5, and 7 have the same expressions as compounds 1, 2, 5, and 7.) The results were obtained by the following method.
Growth inhibition activity test for P388 mouse lymphocytic leukemia cells [Method]
P388 mouse lymphocytic leukemia cells were cultured at 37 ° C. using Eagle Mineral Essential Medium containing 10% fetal bovine serum, and the culture was centrifuged at 900 rpm for 5 minutes when it reached about 7 × 10 ⁵ cells / ml. . The supernatant was discarded, and a certain amount of medium was added to the remaining cells to adjust a cell suspension of 1 × 10 ⁵ cells / ml (initial concentration). On the other hand, the specimen was dissolved in DMSO (10 mg / ml) and diluted to 200, 20, and 2 μg / ml with a medium. The control solution was diluted so that the concentration of DMSO was 2,0.2, 0.02%. 100 μl each of the specimen or control solution and the cell suspension solution are placed in each well of a 96-well microplate, cultured at 37 ° C. for 13 days in a CO ₂ incubator, and then 25 μl of MTT (6 mg / ml, phosphate buffer) is added. In addition, the cells are stained. After 4 hours, 50 μl of sodium dodecyl sulfate (20%, 0.02N HCl) was further added to dissolve formazone, and after standing overnight, the absorbance was measured with a microplate reader (BIO RAD model 450).
The growth (G)% is calculated from the following formula, and the concentration that suppresses cell growth by 50% using a semilogarithmic graph.

Degree ED ₅₀ (μg / ml) was determined.

以上のようにカバノアナタケ由来のトリテルペン化合物に抗癌活性があきらかとなったから癌抑制や生理活性著大なものがある。[result]
The test results are shown in Table 3 below. Of the four test compounds (triterpene compounds) (1), (2), (5) and (7), all of the compounds except (2) were found to have a cell growth inhibitory activity. ((2) has good crystal condensation.)

As described above, the triterpene compounds derived from birch moths have obvious anti-cancer activity, and thus there are significant cancer suppressive and physiological activities.

Compound 1
NMR spectrum ¹ H NMR (CDCl ₃ ): δ 0.73 (3H, s), 0.81 (3H, s), 0.88 (3H, s), 0.94 (3H, d, J = 6.5 Hz) ), 0.84 (3H, s), 1.00 (3H, s), 1.65 (3H, s), 1.75 (3H, s), 3.24 (1H, dd, J = 1.11. 8, 4.5 Hz), 3.67 (1H, ddd, J = 9.0, 5.2, 4.4 Hz), 5.18 (1H, m). Mass spectrum m / z: 442 (29) [M] ⁺ , 427 (34), 411 (44), 409 (16), 372 (28), 357 (59), 339 (16), 299 (18), 187 (23), 69 (100).
Compound 2
NMR spectrum ¹ H NMR (CDCl ₃ ): δ0.75 (3H, s), 0.81 (3H, s), 0.89 (3H, s), 0.97 (3H, s), 1.00 ( 3H, s), 1.59 (3H, s), 1.62 (3H, s), 3.22 (1H, dd, J = 11.8, 4.8 Hz). Mass spectrum m / z: 456 (60) [M] ⁺ , 441 (66), 423 (100), 395 (11), 301 (10), 281 (17), 187 (19).
Compound 3
NMR spectrum ¹ H NMR (CDCl ₃ ): δ 0.69 (3H, s), 0.81 (3H, s), 0.88 (3H, s), 0.91 (3H, d, J = 6.5 Hz) ), 0.98 (3H, s), 1.00 (3H, s), 3.22 (1H, dd, J = 11.8, 4.8 Hz), 5.10 (1H, m). Mass spectrum m / z: 442 (77) [M] ⁺ , 427 (62), 409 (100), 391 (26), 357 (15), 327 (10), 299 (10), 273 (11), 259 (11), 255 (10).
Compound 4
NMR spectrum ¹ H NMR (CDCl ₃ ): δ 0.69 (3H, s), 0.81 (3H, s), 0.87 (3H, s), 0.91 (3H, d, J = 6.5 Hz) ), 0.98 (3H, s), 1.00 (3H, s), 3.22 (1H, dd, J = 11.8, 4.8 Hz), 4.01 (1H, m), 4. 82 (1H, s), 4.93 (1H, s), mass spectrum m / z: 442 (77) [M] ⁺ , 427 (62), 409 (100), 391 (26), 357 (15) , 327 (10), 299 (10), 273 (11), 259 (11), 255 (10).
Compound 5
NMR spectrum ¹ H NMR (CDCl ₃ ): δ 0.69 (3H, s), 0.81 (3H, s), 0.90 (3H, s), 0.96 (3H, s), 1.00 ( 3H, s), 1.57 (3H, s), 1.68 (3H, s), 3.24 (1H, dd, J = 11.5, 4.4 Hz), 5.04 (1H, m) , 9.46 (1H, d, J = 5.5 Hz). Mass spectrum m / z: 440 (54) [M] ⁺ , 425 (100), 407 (97), 389 (16), 358 (68), 299 (59), 288 (51), 281 (59), 273 (30), 247 (24).
Compound 6
NMR spectrum ¹ H NMR (CDCl ₃ ): δ 0.73 (3H, s), 0.80 (3H, s), 0.90 (3H, s), 0.97 (3H, s), 0.99 ( 3H, s), 1.20 (3H, s), 1.22 (3H, s), 3.23 (1H, dd, J = 11.5, 4.4 Hz), 3.72 (1H, m) . Mass spectrum m / z: 458 (45) [M] ⁺ , 443 (32), 425 (100), 407 (90), 389 (13), 299 (45), 281 (28),
Compound 7
NMR spectrum ¹ H-NMR (CDCl ₃ ): δ 0.71 (3H, s, H-18), 0.81 (3H, s, H-29), 0.86 (3H, s, H-30), 0.88 (3H, d, J = 6.5 Hz, H-21), 0.98 (3H, s, H-19), 1.00 (3H, s, H-28), 1.05 (1H , Dd, J = 12.8, 3.0 Hz, H-5), 1.19 (1H, m, H-15α), 1.22 (3H, s, H-27), 1.23 (3H, s, H-26), 1.23 (1H, td, J = 13.5, 4.2 Hz, H-1α), 1.40 (1H, ddd, J = 12.0, 10.8, 7.). 2 Hz, H-17), 1.48 (1H, m, H-16β), 1.50 (1H, m, H-6β), 1.58 (1H, tdd, J = 13.5, 11.7) , 4.2 Hz, H-2β), 1.62 (1H, m, H-15β), 1.65 (1H, m, H-23β), 1.66 (1H, m, H-2α), 1.67 (1H, m, H-6α), 1.70 (1H, m, H-12), 1.73 (1H, td, J = 13.5, 4.2 Hz, H-1β), 1.83 (1H, m , H-16α), 1.83 (1H, d quint., J = 12.0, 6.7 Hz, H-20), 2.01 (1H, m, H-11), 2.01 (1H, m, H-23α), 2.04 (1H, m, H-7), 3.23 (1H, dd, J = 11.7, 4.6 Hz, H-3), 3.92 (1H, dd) , J = 6.4, 4.1 Hz, H-24), 4.26 (1H ddd, J = 10.3, 6.6, 3.7 Hz, H-22). ¹³ C-NMR (CDCl ₃ ): δ12.3 (C-21), 15.4 (C-29), 15.7 (C-18), 18.2 (C-6), 19.1 (C -19), 21.0 (C-11), 21.2 (C-26), 24.3 (C-30), 26.5 (C-7), 27.3 (C-16), 27 .5 (C-27), 27.8 (C-2), 28.0 (C-28), 30.9 (C-12), 31.0 (C-15), 33.3 (C- 23), 35.6 (C-1), 37.0 (C-10), 38.5 (C-20), 38.9 (C-4), 45.0 (C-13), 47. 8 (C-17), 49.3 (C-14), 50.4 (C-5), 78.1 (C-22), 78.5 (C-24), 79.0 (C-3) ), 81.7 (C-25), 134.2 (C-8), 134. (C-9). Mass spectrum m / z: 458 (52) [M] ⁺ , 443 (75), 425 (66), 407 (11), 339 (17), 314 (10), 311 (10), 301 (11), 283 (12), 115 (100), 71 (68).
Compound 8
NMR spectrum ¹ H-NMR (CDCl ₃ ): δ 0.72 (3H, s, H-18), 0.81 (3H, s, H-29), 0.87 (3H, s, H-30), 0.93 (3H, d, J = 6.7 Hz, H-21), 0.98 (3H, s, H-19), 1.00 (3H, s, H-28), 1.05 (1H , Dd, J = 12.5, 2.5 Hz, H-5), 1.18 (1H, m, H-15α), 1.23 (1H, td, J = 12.6, 3.8 Hz, H −1α), 1.41 (1H, m, H-16β), 1.44 (1H, ddd, J = 12.7, 9.6, 7.3 Hz, H-17), 1.50 (1H, m, H-6β), 1.58 (1H, m, H-2β), 1.58 (1H, m, H-23β), 1.63 (1H, m, H-15β), 1.67 ( 1H, dqd, J = 12.7, 9.6, 3.2 Hz, H-20), 1.67 (1H, m, H-23α), 1.68 (1H, m, H-2α), 1.68 (1H, m , H-6α), 1.68 (1H, m, H-12β), 1.73 (1H, m, H-12α), 1.73 (3H, s, H-27), 1.74 (1H , Dt, J = 12.6, 3.8 Hz, H-1β), 1.78 (1H, m, H-16α), 2.01 (1H, m, H-11), 2.04 (1H, m, H-7), 3.23 (1H, dd, J = 11.8, 4.5 Hz, H-3), 3.98 (1H ddd, J = 10.2, 3.2, 2.8 Hz) , H-22), 4.36 (1H, t, J = 4.8 Hz, H-24), 4.94 (1H, q, J = 1.8 Hz, H-26A), 5.11 (1H, q, J = 1.2 Hz, H-26B). ¹³ C-NMR (CDCl ₃ ): δ 12.6 (C-21), 15.4 (C-29), 15.7 (C-18), 18.2 (C-6), 19.1 (C -19), 19.3 (C-27), 21.0 (C-11), 24.3 (C-30), 26.5 (C-7), 27.2 (C-16), 27 .8 (C-2), 28.0 (C-28), 31.0 (C-12), 31.0 (C-15), 33.1 (C-23), 35.6 (C- 1), 37.0 (C-10), 38.9 (C-4), 42.8 (C-20), 44.8 (C-13), 47.2 (C-17), 49. 4 (C-14), 50.4 (C-5), 70.3 (C-22), 73.5 (C-24), 79.0 (C-3), 110.2 (C-26) ), 134.1 (C-8), 134.6 (C-9), 147 3 (C-25). Mass spectrum m / z: 458 (9) [M] ⁺ , 357 (75), 339 (18), 311 (13), 159 (10).
Compound 9
NMR spectrum ¹ H-NMR (CDCl ₃ ): δ 0.72 (3H, s, H-18), 0.81 (3H, s, H-29), 0.87 (3H, s, H-30), 0.94 (3H, d, J = 6.7 Hz, H-21), 0.98 (3H, s, H-19), 1.00 (3H, s, H-28), 1.05 (1H , Dd, J = 13.0, 2.3 Hz, H-5), 1.21 (1H, ddd, J = 14.2, 9.3, 2.5 Hz, H-15α), 1.23 (1H , Td, J = 12.6, 3.8 Hz, H-1α), 1.45 (1H, m, H-16β), 1.46 (1H, ddd, J = 12.7, 9.6, 7 .3 Hz, H-17), 1.51 (1H, m, H-6β), 1.52 (1H, m, H-23β), 1.54 (1H, m, H-23α), 1.58 (1H, qd J = 13.5, 3.2 Hz, H-2β), 1.63 (1H, m, H-15β), 1.67 (1H, m, H-2α), 1.68 (1H, m, H) −6α), 1.70 (1H, dqd, J = 12.7, 6.7, 3.0 Hz, H-20), 1.69 (1H, m, H-12β), 1.71 (1H, m, H-12α), 1.74 (1H, dt, J = 12.6, 3.8 Hz, H-1β), 1.76 (3H, s, H-27), 1.78 (1H, m , H-16α), 2.02 (1H, m, H-11), 2.04 (1H, m, H-7), 3.24 (1H, dd, J = 11.7, 4.5 Hz, H-3), 3.96 (1H dt, J = 9.2, 3.0 Hz, H-22), 4.26 (1H, dd, J = 9.2, 3.5 Hz, H-24), 4.84 (1H, dq, J = 3.8, 1 8Hz, H-26A), 5.01 (1H, quint., J = 1.2Hz, H-26B). ¹³ C-NMR (CDCl ₃ ): δ 12.7 (C-21), 15.4 (C-29), 15.8 (C-18), 17.9 (C-27), 18.2 (C -6), 19.1 (C-19), 21.0 (C-11), 24, 4 (C-30), 26.5 (C-7), 27.2 (C-16), 27 .8 (C-2), 28.0 (C-28), 30.9 (C-12), 30.9 (C-15), 34.6 (C-23), 35.6 (C- 1), 37.0 (C-10), 38.9 (C-4), 42.5 (C-20), 44.8 (C-13), 47.3 (C-17), 49. 4 (C-14), 50.4 (C-5), 74.6 (C-22), 76.5 (C-24), 79.0 (C-3), 110.8 (C-26) ), 134.1 (C-8), 134.6 (C-9), 147 6 (C-25). Mass spectrum m / z: 458 (9) [M] ⁺ , 357 (75), 339 (18), 311 (13), 159 (10).
Compound 10
NMR spectrum ¹ H NMR (CDCl ₃ ): δ 0.70 (3H, s), 0.81 (3H, s), 0.88 (3H, s), 0.92 (3H, d, J = 6.5 Hz) ), 0.98 (3H, s), 1.00 (3H, s), 3.24 (1H, dd, J = 11.2, 4.6 Hz), 3.62 (2H, m). Mass spectrum m / z: 402 (37) [M] ⁺ , 387 (100), 369 (90), 273 (16), 187 (27).
Compound 11
NMR spectrum ¹ H NMR (CDCl ₃ ): δ 0.72 (3H, s), 0.81 (3H, s), 0.90 (3H, s), 0.99 (3H, s), 1.00 ( 3H, s), 1.61 (3H, s), 1.69 (3H, s), 3.24 (1H, dd, J = 11.7, 4.3 Hz), 3.68 (1H, dd, J = 11.2, 4.6 Hz), 3.73 (1H, dd, J = 11.2, 3.0 Hz), 5.12 (1H, m). Mass spectrum m / z: 442 (57) [M] ⁺ , 427 (49), 409 (28), 189 (12), 187 (11), 109 (100).

Claims (10)

A triterpene compound represented by the formula (I) or a pharmaceutically acceptable salt thereof.

A method for producing a triterpene compound, comprising the step of extracting the triterpene compound or a pharmaceutically acceptable salt thereof according to claim 1 from a basidiomycete mushroom. The method for producing a triterpene compound according to claim 1 or 2, wherein the basidiomycete mushroom is birch fungus. A cancer suppressant comprising administering to a mammal (including a human) an active ingredient amount of the triterpene compound according to claim 1 or a pharmaceutically acceptable salt thereof or a prodrug thereof. The cancer inhibitor according to claim 4, comprising one or more of the triterpene compound or a pharmaceutically acceptable salt thereof as an active ingredient. The cancer suppressant according to claim 4, wherein the triterpene compound or a pharmaceutically acceptable salt thereof is used in combination with another anticancer agent. A composition for inhibiting carcinogenesis promotion comprising the triterpene compound according to claim 1 or a pharmaceutically acceptable salt thereof as an active ingredient, which is contained in another food or medicine. (1) Birch tree mycelium naturally grown on birch stands, or mycelia (2) Birch tree mycelium or hyphae artificially inoculated and grown on birch trees, (3) These birch fungi Nucleus or mycelium is collected from the bark of the standing tree and the tissue of the wood part, or (4) birch oyster mycelium artificially cultured in solid medium, or mycelium (5) after population culture in solid medium, medium 4. The cancer according to claim 3, wherein the mycelium or biliary mycelia collected together with (6) liquid culture, then the mycelia collected together with the culture solution is selected, and the triterpene compound is extracted from any selected starting material. Inhibitor. The method according to claim 1, comprising using chloroform at least in the first stage in the basidiomycete mushroom extraction step. The method according to claim 9, wherein the basidiomycete mushroom is the birch salmon mushroom in claim 8.