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Boletín de la Sociedad Chilena de Química

Print version ISSN 0366-1644

Bol. Soc. Chil. Quím. vol.46 n.2 Concepción June 2001

http://dx.doi.org/10.4067/S0366-16442001000200019 

OSTOPANIC ACID, A CYTOTOXIC FATTY ACID
FROM Gymnopilus spectabilis

J. NUÑEZ-ALARCON; J. C. CARLOS PAREDES; M.T. CARMONA;
M. QUIÑONES.

Instituto de Química, Universidad Austral de Chile, Valdivia. Chile.
Fax: 221597, E-mail: jnunez@uach.cl
(Received: March 28, 2000 - Accepted: December 20, 2000)

ABSTRACT

(E,E)-7,12-Dioxooctadeca-8,10-dienoic acid (ostopanic acid), a cytotoxic fatty acid, has been isolated from the fruit body of the hallucinogenic mushroom Gymnopilus spectabilis.

Ergosterol, a very common metabolite in mushrooms, was also isolated.

KEY WORDS: Gymnopilus spectabilis; Basidiomycetes; ostopanic acid and ergosterol.

RESUMEN

Del cuerpo fructífero de Gymnopilus spectabilis, un hongo con propiedades alucinógenas, se aisló el ácido (E,E)-7,12-dioxooctadeca-8,10-dienoico (ácido ostopánico), un ácido graso citotóxico.

Ergosterol, un metabolito muy frecuente en hongos, fue también aislado.

PALABRAS CLAVES: Gymnopilus spectabilis; Basidiomycetes; ácido ostopánico y ergosterol.

In the course of our investigation of the constituents of the mushrooms that grow in southern Chile, we report here the isolation and identification of (E,E)-7,12-dioxooctadeca-8,10-dienoic acid (ostopanic acid) and ergosterol, which were isolated from the mushroom Gymnopilus spectabilis, (Cortinariaceae, Basidiomycetes.)

Gymnopilus spectabilis has been described as an hallucinogenic mushroom 1).

Ostopanic acid was isolated for the first time from the stems and fruits of Ostodes paniculata Blume, (Euphorbiaceae). It has been shown to inhibit the growth of P-388 lymphocytic leukemia cells in vitro with an ED50 of 1.5 mg/mL 2).

Previous workers had reported the isolation of gymnoprenols (gymnoprenol-A, -B and -F), a novel type of polyisoprenepolyols with 45 to 50 carbon atoms, from the fruit bodies of Gymnopilus spectabilis collected at Yamagata, Japan.

From the same species collected in Germany was isolated gymnopilin, a bitter principle, which proved to be a half-ester of b-methyl-b-hydroxyglutaric acid with gymnoprenol-A 3,4).

The interesting (E,E)-dienyldiketone structure of ostopanic acid, together with its biological activity has led some investigators to synthesize this compound 5,6,7).

The molecular structures of ergosterol and ostopanic acid were determined by spectroscopic techniques and comparison of their spectroscopic data with those from the literature 2,5,8).

The fruit bodies of Gymnopilus spectabilis (2200g) were collected in Valdivia in the Universidad Austral Botanical Garden in March ­ May (autumn), 1997.

Fresh fruit bodies were cut into small pieces and repeatedly extracted with MeOH (500 ml, each time) at room temp. The combined extracts were concd. in vacuo to give a crude residue which was fractionated by CC over silica gel using a CHCl3-MeOH gradient to obtain 15 fractions. The combined fr. 4-10 were subjected to repeated CC over silica gel with CH2Cl2-EtOAc gradient and then purified on a Sephadex column followed by further crystallization, when necessary, to obtain ostopanic acid (58 mg) and ergosterol (240 mg).

Ostopanic acid was isolated as white crystals from CH2Cl2 / MeOH, m.p.: 120-122C (lit. 122-123C) 2). IR, nmax ( KBr) : 3430, 2987, 2954, 2852, 1694, 1679, 1590, 1470, 1407, 1374, 1310, 1234, 1197, 1129, 1070, 1000, 710. 1H-NMR, in CDCl3, d (ppm) (300 MHz) : 7.19 (1H, m, 9-H or 10-H); 7.16 ( 1H, m, 10-H or 9-H); 6.47 (1H, t, J=2.7 Hz, 8-H or 11-H); 6.51 (1H, t, J=3.0 Hz, 11-H or 8-H); 2.61(2H, t, J=7.5, 6-H2, or 13-H2); 2.60 (2H, t, J=7.5, 6-H2 or 13-H2); 2.35 (2H, t, J=7.5, 2-H2); 1.62 (6H, m, 3-, 5-, 14-H2); 1.34 (8H, m, 4-, 15-, 16-, 17-H2). 13C-NMR, in CDCl3, d, (ppm) (75 MHz) : 200.6 (C-7 or C-12); 200.5 (C-12 or C-7); 179.7 ( C-1); 138.9 (C-9 or C-10); 138.8 (C-10 or C-9); 136.4 (C-8 or C-11); 136.3 (C-11 or C-8); 40.1 (C-6 or C-13); 40.0 (C-13 or C-6); 33.8 (C-2); 29.0 (C-4,C-15 or C-16); 28.9 (C-15, C-16 or C-4); 28.7 (C-16, C-4 or C-15); 26.0 (C-3); 24.5 (C-5 or C-14); 23.8 (C-14 or C-5); 22.3 (C-7); 13.8 (C-8). HR-MS m/z (rel. int.) : 308.2 (45.07) (M+, C18 H28 O4); 290.2 (M+- H2O); 238.2 (M - C5H10, Mc Lafferty)+; 223.1 (54.31) (M-C6H13)+; 205.1 (12.04) (223 - H2O)+; 165.1 (24.56) [(M­ C6H11O2)-CO] +; 138.1 (58.89) (238 ­ C5H8O2, Mc Lafferty)+; 123.1 (27.93) (223.1 ­ C5H 8O2, Mc Lafferty)+.

Ergosterol was identified by comparison with reported physical data and by direct comparison with authentic material available in our laboratory.

The molecular formula of ostopanic acid ( C18 H28O4 ) was assigned by HR-EI mass spectroscopy with m/z 308.1999 [M+] calc. 308.415. The other fragment ions are consistent with the structure of ostopanic acid. The IR spectrum exhibited absorption bands for an acid carbonyl (1590) . The bands at 1679 and 1694 reveled the presence of an a-b unsaturated ketone. The four olefinic proton resonances at d 7.16 and 6.47 ( 2H each ) confirm the presence of two conjugated enone system.

The 13C-NMR spectrum and DEPT experiments gave a total of 18 resonance lines ( see experimental ) and indicated the presence of three quaternary carbons , four olefinic CH groups , ten CH2 groups and one CH3 carbon.

The 1H-NMR and 13C- NMR signals were assigned by 1H-1H and 1H-13C- NMR COSY.

ACKNOWLEDGMENTS

One (J. N-A) of the authors thanks D.I.D ( Dirección de Investigación y Desarrollo), Universidad Austral de Chile, for financial support.

The authors are grateful to Prof. W. Steglich and B. Sontag, Institut für Organische Chemie, Universität München, Germany, for the N.M.R., I.R. and Mass spectra.

Thanks are also due to Dr. Eduardo Valenzuela, Microbiology Institute, Universidad Austral de Chile, for identification of the mushroom.

REFERENCES

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