Heck-matsuda Arylation As A Strategy To Access Kavalactones Isolated From Polygala Sabulosa, Piper Methysticum, And Analogues

Herein, we describe the total syntheses of three bioactive pyrones isolated from Polygala sabulosa (i.e., 1, 4, and 7) and eight isolated from Piper methysticum (i.e., 8-10, 13, 15, and 18-20) using the Heck-Matsuda arylation as the key strategy. The evaluation of this methodology by employing different arenediazonium tetrafluoroborates revealed that the Heck arylation was more efficient when the olefin undergoing arylation possessed the vinyl-2-pyrone structural unit instead of the vinyl dihydro-2-pyrone moiety. The Heck-Matsuda arylation of many of the examined olefins proceeded in a practical manner with total regio- and stereocontrol. © 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.1936073616Pizzolatti, M.G., Cunha, A., Pereira, W.S., Delle Monache, F., (2004) Biochem. Syst. Ecol., 32, p. 603Pizzolatti, M.G., Luciano, C., Delle Monache, F., (2000) Phytochemistry, 55, p. 819Bilia, A.R., Scalise, L., Bergonzi, M.C., Vincieri, F.F., (2004) J. Chromatogr., B, 812, p. 203Côté, C.S., Kor, C., Cohen, J., Auclair, K., (2004) Biochem. Biophys. Res. Commun., 322, p. 147Lasme, P., Davrieux, F., Montet, D., Lebot, V., (2008) J. Agric. Food Chem., 56, p. 4976Scherer, J., (1998) Adv. Ther., 15, p. 261Bilia, A.R., Gallon, S., Vincieri, F.F., (2002) Life Sci., 70, p. 2581Ernst, E., (2007) Br. J. Clin. Pharmacol., 64, p. 415Duarte, F.S., Marder, M., Hoeller, A.A., Duzzioni, M., Mendes, B.G., Pizzolatti, M.G., De Lima, T.C.M., (2008) Psychopharmacology (Berlin), 197, p. 351Duarte, F.S., Duzzioni, M., Mendes, B.G., Pizzolatti, M.G., De Lima, T.C.M., (2007) Pharmacol. Biochem. Behav., 86, p. 150Duarte, F.S., (2007), Ph. D. Thesis, Federal University of Santa Catarina, BrazilAmaral, P.A., Gouault, N., Le Roch, M., Eifler-Lima, V., David, M., (2008) Tetrahedron Lett., 49, p. 6607Pierres, C., George, P., Hijfthe, L.V., Ducep, J., Hibert, M., Mann, A., (2003) Tetrahedron Lett., 44, p. 3645Hashimoto, T., Suganuma, M., Fujiki, H., Yamada, M., Kohno, T., Asakawa, Y., (2003) Phytomedicine, 10, p. 309Younis, Y.M., Al-Shihry, S.S., (2000) Aust. J. Chem., 53, p. 589Lygo, B., (1995) Tetrahedron, 51, p. 12859Israeli, Z.H., Smissman, E.E., (1976) J. Org. Chem., 41, p. 4070Klohs, M.W., Keller, K., Williams, R.E., (1959) J. Org. Chem., 24, p. 1829Taylor, J.G., Moro, A.V., Correia, C.R.D., (2011) Eur. J. Org. Chem., p. 1403Felpin, F.X., Nassar-Hardy, L., Le Callonnec, F., Fouquet, E., (2011) Tetrahedron, 67, p. 2815Roglans, A., Pla-Quitana, A., Moreno-Manas, M., (2006) Chem. Rev., 106, p. 4622Prediger, P., Barbosa, L.F., Génisson, Y., Correia, C.R.D., (2011) J. Org. Chem., 76, p. 7737Moro, A.V., Santos, M.R., Correia, C.R.D., (2011) Eur. J. Org. Chem., p. 7259Azambuja, F., Correia, C.R.D., (2011) Tetrahedron Lett., 52, p. 42Taylor, J.G., Correia, C.R.D., (2011) J. Org. Chem., 76, p. 857Felpin, F.X., Miqueu, K., Sotiropoulos, J.M., Fouquet, E., Ibarguren, O., Laudien, J., (2010) Chem. Eur. J., 16, p. 5191Stern, T., Ruckbrod, S., Czekelius, C., Donner, C., Brunner, H., (2010) Adv. Synth. Catal., 352, p. 1983Coy, E.D., Jovanovic, B.L., Sefkow, M., (2010) Org. Lett., 12, p. 1976Laudien, J., Fouquet, E., Zakri, C., Felpin, F.X., (2010) Synlett, p. 1539Moro, A.V., Tiekink, E.R.T., Zukerman-Schpector, J., Lüdtke, D.S., Correia, C.R.C., (2010) Eur. J. Org. Chem., p. 3696Siqueira, F.A., Taylor, J.G., Correia, C.R.D., (2010) Tetrahedron Lett., 51, p. 2102Pastre, J.C., Génisson, Y., Saffon, N., Dandurandd, J., Correia, C.R.D., (2010) J. Braz. Chem. Soc., 21, p. 821Pastre, J.C., Correia, C.R.D., (2009) Adv. Synth. Catal., 351, p. 1217De Sousa, M.A., Patto, D.C.S., Azevedo, L.F.S., Bombonato, F.I., Correia, C.R.D., (2009) Tetrahedron Lett., 50, p. 1222. , A. H. L. MachadoFelpin, F.X., Ibarguren, O., Nassar-Hardy, L., Fouquet, E., (2009) J. Org. Chem., 74, p. 1349Felpin, F.X., Coste, J., Zakri, C., Fouquet, E., (2009) Chem. Eur. J., 15, p. 7238Cacchi, S., Fabrizi, G., Goggiamani, A., Sferrazza, A., (2009) Synlett, p. 973Cacchi, S., Fabrizi, G., Goggiamani, A., Sferrazza, A., (2009) Synlett, p. 1277Bartoli, G., Cacchi, S., Fabrizi, G., Goggiamani, A., (2008) Synlett, p. 2508Moro, A.V., Cardoso, F.S.P., Correia, C.R.D., (2008) Tetrahedron Lett., 49, p. 5668Moro, A.V., Correia, C.R.D., (2007) Synthesis, p. 2279. , P. R. R. MeiraGarcia, A.L.L., Miranda, K.C., Correia, C.R.D., (2006) Synlett, p. 3145. , A. C. B. BurtolosoDa Silva, K.P., Godoi, M.N., Correia, C.R.D., (2007) Org. Lett., 9, p. 2815Pastre, J.C., Correia, C.R.D., (2006) Org. Lett., 8, p. 1657Sabino, A.A., MacHado, A.H.L., Correia, C.R.D., Eberlin, M.N., (2004) Angew. Chem., 116, p. 2568. , Angew. Chem. Int. Ed. 2004, 43, 2514Sabino, A.A., MacHado, A.H.L., Correia, C.R.D., Eberlin, M.N., (2004) Angew. Chem., 116, p. 4489. , Angew. Chem. Int. Ed. 2004, 43, 4389Severino, E.A., Costenaro, E.R., Garcia, A.L.L., Correia, C.R.D., (2003) Org. Lett., 5, p. 305Moro, A.V., Cardoso, F.S.P., Correia, C.R.D., (2009) Org. Lett., 11, p. 3642Soldi, C., (2011), Ph. D. Thesis, Federal University of Santa Catarina, BrazilBloomer, J.L., Zaidi, S.M.H., Strupcze, J.T., Brosz, C.S., Gudzyk, L.A., (1974) J. Org. Chem., 39, p. 3615Fang, Z., Liao, P.-C., Yang, Y.-L., Yang, F.-L., Chen, Y.-L., Lam, Y., Hua, K.-F., Wu, S.-H., (2010) J. Med. Chem., 53, p. 7967Still, W.C., Kahn, M., Mitra, A., (1978) J. Org. Chem., 43, p. 2923Shaik, A.A., Hermanson, D.L., Xing, C., (2009) Bioorg. Med. Chem. Lett., 19, p. 5732Israili, Z.H., Smissman, E.E., (1976) J. Org. Chem., 41, p. 4070Abourashed, E.A., Khan, I.A., (2000) Chem. Pharm. Bull., 48, p. 1996Dharmaratne, H.R.W., Nanayakkara, N.P.D., Khan, I.A., (2002) Phytochemistry, 59, p. 429Dong, H., Chen, S.X., (1998) J. Nat. Prod., 61, p. 142Fujita, T., Nishimura, H., Kaburagi, K., Mizutani, J., (1994) Phytochemistry, 36, p. 2

Chemical and preliminary analgesic evaluation of geraniin and furosin isolated from Phyllanthus sellowianus

The present study describes the occurrence of two ellagitannins in the ethanolic extract of the leaves and stems of Phyllanthus sellowianus (Euphorbiaceae). Their preliminary antinociceptive properties were also evaluated. The two ellagitannins were identified on the basis of 1H- and 13C-NMR spectra data and by mixed co-TLC and co-HPLC injection with an authentic sample of furosin and geraniin. Preliminary pharmacological analysis revealed that both furosin and geraniin (3 to 30 mg/kg, i.p.), given 30 min before testing, exhibited significant and dose-related antinociceptive properties against acetic acid-induced abdominal constrictions in mice. Ceraniin and furosin were about six- to seven-fold more potent at the ID50 level (μmol/kg) as analgesics than aspirin and acetaminophen, respectively, although they were less efficacious when compared with the standard drugs. These data extend our previous studies and indicate that the two ellagitannins isolated from P. sellowianus, identified as furosin and geraniin, are, at least in part, responsible for the antinociceptive actions reported previously for the hydroalcoholic extract of P. sellowianus and other plants belonging to the genus Phyllanthus

Myricitrin, a nitric oxide and protein kinase C inhibitor, exerts antipsychotic-like effects in animal models

AbstractMyricitrin is a nitric oxide (NO) and protein kinase C (PKC) inhibitor that has central nervous system activity, including anxiolytic-like action. Nitric oxide inhibitors blocked the behavioral effects of apomorphine, suggesting an antipsychotic-like effect. Furthermore, PKC inhibition reduced psychotic symptoms in acute mania patients and blocked amphetamine-induced hyperlocomotion, suggesting a potential antipsychotic-like effect. The present study evaluated the effects of myricitrin in animal models that assess antipsychotic-like effects (apomorphine-induced stereotypy and climbing and the paw test) and extrapyramidal side effects (catalepsy test and paw test). Olanzapine was used as a positive control. 7-Nitroindazole (7-NI), a NOS inhibitor, and l-arginine, a NO precursor, were used to evaluate nitrergic modulation, and tamoxifen was used to test the effect of PKC inhibition. In mice, myricitrin dose-dependently and olanzapine blocked the stereotypy and climbing induced by apomorphine at doses that did not induce catalepsy. 7-Nitroindazole also blocked apomorphine-induced stereotypy and climbing, which were reversed by l-arginine pretreatment. l-arginine only attenuated the effects of myricitrin on apomorphine's effects. Tamoxifen also blocked apomorphine-induced stereotypy and climbing. In the paw test in rats, myricitrin and olanzapine increased hindlimb retraction time at doses that did not affect forelimb reaction time, whereas haloperidol affected both parameters at the same dose. Myricitrin did not induce catalepsy in the bar test. Tamoxifen did not affect hindlimb retraction time or forelimb retraction time, whereas 7-NI significantly increased hindlimb reaction time. Thus, myricitrin exhibited an antipsychotic-like profile at doses that did not induce catalepsy, and this effect may be related to nitrergic action