Synthesis and Biological Activity of ABC-Ring Analogues of Stephaoxocanidine and Eletefine

TEODORO S. KAUFMAN

Itapema, Brasil

Conferencia; 12 Brazilian Meeting on Organic Synthesis (12 BMOS); 2007

The stephaoxocanes are a small family of natural products isolated from Menispermaceae such as Stephania cepharantha, S. excentrica, S. longa and Cissampelos glaberrima, used in folk medicine in the China, Taiwan and Brazil. All of them display the novel tetracyclic skeleton 1, for which the name “stephaoxocane” was coined. Stephaoxocanidine (2), isolated from S. cepharantha Hayata cultivated in Japan and Eletefine (3) isolated from C. glaberrima in Brazil[i] are the structurally simplest representatives of this family.  Two approaches towards the synthesis of the 8-oxa-1-aza-phenalene derivatives 4 and 5, which embody the ABC ring system of stephaoxocanidine and eletefine, will be discussed.[i] In addition, the acetylcholinesterase inhibitory activity[ii] of a series of ABC-ring analogs of stephaoxocanidine will be presented. [i]         a) Bianchi, D. A.; Cipulli, M. A.; Kaufman, T. S. Eur. J. Org. Chem. 4731 (2003); b) Bianchi, D. A.; Kaufman, T. S. Arkivoc x, 178 (2003); c) Bianchi, D. A.; Rúa, F.; Kaufman, T. S. Tetrahedron Lett. 45, 411 (2004). [ii]        Bianchi, D. A.; Bracca, A. B. J.; Schmeda-Hirschmann, G.; Theoduloz, C.; Kayfman, T. S. Bioorg. Med. Chem. Lett. 15, 2711 (2005). [i]         a) Kashiwaba, N.; Morooka, S.; Kimura, M.; Ono, M.; Toda, J.; Suzuki, H.; Sano, T. Nat. Prod. Lett. 9, 177 (1997); b) da-Cunha, E. V. L.; Lopes Cornélio, M.; Barbiosa-Filho, J. M.; Braz-Filho, R.; Gray, A. I. J. Nat. Prod. 61, 1140 (1998). [i]         a) Bianchi, D. A.; Cipulli, M. A.; Kaufman, T. S. Eur. J. Org. Chem. 4731 (2003); b) Bianchi, D. A.; Kaufman, T. S. Arkivoc x, 178 (2003); c) Bianchi, D. A.; Rúa, F.; Kaufman, T. S. Tetrahedron Lett. 45, 411 (2004). [ii]        Bianchi, D. A.; Bracca, A. B. J.; Schmeda-Hirschmann, G.; Theoduloz, C.; Kayfman, T. S. Bioorg. Med. Chem. Lett. 15, 2711 (2005). [i]         a) Kashiwaba, N.; Morooka, S.; Kimura, M.; Ono, M.; Toda, J.; Suzuki, H.; Sano, T. Nat. Prod. Lett. 9, 177 (1997); b) da-Cunha, E. V. L.; Lopes Cornélio, M.; Barbiosa-Filho, J. M.; Braz-Filho, R.; Gray, A. I. J. Nat. Prod. 61, 1140 (1998).