Synthesis of naturally occurring trioxygenated coumarins as anti-leukemia agents

MAES D; RIVEIRO M.E; DEBENEDETTI S; DAVIO C; DE KIMPE N

Thessaloniki, Grecia

Congreso; 4th Eurasian Meeting on Heterocyclic Chemistry; 2006

International Society of Heterocyclic Chemistry

A very large number of coumarins has been isolated from plants. The last decennia, there is a renewed interest in coumarins which have two or more oxygen substituents. Since the 1990´s a large number of in vivo and in vitro studies has revealed a diverse array of pharmacological and biochemical properties for these polyoxygenated coumarins, some of which are of potential pharmaceutical interest. Recently, it was discovered that several 5,6,7-trioxygenated coumarins, isolated from the Argentine medicinal plants Pterocaulon virgatum and Pterocaulon polystachyum, show substantial anti-leukemia activity. More specifically, these coumarins are able to inhibitproliferation and to induce differentiation in in vitro cultures of human leukemia U-937 cells. This discovery initiated us to develop a synthesis towards several natural trioxygenated coumarins. In that way, 5-hydroxy-6,7methylenedioxycoumarin 1, 5-methoxy-6,7-methylenedioxycoumarin 2, 5-(3-methyl-2-butenyloxy)-6, 7-methylenedioxycoumarin 3, 5-(2,3-dihydroxy3-methylbutoxy)-6,7-methylenedioxycoumarin 4,  5-(2-hydroxy-3-methoxy-3-methylbutoxy)-6,7-methylenedioxycoumarin 5 and 5-(2,3-dihydroxy-3methylbutoxy)-6,7-methylenedioxycoumarin 6 were synthesized. All thesecoumarins were isolated from plants of the Pterocaulon genus.