Synthesis and antimalarial activity of fagaronine
Fagaronine 1, a benzo[c]phenanthridine first isolated from Fagara zanthoxyloïdes in 1972 is known for its in vitro activity against P. falciparum in the nanomolar range. In order to study its antimalarial potential further, we performed a short synthesis for this molecule, inspired from the synthesis already published by Luo for nornitidine. This allowed us to obtain fagaronine 1 in 7 steps with a 10% yield. The key step is a nickel catalyzed annulation reaction between alkyne 5 and bromobenzaldehyde 3.
An antimalarial activity in vivo on mice comparable to the activity of chloroquine was evidenced. Fagaronine appears as a good potential lead for the design of new antimalarial molecules.