Antimalarial agents, 4. Synthesis of a brusatol analog and biological activity of brusatol-related compounds.

The quassinoids bruceoside-A [1], brusatol [2], and bruceolide [3] were tested for antimalarial activity in vitro against the chloroquine-resistant (Smith) isolates of Plasmodium falciparum. Compound 2 was quite active, 1 was not active, and 3 showed only a trace of activity. The fact that 15 [(E)-non-2-enoyl] bruceolide [7] synthesized from 2 was eight times less active than 2 would indicate that the requirement of a C-15 ester moiety for enhanced antimalarial activity among brusatol related quassinoids could be quite specific.