Synthesis and Potent Antimalarial Activity of Kalihinol B

Of the 50+ kalihinane diterpenoids
reported to date, only five
had been tested for antimalarial activity, in spite of the fact that
kalihinol A is the most potent among the members of the larger family
of antimalarial isocyanoterpenes. We have validated a strategy designed
to access many of the kalihinanes with a 12-step enantioselective
synthesis of kalihinol B, the tetrahydrofuran isomer of kalihinol
A (a tetrahydropyran). Kalihinol B shows similarly high potency against
chloroquine-resistant Plasmodium falciparum.