Total Syntheses of Strasseriolide A and B, Antimalarial Macrolide Natural Products

We report the first total syntheses
of strasseriolide A and B.
Strasseriolide B shows potent activity against the wild-type malaria
parasite Plasmodium falciparum and
good activity against a chloroquine-resistant strain. A convergent
strategy was envisioned with an aldehyde-acid fragment and a vinyl
iodide-alcohol fragment. Both fragments were prepared using chiral
pool starting materials. They were combined with a Yamaguchi esterification
and cyclized with a Nozaki-Hiyama-Kishi reaction. Strasseriolide B
was assembled in a 16-step LLS.