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.

Automated summary

This study reports the first total syntheses of strasseriolide A and B. Strasseriolide B exhibits potent activity against the wild-type malaria parasite Plasmodium falciparum and good activity against a chloroquine-resistant strain. A convergent strategy was employed, utilizing an aldehyde-acid fragment and a vinyl iodide-alcohol fragment, both prepared from chiral pool starting materials. The fragments were combined through a Yamaguchi esterification and cyclized with a Nozaki-Hiyama-Kishi reaction, resulting in the assembly of strasseriolide B in a 16-step LLS.