Total Syntheses of Strasseriolide A and Strasseriolide B, Potent Antimalarial Agents.

Abstract

We describe the convergent total syntheses of strasseriolides A and B, which are potent antimalarial agents recently isolated from an unnamed plant found in a remote region of New Zealand. Both natural products exhibited potent activity against malaria parasite, Plasmodium falciparum. The synthesis involved asymmetric syn-aldol, asymmetric alkylation, and asymmetric Johnson-Claisen rearrangement to set six of the seven chiral centers of strasseriolide B. The synthesis also highlights the formation of an 18-membered macrolactone from a diacid by using a Yamaguchi macrolactonization protocol. Other key transformations involved Grubbs' cross-metathesis, selective 1,4-reduction, hydrostannylation reaction, and NHK coupling reaction. The convergent synthesis of strasseriolide A required 27 total synthetic steps and 16 longest linear steps from known readily available intermediates.