Synthesis and activity of cereulide, a cyclic dodecadepsipeptide ionophore as emetic toxin from Bacillus cereus

Cereulide is the emetic toxin caused by Bacillus cereus as food contaminant. This cyclic depsipeptide was synthesized from L-O-Val, L-Val, L-O-Leu and D-Ala by coupling the former 2 and the latter 2, with inversion of the configuration of L-O-Leu into D-O-Leu, to form a tetrapeptide having TBDMS and benzyl protection. After selective deprotection of this tetrapeptide into the corresponding alcohol and acid, they were coupled twice and then transformed into a dodecapeptide (seco-acid) that was finally cyclized under high-dilution condition to afford cereulide. The final preparation showed, in fact, emetic toxicity as well as vacuole formation to HEp2 cells as the same level as the natural cereulide.