Total Synthesis of (−)-Platensimycin, a Novel Antibacterial Agent

An enantioselective synthesis of platensimycin, a novel antibiotic natural product that inhibits bacterial beta-ketoacyl-(acyl-carrier-protein) synthase (FabF), is described. Our synthetic strategy for the construction of the oxatetracyclic core involved an intramolecular Diels-Alder reaction. Our preliminary studies provided a complex tetracyclic product by first undergoing an interesting 1,5-hydride shift followed by a Diels-Alder reaction. Further optimization of the diene's electronic properties, by incorporation of a methoxy group, led to the oxatetracyclic core of platensimycin. The three required chiral centers, including two all-carbon quaternary chiral centers, were built in the intramolecular Diels-Alder step. The synthesis utilized natural (+)-carvone as the key chiral starting material, which determined the stereochemistry of the final product. The synthesis also featured an efficient Petasis olefination, a hydroboration sequence, a Gais's asymmetric Horner-Wadsworth-Emmons reaction, and a mercury salt catalyzed enol ether isomerization.