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

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journal contribution
posted on 06.02.2009, 00:00 authored by Arun K. Ghosh, Kai Xi
An enantioselective synthesis of platensimycin, a novel antibiotic natural product that inhibits bacterial β-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.