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Total synthesis of (-)-platensimycin, a novel antibacterial agent.

ABSTRACT: 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.

SUBMITTER: Ghosh AK

PROVIDER: S-EPMC2812928 | biostudies-other | 2009 Feb

REPOSITORIES: biostudies-other

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Total synthesis of (-)-platensimycin, a novel antibacterial agent.

Ghosh Arun K AK Xi Kai K

The Journal of organic chemistry 20090201 3

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 proper ...[more]

PMID: 19123842

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