American Chemical Society
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An Expeditious Synthesis of the MDM2–p53 Inhibitor AM-8553

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journal contribution
posted on 2016-02-20, 16:04 authored by Brian S. Lucas, Benjamin Fisher, Lawrence R. McGee, Steven H. Olson, Julio C. Medina, Eugene Cheung
The development of the structurally complex MDM2/p53 inhibitor AM-8553 was impeded by the low yield of the initial synthesis. A second generation synthesis is described that features a Noyori dynamic kinetic resolution, a highly diastereoselective allylation, and a novel oxazoline-assisted piperidinone forming reaction to provide AM-8553 in 35.6% yield and 11 steps.