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

Lucas, Brian S.; Fisher, Benjamin; McGee, Lawrence
R.; Olson, Steven H.; Medina, Julio C.; Cheung, Eugene

doi:10.1021/ja305123v.s001

ja305123v_si_001.pdf (281.93 kB)

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

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.