News & Events

When

Date - November 30, 2016
1:00 pm

What

Ph.D. Thesis Defense – 752

Title: “Synthesis and Biological Evaluation of Potent Neuroprotective Agents against Stroke and Research on a Novel Type of Decarboxylation Reaction”

Abstract:

Isocarbacyclin is a valuable synthetic target due to its neuroprotection from the oxidative damage after a stroke. The Croatt Group’s synthetic route utilizes a palladium-catalyzed decarboxylative coupling of a pentadienyl dienoate, a rhodium-catalyzed diene-diene [2+2+1] cycloaddition, and a ruthenium-catalyzed cross-metathesis reaction. The metathesis reaction is particularly valuable since it allows for late-stage diversification. These three metal-catalyzed reactions enable us to complete the synthesis of isocarbacyclin in nine steps, instead of the 15 or more steps that have been previously reported. Another new synthetic route will be presented that includes the same combination of the three metal-catalyzed reactions for the synthesis of a tricyclic isocarbacyclin analogue. During the course of our synthesis of isocarbacyclin analogues, we discovered a decarboxylation reaction of a pentadienyl dienoate that did not require an anion stabilizing group. This novel decarboxylative coupling reaction, optimization, mechanistic evaluation, and substrate scope will also be presented.