Synthesis and biological evaluation of potent neuroprotective agents against stroke and research on a novel type of decarboxylation reaction

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Ghina'a Ismail Abu Deiab (Creator)
The University of North Carolina at Greensboro (UNCG )
Web Site:
Mitchell Croatt

Abstract: Isocarbacyclin is a valuable synthetic target that has been recognized as a potential neuroprotective agent against ischemic stroke. Herein we describe a step-economical synthesis of isocarbacyclin in an enantioselective fashion. The 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; as a result other analogues were synthesized from the same building block. Another new synthetic route will be described that was designed to use the same combination of metal-catalyzed reactions for the synthesis of a tricyclic isocarbacyclin analogue. Instead of completing the tricyclic analogue, a novel cyclization was discovered. 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 described in detail.

Additional Information

Language: English
Date: 2017
Decarboxylation, Isocarbacyclin, Neuroprotection, Stroke, Synthesis, Tricyclic
Prostacyclin $x Therapeutic use
Neuroprotective agents $x Therapeutic use
Cerebrovascular disease $x Prevention

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