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)
- Institution
- The University of North Carolina at Greensboro (UNCG )
- Web Site: http://library.uncg.edu/
- Advisor
- 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.
Synthesis and biological evaluation of potent neuroprotective agents against stroke and research on a novel type of decarboxylation reaction
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Created on 5/1/2017
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Additional Information
- Publication
- Dissertation
- Language: English
- Date: 2017
- Keywords
- Decarboxylation, Isocarbacyclin, Neuroprotection, Stroke, Synthesis, Tricyclic
- Subjects
- Prostacyclin $x Therapeutic use
- Neuroprotective agents $x Therapeutic use
- Decarboxylation
- Cerebrovascular disease $x Prevention