Investigations in the synthesis of isocarbacyclin analogs involving transition metal catalysis with explorations into palladium catalyzed decarboxylation.

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Kristen Elizabeth Gettys (Creator)
The University of North Carolina at Greensboro (UNCG )
Web Site:
Mitchell Croatt

Abstract: Isocarbacyclin, a synthetic form of prostacyclin, has been recognized as a potential neuroprotective drug which could be used for patients of ischaemic stroke. The first goal described in this thesis was to create a new set of analogs of isocarbacyclin which had a saturated ring system and perform biological testing on these compounds using conditions that mimicked ischaemic stroke symptoms. The synthesis of these compounds was to contain three transition metal catalyzed steps which installed a great deal of complexity into the molecule in only a few steps. These three steps included a palladium catalyzed decarboxylation, a rhodium catalyzed cycloaddition, and a ruthenium catalyzed cross metathesis. However, when the first of these three steps, a decarboxylation, failed to yield product, efforts went to the discovery of the mechanism of this reaction. A second generation synthesis was then conceived, which also contained the same three transition metal catalyzed steps, but the decarboxylation step again failed to yield sufficient product. Due to the complications discovered with transition metal catalyzed decarboxylation reactions, the final investigations described include the results of experiments which give light to the necessary elements for decarboxylation to occur. Herein is presented the efforts of the total synthesis of isocarbacyclin analogs along with the results of explorations into palladium catalyzed decarboxylations.

Additional Information

Language: English
Date: 2013
Isocarbacyclin, Neuroprotective drug, Ischaemic stroke
Prostacyclin $x Therapeutic use
Neuroprotective agents $x Therapeutic use
Cerebrovascular disease $x Prevention

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