We report the development of a general route to the synthesis of [4.3.1], [3.3.1],
an especially [3.2.1] bicyclic compounds structurally related to vitisinol D, a natural
product. This allows for diastereoselective synthesis of bicyclic compounds with
five adjacent chiral centers. This route was employed in a preliminary SAR
investigation into the neuroprotectant effect of small molecules in an in vivo
experiment measuring the degree of restorative effect of synaptic transmission in
the neuromuscular junction of Drosophila melanogaster larvae under acute
oxidative stress. One of the compounds exhibited intriguing potential as a
neuroprotectant and outperformed resveratrol in restoring synaptic function under
oxidative stress. The hypothesis that bridged bicyclic compounds may hold promise as drug scaffolds due to their conformational rigidity and ability to orient
functional appendages in unique orientations is developed.
The second focus is a mechanistic investigation into a tetrabutylammoniumcatalyzed
cycloaddition as evidence of a novel ammonium-alkyne interaction. A
carbamate nitrogen adds to a non-conjugated carbon–carbon triple bond under the
action of an ammonium catalyst leading to a cyclic product. Studies in
homogeneous systems suggest that the ammonium agent facilitates cyclitive
nitrogen–carbon bond formation through a cation–π interaction with the alkyne
unit. Using Raman spectroscopy, this cation–π interaction is directly observed for
the first time. DFT modeling elucidated the mechanistic factors in this
cycloaddition.
A teaching experiment was developed based on this mechanistic investigation.
Control experiments were employed to demonstrate the testing of two alternative
mechanistic hypotheses. Cyclization reactions were performed with a soluble base
(sodium phenoxide) with and without tetrabutylammonium bromide under
homogeneous conditions. Students observed that ammonium salt accelerates the
reaction. They were encouraged to develop a testable hypothesis for the role of
the ammonium salt in the cyclization mechanism: typical phase transfer or other.
IR spectroscopy was used to directly observe a dose dependent shift of the alkyne
stretching mode due to a cation−π interaction. Undergraduates were able to
employ the scientific method on a contemporary system and see how data are
generated and interpreted to adjudicate between rival hypotheses in a way that
emulates authentic and current research in a lab setting. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2018. / FAU Electronic Theses and Dissertations Collection
| Identifer | oai:union.ndltd.org:fau.edu/oai:fau.digital.flvc.org:fau_40756 |
| Contributors | St.Germain, Elijah (author), Lepore, Salvatore D. (Thesis advisor), Florida Atlantic University (Degree grantor), Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry |
| Publisher | Florida Atlantic University |
| Source Sets | Florida Atlantic University |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation, Text |
| Format | 206 p., application/pdf |
| Rights | Copyright © is held by the author, with permission granted to Florida Atlantic University to digitize, archive and distribute this item for non-profit research and educational purposes. Any reuse of this item in excess of fair use or other copyright exemptions requires permission of the copyright holder., http://rightsstatements.org/vocab/InC/1.0/ |
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