Resveratrol

This work encompasses the synthesis, analysis, and optimization of [3.2.1] all-carbon bridged bicyclic compounds, known as resveramorphs (RVM), Studies were conducted using a Caenorhabditis elegans model, where RVMs were tested for antiseizure capabilities. In both applications, RVMs proved potent with activities in the sub-nanomolar level in one case. A structure-activity relationship (SAR) was hypothesized for the identification of the pharmacophore. The six to seven step synthesis route towards the RVM analogues is discussed in further detail. The bicyclization of the RVMs is achieved through a reductive aldol reaction. The reaction suffers from selectivity issues leading to multiple bicyclic products. By following a one-factor-at-a-time (OFAT) methodology, attempts at optimization for this reaction were made, however, despite important gains, the overall yields of the bicyclic product remain low. Other products from this reaction have been used to understand the reaction mechanism, which will be the basis for future efforts to further optimize this key step.

Synaptic transmission is a mechanism that makes life possible for many organisms. Damaging this crucial process, such as with a buildup of Reactive Oxygen Species (ROS), is extremely detrimental for the entire organism. Previously, the Dawson-Scully lab has determined that exposure of the Drosophila melanogaster neuromuscular junction (NMJ) to ROS accumulation can result in synaptic failure at a faster rate than saline controls (Caplan et al., 2013). To combat such effects, novel three-dimensional Resveramorph compounds were created to act as a neuroprotective agent against the harmful effects of acute oxidative stress (Bollinger et al., 2019; Sial et al., 2019). With the initial Resveramorph compounds demonstrating neuroprotective effects, additional analysis of other Resveramorph compounds were of interest to better understand their role in neuroprotection. Further testing of these compounds allows for the investigation of how chemical structure affects a compound’s neuroprotective activity.