We are currently engaged in the total synthesis of vitisinol D, a congested [3.2.1] bicyclic dimer of resveratrol. The all-carbon bicyclic core of this natural product serves as a unique scaffold that is underrepresented in drug screen operations. In this presentation, an optimized and abbreviated synthesis of a small library of natural product inspired compounds (called resveramorphs), with up to six consecutive stereocenters, will be discussed. Our synthesis route allows for complete control over relative stereochemistry effectively allowing us to access three-dimensional chemical space with superb positional control of the substituents decorating the bicyclic scaffold. During exploratory biological screenings, these compounds exhibited neuroprotective activity at sub-nanomolar concentrations in a <i>Drosophila melanogaster</i> neural tissue model under oxidative stress. An initial SAR study has been accomplished and will be described along with our efforts to identify potential biological targets.

Natural product inspired bridged bicyclic compounds as neuroprotective agents

2019 Spring National Meeting

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