We are currently engaged in the total synthesis of vitisinol D, recently isolated as a minor constituent from the roots of Vitis thunbergii, a folk-medicine plant of Taiwan. Although several attempts have been made to construct this resveratrol natural product, only simplified versions of its [3.2.1] bicyclic core have been generated to date. In this presentation, we discuss an approach to this congested [3.2.1] bicyclic structure in which an allenyl ester is utilized as a key building block for the rapid assembly of the bicyclic skeleton. In this approach, an allenyl ester was reacted with a cyclic ketone under thermodynamic conditions to give a bicyclic lactone. Reduction of the lactone produces an enolate-aldehyde intermediate that undergoes an intramolecular aldol reaction to give the desired bicyclic structure. Currently, the project poses three major challenges, which include introduction of unsaturation, late stage aryl addition, and finally a resistant decarboxylation. In addition to these synthesis studies, a limited SAR of simplified analogs of vitisinol D will be described. These analogs exhibit a neuroprotective effect in synaptic failure experiments in a <i>Drosophila melanogaster</i> neural tissue model under oxidative stress.

Studies toward the total synthesis of vitisinol D and evaluation of its analogs as neuroprotective agents

255th National Meeting (2018)

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