Date of Award
Doctor of Philosophy (PhD)
Amos B. Smith
The total synthesis of (+)-18-epi-latrunculol A was undertaken to provide synthetic access to a sufficient amount of the scarce, sponge-derived macrolide to facilitate further biological evaluation. Preliminary bioassays revealed (+)-18-epi-latrunculol A to exhibit a selective, solid tumor cytotoxicity, while being devoid of the actin depolymerization activity customary to the latrunculin family of natural products, making the epimeric natural product a compound of interest for chemotherapeutics. An enantioselective total synthesis of (+)-18-epi-latrunculol A was accomplished; key features of the synthesis include a functional group compatible cross metathesis reaction, an acid mediated cyclization/equilibration, a Carreira alkynylation, and a late-stage Mitsunobu macrolactonization. Finally, a novel method was also discovered to achieve the cyclization of delta-hydroxy-E-enones under mild, photochemical conditions.
Williams, Brett Daniel, "Total Synthesis of (+)-18-Epi-Latrunculol A" (2013). Publicly Accessible Penn Dissertations. 946.