University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 1-1-2013 Total Synthesis of (+)-18-Epi-Latrunculol A Brett aD niel Williams University of Pennsylvania,
[email protected] Follow this and additional works at: http://repository.upenn.edu/edissertations Part of the Organic Chemistry Commons Recommended Citation Williams, Brett aD niel, "Total Synthesis of (+)-18-Epi-Latrunculol A" (2013). Publicly Accessible Penn Dissertations. 946. http://repository.upenn.edu/edissertations/946 This paper is posted at ScholarlyCommons. http://repository.upenn.edu/edissertations/946 For more information, please contact
[email protected]. Total Synthesis of (+)-18-Epi-Latrunculol A Abstract The ott al 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