Researcher(s)
- Sara Standish, Chemistry, University of Delaware
Faculty Mentor(s)
- William Chain, Chemistry and Biochemistry, University of Delaware
Abstract
Icetexanes are a diverse family of natural products that feature a 6-7-6 tricyclic core and show promise as leads for breast cancer therapeutics. Within this family of natural products is a unique heterodimeric diterpenoid known as premnalatifolin A. This natural product, first isolated in 2011 by Babu and colleagues from the stem-bark of an Indian medicinal plant, Premna latifolia, exhibits excellent activity towards breast cancer and colon cancer (MCF-7, IC50 = 1.77 μM; HT-29, IC50 = 19.4 μM). Due to premnalatifolin A’s significant biological activity and synthetically interesting heterodimeric functionality, the Chain Lab has been working towards achieving the first total synthesis. To this end, I have been pursuing a modified and more efficient strategy to form the aromatic functionality of the core. My work utilizes reactions such as a Wittig, a methylation and a hydroxymethylation in order to access the desired penta-substituted aromatic ring. This will serve as a key component for an alkylation-metathesis sequence developed by the Chain Lab. Furthermore, in efforts to make our synthesis enantioselective, I have begun by optimizing a racemic nickel-catalyzed reductive conjugate addition to synthesize the vinyl precursor necessary for our alkylation sequence. With the desired product in hand, future work will be focused on testing chiral ligands using UD’s High Throughput Experimentation Core in order to make the method enantioselective.