Total Synthesis of Belizentrin
Shahien Shahsavari
Original Research Proposal
Michigan Technological University
Department of Chemistry
Advisor- Dr. Shiyue Fang
Monday July 6, 2015
10:00 am
Chem-Sci 101
Abstract
Marine organisms are known to produce some of the most bioactive secondary metabolites found in nature. Currently, many of these marine-derived molecules are used as “first-in-class” drugs in the market. This proposal describes the total synthesis of belizentrin, a novel polyketide-derived macrocycle isolated from the marine dinoflagellate Prorocentrum belizeanum. Belizentrin has already demonstrated effective changes in neuronal survival assays in vitro at nanomolar concentrations. Additionally, its highly bioactive properties and structural similarities with other known immunosuppressant compounds make it a valuable target for medical research. However, since the extraction yield is minimal, it is essential to produce this compound in larger quantities from readily available starting materials for a complete investigation of its biological activities. The overall synthetic strategy involves a convergent late-stage coupling of three major fragments. The key features of the synthesis include iterative asymmetric allylic substitutions, titanium-catalyzed asymmetric epoxidation of terminal olefins, and the Yamaguchi macrolactonization to form the macrocyclic core of the molecule.