BMS Lectureship in Synthetic Chemistry

3:30PM  Christopher Sfouggatakis

Discovery and Development of a Stereoselective Synthesis of BMS-986001: A Nucleoside Reverse Transcriptase Inhibitor (NRTI) for the Treatment of HIV Infection

Nucleoside Reverse Transcriptase Inhibitors (NRTI’s) were first synthesized in the 1960’s and have been developed as treatments for HIV over the last 30 years. BMS-986001 is an investigational nucleoside analog being developed by Bristol Myers-Squibb as a potential new treatment in this area, and the discovery of a safe, efficient and economical synthesis of this compound was critical to its continued development.  Key aspects of the new synthesis include: [1] a highly diastereoselective Li-acetylide addition to a ketone; [2] an efficient ring contraction of a decorated pyranose ring; [3] a b-selective introduction of thymine at the anomeric position; and [4] pyrolysis of a rare sulfilimine intermediate to generate the dihydrofuran moiety.  The innovative synthetic approach provides the densely functionalized drug substance in 5 steps (5 isolations) and 32% overall yield scale from known starting materials. It was discovered, developed, and implemented on multi-kilogram scale in less than one year – leveraging simultaneous optimization and execution.

4:30PM  Brett Fors

Development and Applications of New Synthetic Strategies for Polymer Science

Synthetic polymers are of almost inconceivable importance in all aspects of modern life, and during the last few decades, these materials have facilitated major societal advances. Innovative polymeric materials have the potential to address humankind’s next grand scientific and technological challenges; however, taking advantage of the opportunities presented by these materials requires new methods for gaining precise control of polymer structure and function. To address this challenge, our research group focuses on the development of new synthetic methods and catalyst systems to control polymer architecture, composition, and function to yield next-generation materials for energy storage, plastics, water filtration, electronics, and health-related applications. Specifically, this presentation will detail (1) the development of cationic polymerization reactions where polymer chain growth and sequence are regulated with light and (2) a modular strategy to dictate the shape and composition of polymer molecular weight distribution to precisely control properties.

Reception to follow