Merck Seminar: Dr. Cheol K. Chung, Associate Principal Scientist, Merck Research Laboratories

"Toward Greener Drug Manufacturing Process: Development of Organocatalytic Asymmetric Aza-Michael Route for Letermovir"

About the Seminar:

Human cytomegalovirus (HCMV) causes serious morbidity and mortality in immunocompromised patients, particularly those with advanced HIV and those undergoing organ transplant. Existing therapies almost universally target DNA polymerase, and thus suffer from severe toxicity and increasingly prevalent drug resistance. Letermovir is a potent DNA terminase inhibitor (EC50 = ca 5 nM) with no observed dose-dependent toxicity, and has been awarded both fast track and orphan drug status in 2011. The first generation synthesis of letermovir involving a classical resolution was considered sufficient for initial clinical supplies; however, in view of its racemic mode and significant raw material costs, a more efficient and cost effective route, appropriate for sustainable long-term supply, was desirable. This presentation will describe our recent chemistry development efforts toward a concise and efficient asymmetric synthesis which culminated in the development of a novel catalytic asymmetric aza-Michael cyclization reaction exploiting two classes of organocatalysis, bis-quaternized phase-transfer catalysis and hydrogen-bonding catalysis.

About the Speaker:

Dr. Cheol K. Chung received his B.S. and M.S. degree in chemistry from Seoul National University in Korea. After working for LG Life Sciences for 5 years, he moved to the United States and joined the research group of Professor Barry Trost at Stanford University, where he explored the transition metal catalyzed transformations of alkynes and their application to natural product synthesis. After completion of his Ph.D. in 2006, Cheol moved to California Institute of Technology for postdoctoral training to further his knowledge in organometallic catalysis under the supervision of Professor Robert Grubbs. In 2008, he joined the Merck Research Laboratories in Rahway, New Jersey, where he currently holds the position of Associate Principal Scientist in Process R & D Department. His main areas of interest are the application of catalytic reactions in organic synthesis, designing efficient and practical synthesis of complex drug candidates, and development of new reactions using high-throughput experimentation.