Past Event

Merck Lecture 2023, Presented by Prof. Keary Engle, Scripps Research Institute

January 19, 2023
4:00 PM - 5:30 PM
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Havemeyer 209



Alkenes as Universal Functional Group Progenitors

Presented by Prof. Keary Engle
Hosted by Prof. Tekle-Smith

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Alkenes are inexpensive, widely available chemical feedstocks that can be sourced from petroleum or renewable resources. The goal of research in the Engle lab is to develop novel catalytic alkene functionalization reactions that introduce new functional groups at each of the alkenyl carbon atoms in a programmable fashion. In addition this way simple, planar starting materials can be directly converted into densely functionalized, stereochemically defined products, which can then serve as building blocks for structurally complex target molecules that are of academic and industrial importance, including many widely used pharmaceutical agents. To this end, the Engle lab has developed strategies involving directing auxiliaries, native directing groups, and transient directing groups, as well as complementary non-directed approaches that are compatible with a variety of metals, redox manifolds, and coupling partners. Detailed mechanistic studies have shed light on the interplay between the substrate, metal, and ancillary ligands in dictating reaction outcomes, informing new catalyst designs through an iterative feedback loop.



Foreword Lecture Presented by Dr. David Thaisrivongs, Merck & Co, Inc.


Dr. David Thaisrivongs

Synthetic macrocyclic peptides that target protein-protein interactions: the discovery and early chemistry development of a PCSK9 inhibitor

Presented by Dr. David Thaisrivongs


Inhibition of Proprotein Convertase Subtilisin/Kexin type-9 (PCSK9) improves cardiovascular outcomes in patients requiring additional low-density lipoprotein cholesterol reduction on top of statins, but there has been limited uptake of the two commercialized PCSK9 antibody inhibitors due in part to cost and route of administration. The protein-protein interaction between PCSK9 and the low-density lipoprotein receptor which is targeted by these therapies is a large, flat surface, which has made the discovery of orally-bioavailable small molecule inhibitors highly challenging. This talk will introduce the use of macrocyclic peptides to interrupt such protein-protein interactions, and describe the discovery and early chemistry development of such a PCSK9 inhibitor.

David Thaisrivongs is a Director of Process Chemistry in the Process Research and Development organization at Merck & Co., Inc. He obtained an A.B. in Biochemical Sciences from Harvard University and a Ph.D. in Chemistry from Stanford University. During his time with Merck he has had the opportunity to contribute to discovery and development programs across multiple therapeutic areas, including oncology, cardiovascular disease, HIV, HCV, and Alzheimer’s disease, and has led teams to develop and commercialize robust, sustainable manufacturing processes to support the supply of Merck’s medicines to patients, worldwide. He is the founder of the Merck Research Award for Underrepresented Chemists of Color, which seeks to mentor and develop the next generation of scientists.


Contact Information

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