To kick off Season 5, Dani and LC discuss a recent perspective published in the Journal of Organic Chemistry that highlights innovations in synthetic chemistry which trace their origins to the work of discovering, developing and commercializing novel therapeutics. This publication was the most accessed paper published in JOC in 2025!

Dani and LC explore the motivations on writing it, its main thesis and lesson learned from reexamining nearly 75 years of chemistry innovations at Merck.

Be sure to listen through to the very end for a special Season 5 theme reveal!

Read and listen to some of the papers we discussed today:

From Cortisone to Enlicitide: A Journey of Synthetic Chemistry Innovations at Merck

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In Part 2 of our Pharm to Table deep dive on MK‑7845, Dani and LC shift from invention to implementation, welcoming process chemists Nastaran Salehi Marzijarani and Ben Turnbull to the pod. We explore how the team re‑imagined the synthesis to enable robust, scalable supply—and why a classic multicomponent reaction you probably remember from school, the Joullié–Ugi reaction, ended up stealing the show. Along the way, we unpack route selection trade‑offs, lifecycle thinking in process chemistry, and what it really takes to bring an antiviral to life at scale.

Read and listen to some of the papers we discussed today:

Asymmetric Synthesis of MK-7845, an Investigational Treatment for COVID-19 - Org. Lett.

Part 1 of MK-7845 series: SE4:E7: From Discovery to Process, Part 1: Building a 3CL Protease Inhibitor Through Smart Fluorine Placement and Design Intuition

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In this first installment of our two‑part Pharm to Table special on MK‑7845, Dani and LC sit down with medicinal chemist Valerie Shurtleff to unpack the discovery journey behind this 3CL protease inhibitor—from early structural insights to an unexpectedly effective difluorobutyl isostere. Val walks us through how the team balanced potency, VLE, metabolic challenges, and design intuition to land on a well‑rounded preclinical candidate - one of the most dynamic programs of her career. Along the way, she reminds us why asking good questions, collaborating relentlessly, and occasionally surviving a “Hot Ones” challenge are all essential scientific skills. It’s an episode packed with chemistry, creativity, and just enough fluorine to keep things spicy.

Stay tuned for Part 2, where we shift from invention to implementation and explore how the process chemistry team brought MK‑7845 to life at scale.

Read some of the papers we discussed today:

Invention of MK-7845, a SARS-CoV-2 3CL Protease Inhibitor Employing a Novel Difluorinated Glutamine Mimic - J. Med. Chem.

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⁠⁠⁠⁠Visit our website at ⁠⁠⁠⁠⁠⁠⁠⁠⁠https://podcasters.spotify.com/pod/show/pharm-to-table⁠⁠⁠⁠⁠