Pharm to Table

What happens when the textbook SAR playbook stops working? On this episode of Pharm to Table, Rob Garbaccio joins Dani and LC to share the discovery story behind enlicitide (MK-0616), a journey filled with unusual SAR, creative problem-solving, and plenty of chemistry twists along the way. From issue-driven drug design to non-canonical amino acids and modular synthesis strategies, this conversation offers a behind-the-scenes look at how real medicines are discovered. If you're training as a chemist today, this is a story you won't want to miss.

If you enjoyed this chapter of the enlicitide story, stay tuned—we've got plenty more peptide chemistry, process development adventures, and behind-the-scenes drug discovery stories coming your way this season.

Read some of the papers we discussed today:
Discovery Process of Enlicitide, a Highly Engineered Macrocyclic Peptide Therapeutic, through Issue-Driven Fragment-Based Synthetic Assembly and SAR - ⁠J. Med. Chem.⁠
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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
Follow the Pharm to Table podcast on X - ⁠⁠⁠⁠@PharmtoTablePod
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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.
Follow the Pharm to Table podcast on X - ⁠⁠⁠⁠@PharmtoTablePod
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Join us for a conversation with Yining Ji Chen, recipient of the 2025 ACS Rising Star Award, on how mechanistic insight powers innovation in pharmaceutical process research. We dive into her career journey and standout projects—from Pd-catalyzed C–N coupling for HCV therapy to dynamic phosphorylation in nucleotide synthesis—plus her creation of LED‑NMR for real-time photochemical reaction monitoring. Hear how deep mechanistic understanding drives robustness and safety, why she moved to the Data‑Rich Measurements group, and which emerging analytical technologies excite her most. A celebration of scientific rigor shaping efficient, reliable pharma processes!
Read some of the papers we discussed today:
A multifunctional catalyst that stereoselectively assembles prodrugs - Science
A rational pre-catalyst design for bis-phosphine mono-oxide palladium catalyzed reactions - Chem Sci
LED-Illuminated NMR Spectroscopy: A Practical Tool forMechanistic Studies of Photochemical Reactions - ChemPhotoChem
From at-line to online NMR: coupling probe-based autosampler with benchtop NMR - Reaction Chemistry and Engineering
Follow the Pharm to Table podcast on X - ⁠⁠⁠⁠@PharmtoTablePod
⁠⁠⁠⁠Visit our website at ⁠⁠⁠⁠⁠⁠⁠⁠https://podcasters.spotify.com/pod/show/pharm-to-table⁠⁠⁠⁠