Pharm to Table

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 MerckFollow the Pharm to Table podcast on X - ⁠⁠⁠⁠@PharmtoTablePod⁠⁠⁠⁠Visit our website at ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://podcasters.spotify.com/pod/show/pharm-to-table⁠⁠⁠⁠⁠⁠⁠

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

In this episode, Dani and LC welcome Jeff Moore, recipient of the 2025 ACS Affordable Green Chemistry Award, to discuss his pioneering work in biocatalysis at Merck. The conversation explores the evolution (pun intended) of biocatalytic processes in pharmaceutical manufacturing, highlighting key milestones such as the adoption of transaminases and imine reductases, and their impact on drug synthesis and sustainability. Jeff shares stories from his career, including how being 'lazy' when doing science can lead to major innovations and the practical benefits of enzyme-driven chemistry. He even leaves us with insights into the future frontiers of biocatalysis, from cascade reactions to microfluidics.Read some of the papers we discussed today:Convergent Kilogram-Scale Synthesis of Dual Orexin Receptor Antagonist - Organic Letters Biocatalytic Asymmetric Synthesis of Chiral Amines from Ketones Applied to Sitagliptin Manufacture - ScienceEnabling Biocatalysis by High-Throughput Protein Engineering Using Droplet Microfluidics Coupled to Mass Spectrometry - ACS OmegaFollow the Pharm to Table podcast on X - ⁠⁠⁠⁠@PharmtoTablePod⁠⁠⁠⁠Visit our website at ⁠⁠⁠⁠⁠⁠⁠https://podcasters.spotify.com/pod/show/pharm-to-table⁠⁠⁠

This month we sit down with Damien Valette, Olivia Boyd and David Petrone to chat about their latest paper in Organic Letters on the desymmetrization of prochiral dienones to control all-carbon quaternary centers. This reaction leverages biocatalysis, specifically an ene-reductase [ERED] enzymes (which are making their second appearance on the pod - see S1:E5).David, Damien and Olivia walk us through the discovery of the reaction and why it's uniquely suited to set these challenging stereocenters. This work was done in the context of work at the med-chem/process interface which we explore as well.Damien and Olivia hail from our London UK MSD site and give us details on the progress of our company's build in the region as well as chat with us about how to be successful when collaborating with scientists on another continent (David).Read the papers we discussed today:HTE-Enabled Development of an Ene-Reductase-Catalyzed Desymmetrization: Remote Control of All-Carbon Quaternary γ-Centers ⁠- Org Lett 2024Follow the Pharm to Table podcast on X - ⁠⁠⁠⁠@PharmtoTablePod⁠⁠⁠⁠Visit our website at ⁠⁠⁠⁠⁠https://podcasters.spotify.com/pod/show/pharm-to-table⁠

Antibody drug conjugates, or ADCs, are all the rage in the industry right now and chemists play an important role in their development. This month we sat down with Serge Ruccolo and Marion Emmert to talk about their papers in this area. Their work addresses two main challenges of ADC development: 1) potent handling of cytotoxic payloads and 2) selective unmasking of cysteine residues to enable conjugation to the antibody. Tune in to hear how one develops these chemistries; How electrochemistry and microfluidics can be useful tools for the chemistry of these important molecules. You'll learn a ton, we did! Read the papers we discussed today: “Build Your Own” ADC Mimics: Identification of Nontoxic Linker/Payload Mimics for HIC-Based DAR Determination, High-Throughput Optimization, and Continuous Flow Conjugation - OPRD Electrocatalytic Reduction of Disulfide Bonds across Chemical Modalities - Org Lett Follow the Pharm to Table podcast on X - ⁠⁠⁠⁠@PharmtoTablePod⁠⁠⁠⁠ Visit our website at ⁠⁠⁠⁠https://podcasters.spotify.com/pod/show/pharm-to-table

Join Dani and LC as they peel back the layers on podcasting in chemistry. This insightful episode dives into their recently published Organic Letters editorial "Should You Start a Chemistry Podcast?" with special contributor and corresponding author Matt Horwitz from Synthesis Workshop sharing his unique perspective. But that's not all - get ready for an artistic twist as Brendan Burkett from Chemscrapes reveals how he transforms chemistry concepts into visually striking designs for the chemistry community (including CEN!). Whether you're an aspiring podcaster, a chemistry communicator, or just someone fascinated by the interplay of science and art, this episode promises an engaging exploration. Tune in for a candid discussion blending personal experiences, creative insights, and a passion for making chemistry more accessible to all. Don't miss this multimedia showcase!" Follow the Pharm to Table podcast on X - ⁠⁠⁠⁠@PharmtoTablePod⁠⁠⁠⁠ Visit our website at ⁠⁠⁠⁠https://podcasters.spotify.com/pod/show/pharm-to-table Org. Lett. featured: https://pubs.acs.org/doi/full/10.1021/acs.orglett.3c04181

Alexandra Sun and Harrison Rose join the pod to share their work on a vision-guided automated liquid-liquid extraction (LLE) platform. That's right, before our robot overlords overtake us, they are going to help chemists and engineers with work-ups first! Even though it's often taken for granted, liquid-liquid extractions are part of virtually every chemical reaction for product isolation. Developing these unit operations is critical to chemists and engineers who design processes and Harrison and Alex's new tool can help expedite this. We also asked them for their secret to developing the best phase cuts! We learned a lot on this episode, and we hope you do too! Read the papers we discussed today: ⁠Vision-Guided Automation Platform for Liquid–Liquid Extraction and Workup Development - OPRD General Principles and Strategies for Salting-Out Informed by the Hofmeister Series - OPRD Follow the Pharm to Table podcast on X - ⁠⁠⁠⁠@PharmtoTablePod⁠⁠⁠⁠ Visit our website at ⁠⁠⁠⁠https://podcasters.spotify.com/pod/show/pharm-to-table

Nadine Kuhl (process chemist) and Jacob Forstater (engineer and physicist) join the pod to share a pretty neat story that had its origins from a chemical catalog brochure advertising a new and green solvent called Cyrene. From that brochure blossomed a really amazing biocatalytic transamination to make a key chiral amine building block. In order to make this process more robust and tolerant of organic solvents, the team immobilized the transaminase enzyme and leveraged a Spinchem rotating bed reactor (we also had no idea what this was, but now we do) to make a robust process. We learned a lot on this episode, and we hope you do too! Read the papers we discussed today: Amination of a green solvent via immobilized biocatalysis for the synthesis of nemtabrutinib - ACS Catalysis Utilizing biocatalysis and a sulfolane-mediated reductive acetal opening to access nemtabrutinib from cyrene - Green Chemistry Follow the Pharm to Table podcast on Twitter - ⁠⁠⁠@PharmtoTablePod⁠⁠⁠ Visit our website at ⁠⁠⁠https://podcasters.spotify.com/pod/show/pharm-to-table

For our special Holiday extravaganza, Dani and LC share their holiday plans before diving into the cookie jar of questions from some of our favorite listeners! How is R&D in industry similar to and different from how research is done in academia? (@DrSauce96) What is the most annoying academic misconception about work in the pharmaceutical industry? (@Teachforaliving) What things do you wish you knew before starting in industry? (@lifeof_dan) What is your favorite coupling reaction to run? Doesn’t have to be one you use most or the one with the broadest scope, just the one you look forward to setting up. (@ndchiappini) What can be done to help educate PhD students about industrial careers? The majority of them won’t go to academia, but it seems many profs know very little about non-academic pathways? (@Chem_Walker) So top off that nog and join us for a Holiday Snack! Follow the Pharm to Table podcast on Twitter - ⁠@PharmtoTablePod⁠ Visit our website at ⁠https://podcasters.spotify.com/pod/show/pharm-to-table

For this month's episode, Dani and LC go all in on Ni-catalyzed cyanations with Caleb Hethcox who recently published 2 papers on the topic - one with a phenomenal intern, Geraldo Duran-Camacho. Caleb shares how the internal team first identified this challenge and the solutions they explored to replace precious metal catalysts for cyanation reactions! Ultimately, the team identified a Ni-catalyzed system (go base metals!) and depending on the application, different reduction conditions which led to the different publications. As part of Merck's Future Talents Program, Caleb was joined by Geraldo who came to Merck and worked in our laboratories on this project. In addition, Geraldo gives us some of his learnings and insights from the experience which will be of great interest to potential future interns who listen to this episode. Read the paper we discussed today here: Nickel-Catalyzed Cyanation of (Hetero)aryl Bromides Using DABAL-Me3 as a Soluble Reductant - Org. Lett. Air-Tolerant Nickel-Catalyzed Cyanation of (Hetero)aryl Halides Enabled by a Green Reductant - J. Org. Chem. Merck Future Talent Program Follow the Pharm to Table podcast on Twitter - ⁠@PharmtoTablePod⁠ Visit our website at ⁠https://podcasters.spotify.com/pod/show/pharm-to-table

For our special Holiday extravaganza, Dani and LC reminisce about the holidays while in grad school (think candy throw downs and chainsaws) before diving into the cookie jar of questions from some of our favorite listeners!    What is a good way to figure out if you'd be a better fit for a medicinal chemistry or process chemistry role? (@billthechemist) What do you know now that you wished you knew during your undergraduate or early graduate school? (@MichaelAxiotes) How is pregnancy and parenthood handled in industry? (@EleanorMLandwe1) How do you decide with whom you collaborate with in academia? (@AnneJMcNeil) What recent chemistry breakthrough over the last few year has been the biggest surprise? (@AlexSolivan) If you could draw any chemical transformation on paper and have it work in the lab, what would it be and why? (@stanna_dorn) So top off that nog and join us for a Holiday Snack! Follow the Pharm to Table podcast on Twitter - @PharmtoTablePod Visit our website at https://anchor.fm/pharm-to-table

We kick off season 2 with a bang, talking about complex molecule synthesis with John McIntosh and Nastaran Salehi. Cyclic dinucleotides (CDNs) are a total synthesis fan's dream with 10 stereocenters (including 2 at phosphorus) arranged around a 13 membered macrocycle formed by 2 non-canonical nucleosides. These endogenous secondary messenger molecules have attracted attention because of their activation of the immune system via the STING pathway. We go into all aspects of the innovative biocatalytic cascade that the team designed for their synthesis, including: 1) How a bald eagle cyclic guanosine-adenosine synthase (cGAS) was engineered to form the macrocycle; 2) How cGAS was leveraged by medicinal chemists to greatly accelerate drug discovery; 3) How the team strung together and optimized a 4-enzyme cascade to deliver a CDN directly from nucleotide building blocks. Read the papers we discussed today here:  A kinase-cGAS cascade to synthesize a therapeutic STING activator - Nature New Mechanism for Cinchona Alkaloid-Catalysis Allows for an Efficient Thiophosphorylation Reaction - J. Am. Chem. Soc. Follow Nastaran Salehi - @Nastaran198 Follow the Pharm to Table podcast on Twitter - @PharmtoTablePod Visit our website at https://anchor.fm/pharm-to-table

For the 10th, and final course of season 1, Dani and LC jump in the hot tub flow time machine with Cecilia Bottecchia and Francois Levesque, co-recipient of the Peter Dunn Green Chemistry Award, and learn how to discover, develop and scale-up a photobromination in flow! But don't let this deceptively simple bromination fool you - this reaction turned out to be a full course meal of challenges! We go into all aspects of the reaction, including: 1) Why they decided to use light vs AIBN to facilitate this reaction; 2) How to design a photoreactor you can use on kilo scale; 3) How to design a robust reaction that can run on >50kg scale; 4) What does hot tub chemistry have to do with a radical bromination reaction.  Read the paper we discussed today here: A Continuous Flow Visible-Light-Induced Benzylic Bromination - Organic Process Research and Development Elucidation of Reaction Mechanisms Using In Situ LED-NMR - Journal of Organic Chemistry Design of a Kilogram Scale, Plug Flow Photoreactor Enabled by High Power LEDs - Organic Process Research and Development Follow Cecilia Bottecchia - @cecibottecchia Follow the Pharm to Table podcast on Twitter - @PharmtoTablePod Visit our website at https://anchor.fm/pharm-to-table