Pharm to Table

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

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 - ScienceA rational pre-catalyst design for bis-phosphine mono-oxide palladium catalyzed reactions - Chem SciLED-Illuminated NMR Spectroscopy: A Practical Tool forMechanistic Studies of Photochemical Reactions - ChemPhotoChemFrom at-line to online NMR: coupling probe-based autosampler with benchtop NMR - Reaction Chemistry and EngineeringFollow 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 interview Dr. Shane Krska, recipient of the ACS Arthur C. Cope Award, and Dr. Petr Vachal, recipient of the ACS Earle B. Barnes Award for Leadership in Chemical Research Management. Shane shares his pioneering work in catalytic methods and high-throughput experimentation (HTE) for drug discovery, while Petr discusses his leadership role driving innovation at Merck. They reflect on their career journeys from graduate school to industry, emphasizing personal growth and the importance on taking on diverse roles. We wrap it up by asking Shane and Petr what has made them the most proud over their 20+ year careers - which spans from innovations in direct-to-biology for accelerating design-make-test to advancing peptides as a modality of the future!Read the papers we discussed today:The Catalysis Laboratory at Merck: 20 Years of CatalyzingInnovationThe medicinal chemist's toolbox for late stage functionalization of drug-like moleculesHighly Efficient Asymmetric Synthesis of SitagliptinFollow the Pharm to Table podcast on X - ⁠⁠⁠⁠@PharmtoTablePod⁠⁠⁠⁠Visit our website at ⁠⁠⁠⁠⁠⁠https://podcasters.spotify.com/pod/show/pharm-to-table⁠⁠

Join us on the Pharm to Table podcast for a delightful chat with Ethan Wappes from our South San Francisco site, as we dive into the exciting world of thiophene synthesis! Ethan is a member of our Discovery Process Chemistry group and worked alongside medicinal chemists to devise a better synthetic route towards substituted thiophenes. Ethan shares insights from his recent Org. Lett. on a novel Rh-catalyzed [3+2] method that opens the door to highly substituted dihydrothiophenes, enhancing our medicinal chemistry toolkit. We explore how this strategy not only simplifies complex thiophene syntheses but also paves the way for new drug development possibilities!Read the papers we discussed today:Fully Substituted Thiophene Synthesis via (3 + 2) with Thiadiazoles - Org Lett 2024Follow the Pharm to Table podcast on X - ⁠⁠⁠⁠@PharmtoTablePod⁠⁠⁠⁠Visit our website at ⁠⁠⁠⁠https://podcasters.spotify.com/pod/show/pharm-to-table

Ready to go with the flow? Then this episode is for you! In this episode, we dive into the exciting world of Continuous-Flow Solid-Phase Peptide Synthesis (CF-SPPS) with special guests Kyle Ruhl and Mike DiMaso. We kick off the episode with a brief overview on various techniques used to synthesize peptides and how each method fits within the drug discovery/development timeline. From there, we serve up their recent paper on leveraging flow to synthesize peptides - exploring the challenges they faced, such as accommodating resin swelling and optimizing synthesis times. We do our best to shield you from any discussions about math when they dive into linear velocity which helped drive peptide synthesis optimization. Discover how CF-SPPS is unleashing rapid, multigram peptide deliveries, culminating in a remarkable 20-gram yield of a 10-mer peptide in just 4 hours! Read the paper we discussed today: Continuous-Flow Solid-Phase Peptide Synthesis to Enable Rapid, Multigram Deliveries of Peptides Follow the Pharm to Table podcast on X - ⁠⁠⁠⁠@PharmtoTablePod⁠⁠⁠⁠ Visit our website at ⁠⁠⁠⁠https://podcasters.spotify.com/pod/show/pharm-to-table

Time for the main course! Our #MerckChemistry hiring experts are dishing out more savory tips to help you get hired in pharma. In this second part, they'll guide you through mastering the job talk, nailing those crucial on-site interviews, and evaluating offers strategically. Learn how to deliver an engaging presentation, handle tough questions, and leave a lasting impression. Get advice on navigating those 1:1 interviews with poise. Once you've aced the interviews, find out how to weigh compensation packages and negotiate the most appetizing offer for your career growth. Whether you're a fresh grad looking to land that first gig or a seasoned pro ready for the next opportunity, this episode is the secret sauce you need! Follow the Pharm to Table podcast on X - ⁠⁠⁠⁠@PharmtoTablePod⁠⁠⁠⁠ Visit our website at ⁠⁠⁠⁠https://podcasters.spotify.com/pod/show/pharm-to-table

Patrick Fier and Suhon Kim join the pod to share their lates collaboration on a new C-N cross-coupling protocol which leverages a novel multifunctional template reagent. The work emerged from a side-project that started many years ago on the creation of the "Aminator" reagent which inspired the latest reaction. The couplings have very broad scope and Suhong and Patrick explain their motivation for pursuing the work and insights about the reaction enabled by this reagent. We learned a lot on this episode, and we hope you do too! Read the papers we discussed today: ⁠Transition-Metal-Free C–N Cross-Coupling Enabled by a Multifunctional Reagent - JACS A Multifunctional Reagent Designed for the Site-Selective Amination of Pyridines - JACS Follow the Pharm to Table podcast on Twitter - ⁠⁠⁠⁠@PharmtoTablePod⁠⁠⁠⁠ Visit our website at ⁠⁠⁠⁠https://podcasters.spotify.com/pod/show/pharm-to-table

Charles Yeung (@Charles_chem) joins the pod to share some of the latest results from a collaboration with Prof. Wickens' lab (@WickensGroup) at the University of Wisconsin Madison. In their latest paper published in Angewandte Chemie, they disclose a practical and general protocol for alcohol dehydrogenation - putting the Barton-McCombie on notice! The work was supported by a Merck post-doctoral fellow, Myriam Mikhael (@MyriaMikhael), who shares her experience as an industrial PDF. Read the papers we discussed today: Practical and General Alcohol Deoxygenation Protocol - ACIE Translating Planar Heterocycles into Three-Dimensional Analogs by Photoinduced Hydrocarboxylation - ACIE 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 serve up a recently published JACS article on Ni-catalyzed pyridinium cross-electrophile coupling for non-canonical amino acid synthesis and peptide late-stage functionalization which was done in collaboration with Professor Mary Watson’s group. In this episode, Dani and LC share the importance of investing in non-canonical amino acid chemistry with #MerckChemistry scientists Amélie Dion and Dipa Kalyani. We discuss what drew them to pyridinium cross-electrophile coupling and how Professor Watson’s expertise enabled the extension of this chemistry towards amino acid and peptide diversification via lysine deamination. By leveraging Dipa’s expertise in Discovery and high-throughput experimentation (HTE) – the team was able to create reaction generality for range of pharma relevant heteroaryl halides. In addition, Amélie was able to show that the lysine-derived pyridiniums survived solid-phase peptide synthesis and that the Ni-catalyzed cross-electrophile coupling could be achieved on-resin (rare!) – directly fitting into traditional medchem workflows. Professor Watson shares her insights on how working outside one’s area of expertise spurs innovation and ultimately what made this collaboration so successful. Many aspects of this collaboration were unique, which included real-time data sharing with our Discovery colleagues in addition to the team being largely composed of women! #WomenInChemistry Read the paper we discussed today here: ⁠Diversifying Amino Acids and Peptides via Deaminative Reductive Cross-Couplings Leveraging High-Throughput Experimentation - JACS Beyond 20 in the 21st Century: Prospects and Challenges of Non-canonical Amino Acids in Peptide Drug Discovery - ACS Med. Chem. Lett. Are Heterogeneous Catalysts Precursors to Homogeneous Catalysts? - JACS 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 dive into the challenges of strained cyclic peptide synthesis with Niki Patel and Dave Petrone who recently completed the total synthesis of Darobactin A in collaboration with Professor Sarlah's group at UIUC. Now this wasn't Merck's first foray into natural product total synthesis, in fact Darobactin A is part of a rich legacy of total syntheses at Merck that spans 80 years!  Niki and Dave share how the internal Merck team first envisioned putting this molecule together - including how to construct the complex non-canonical amino acids and ultimately how to forge the highly strained bis-macrolactams. They then walk us through how the team ended up collaborating with Professor Sarlah's team at UIUC combining efforts to complete the total synthesis. Niki, Dave, and Professor Sarlah describe that first meeting and share how they ultimately overcame the macrocyclization challenges which resulted in the total synthesis of Darobactin A! This episode is filled lots of learnings which include how to construct strained cyclic peptide but more importantly, how a strong network can elevate problem solving and potentially lead to a fruitful academic-industrial collaboration.  Read the paper we discussed today here: Total Synthesis of Darobactin A - JACS Follow the Pharm to Table podcast on Twitter - @PharmtoTablePod Visit our website at https://anchor.fm/pharm-to-table

For S2E2, we’re joined by drug hunting legends Doug Beshore and Izzat Raheem who recently co-authored a recent (and popular) paper in J. Med. Chem. on building a culture of knowledge exchange.  Ironically, it’s easier to learn through the literature than from your organization, colleagues or group members - especially if colleagues have taken on different roles. As a result, building and maintaining a culture where prior knowledge is easily accessible and updatable is paramount to a healthy learning culture.  In this episode we go into the 4 pillars that made knowledge exchange with Merck Discovery successful, which includes (1) IT; (2) knowledge capture; (3) participation and most importantly (4) culture. Knowledge management is not unique to industry - in fact, many of the lessons learned can be directly applied to an academic culture as well - and span beyond science and into DEI as well. So tune in to hear how simple practices can boost learning and knowledge exchange in your research.  Read the papers we discussed today here: Building a Culture of Medicinal Chemistry Knowledge Sharing - J. Med. Chem.  Follow the Pharm to Table podcast on Twitter - @PharmtoTablePod Visit our website at https://anchor.fm/pharm-to-table

For our kickoff of Season 2, LC and Dani get together (in person!) to reflect on what’s changed since the Pharm to Table pod started in late 2020, answer a listener question (only 9 months late!) on whether a postdoc is needed for an industrial job, and give a sneak peak on what’s to come for Season 2.  Whether you listen in the car or in the lab - buckle up and don that PPE - as Season 2 is destined to be full of energy, laughs and awesome #MerckChemistry. Follow the Pharm to Table podcast on Twitter - @PharmtoTablePod Visit our website at https://anchor.fm/pharm-to-table

For the 9th course, Dani and LC do the robot dance with Melodie Christensen (@chemchristensen on Twitter) #MerckChemistry Enabling Technologies group. Melodie shares her unique career path with us, including her current PhD with @procastiprof - more >10 years after starting her career in pharma. Resident expert in reaction automation, robotics and self-optimizing reactions, Melodie shares her journey in high-throughput and data-rich experimentation. We discuss her award winning paper in JOC and how she was able to use some of the insights of this work to develop an autonomously optimized Suzuki reaction! Finally, Melodie schools us on her best smoothie recipes and three letter acronyms. Read the paper we discussed today here: Enantioselective Synthesis of α-Methyl-β-cyclopropyldihydrocinnamates - Journal of Organic Chemistry Data-science driven autonomous process optimization - Communications Chemistry The Evolution of High-Throughput Experimentation in Pharmaceutical Development and Perspectives on the Future - OPRD Automation isn't automatic - Chemical Science Follow Melodie Christensen - @chemchristensen Follow the Pharm to Table podcast on Twitter - @PharmtoTablePod Visit our website at https://anchor.fm/pharm-to-table