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

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

Looking to kickstart your career in the pharmaceutical industry? This episode is a must-listen! We have special guests Jamie McCabe Dunn, Val Shurtleff and our very own Dani Schultz - hiring managers in Discovery and Process Chemistry - to share insider tips. In part 1 we talk about building a rock-solid network, crafting a standout CV that gets noticed, and acing those crucial first interviews. We also answer listener questions submitted on LinkedIn. Whether you're a fresh grad or an experienced pro, our experts will give you the competitive edge to land your dream job in pharma! Plus, stay tuned for Part 2 we tackle how to ace your job talk, prepare for interviews and steps to take after receiving an offer! Follow the Pharm to Table podcast on X - ⁠⁠⁠⁠@PharmtoTablePod⁠⁠⁠⁠ Visit our website at ⁠⁠⁠⁠https://podcasters.spotify.com/pod/show/pharm-to-table

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

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

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

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

L.-C. and Dani talk about the next era in the Catalysis Lab's evolution, highlighting the democratization of high-throughput experimentation tools for end-users and the development of nanomole-scale HTE. It was also in this period that the Catalysis Laboratory's expanded its capabilities in photochemistry developing screening tools to invent and scale-up novel photochemical synthetic methods, including decatungstate mediate reactions and photoredox catalysis. Read the paper we discussed today here: The Catalysis Laboratory at Merck: 20 Years of Catalyzing Innovation - ACS Catalysis Nanomole-scale high-throughput chemistry for the synthesis of complex molecules - Science Enantioselective Synthesis of Hemiaminals via Pd-Catalyzed C–N Coupling with Chiral Bisphosphine Mono-oxides - JACS A rational pre-catalyst design for bis-phosphine mono-oxide palladium catalyzed reactions - Chemical Science Development of a Direct Photocatalytic C–H Fluorination for the Preparative Synthesis of Odanacatib - Organic Letters Follow the Pharm to Table podcast on Twitter - @PharmtoTablePod Visit our website at https://anchor.fm/pharm-to-table

In this month's episode, and our 1st of 3 parts dedicated the 20th anniversary of Merck's Catalysis Laboratory, Dani and L.-C. sit down and chat with Shane Krska (@swkrska) who was one of the founding members of the Catalysis Laboratory. Shane walks us through the genesis of the group, its early impact on our projects and people. In this first 10 years of the laboratory, there was a heavy focus on asymmetric hydrogenation and cross-coupling, as well as developing all the tools necessary to rapidly identify reaction conditions using high-throughput experimentation, all of which helped shape the field of catalysis that we know today! We also hear how industry-academia partnerships contributed to new directions for the team - with longtime collaborator and friend, Professor Paul Chirik, sharing his thoughts. Read the paper we discussed today here: The Catalysis Laboratory at Merck: 20 Years of Catalyzing Innovation - ACS Catalysis Highly Efficient Synthesis of β-Amino Acid Derivatives via Asymmetric Hydrogenation of Unprotected Enamines - JACS Highly Efficient Asymmetric Synthesis of Sitagliptin - JACS Cobalt Precursors for High-Throughput Discovery of Base Metal Asymmetric Alkene Hydrogenation Catalysts - Science Follow Shane Krska on Twitter - @swkrska Follow the Pharm to Table podcast on Twitter - @PharmtoTablePod Visit our website at https://anchor.fm/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 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

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

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 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

Cecilia Bottecchia is originally from Italy and Francois Levesque is native of Canada. Both have had very international pathways during their studies which have ultimately brought them to #MerckChemistry in the US. We asked them to tell us a little bit about this transition and have a little fun with a Canadian vs Italian food quiz!

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

ChemTwitter told us it takes 3 minutes to run a TLC plate, so today we‘re bringing you 3 good minutes with David Thaisrivongs (Director) and Jenny Obligacion (Associate Principal Scientist) from our Rahway, NJ Process Chemistry group. David and Jenny tell us about a symposia featuring Outstanding Chemists of Color, their motivation for creating this event and the broader implications highlighting Chemists of Color can have on the equity, diversity and inclusion in our field. Complete speaker lineup for Outstanding Chemists of Color Chemists of Color informational video on YouTube Register for Spring 2022 ACS (in-person, hybrid, and virtual) Follow David on Linkedin Follow Jenny on Linkedin and on Twitter (@jobligac) Follow the Pharm to Table podcast on Twitter - @PharmtoTablePod Visit our website at https://anchor.fm/pharm-to-table

ChemTwitter told us it takes 3 minutes to run a TLC plate, so today we‘re bringing you 3 good minutes with Xiaoshen Ma, Associate Principal Scientist in our Boston Discovery Chemistry group. Xiaoshen joined #MerckChemistry in 2018 and has been influential in advancing drug discovery through the exploration of bicyclo[1.1.1]pentanes (aka BCP's) as bioisosteres for arenes - the work of which is already making an impact (Google Scholar). Today, Xiaoshen stopped by to give a sneak peak on Synthetic Advances Toward Novel Bicyclo[1.1.1]pentanes - a symposium that he organized at the upcoming Spring ACS in San Diego. We discuss what inspired Xiaoshen to take on this symposium, highlight the speakers and share what he hopes the audience walks away with.   Complete speaker lineup for Synthetic Advances Toward Novel Bicyclo[1.1.1]pentanes  Register for Spring 2022 ACS (in-person, hybrid, and virtual) Follow Xiaoshen on Twitter - @XMa75870843  Follow the Pharm to Table podcast on Twitter - @PharmtoTablePod Visit our website at https://anchor.fm/pharm-to-table

For the 8th course, Dani and LC ride the biocatalytic cascade with Ania Fryszkowska (@fryania on Twitter) and Greg Hughes (@greg_hughes on Twitter) from the #MerckChemistry Process Chemistry group. Greg, a process chemistry pro, kicks off this episode by giving a high-level overview of the drug development process and the differences in designing clinical supply route vs. a final commercial route. Ania, a biocatalysis superstar, then takes us on a retrosynthetic journey that ultimately led to a multi-enzyme biocatalytic cascade for the construction of non-canonical nucleosides - published in Science. Directed evolution was critical throughout this process, and Ania shares how #MerckChemistry internal capabilities allowed the discovery and optimization of each biocatalytic step (5 total!). We end with Greg and Ania sharing how far biocatalysis has come in commercial route development and the future that biocatalysis holds for sustainable pharmaceutical manufacturing. Read the paper we discussed today here: Design of an in vitro biocatalytic cascade for the manufacture of an antiviral (Science) Biocatalysis in drug discovery and development Follow Ania Fryszkowska - @fryania Follow Greg Hughes - @greg_hughes Follow the Pharm to Table podcast on Twitter - @PharmtoTablePod Visit our website at https://anchor.fm/pharm-to-table