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

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! (@DrSauce96)(@Teachforaliving)What things do you wish you knew before starting in industry(@lifeof_dan)(@ndchiappini) (@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 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 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

Dr. Becky Ruck joins Dani and LC for the grand finale of our journey reviewing the history of the Merck Catalysis Laboratory. She highlights how her background in physical organic chemistry led to deeper role of understanding mechanism and kinetics in development of reactions - a strength of Becky's which ultimately influenced the direction of the Catalysis group. Becky also gives a forward looking perspective as leader of the Process Research & Development Enabling Technologies organization where her team is taking on small molecules, biologics and vaccines! Read the paper we discussed today here: The Catalysis Laboratory at Merck: 20 Years of Catalyzing Innovation - ACS Catalysis Follow Becky on Twitter - @Ruck_chem Follow the Pharm to Table podcast on Twitter - @PharmtoTablePod Visit our website at https://anchor.fm/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! 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

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

ChemTwitter told us it takes 3 minutes to run a TLC plate, so today we‘re bringing you 3 good minutes with Sue Zultanski (Associate Principal Scientist, Discovery Process Chemistry). Sue first joined our #MerckChemistry Discovery group in 2006 before obtaining her PhD and then starting in Merck Process in 2016. Since joining, Sue has sought solutions across boundaries, weaving deep mechanistic understanding into developing robust manufacturing routes (OPRD) and also through an academic-industrial partnership Prof. Nilay Hazari (JACS). In our last installment of the 'Spring ACS Sneak Peaks' - we're flipping the tables and having Sue interview Dani on what motivated her to create a symposium on ‘Taming non-canonical amino acid synthesis’ – a symposium that they collaboratively organized for the upcoming Spring ACS in San Diego. We discuss what inspired Dani and Sue to take on this symposium together, highlight the speakers and share what they hope the audience walks away with. Complete speaker lineup for Taming the Unnatural - Innovative Noncanonical Amino Acid Synthesis for Drug Discovery and Beyond: H.C. Brown Award Symposium Register for Spring 2022 ACS (in-person, hybrid, and virtual) Follow Sue on LinkedIn - HERE 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 Marion Emmert (Principal Scientist, Catalysis and Enabling Technologies) and Colin Lam (Associate Principal Scientist, Computational and Structural Chemistry). Marion joined #MerckChemistry in 2018 (after a successful career in academia) and has brought her love for catalysis into drug discovery (Google Scholar). Colin joined #MerckChemistry in 2016 and has flexed his computational might on a myriad of projects spanning the portfolio (Google Scholar). Today, Marion and Colin stopped by to give a sneak peak on 'Theory to Therapy' - a symposium that they collaboratively organized for the upcoming Spring ACS in San Diego. We discuss what inspired Marion and Colin to take on this symposium together, highlight the speakers and share what they hope the audience walks away with. Complete speaker lineup for From Theory to Therapy: New Developments in Quantum Mechanical Calculations for Driving Best Chemistry in Academia and Industry Register for Spring 2022 ACS (in-person, hybrid, and virtual) Follow Marion on Twitter - @emmertlab Follow Colin on Twitter - @yhcolin Follow the Pharm to Table podcast on Twitter - @PharmtoTablePod Visit our website at https://anchor.fm/pharm-to-table