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

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

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

For the 7th course, Dani and LC serve up a hearty helping of nucleoside chemistry with Artis Klapars and Dan DiRocco from the #MerckChemistry Rahway NJ Process Chemistry group. We tee off this episode by diving into the ProTide pool to find out what exactly ProTides are why they are so important for the development of common antiviral and anticancer drugs. Then, Artis and Dan tell us about their efforts to develop a green solution to the ProTide synthesis problem by designing a multifunctional catalyst that stereoselectively assembles ProDrugs - the results of which were published in Science and recognized by the 2020 EPA Green Chemistry Challenge award! Designing this catalysts was no small feat - with Artis and Dan sharing their approach to catalysts design (think HTE, RPKA, and modeling) and how to persevere through the ups and downs of industrial research. We end our discussion by getting their perspectives on green manufacturing and what challenges still exist for constructing non-canonical nucleosides.  Read the paper we discussed today here: A multifunctional catalyst that stereoselectively assembles prodrugs - Science  Efficient synthesis of antiviral agent uprifosbuvir enabled by new synthetic methods - Chem Sci Follow the Pharm to Table podcast on Twitter - @PharmtoTablePod Visit our website at https://anchor.fm/pharm-to-table

For the 6th course, Dani and LC serve up a delicious discussion with Steve Silverman (@asymtmm on Twitter) from the #MerckChemistry Kenilworth NJ Discovery Process Chemistry group. Steve tells us about an industrial-academic collaboration he's leading with Professor Rob Britton's laboratory at Simon Fraser University (@BrittonLab on Twitter) where they discovered a short de novo route to nucleoside analogs. We discuss why nucleoside analogues are so important to pharmaceutical development and why, despite decades of research, they still pose a significant synthetic challenge for chemists. We also learn what inspired this collaboration (the real story) and get to hear from Rob himself about his motivations in joining forces on this project! Read the paper we discussed today here: A short de novo synthesis of nucleoside analogs Diversity-oriented synthesis of glycomimetics Follow the Pharm to Table podcast on Twitter - @PharmtoTablePod Visit our website at https://anchor.fm/pharm-to-table

For our special Holiday Snack episode we invite Eric Ashley (Director of Discovery Process Chemistry, @DrERAChem), Yeon-Hee Lim (Director of Discovery Chemistry, @alchemistyhl) and James Roane (Senior Scientist, Discovery Chemistry) from our South San Francisco research laboratories to join us and answer YOUR questions! What topics or case studies to help students understand drug discovery better? What was the most surprising thing about starting your career and navigating the transition from grad school to industry? What is a moment in your career that you were the proudest and what was the impact of the work that you were doing? We also ask our guests why they decided to join and stay at #MerckChemistry. So get your Holiday Egg Nog on and join us for a Holiday Snack!

ChemTwitter told us it takes 3 minutes to run a TLC plate, so today we‘re brining you 3 good minutes with Cecilia Bottecchia, Senior Scientist in Flow Chemistry group. Cecilia joined #MerckChemistry a little >2 years ago bringing her flow experience to Merck and immediately having an impact  (Google Scholar). She was recently the co-recipient of the Peter Dunn Green Chemistry Award for the development of a greener manufacturing process featuring a photo-flow bromination. We discuss her experience as a new scientist at Merck, her award and answer the real important questions, like: Does pineapple belong on pizza?! Register for C&EN's write-up of the Peter Dunn award see: https://cen.acs.org/acs-news/Merck-team-wins-2021-Peter/99/i17 Follow Cecilia on Twitter - @cecibottecchia Follow the Pharm to Table podcast on Twitter - @PharmToTablePod Visit our website at https://anchor.fm/pharm-to-table

For the 5th course, join Dani and LC as they sit down with #MerckChemistry's Meg Shaw and Chihui An to discuss their biocatalytic approach in transforming readily available acrylic acids to chiral α-substituted carboxylic acids - a reoccurring motif in drug development. As this story evolved (no pun intended),  we’ll hear how Meg (Process Chemistry) and Chihui (Biocatalysis) joined forces to develop an ene-reductase (ERED) to effect the asymmetric reduction of acrylic acids and ultimately why transition metal catalyzed approaches were ditched. In addition, the duo discuss what brought them to pursue a career in industry, how they discovered this reaction (the real story) and what it's like to run enzymatic reactions (turns out it's easy!). We also feature Merck Future Talents Program intern, Annika Tharp, who shares how she secured her internship and provides insider tips on how to crush your interview! Read the paper we discussed today here: Enantioselective Enzymatic Reduction of Acrylic Acids 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 brining you 3 good minutes with Becky Ruck, Executive Director and Head of Enabling Technologies in Small Molecule Process R&D. Becky has amassed an amazing portfolio of amazing science (Google Scholar) in a variety of roles at #MerckChemistry. She recently took on a role as a Topic Editor for ACS Catalysis to help bring more industrial science to the journal. Having led recruiting for many years, Becky gives prospective new hires and applicants some insider information on how to be successful in starting an industrial career. Follow Becky on Twitter - @Ruck_chem Follow ACS Catalysis on Twitter - @ACSCatalysis Follow the Pharm to Table podcast on Twitter - @PharmToTablePod

For our 4th course, we sit down with Dipa Kalyani to chat about her journey from a tenured professor position at St-Olaf to associate principal scientist within our Discovery organization via an academic-industrial collaboration with Dani. This episode explores how pairing state-of-the-art capabilities in HTE (the high-throughput experimentation kind) with great problem selection can lead to a nice impactful method for direct arylation of heterocycles with pharmaceutically relevant aryl chlorides. This work was served up in the Journal of Organic Chemistry and also featured in an ACS special virtual issue titled “Celebrating Women in Organic Chemistry” (all female authors!). Last but not least, we also discuss our musical prowess (P.S. Dipa wins). Listen to find out! Read the paper we discussed today here: Ni-Catalyzed C–H Arylation of Oxazoles and Benzoxazoles Using Pharmaceutically Relevant Aryl Chlorides and Bromides Follow Dipa on Twitter - @DipaKalyani1 Follow the Pharm to Table podcast on Twitter - @PharmToTablePod

ChemTwitter told us it takes 3 minutes to run a TLC plate, so today we‘re brining you 3 good minutes with Patrick Fier, Principal Scientist in Process Chemistry. Patrick has a had a roaring start to his career at Merck in the last 5 years (Google Scholar) and was just named to C&EN's Talented 12 for 2021. Building on this season's Episode 2: Phenols and Sulfonamides are Cool, Patrick returns to the pod to discuss this recognition and answer the real important questions, like: Who did he tell first about the award? What his favorite reaction and ice cream flavor is? We also find out about his first job! Register for C&EN's Talented 12 event here: https://connect.acspubs.org/Talented12_2021 Follow Patrick on Twitter - @PatrickFier Follow the Pharm to Table podcast on Twitter - @PharmToTablePod

For our 3rd course we serve up another #MerckChemistry duo, Libby Hennessy (aka Simon) and Aaron Sather (aka Garfunkel) who join us to discuss their discovery of a new way to access N-(hetero)aryl piperidines. We'll discover how to convince your grandma why piperidines are so important to drug discovery and learn how chemistry advances are made at the interface of Process and Medicinal Chemistry at Merck. We'll also dive into the Merck Future Talents program which brings in interns to come work with us. Lastly, Dani and LC probe Libby & Aaron on which superpower would take this chemistry to the next level (or not) .... Listen to find out! Read the paper we discussed today here: A Modular and Diastereoselective 5 + 1 Cyclization Approach to N-(Hetero)Aryl Piperidines Follow the Pharm to Table podcast on Twitter - @PharmToTablePod

ChemTwitter told us it takes 3 minutes to run a TLC plate, so today we‘re brining you 3 good minutes with Jamie McCabe Dunn, Director of Process Chemistry who, on top of delivering amazing science (Google Scholar), is also leading recruiting of new hires for our Process Chemistry teams. While this episode is short, we get answers to some serious questions such as “Is South Dakota considered the Midwest or central USA?”; “Will building a network really impact my chances of getting a job?”; and most importantly “What makes a good vs great job talk?”  Follow Jamie on Twitter - @mccabedunn Follow the Pharm to Table podcast on Twitter - @PharmToTablePod

ChemTwitter told us it takes 3 minutes to run a TLC plate, so today we‘re brining you 3 good minutes with Ania Fryszkowska, a biocatalysis whiz who recently co-authored an article in Science on innovative biocatalytic cascades to access sugars (link HERE). While this episode is short, we get answers to some serious questions such as “which Nobel laureate zoom-bombed the Virtual Biocatalysis and Protein Engineering Meetups?”; “what does the future of biocatalysis hold?”; and most importantly “cats or dogs?” and “cookies or candy?” - trick questions 😉. Follow Ania on Twitter - @fryania Follow the Pharm to Table podcast on Twitter - @PharmToTablePod

For our 2nd course, a #winning #MerckChemistry duo, Patrick Fier and Kevin Maloney, join us to discuss their discovery of the Maloney-Fier reaction (campaigning to be in the 2nd edition of the indispensable Strategic Applications of Named Reaction in Organic Synthesis by Kurti/Czako)  as well as other projects they've collaborated on in the last few years. We'll uncover why these two work so well together and how they balance exploring scientific curiosities while having day jobs as successful process chemists. Dani and LC also try to find out which famous duo they are most like: Batman and Robin? Han Solo and Chewy? Listen to find out! Read their papers we discussed today here: Direct Conversion of Haloarenes to Phenols under Mild, Transition-Metal-Free Conditions Synthesis of Complex Phenols Enabled by a Rationally Designed Hydroxide Surrogate Reagent Design and Ligand Evolution for the Development of a Mild Copper-Catalyzed Hydroxylation Reaction NHC-Catalyzed Deamination of Primary Sulfonamides: A Platform for Late-Stage Functionalization Reductive Cleavage of Secondary Sulfonamides: Converting Terminal Functional Groups into Versatile Synthetic Handles Follow the Pharm to Table podcast on Twitter - @PharmToTablePod

Every great meal starts with an inspiration.... Find out how Pharm to Table was created from an idea to our release. You'll find out how we gathered all the essential ingredients - including our name, logo, music and also folks that gave us great advice along the way. You will also get to meet a key early contributor, our Merck Future Talent program intern Jimmy Olsen (now a graduate student with Professor John Wood at Baylor!), who helped us get off the ground last year! Follow the Pharm to Table podcast on Twitter - @PharmToTablePod

For our 1st course (and inaugural episode!!), Dani and L.-C. serve up the true Pharm to Table experience by discussing the importance of academic-industrial collaborations through the lens of their comment piece published in Nature Chemistry titled “Harder, Better, Faster.” This article struck a cord with a lot of folks in the chemistry community (>22k views) and created a social media buzz where academics and industrial scientists debated the age old question “Why don’t you use my [insert science here]”? To learn more about the origin story our article (think Stu Cantrill + Vanilla Ice + Twitter), how to improve industrial-academic relations, and how to get started in building your network and start collaborating – then tune in! You can read the paper here: Harder, Better, Faster Follow the Pharm to Table podcast on Twitter - @PharmToTablePod

Another teaser! Here is our delicious theme song. Thanks to Mark Partridge (twitter: @markrightmedia) for this original piece! One more week to the launch! The 1st episode drops July 5th. Please subscribe so you never miss new content.

Check out our trailer! Join L.-C. Campeau and Dani Schultz as they explore the amazing stories and people behind the papers from #MerckChemistry. We promise to always bring tasty (pun intended) #MerckChemistry content to our table that is guaranteed to have you coming back for another dose (pun intended, again). Subscribe to get all our new episodes.