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!

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:

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!

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:

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:

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:

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:

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:

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:

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!

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. 

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.

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.

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:

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!).

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:

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:

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!

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!