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 CatalyzingInnovation
The medicinal chemist's toolbox for late stage functionalization of drug-like molecules
Highly Efficient Asymmetric Synthesis of Sitagliptin
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This month we sit down with Damien Valette, Olivia Boyd and David Petrone to chat about their latest paper in Organic Letters on the desymmetrization of prochiral dienones to control all-carbon quaternary centers. This reaction leverages biocatalysis, specifically an ene-reductase [ERED] enzymes (which are making their second appearance on the pod - see S1:E5).
David, Damien and Olivia walk us through the discovery of the reaction and why it's uniquely suited to set these challenging stereocenters. This work was done in the context of work at the med-chem/process interface which we explore as well.
Damien and Olivia hail from our London UK MSD site and give us details on the progress of our company's build in the region as well as chat with us about how to be successful when collaborating with scientists on another continent (David).
Read the papers we discussed today:
HTE-Enabled Development of an Ene-Reductase-Catalyzed Desymmetrization: Remote Control of All-Carbon Quaternary γ-Centers - Org Lett 2024
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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 2024
Follow the Pharm to Table podcast on X - @PharmtoTablePod
Visit our website at https://podcasters.spotify.com/pod/show/pharm-to-table
We're kicking off Season 4 (holy cow!) by having a lively discussion answering listener questions on everything from our favorite Boc deprotection methods to the role of AI in the world of chemistry. We also share how flow chemistry is being used in discovery and process chemistry and conclude with what we feel would be disruptive chemistry innovations that could shape 2025. Plus, find out how you can influence the conversation by sharing what you want to hear more of in 2025!
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
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
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
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!
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.
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
