Pharm to Table LC Campeau & Dani Schultz

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



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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



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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!

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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

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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

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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

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Visit our website at https://anchor.fm/pharm-to-table