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A podcast hosted by L.-C. Campeau and Dani Schultz that dives into the stories about the people behind the chemistry and science that happens at #MerckChemistry. Follow us on Twitter at @PharmToTablePod, @DrLCSquare, @danithechemist Email us comments and suggestions at pharmtotablepod@gmail.com
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
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.
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.
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
Amanda is a wife. A mother. A blogger. A Christian.
A charming, beautiful, bubbly, young woman who lives life to the fullest.
But Amanda is dying, with a secret she doesn’t want anyone to know.
She starts a blog detailing her cancer journey, and becomes an inspiration, touching and
captivating her local community as well as followers all over the world.
Until one day investigative producer Nancy gets an anonymous tip telling her to look at Amanda’s
blog, setting Nancy on an unimaginable road to uncover Amanda’s secret.
Award winning journalist Charlie Webster explores this unbelievable and bizarre, but
all-too-real tale, of a woman from San Jose, California whose secret ripped a family apart and
left a community in shock.
Scamanda is the true story of a woman whose own words held the key to her secret.
New episodes every Monday.
Follow Scamanda on Apple Podcasts, Spotify, or wherever you listen.
Amanda’s blog posts are read by actor Kendall Horn.
