Pharm to Table LC Campeau & Dani Schultz

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!