S2.E8: Peptides, Cross-Electrophile Coupling and Maple Syrup!

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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