Special Organic Chemistry Seminar

Peptide synthesis is practiced in labs around the world, perhaps nonstop. An industry created over the last half-century supports this activity and its diverse endpoints, including drug discovery and development. These admirable endpoints often obscure the limitations of the reaction, including restrictions on structural diversity, expensive coupling reagents, wasteful co-product formation that fuels intensive purification, and the peril of critical reagents known to be sensitizers used in super-stoichiometric amounts. We developed Umpolung Amide Synthesis to break this singular paradigm in peptide synthesis, while prioritizing the solution of persistent shortcomings of amide synthesis to develop a truly complementary method. Consequently, we embarked on a mission to dovetail the application of both paradigms within a complex synthesis so that the ideals of total synthesis are served. This has culminated in a total synthesis of the aryl glycine-rich tridecapeptide feglymycin and new retrosynthetic disconnections for catalytic, enantioselective amide synthesis. Our use of minimalism to drive reaction development is a unifying theme, despite the complexity that lies beneath. Our efforts to capitalize on the principle of minimalism in catalyst and reaction development will also highlight its critical supporting role to advance sustainable amide synthesis by sourcing dirt-cheap starting materials.