These are my notes from lecture 14 of Harvard’s Chemistry 101: Chemical Biology Towards Precision Medicine course, taught by Dr. Stuart Schreiber on October 22, 2015.
- Catalytic diastereoselective reactions as a way to access all possible diasteremers.
- An oligomer-based approach to the all-by-all matrix of possible stereoisomeric products.
- Innovation and execution, achieving diversity in “production mode”
We’ve previously discussed some uses of diastereoselective catalysts in Kishi’s syntheis of halichondrin, lecture 6. Some other interesting examples are [Chavez & Jacobsen 2003, Balskus & Jacobsen 2007, Coric & List 2012].
One approach is Povarov reactions to form every possible stereochemical product at the coupling stage. For example compare the endo product of [Liu 2009] to the exo product of [Gerard 2012]. The first of today’s readings [Spiegel 2006] is really an attempt to pick a set of simple building blocks and, similar to nature’s strategy, couple them in diverse combinations of 2-, 3-, and 4-mers. There is also reagent-based diversification through pair-click reactions [Kelly 2009]. Note that “click reactions” are exactly the same thing as Huisgen reactions, but the name “click” has made this reaction much more famous because it sounds catchy.