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.

Today’s readings are [Spiegel 2006, Marcaurelle 2010]. Themes for today are:

  1. Catalytic diastereoselective reactions as a way to access all possible diasteremers.
  2. An oligomer-based approach to the all-by-all matrix of possible stereoisomeric products.
  3. 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.