Serendipity in discovery of proteasome inhibitors

Among its various catalytic activities, the 'chymotrypsin-like' activity of the Proteasome, a large multicatalytic proteinase complex has emerged as the focus of drug discovery efforts in Cancer therapy. Herein, a series of first generation (2S, 3R)-2-amino-3-hydroxybutyric acid derived Proteasome inhibitors that were discovered serendipitously en route to original goal of generating a series of sterically constrained oxazoline derivatives has been reported.