Title, Authors, Journal name: Proteasome Inhibition by a Totally Synthetic .beta.-Lactam Related to Salinosporamide A and Omuralide. Hogan, Philip C.; Corey, E. J.. Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA. Journal of the American Chemical Society (2005), 127(44), 15386-15387.

Abstract: A new and effective proteasome inhibitor, .beta.-lactam I, has been accessed enantioselectively by multistep synthesis from the readily prepd. intermediates II and III which were joined by a [2 + 2]-cycloaddn. reaction to form the spiro .beta.-lactam IV stereoselectively. The intermediate IV was converted to I in seven steps and 30% overall yield. The .beta.-lactam I is stable for many days in water at pH 7, in contrast to the natural .beta.-lactones salinosporamide A and omuralide. In common with salinosporamide A and omuralide, the .beta.-lactam I effectively inhibits the mammalian proteasome.