Proteasome Inhibition by a Totally Synthetic β-Lactam Related to Salinosporamide A and Omuralide
- 14 October 2005
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 127 (44) , 15386-15387
- https://doi.org/10.1021/ja056284a
Abstract
A new and effective proteasome inhibitor, β-lactam 3, has been accessed enantioselectively by multistep synthesis from the readily prepared intermediates 7 and 8 which were joined by a [2 + 2]-cycloaddition reaction to form the spiro β-lactam 9 stereoselectively. The intermediate 9 was converted to 3 in seven steps and 30% overall yield. The β-lactam 3 is stable for many days in water at pH 7, in contrast to the natural β-lactones salinosporamide A (1) and omuralide (2). In common with 1 and 2, the β-lactam 3 effectively inhibits the mammalian proteasome.Keywords
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