A Total Synthesis of Salinosporamide A

Abstract

Salinosporamide A is a β-lactone proteasome inhibitor currently in clinical trials for the treatment of multiple-myeloma. Herein we report a short synthesis of this small, highly functionalized, biologically important natural product that uses an oxidative radical cyclization as a key step and allows for the preparation of gram quantities of advanced synthetic intermediates.

Keywords: cyclization; natural products; proteasome inhibitor; radicals; total synthesis.