A Total Synthesis of Salinosporamide†A.

Salinosporamide A is a ß-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.

Synthesis of bicyclic tetrahydrofurans from linear precursors using manganese(III) acetate.

We have recently developed methodology based on oxidative radical reactions for the synthesis of [3.3.0]-bicyclic lactones containing both cyclopentanes and γ-lactams along with application of this methodology to the synthesis of natural products and complex molecular architectures. Herein we report an extension of this methodology to the synthesis of oxygen heterocycles including bicyclic bis-lactones.

Diastereoselective synthesis of fused lactone-pyrrolidinones; application to a formal synthesis of (-)-salinosporamide A.

A mild, diastereoselective synthesis of fused lactone-pyrrolidinones using an oxidative radical cyclization is reported. The methodology is demonstrated in a formal synthesis of (-)-salinosporamide A.