Concise Formal Synthesis of (−)-Salinosporamide A (Marizomib) Using a Regio- and Stereoselective Epoxidation and Reductive Oxirane Ring-Opening Strategy

Expedient access to a highly functionalized 2-pyrrolidinone (8), the γ-lactam core of 20S proteasome inhibitor (−)-salinosporamide A (marizomib; NPI-0052; 1), using a regio- and stereoselective epoxide formation/reductive oxirane ring-opening strategy is presented. Notably, the sequential construction of the C-4, C-3, and C-2 stereocenters of 1 in a completely stereocontrolled fashion is a key feature of streamlining the synthesis of intermediate 12. A related strategy is also discussed.