Concise Total Synthesis of (±)-Salinosporamide A, (±)-Cinnabaramide A, and Derivatives via a Bis-cyclization Process: Implications for a Biosynthetic Pathway?

Abstract

4-Alkylidene-β-lactones (hetero ketene dimers) and α-amino acids are useful precursors for total syntheses of the β-lactone-containing proteasome inhibitors salinosporamide A, cinnabaramide A, and derivatives. A key step is a nucleophile-promoted, bis-cyclization of keto acids that simultaneously generates the γ-lactam and β-lactone of these natural products. This reaction sequence may have implications for the biosynthesis of these natural products.