Bioinspired Skeletal Reorganization Approach for the Synthesis of Terpenoid Natural Products

Terpenoids are a large and structurally diverse family of natural products with significant pharmacological activities. A key structural feature found in many of these molecules-including certain Schisandra nortriterpenoids and limonoids-is a unique tetrahydrofuran-lactone-fused motif. Despite its prevalence, a general and efficient method for constructing this framework has remained elusive. Inspired by the biosynthetic pathway proposed for Schisandra nortriterpenoids, our group has developed a bioinspired skeletal reorganization strategy that leverages a biomimetic transesterification/oxa-Michael addition (TOMA) cascade to efficiently build the complex fused-ring systems from readily prepared precursors. The utility of this TOMA cascade has been demonstrated through the successful synthesis of three terpenoid natural products:propindilactone G, rubriflordilactone B, and deoxylimonin.