Total Synthesis of Alanense B via Stereoselective Enolate Alkylation

A total synthesis of (±)-alanense B, a unique and unprecedented 2-aryl substituted cadinane-type sesquiterpenoid that exhibits spontaneous calcium channel oscillations in primary cultured neocortical neurons, has been accomplished. Intramolecular Friedel-Crafts acylation and enolate methylation using KHMDS in 1,2-dimethoxyethane yielded the pentasubstituted 1-tetralone bearing a quaternary stereogenic center at the C2 position with complete diastereoselectivity. Cleavage of three phenolic methyl ethers prior to DDQ oxidation was essential for reaching the final product.