Concise Synthesis of (−)-GA₁₈ Methyl Ester

Abstract

Gibberellins (GAs) are important plant hormones, but some of their family members are in extremely limited natural supply including GA₁₈. Herein, we report a concise synthesis of (-)-GA₁₈ methyl ester, a member of the C₂₀ gibberellins, from commercially available and cheap andrographolide. Our synthesis features an intramolecular ene reaction to form the C ring, an oxidative cleavage followed by aldol condensation to realize a ring contraction and form the challenging <i>trans</i>-hydrindane (AB ring), and a photochemical [2+2] cycloaddition accompanied by a subsequent SmI₂-mediated skeletal rearrangement to construct the methylenebicyclo[3.2.1]octanol moiety (CD ring).