Concise Synthesis of (-)-GA18 Methyl Ester

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 trans-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).

Automated summary

A concise synthesis of (-)-GA18 methyl ester from commercially available and cheap andrographolide is reported. The synthesis involves intramolecular ene reaction, oxidative cleavage and aldol condensation, photochemical cycloaddition, and skeletal rearrangement.