Advanced Synthetic Strategies toward Ginkgolide Diterpenoids: Total Synthesis of (±)-Ginkgolide C and Formal Syntheses of (±)-Ginkgolides A and B

Ginkgolides are highly oxygenated diterpenes isolated from <i>Ginkgo biloba</i> that exhibit potent anti-inflammatory and neuroprotective properties. Their compact hexacyclic architecture─featuring multiple contiguous stereocenters, a spirocyclic core, and a rare <i>tert</i>-butyl group─presents a formidable challenge in synthetic organic chemistry. Herein, we report the first total synthesis of ginkgolide C (<b>3</b>), the most structurally complex member of this family, completed in 26 steps from commercially available materials. The synthesis is guided by a functional group-driven strategy that enables the convergent construction of the polycyclic core through key diastereoselective carbon-carbon bond formations, selective oxidations, and late-stage epoxide-opening lactonizations. In parallel, the formal syntheses of ginkgolides A (<b>1</b>) and B (<b>2</b>) were accomplished via interception of a late-stage intermediate in 17 steps, the shortest route to these targets reported to date. This work provides a unified synthetic platform for accessing the ginkgolide family and offers new opportunities for the synthesis and biological evaluation of related analogues.