Total Synthesis of Cephanolide A and Harringtonolide: A Unified Strategy Connecting Benzenoid and Troponoid Cephalotaxus Diterpenoids

The fascinating benzenoid and troponoid Cephalotaxus diterpenoids are highly related biosynthetically, both of which are popular targets for total synthesis. Herein, we describe a unified strategy for the concise synthesis of cephanolide A and harringtonolide in 14 and 16 steps respectively. Palladium catalyzed Csp2-Csp3 cross-coupling followed by doubly electron-deficient intramolecular Diels-Alder reaction secure the rapid construction of the Cephalotaxus carbon framework. Late-stage benzenoid-to-troponoid ring expansion was accomplished employing Büchner-Curtius-Schlotterbeck (BCS) reaction, furnishing harringtonolide in two steps from cephanolide A. This work shed light on the chemical synthetic connection between benzenoid and troponoid Cephalotaxus diterpenoids.