Evolution of a Short and Stereocontrolled Synthesis of (+)-7,20-Diisocyanoadociane.
Philipp C Roosen, Alexander S Karns, Bryan D Ellis, Christopher D Vanderwal
Author Information
Philipp C Roosen: Department of Chemistry, University of California, 1102 Natural Science II, Irvine, California 92697-2025, United States.
Alexander S Karns: Department of Chemistry, University of California, 1102 Natural Science II, Irvine, California 92697-2025, United States.
Bryan D Ellis: Department of Chemistry, University of California, 1102 Natural Science II, Irvine, California 92697-2025, United States.
Christopher D Vanderwal: Department of Chemistry, University of California, 1102 Natural Science II, Irvine, California 92697-2025, United States. ORCID
A full account of the development of a concise and highly stereoselective synthesis of (+)-7,20-diisocyanoadociane (DICA)─a structurally complex isocyanoditerpene with potent antiplasmodial activity─is described. The strategy that evolved relies on the rapid construction of unsaturated tricyclic precursors designed to undergo stereocontrolled Birch reductions and a subsequent "bay ring" formation to generate the isocycloamphilectane core. This report is divided into three sections: (1) a description of the initial strategy and the results that focused our efforts on a single route to the DICA core, (2) a discussion of the precise choreography needed to enable a first-generation formal synthesis of (±)-DICA, and (3) the execution of a 13-step second-generation synthesis of (+)-DICA that builds on important lessons learned from the first-generation effort.
