Concise Synthesis of the Antiplasmodial Isocyanoterpene 7,20-Diisocyanoadociane.
Alexander S Karns, Bryan D Ellis, Philipp C Roosen, Zeinab Chahine, Karine G Le Roch, Christopher D Vanderwal
Author Information
Alexander S Karns: 1102 Natural Sciences II, Department of Chemistry, University of California, Irvine, CA, 92697-2025, USA.
Bryan D Ellis: 1102 Natural Sciences II, Department of Chemistry, University of California, Irvine, CA, 92697-2025, USA.
Philipp C Roosen: 1102 Natural Sciences II, Department of Chemistry, University of California, Irvine, CA, 92697-2025, USA.
Zeinab Chahine: Institute for Integrative Genome Biology, Center for Infectious Disease and Vector Research, Department of Molecular, Cell, and Systems Biology, University of California, Riverside, 900 University Avenue, Riverside, CA, 92521, USA.
Karine G Le Roch: Institute for Integrative Genome Biology, Center for Infectious Disease and Vector Research, Department of Molecular, Cell, and Systems Biology, University of California, Riverside, 900 University Avenue, Riverside, CA, 92521, USA.
Christopher D Vanderwal: 1102 Natural Sciences II, Department of Chemistry, University of California, Irvine, CA, 92697-2025, USA. ORCID
The flagship member of the antiplasmodial isocyanoterpenes, 7,20-diisocyanoadociane (DICA), was synthesized from dehydrocryptone in 10 steps, and in 13 steps from commercially available material. Our previous formal synthesis was reengineered, leveraging only productive transformations to deliver DICA in fewer than half the number of steps of our original effort. Important contributions, in addition to the particularly concise strategy, include a solution to the problem of axial nucleophilic methylation of a late-stage cyclohexanone, and the first selective synthesis and antiplasmodial evaluation of the DICA stereoisomer with both isonitriles equatorial.
