Concise Synthesis of the Antiplasmodial Isocyanoterpene 7,20‐Diisocyanoadociane

Abstract

The flagship member of the antiplasmodial isocyanoterpenes,7,20-diisocyanoadociane (DICA), was synthesized from dehydrocryptone in 10 steps,a nd 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,i n addition to the particularly concise strategy,include asolution to the problem of axial nucleophilic methylation of alate-stage cyclohexanone,a nd the first selective synthesis and antiplasmodial evaluation of the DICA stereoisomer with both isonitriles equatorial.