Concise Synthesis of the Antiplasmodial Isocyanoterpene 7, 20‐Diisocyanoadociane. (23rd August 2019)

• Record Type: Journal Article
• Authors: Karns, Alexander S.; Ellis, Bryan D.; Roosen, Philipp C.; Chahine, Zeinab; Le Roch, Karine G.; Vanderwal, Christopher D.
• Is Part Of: Angewandte Chemie. Volume 131:Number 39(2019)
• Page Start: 13887
• Page End: 13890
• Publication Date: 2019-08-23
• Subjects: Antimalariastoffe -- Birch-Reduktion -- Stereokontrolle -- Terpenoide -- Totalsynthese; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201906834
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: 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. Abstract : Das antiplasmodiale Isocyanoterpen 7, 20‐Diisocyanoadocian (DICA) wurde in zehn Schritten aus einfachen Ausgangsmaterialien hergestellt. Wichtige Aspekte der Studie sind eine Lösung für das Problem der axialen nukleophilen Methylierung eines späten Cyclohexanons und die erste selektive Synthese und antiplasmodiale Evaluierung des DICA‐Stereoisomers mit beiden Isonitrilen in äquatorialer Position.