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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, 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.

SUBMITTER: Karns AS

PROVIDER: S-EPMC6759395 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Concise Synthesis of the Antiplasmodial Isocyanoterpene 7,20-Diisocyanoadociane.

Karns Alexander S AS Ellis Bryan D BD Roosen Philipp C PC Chahine Zeinab Z Le Roch Karine G KG Vanderwal Christopher D CD

Angewandte Chemie (International ed. in English) 20190827 39

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 met ...[more]

PMID: 31270921

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