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Thionium ion initiated medium-sized ring formation: the total synthesis of asteriscunolide D.

ABSTRACT: The first synthesis of the biologically active humulene natural product asteriscunolide D has been accomplished in nine steps without the use of protecting groups. The challenging 11-membered ring was forged via a diastereoselective thionium ion initiated cyclization, which constitutes a formal aldol disconnection to form a strained macrocycle. A stereospecific thioether activation-elimination protocol was developed for selective E-olefin formation, thus providing access to the most biologically active asteriscunolide. The absolute stereochemical configuration was established by the Zn-ProPhenol catalyzed enantioselective addition of methyl propiolate to an aliphatic aldehyde to afford a ?-hydroxy propiolate as a handle for butenolide formation via Ru-catalyzed alkene-alkyne coupling.

SUBMITTER: Trost BM

PROVIDER: S-EPMC3268366 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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Thionium ion initiated medium-sized ring formation: the total synthesis of asteriscunolide D.

Trost Barry M BM Burns Aaron C AC Bartlett Mark J MJ Tautz Thomas T Weiss Andrew H AH

Journal of the American Chemical Society 20120110 3

The first synthesis of the biologically active humulene natural product asteriscunolide D has been accomplished in nine steps without the use of protecting groups. The challenging 11-membered ring was forged via a diastereoselective thionium ion initiated cyclization, which constitutes a formal aldol disconnection to form a strained macrocycle. A stereospecific thioether activation-elimination protocol was developed for selective E-olefin formation, thus providing access to the most biologically ...[more]

PMID: 22236456

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