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Total synthesis of the antimitotic marine macrolide (-)-leiodermatolide.

ABSTRACT: Leiodermatolide is an antimitotic macrolide isolated from the marine sponge Leiodermatium sp. whose potentially novel tubulin-targeting mechanism of action makes it an exciting lead for anticancer drug discovery. In pursuit of a sustainable supply, we report a highly stereocontrolled total synthesis (3.2% yield) based on a convergent sequence of palladium-mediated fragment assembly and macrolactonization. Boron-mediated aldol reactions were used to configure the three key fragments 2, 5, and 6 by employing the appropriate enantiomer of the lactate-derived ketone 7.

SUBMITTER: Paterson I

PROVIDER: S-EPMC4499261 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Total synthesis of the antimitotic marine macrolide (-)-leiodermatolide.

Paterson Ian I Ng Kenneth K-H KK Williams Simon S Millican David C DC Dalby Stephen M SM

Angewandte Chemie (International ed. in English) 20140130 10

Leiodermatolide is an antimitotic macrolide isolated from the marine sponge Leiodermatium sp. whose potentially novel tubulin-targeting mechanism of action makes it an exciting lead for anticancer drug discovery. In pursuit of a sustainable supply, we report a highly stereocontrolled total synthesis (3.2% yield) based on a convergent sequence of palladium-mediated fragment assembly and macrolactonization. Boron-mediated aldol reactions were used to configure the three key fragments 2, 5, and 6 b ...[more]

PMID: 24481746

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Leiodermatolide, a potent antimitotic macrolide from the marine sponge Leiodermatium sp.

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