Angewandte Chemie. International edition in English 2014-03-03

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

Ian Paterson, Kenneth K-H Ng, Simon Williams, David C Millican, Stephen M Dalby

Index: Angew. Chem. Int. Ed. Engl. 53(10) , 2692-5, (2014)

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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.© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.