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Synthesis of the macrocyclic core of (-)-pladienolide B
Philip R Skaanderup1, Thomas Jensen
1Department of Chemistry, Technical University of Denmark, Building 201, Kemitorvet, DK-2800 Kgs. Lyngby, Denmark.
Abstract:
An efficient synthesis of the macrocyclic core of (-)-pladienolide B is disclosed. The concise route relies on a chiral auxiliary-mediated asymmetric aldol addition and an osmium-catalyzed asymmetric dihydroxylation to install the three oxygenated stereocenters of the macrocycle. This purely reagent-controlled and flexible strategy sets the stage for future analogue syntheses and structure-activity relationship plotting of the appealing anticancer lead structure pladienolide B.
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