Synthesis of the macrocyclic core of (-)-pladienolide B.

Philip R Skaanderup, Thomas Jensen

Department of Chemistry, Technical University of Denmark, Building 201, Kemitorvet, DK-2800 Kgs. Lyngby, Denmark.

Organic letters 2008 Jul 3

filter terms:

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.