Synthesis of the macrocyclic core of (-)-pladienolide B.
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.
Skaanderup
Philip R
PR
Department of Chemistry, Technical University of Denmark, Building 201, Kemitorvet, DK-2800 Kgs. Lyngby, Denmark.
Jensen
Thomas
T
D000475:Alkenes / Q000138:chemical synthesis / Q000737:chemistry; D018360:Crystallography, X-Ray; D004852:Epoxy Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D013302:Streptomyces / Q000737:chemistry / Q000378:metabolism
D000475:Alkenes; D004852:Epoxy Compounds; D018942:Macrolides; C522342:pladienolide B