title: Concise Total Synthesis of Enigmazole A.
abstract: An efficient entry into the phosphorylated marine macrolide enigmazole A is described. Enigmazole A interferes with c-Kit signaling by an as yet unknown mode of action and is therefore a potential lead in the quest for novel anticancer agents. Key to success is a gold-catalyzed cascade comprising a [3,3]-sigmatropic rearrangement of a propargyl acetate along the periphery of a macrocyclic scaffold, followed by a transannular hydroalkoxylation of the resulting transient allenyl acetate. This transformation mandated the use of a chiral gold catalyst to ensure a matching double-asymmetric setting. Other noteworthy steps are the preparation of the oxazole building block by a palladium-catalyzed C-H activation, as well as the smooth ring-closing alkyne metathesis of a diyne substrate bearing a propargylic leaving group, which has only little precedent.
authors.affiliation: Max-Planck-Institut für Kohlenforschung, 45470, Mülheim/Ruhr, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Ahlers
authors.affiliation: Max-Planck-Institut für Kohlenforschung, 45470, Mülheim/Ruhr, Germany.
authors.forename: Teresa
authors.initials: T
authors.lastname: de Haro
authors.affiliation: Max-Planck-Institut für Kohlenforschung, 45470, Mülheim/Ruhr, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Gabor
authors.affiliation: Max-Planck-Institut für Kohlenforschung, 45470, Mülheim/Ruhr, Germany. fuerstner@kofo.mpg.de.
authors.forename: Alois
authors.initials: A
authors.lastname: Fürstner
mesh_terms: D002384:Catalysis; D018942:Macrolides / Q000138:chemical synthesis*; D009943:Organophosphorus Compounds / Q000138:chemical synthesis*; D010080:Oxazoles / Q000138:chemical synthesis*
chemical_list: D018942:Macrolides; D009943:Organophosphorus Compounds; D010080:Oxazoles; C553539:enigmazole A
keywords: alkynes; gold; metathesis; natural products; transannular reactions