title: A synthesis of (+)-FR182877, featuring tandem transannular Diels-Alder reactions inspired by a postulated biogenesis.
abstract: An efficient biomimetic synthesis of the reported structure of the hexacyclic, cytotoxic secondary metabolite FR182877 is described. The successful route features the synthesis of a 19-membered ring carbocycle using two pi-allyl palladium(II)-mediated C-C bond-forming reactions. This polyunsaturated macrocycle undergoes tandem transannular Diels-Alder reactions that create five rings and seven stereogenic centers in one operation under mild conditions, representing the first double transannular Diels-Alder reaction. The absolute stereochemistry of the natural product is demonstrated to be opposite of that reported previously. Significant quantities of both enantiomers of this microtubule-stabilizing natural product and related structures are now available via this approach.
authors.affiliation: Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Vosburg
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Vanderwal
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Sorensen
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D011083:Polycyclic Compounds / Q000138:chemical synthesis*
chemical_list: D000970:Antineoplastic Agents; C408303:FR 182877; D011083:Polycyclic Compounds