title: The total synthesis of (+)-migrastatin.
abstract: The first total synthesis of (+)-migrastatin, a macrolide natural product with interesting antimetastatic properties, has been accomplished. Our concise and flexible approach utilizes a Lewis acid-catalyzed diene aldehyde condensation to install the three contiguous stereocenters and the trisubstituted (Z)-alkene of migrastatin. Construction of the two remaining stereocenters and incorporation of the glutarimide-containing side chain have been achieved via an anti-selective aldol reaction, followed by a Horner-Wadsworth-Emmons olefination. Finally, the assembly of the macrocycle has been realized by a highly (E)-selective ring-closing metathesis.
authors.affiliation: Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10021, USA.
authors.forename: Christoph
authors.initials: C
authors.lastname: Gaul
authors.forename: Jon T
authors.initials: JT
authors.lastname: Njardarson
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Danishefsky
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D007783:Lactones / Q000138:chemical synthesis*; D018942:Macrolides; D010881:Piperidones / Q000138:chemical synthesis*; D013237:Stereoisomerism; D013302:Streptomyces / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D007783:Lactones; D018942:Macrolides; D010881:Piperidones; C418199:migrastatin