title: Highly convergent three component benzyne coupling: the total synthesis of ent-clavilactone B.
abstract: The first total synthesis of (+)-clavilactone B, a potent antifungal agent and novel tyrosine kinase inhibitor, is described. The absolute configuration of clavilactones has been unambiguously established by using Sharpless asymmetric epoxidation to generate the enantiomerically pure substrate. The strategy highlights the use of a powerful and convergent three-component benzyne coupling with a methylallyl Grignard and a chiral epoxy-aldehyde to generate two C-C bonds and install the carbon skeleton of clavilactone. Oxidative lactonization, ten-membered ring construction by ring closing metathesis, and oxidation gave clavilactone B.
authors.affiliation: Department of Chemistry, Imperial College London, London SW7 2AZ, England.
authors.forename: Igor
authors.initials: I
authors.lastname: Larrosa
authors.forename: Marianne I
authors.initials: MI
authors.lastname: Da Silva
authors.forename: Patricio M
authors.initials: PM
authors.lastname: Gómez
authors.forename: Peter
authors.initials: P
authors.lastname: Hannen
authors.forename: Eunjung
authors.initials: E
authors.lastname: Ko
authors.forename: Steven R
authors.initials: SR
authors.lastname: Lenger
authors.forename: Simon R
authors.initials: SR
authors.lastname: Linke
authors.forename: Andrew J P
authors.initials: AJ
authors.lastname: White
authors.forename: Donna
authors.initials: D
authors.lastname: Wilton
authors.forename: Anthony G M
authors.initials: AG
authors.lastname: Barrett
mesh_terms: D001555:Benzene Derivatives / Q000737:chemistry*; D002384:Catalysis; D007536:Isomerism; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D001555:Benzene Derivatives; D007783:Lactones; C522714:clavilactone B