title: MetAP-2 inhibitors based on the fumagillin structure. Side-chain modification and ring-substituted analogues.
abstract: The preparation of a series of new fumagillin-derived MetAP-2 inhibitors is described. The synthetic approach was designed so as to permit modification of the fumagillin backbone at sites inaccessible through semisynthesis or previously existing total syntheses. An Evans aldolization and a ring-closing metathesis allowed the preparation of a pivotal intermediate which could then be functionalized in various ways using already established or newly developed methodologies.
authors.affiliation: Laboratoire de Chimie Organique et Bioorganique Associé au CNRS, Université de Haute-Alsace, Ecole Nationale Supérieure de Chimie de Mulhouse, 3 rue Alfred Werner, F-68093 Mulhouse Cedex, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Rodeschini
authors.forename: Jean-Guy
authors.initials: JG
authors.lastname: Boiteau
authors.forename: Pierre
authors.initials: P
authors.lastname: Van de Weghe
authors.forename: Céline
authors.initials: C
authors.lastname: Tarnus
authors.forename: Jacques
authors.initials: J
authors.lastname: Eustache
mesh_terms: D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D020533:Angiogenesis Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D003510:Cyclohexanes; D005231:Fatty Acids, Unsaturated / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D012717:Sesquiterpenes
chemical_list: D020533:Angiogenesis Inhibitors; D003510:Cyclohexanes; D005231:Fatty Acids, Unsaturated; D012717:Sesquiterpenes; C026211:fumagillin; D000626:Aminopeptidases; C106541:methionine aminopeptidase 2; D008666:Metalloendopeptidases