MetAP-2 inhibitors based on the fumagillin structure. Side-chain modification and ring-substituted analogues.
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.
Rodeschini
Vincent
V
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.
Boiteau
Jean-Guy
JG
Van de Weghe
Pierre
P
Tarnus
Céline
C
Eustache
Jacques
J
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
D020533:Angiogenesis Inhibitors; D003510:Cyclohexanes; D005231:Fatty Acids, Unsaturated; D012717:Sesquiterpenes; C026211:fumagillin; D000626:Aminopeptidases; C106541:methionine aminopeptidase 2; D008666:Metalloendopeptidases