Enantioselective approaches to potential MetAP-2 reversible inhibitors.
[reaction: see text] Enantioselective deprotonation of 4-substituted cyclohexanones and highly stereoselective conjugate addition of higher order mixed cuprates were the key steps in a concise synthesis of fumagalone-related molecules. The origin of the (low) biological activity of the new compounds as compared to fumagalone is briefly discussed.
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.
Van de Weghe
Pierre
P
Salomon
Emmanuel
E
Tarnus
Céline
C
Eustache
Jacques
J
D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D003510:Cyclohexanes; D003512:Cyclohexanones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004852:Epoxy Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000737:chemistry; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D008968:Molecular Conformation; D012717:Sesquiterpenes; D013237:Stereoisomerism
D003510:Cyclohexanes; D003512:Cyclohexanones; D004791:Enzyme Inhibitors; D004852:Epoxy Compounds; D005231:Fatty Acids, Unsaturated; D012717:Sesquiterpenes; C476592:fumagalone; C026211:fumagillin; D000626:Aminopeptidases; C106541:methionine aminopeptidase 2; D008666:Metalloendopeptidases