New asymmetric synthesis of protein farnesyltransferase inhibitors via palladium-catalyzed cross-coupling reactions of 2-iodo-imidazoles.
Palladium catalyzed cross-coupling reactions of 2-iodoimidazole have been studied to synthesize imidazole-containing protein farnesyltransferase inhibitors. The Suzuki coupling reaction proved to be very efficient to introduce functionalized alkyl chains at the 2-position of the imidazole ring and a new synthesis of the required alkenylboronates was realised by a reaction of cross metathesis. Asymmetric synthesis of allyl succinic derivatives allowed us to synthesize chiral protein farnesyltransferase inhibitors through Suzuki coupling and to determine the influence of the stereochemistry of our inhibitors on the enzymatic activity.
Kerhervé
Jennifer
J
Institut de Chimie des Substances Naturelles, UPR2301 CNRS, Centre de Recherche de Gif-sur-Yvette, Avenue de la Terrasse, 91198 Gif-sur-Yvette cedex, France.
Botuha
Candice
C
Dubois
Joëlle
J
D002384:Catalysis; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors*; D007093:Imidazoles / Q000737:chemistry*; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D013237:Stereoisomerism
D004791:Enzyme Inhibitors; D007093:Imidazoles; D010165:Palladium; C029899:imidazole; D051231:Farnesyltranstransferase