New asymmetric synthesis of protein farnesyltransferaseinhibitorsviapalladium-catalyzed cross-coupling reactions of 2-iodo-imidazoles

Abstract

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.