A novel strategy to assemble the β-diketo acid pharmacophore of HIV integrase inhibitors on purine nucleobase scaffolds

Claisen condensation, the key step in constructing the pharmacophore of aryl beta-diketo acids (DKA) as integrase inhibitors, fails in certain cases of highly electron-deficient heterocycles such as purines. A general synthetic strategy to assemble the DKA motif on the purine scaffold has been accomplished. The synthetic sequence entails a palladiumcatalyzed cross-coupling, a C-acylation.involving a tandem addition/elimination reaction, and a novel ferric ion-catalyzed selective hydrolysis of an enolic ether in the presence of a carboxylic acid ester.