title: A novel strategy to assemble the beta-diketo acid pharmacophore of HIV integrase inhibitors on purine nucleobase scaffolds.
abstract: 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 palladium-catalyzed 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.
authors.affiliation: The Center for Drug Discovery, Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, Georgia 30602, USA.
authors.forename: Vinod
authors.initials: V
authors.lastname: Uchil
authors.forename: Byung
authors.initials: B
authors.lastname: Seo
authors.forename: Vasu
authors.initials: V
authors.lastname: Nair
mesh_terms: D019427:HIV Integrase / Q000187:drug effects*; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006868:Hydrolysis; D007651:Keto Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D011687:Purines / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D019428:HIV Integrase Inhibitors; D007651:Keto Acids; D011687:Purines; D019427:HIV Integrase