A novel strategy to assemble the beta-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 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.
Uchil
Vinod
V
The Center for Drug Discovery, Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, Georgia 30602, USA.
Seo
Byung
B
Nair
Vasu
V
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
D019428:HIV Integrase Inhibitors; D007651:Keto Acids; D011687:Purines; D019427:HIV Integrase