title: An efficient and highly diastereoselective synthesis of GSK1265744, a potent HIV integrase inhibitor.
abstract: A novel synthesis of GSK1265744, a potent HIV integrase inhibitor, is described. The synthesis is highlighted by an efficient construction of the densely functionalized pyridinone core as well as a highly diastereoselective formation of the acyl oxazolidine moiety. The latter exploits the target molecule's ability to chelate to Mg(2+), a key feature in the integrase inhibitor's mechanism of action.
authors.affiliation: Global API Chemistry, ‡MDR Chemical Science, §Analytical Sciences, GlaxoSmithKline , 709 Swedeland Road, King of Prussia, Pennsylvania 19406, United States.
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Kowalski
authors.forename: Ami S
authors.initials: AS
authors.lastname: Lakdawala
authors.forename: Frederick G
authors.initials: FG
authors.lastname: Vogt
authors.forename: Lianming
authors.initials: L
authors.lastname: Wu
mesh_terms: D002614:Chelating Agents / Q000737:chemistry / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008274:Magnesium / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D011728:Pyridones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D054659:Diketopiperazines
chemical_list: D002614:Chelating Agents; D019428:HIV Integrase Inhibitors; D008274:Magnesium; D011728:Pyridones; C584914:cabotegravir; D054659:Diketopiperazines