title: The preparation of zaragozic acid A analogues by directed biosynthesis.
abstract: Zaragozic acid A analogues are produced by an unidentified sterile fungus when it is exogenously supplied with 2-thiophenecarboxylic acid, 3-thiophenecarboxylic acid, 2-furoic acid, 2-fluorobenzoic acid, 3-fluorobenzoic acid, or 4-fluorobenzoic acid. The analogues carry 2-thiophenyl, 3-thiophenyl, 2-furyl, o-fluorophenyl, m-fluorophenyl, or p-fluorophenyl group, respectively, at C-6' of the C-1 alkyl side chain replacing the phenyl group of natural zaragozic acid A. All the new analogues of zaragozic acid A possess picomolar inhibitory activity against squalene synthase in vitro.
authors.affiliation: Merck Research Laboratories, Rahway, New Jersey 07065.
authors.forename: T S
authors.initials: TS
authors.lastname: Chen
authors.forename: B
authors.initials: B
authors.lastname: Petuch
authors.forename: J
authors.initials: J
authors.lastname: MacConnell
authors.forename: R
authors.initials: R
authors.lastname: White
authors.forename: G
authors.initials: G
authors.lastname: Dezeny
authors.forename: B
authors.initials: B
authors.lastname: Arison
authors.forename: J D
authors.initials: JD
authors.lastname: Bergstrom
authors.forename: L
authors.initials: L
authors.lastname: Colwell
authors.forename: L
authors.initials: L
authors.lastname: Huang
authors.forename: R L
authors.initials: RL
authors.lastname: Monaghan
mesh_terms: D001643:Bridged Bicyclo Compounds / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000037:antagonists & inhibitors*; D005658:Fungi / Q000187:drug effects / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D014233:Tricarboxylic Acids / Q000378:metabolism*
chemical_list: D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D014233:Tricarboxylic Acids; C075117:squalestatin 1; D013186:Farnesyl-Diphosphate Farnesyltransferase