title: Divergent strategy for the synthesis of alpha-aryl-substituted fosmidomycin analogues.
abstract: Fosmidomycin is the first representative of a new class of antimalarial drugs acting through inhibition of 1-deoxy-D-xylulose 5-phosphate (DOXP) reductoisomerase (DXR), an essential enzyme in the non-mevalonate pathway for the synthesis of isoprenoids. This work describes a divergent strategy for the synthesis of a series of alpha-aryl-substituted fosmidomycin analogues, featuring a palladium-catalyzed Stille coupling as the key step. An alpha-(4-cyanophenyl)fosmidomycin analogue emerged as the most potent analogue in the present series. Its antimalarial activity clearly surpasses that of the reference compound fosmidomycin.
authors.affiliation: Laboratory for Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Ghent University, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Devreux
authors.forename: Jochen
authors.initials: J
authors.lastname: Wiesner
authors.forename: Hassan
authors.initials: H
authors.lastname: Jomaa
authors.forename: Jef
authors.initials: J
authors.lastname: Rozenski
authors.forename: Johan
authors.initials: J
authors.lastname: Van der Eycken
authors.forename: Serge
authors.initials: S
authors.lastname: Van Calenbergh
mesh_terms: D000107:Acetylation; D004926:Escherichia coli / Q000737:chemistry; D005578:Fosfomycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure
chemical_list: D005578:Fosfomycin; C024640:fosmidomycin