title: 17S,20S-Methanofusidic acid, a new potent semi-synthetic fusidane antibiotic.
abstract: A novel fusidic acid type antibiotic having the side chain linked to the tetracyclic ring system via a spiro-cyclopropane system is described. 17S,20S-Methanofusidic acid is obtained by an efficient synthetic route including cyclopropanation of the Delta17(20) bond with attack solely from the least hindered alpha-face. The spiro-cyclopropane system orients the side chain into a bioactive conformational space. The new 17S,20S-methanofusidic acid exerts antibacterial activity against several Gram-positive species with potency essentially equal to natural fusidic acid.
authors.affiliation: LEO Pharma, Industriparken 55, DK-2750 Ballerup, Denmark. tore.duvold@leo-pharma.com
authors.forename: Tore
authors.initials: T
authors.lastname: Duvold
authors.forename: Anne
authors.initials: A
authors.lastname: Jørgensen
authors.forename: Niels R
authors.initials: NR
authors.lastname: Andersen
authors.forename: Anne S
authors.initials: AS
authors.lastname: Henriksen
authors.forename: Morten
authors.initials: M
authors.lastname: Dahl Sørensen
authors.forename: Fredrik
authors.initials: F
authors.lastname: Björkling
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D024881:Drug Resistance, Bacterial; D005672:Fusidic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D013329:Structure-Activity Relationship
chemical_list: C475534:17,20-methanofusidic acid; D000900:Anti-Bacterial Agents; D005672:Fusidic Acid